Atrial septal defect

From Wikipedia, the free encyclopedia

Atrial septal defect

Classification and external resources

Illustration of an atrial septal defect.

Atrial septal defect (ASD) is a form of congenital heart defect that enables blood flow between two
compartments of the heart called the left and right atria. Normally, the right and left atria are separated by a
septum called the interatrial septum. If this septum is defective or absent, then oxygen-rich blood can flow
directly from the left side of the heart to mix with the oxygen-poor blood in the right side of the heart, or vice
versa.[1] This can lead to lower-than-normal oxygen levels in the arterial blood that supplies the brain, organs,
and tissues. However, an ASD may not produce noticeable signs or symptoms, especially if the defect is small.
A "shunt" is the presence of a net flow of blood through the defect, either from left to right or right to left. The
amount of shunting present, if any, determines the hemodynamic significance of the ASD (see Pathophysiology
below). A "right-to-left-shunt" typically poses the more dangerous scenario. (see Pathophysiology below.)

During development of the fetus, the interatrial septum develops to separate the left and right atria. However, a
hole in the septum called the foramen ovale /fremn ovli/, allows blood from the right atrium to enter the
left atrium during fetal development. This opening allows blood to bypass the nonfunctional fetal lungs while the
fetus obtains its oxygen from the placenta. A layer of tissue called the septum primum acts as a valve over the
foramen ovale during fetal development. After birth, the pressure in the right side of the heart drops as the
lungs open and begin working, causing the foramen ovale to close entirely. In approximately 25% of adults,
[2]
the foramen ovale does not entirely seal.[3] In these cases, any elevation of the pressure in the pulmonary
circulatory system (due to pulmonary hypertension, temporarily while coughing, etc.) can cause the foramen
ovale to remain open. This is known as a patent foramen ovale (PFO), which is a type of atrial septal defect.

Pathophysiology[edit]

In unaffected individuals, the chambers of the left side of the heart are under higher pressure than the
chambers of the right side of the heart. This is because the left ventricle has to produce enough pressure to
pump blood throughout the entire body, while the right ventricle needs only to produce enough pressure to
pump blood to the lungs.

In the case of a large ASD (>9mm), which may result in a clinically remarkable left-to-right shunt, blood will
shunt from the left atrium to the right atrium. This extra blood from the left atrium may cause a volume overload
of both the right atrium and the right ventricle. If untreated, this condition can result in enlargement of the right
side of the heart and ultimately heart failure. [4]

Any process that increases the pressure in the left ventricle can cause worsening of the left-to-right shunt. This
includes hypertension, which increases the pressure that the left ventricle has to generate in order to open
the aortic valve during ventricular systole, and coronary artery disease which increases the stiffness of the left
ventricle, thereby increasing the filling pressure of the left ventricle during ventricular diastole. The left-to-right
shunt increases the filling pressure of the right heart (preload) and forces the right ventricle to pump out more
blood than the left ventricle. This constant overloading of the right side of the heart will cause an overload of the
entire pulmonary vasculature. Eventually, pulmonary hypertension may develop.

The pulmonary hypertension will cause the right ventricle to face increased afterload. The right ventricle will be
forced to generate higher pressures to try to overcome the pulmonary hypertension. This may lead to right
ventricular failure (dilatation and decreased systolic function of the right ventricle).
When the pressure in the right atrium rises to equal the pressure in the left atrium, there is no longer a pressure
gradient between these heart chambers, and the left-to-right shunt will diminish or cease. In other words, there
is no longer a net flow of blood across the ASD.

If the ASD is left uncorrected, the pulmonary hypertension progresses and the pressure in the right side of the
heart will become greater than the left side of the heart. This reversal of the pressure gradient across the ASD
causes the shunt to reverse; a right-to-left shunt will exist. This phenomenon is known as Eisenmenger's
syndrome. Once right-to-left shunting occurs, a portion of the oxygen-poor blood will get shunted to the left side
of the heart and ejected to the peripheral vascular system. This will cause signs of cyanosis.

Heart of human embryo of about thirty-five days

Atrial septal defect with left-to-right shunt

Illustration depicting atrial septal defect.

Epidemiology[edit]

As a group, atrial septal defects are detected in 1 child per 1500 live births. PFO are quite common (appearing
in 1020% of adults) but asymptomatic and therefore undiagnosed. ASDs make up 30 to 40% of all congenital
heart diseases that are seen in adults.[5]

The ostium secundum atrial septal defect accounts for 7% of all congenital heart lesions. This lesion shows a
female preponderance, with a male:female ratio of 1:2. [6]

Genetic research[edit]

In May 2013 team of researchers led by Professor Bernard Keavney of British Heart Foundation (BHF)
discovered a new gene associated with the disease. According to them a common genetic variation near a
gene called MSX1 is strongly associated with the risk of an ASD and this discovery of the particular gene is an
important step forward as it will lead to better understanding of why some patients are born with ASD. [7]

Types of atrial septal defects[edit]

Schematic drawing showing the location of different types of ASD, the view is into an opened right atrium. HV: right
ventricle; VCS: superior vena cava; VCI: inferior vena cava; 1: upper sinus venosus defect; 2: lower sinus venosus defect; 3:
secundum defect; 4: defect involving coronary sinus; 5; primum defect.
There are many types of atrial septal defects. They are differentiated from each other by whether they involve
other structures of the heart and how they are formed during the developmental process during
early fetal development.

Ostium secundum atrial septal defect[edit]

The ostium secundum atrial septal defect is the most common type of atrial septal defect, and comprises 6
10% of all congenital heart diseases.

The secundum atrial septal defect usually arises from an enlarged foramen ovale, inadequate growth of
the septum secundum, or excessive absorption of the septum primum. Ten to twenty percent of individuals with
ostium secundum ASDs also have mitral valve prolapse.[8]

If the ostium secundum ASD is accompanied by an acquired mitral valve stenosis, that is called Lutembacher's
syndrome.[9]\DR ABO EL ASRAR AT M.D

Natural history[edit]

Most individuals with an uncorrected secundum ASD do not have significant symptoms through early
adulthood. More than 70 percent develop symptoms by about 40 years of age. Symptoms are typically
decreased exercise tolerance, easy fatigueability,palpitations, and syncope.

Complications of an uncorrected secundum ASD include pulmonary hypertension, right-sided heart

failure, atrial fibrillation orflutter, stroke, and Eisenmenger's syndrome.

While pulmonary hypertension is unusual before 20 years of age, it is seen in 50 percent of individuals above
the age of 40. Progression to Eisenmenger's syndrome occurs in 5 to 10 percent of individuals late in the
disease process.[9]

Patent foramen ovale[edit]

A patent foramen ovale (PFO) is a small channel that has some hemodynamic consequence; it is a remnant
of the fetal foramen ovale. Clinically it is linked to decompression sickness, paradoxical embolism
and migraine. On echocardiography, there may not be any shunting of blood noted except when the patient
coughs.

There is debate within the neurology and cardiology communities about the role of a PFO in cryptogenic (i.e. of
unknown cause) neurologic events such as strokes and transient ischemia attacks (TIAs) without any other
potential cause. Some data suggested that PFOs may be involved in the pathogenesis of
some migraine headaches.[citation needed][dubious discuss] Several clinical trials are currently underway to investigate the
role of PFO in these clinical situations.[citation needed]

Ostium primum atrial septal defect[edit]

Main article: Ostium primum atrial septal defect

A defect in the ostium primum is occasionally classified as an atrial septal defect, [10] but it is more
commonly classified as an atrioventricular septal defect.[11][12] Ostium primum defects are less common
than ostium secundum defects.[13]

Sinus venosus atrial septal defect[edit]

A sinus venosus ASD is a type of atrial septum defect in which the defect in the septum involves the
venous inflow of either the superior vena cava or the inferior vena cava.

A sinus venosus ASD that involves the superior vena cava makes up 2 to 3% of all interatrial
communication. It is located at the junction of the superior vena cava and the right atrium. It is frequently
associated with anomalous drainage of the right-sided pulmonary veins into the right atrium (instead of the
normal drainage of the pulmonary veins into the left atrium). [14]

Ultrasound picture of the heart, seen in asubcostal view. The apex towards the right, atria to the left. ASD secundum
seen as a discontinuation of the white band of the atrial septum. Enlarged right atrium below. Enlarged pulmonary veins
seen entering left atrium above.

Common or single atrium[edit]

Common (or single) atrium is a failure of development of the embryologic components that contribute to
the atrial septal complex. It is frequently associated with heterotaxy syndrome.[15]

Mixed atrial septal defect[edit]

The inter atrial septum can be divided into 5 septal zones. If the defect involves 2 or more of the 5 septal
zones, then the defect is termed a mixed atrial septal defect.[4]

Diagnosis[edit]

Abnormal chest X-ray as seen in a patient of Atrial septal defect

Diagnosis in children[edit]

Most individuals with a significant ASD are diagnosed in utero or in early childhood with the use
of ultrasonography or auscultation of the heart sounds during physical examination.

Diagnosis in adults[edit]

Some individuals with an ASD will have undergone surgical correction of their ASD during childhood. The
development of signs and symptoms due to an ASD are related to the size of the intracardiac shunt.
Individuals with a larger shunt tend to present with symptoms at a younger age.

Adults with an uncorrected ASD will present with symptoms of dyspnea on exertion (shortness of breath
with minimal exercise), congestive heart failure, or cerebrovascular accident (stroke). They may be noted
on routine testing to have an abnormal chest x-ray or an abnormal ECG and may haveatrial fibrillation. If
the ASD causes a left-to-right shunt, the pulmonary vasculature in both lungs may appear dilated on chest
x-ray, due to the increase in pulmonary blood flow.[16]

Physical exam auscultation of the heart[edit]

The physical findings in an adult with an ASD include those related directly to the intracardiac shunt, and
those that are secondary to the right heart failure that may be present in these individuals.

Upon auscultation of the heart sounds, there may be a systolic ejection murmur that is attributed to the
pulmonic valve. This is due to the increased flow of blood through the pulmonic valve rather than any
structural abnormality of the valve leaflets.

In unaffected individuals, there are respiratory variations in the splitting of the second heart sound (S2).
During respiratory inspiration, the negative intrathoracic pressure causes increased blood return into the
right side of the heart. The increased blood volume in the right ventricle causes the pulmonic valve to stay
open longer during ventricular systole. This causes a normal delay in the P2 component of S2. During
expiration, the positive intrathoracic pressure causes decreased blood return to the right side of the heart.
The reduced volume in the right ventricle allows the pulmonic valve to close earlier at the end of ventricular
systole, causing P2 to occur earlier.

In individuals with an ASD, there is a fixed splitting of S2. The reason that there is a fixed splitting of the
second heart sound is that the extra blood return during inspiration gets equalized between the left and
right atrium due to the communication that exists between the atria in individuals with ASD.

The right ventricle can be thought of as continuously overloaded because of the left to right shunt,
producing a widely split S2. Because the atria are linked via the atrial septal defect, inspiration produces
no net pressure change between them, and has no effect on the splitting of S2. Thus, S2 is split to the
same degree during inspiration as expiration, and is said to be fixed.

Echocardiography[edit]

In transthoracic echocardiography, an atrial septal defect may be seen on color flow imaging as a jet of
blood from the left atrium to the right atrium.

If agitated saline is injected into a peripheral vein during echocardiography, small air bubbles can be seen
on echocardiographic imaging. It may be possible to see bubbles travel across an ASD either at rest or
during a cough. (Bubbles will only flow from right atrium to left atrium if the RA pressure is greater than
LA).

Because better visualization of the atria is achieved with transesophageal echocardiography, this test may
be performed in individuals with a suspected ASD which is not visualized on transthoracic imaging.

Newer techniques to visualize these defects involve intracardiac imaging with special catheters that are
typically placed in the venous system and advanced to the level of the heart. This type of imaging is
becoming more common and involves only mild sedation for the patient typically.

If the individual has adequate echocardiographic windows, it is possible to use the echocardiogram to
measure the cardiac output of the left ventricle and the right ventricle independently. In this way, it is
possible to estimate the shunt fraction using echocardiograpy.

Transcranial Doppler (TCD) bubble study[edit]

A less invasive method for detecting a PFO or other ASDs than transesophagal ultrasound is Transcranial
Doppler with bubble contrast.[17] This method reveals the cerebral impact of the ASD or PFO.

Electrocardiogram[edit]

The ECG findings in atrial septal defect vary with the type of defect the individual has. Individuals with
atrial septal defects may have a prolonged PR interval (a first degree heart block). The prolongation of the
PR interval is probably due to the enlargement of the atria that is common in ASDs and the increased
distance due to the defect itself. Both of these can cause an increased distance of internodal conduction
from the SA node to the AV node.[18]

In addition to the PR prolongation, individuals with a primum ASD have a left axis deviation of the QRS
complex while those with a secundum ASD have a right axis deviation of the QRS complex. Individuals
with a sinus venosus ASD exhibit a left axis deviation of the P wave (not the QRS complex).

A common finding in the ECG is the presence of incomplete right bundle branch block. The presence of a
right bundle branch block is so characteristic that if it is absent, the diagnosis of ASD should be
reconsidered.
Treatment[edit]

Once someone is found to have an atrial septal defect, a determination of whether it should be corrected
has to be made.

Surgical mortality due to closure of an ASD is lowest when the procedure is performed prior to the
development of significant pulmonary hypertension. The lowest mortality rates are achieved in individuals
with a pulmonary artery systolic pressure of less than 40 mmHg.

If Eisenmenger's syndrome has occurred, there is significant risk of mortality regardless of the method of
closure of the ASD. In individuals who have developed Eisenmenger's syndrome, the pressure in the right
ventricle has raised high enough to reverse the shunt in the atria. If the ASD is then closed,
the afterload that the right ventricle has to act against has suddenly increased. This may cause immediate
right ventricular failure, since it may not be able to pump the blood against the pulmonary hypertension.

Closure of an ASD in individuals under age 25 has been shown to have a low risk of complications, and
individuals have a normal lifespan (comparable to a healthy age-matched population). Closure of an ASD
in individuals between the ages of 25 and 40 who are asymptomatic but have a clinically significant shunt
is controversial. Those that perform the procedure believe that they are preventing long-term deterioration
in cardiac function and preventing the progression of pulmonary hypertension.

Methods of closure of an ASD include surgical closure and percutaneous closure.

Evaluation prior to correction[edit]

Prior to correction of an ASD, an evaluation is made of the severity of the individual's pulmonary
hypertension (If present at all) and whether it is reversible (Closure of an ASD may be recommended for
prevention purposes, to avoid such a complication in the first place. Pulmonary hypertension is not always
present in adults that are diagnosed with an ASD in adulthood).

If pulmonary hypertension is present, the evaluation may include a right heart catheterization. This involves
placing a catheter in the venous system of the heart and measuring pressures and oxygen saturations in
the SVC, IVC, right atrium, right ventricle, pulmonary artery, and in the wedge position. Individuals with a
pulmonary vascular resistance (PVR) of less than 7 wood units show regression of symptoms
(including NYHA functional class). On the other hand, individuals with a PVR of greater than 15 wood units
have increased mortality associated with closure of the ASD.
If the pulmonary arterial pressure is more than 2/3 the systemic systolic pressure, there should be a net
left-to-right shunt of at least 1.5:1 or evidence of reversibility of the shunt when given pulmonary artery
vasodilators prior to surgery. (If Eisenmenger's physiology has set in, it must be proven that the right-to-left
shunt is reversible with pulmonary artery vasodilators prior to surgery.)

Catheter procedure[edit]

Until the early 1990s, surgery was the usual method for closing all ASDs. Now, thanks to medical
advances, doctors can use catheter procedures to close secundum ASDs, the most common type of ASD.
For this procedure, the patient is given medicine so he or she will sleep through it and not feel any pain.
During the procedure, the doctor inserts a catheter (a thin, flexible tube) into a vein in the groin (upper
thigh) and threads it to the heart's septum. The catheter has a tiny umbrella-like device folded up inside it.
When the catheter reaches the septum, the device is pushed out of the catheter and positioned so that it
plugs the hole between the atria. The device is secured in place and the catheter is withdrawn from the
body. Within 6 months, normal tissue grows in and over the device. There is no need to replace the closure
device throughout the patient's life. Doctors often use echocardiography (echo) or transesophageal echo
(TEE) as well as angiography to guide them in threading the catheter to the heart and closing the defect.
TEE is a special type of echo that takes pictures of the heart through the esophagus (the passage leading
from the mouth to the stomach). Catheter procedures are much easier on patients than surgery because
they involve only a needle puncture in the skin where the catheter is inserted. This means that recovery is
faster and easier. The outlook for patients having this procedure is excellent. Closures are successful in
more than 9 out of 10 patients, with no significant leakage. Rarely, a defect is too large for catheter closure
and surgery is needed.

Surgical ASD closure[edit]

Illustration depicting surgical patch closure of ASD

Surgical closure of an ASD involves opening up at least one atrium and closing the defect with a patch
under direct visualization.

Percutaneous ASD closure[edit]

Percutaneous closure of an ASD is currently only indicated for the closure of secundum ASDs with a
sufficient rim of tissue around the septal defect so that the closure device does not impinge upon
the SVC, IVC, or the tricuspid or mitral valves. The Amplatzer Septal Occluder (ASO) is commonly used to
close ASDs. The ASO consists of two self-expandable round discs connected to each other with a 4 mm
waist, made up of 0.0040.005 Nitinol wire mesh filled with Dacron fabric. Implantation of the device is
relatively easy. The prevalence of residual defect is low. The disadvantages are a thick profile of the device
and concern related to a large amount of nitinol (a nickel-titanium compound) in the device and
consequent potential for nickel toxicity.

Percutaneous closure is the method of choice in most centres. [19]

Complications[edit]

Due to the communication between the atria that occurs in ASDs, disease entities or complications from
the condition, are possible. Patients with an uncorrected atrial septal defects may be at increased risk for
developing a cardiac arrhythmia, as well as more frequent respiratory infections. [13]
Decompression sickness[edit]

ASDs, and particularly PFOs, are a predisposing risk factor for decompression sickness in divers because
a proportion of venous blood carrying inert gases, such as helium or nitrogen does not pass through the
lungs.[20][21] The only way to release the excess inert gases from the body is to pass the blood carrying the
inert gases through the lungs to be exhaled. If some of the inert gas-laden blood passes through the PFO,
it avoids the lungs and the inert gas is more likely to form large bubbles in the arterial blood stream
causing decompression sickness.

Eisenmenger's syndrome[edit]

Main article: Eisenmenger's syndrome

If a net flow of blood exists from the left atrium to the right atrium, called a left-to-right shunt, then there is
an increase in the blood flow through the lungs. Initially, this increased blood flow is asymptomatic, but if it
persists, the pulmonary blood vessels may stiffen, causing pulmonary hypertension. The pulmonary
hypertension increases the pressures in the right side of the heart, leading to the reversal of the shunt into
a right-to-left shunt. Once the reversal of the shunt occurs, and the blood begins flowing in the opposite
direction through the ASD, that is called Eisenmenger's syndrome. The syndrome is a rare and late
complication of an ASD.

Paradoxical embolus[edit]

Venous thrombi (clots in the veins) are quite common. Embolizations (dislodgement of thrombi) normally
go to the lung and cause pulmonary emboli. In an individual with ASD, these emboli can potentially enter
the arterial system. This can cause any phenomenon that is attributed to acute loss of blood to a portion of
the body, including cerebrovascular accident (stroke), infarction of thespleen or intestines, or even a distal
extremity (i.e., finger or toe).

This is known as a paradoxical embolus because the clot material paradoxically enters the arterial system
instead of going to the lungs.

Migraine[edit]

Main article: Migraine surgery#Patent foramen ovale closure

Some recent research has suggested that a proportion of cases of migraine may be caused by patent
foramen ovale. While the exact mechanism remains unclear, closure of a PFO can reduce symptoms in
 certain cases.[22][23] This remains controversial. 20% of the general population have a PFO, which for the
most part, is asymptomatic. 20% of the female population have migraines. And, the placebo effect in
migraine typically averages around 40%. The high frequency of these facts makes statistically significant
relationships between PFO and migraine difficult (i.e., the relationship may just be chance or coincidence).
In a large randomized controlled trial the higher prevalence of patent foramen ovale in migraine patients
was confirmed, but migraine headache cessation was not more prevalent in the group of migraine patients
that underwent closure of their patent foramen ovale. [24]

Ventricular septal defect

From Wikipedia, the free encyclopedia

Ventricular septal defect

Classification and external resources

A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and
right ventricles of the heart.

The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively
innervated with conducting cardiomyocytes.

The membranous portion, which is close to the atrioventricular node, is most commonly affected in adults and
older children in the United States.[1] It is also the type that will most commonly require surgical intervention,
comprising over 80% of cases.[2]

Membranous ventricular septal defects are more common than muscular ventricular septal defects, and are the
most common congenital cardiac anomaly. [3]

Diagnosis[edit]

Echocardiographic image of a moderate ventricular septal defect in the mid-muscular part of the septum. The trace in the
lower left shows the flow during one complete cardiac cycle and the red mark the time in the cardiac cycle that the image
was captured. Colours are used to represent the velocity of the blood. Flow is from the left ventricle (right on image) to
the right ventricle (left on image). The size and position is typical for a VSD in the newborn period.

A VSD can be detected by cardiac auscultation. Classically, a VSD causes a pathognomonic holo-
or pansystolic murmur. Auscultation is generally considered sufficient for detecting a significant VSD. The
murmur depends on the abnormal flow of blood from the left ventricle, through the VSD, to the right ventricle. If
there is not much difference in pressure between the left and right ventricles, then the flow of blood through the
VSD will not be very great and the VSD may be silent. This situation occurs a) in the fetus (when the right and
left ventricular pressures are essentially equal), b) for a short time after birth (before the right ventricular
pressure has decreased), and c) as a late complication of unrepaired VSD. Confirmation of cardiac
auscultation can be obtained by non-invasive cardiac ultrasound(echocardiography). To more accurately
measure ventricular pressures, cardiac catheterization, can be performed.

Pathophysiology[edit]

During ventricular contraction, or systole, some of the blood from the left ventricle leaks into the right ventricle,
passes through the lungs and reenters the left ventricle via the pulmonary veins and left atrium. This has two
net effects. First, the circuitous refluxing of blood causes volume overload on the left ventricle. Second,
because the left ventricle normally has a much higher systolic pressure (~120 mmHg) than the right ventricle
(~20 mmHg), the leakage of blood into the right ventricle therefore elevates right ventricular pressure and
volume, causing pulmonary hypertensionwith its associated symptoms.

In serious cases, the pulmonary arterial pressure can reach levels that equal the systemic pressure. This
reverses the left to right shunt, so that blood then flows from the right ventricle into the left ventricle, resulting in
cyanosis, as blood is by-passing the lungs for oxygenation. [4]

This effect is more noticeable in patients with larger defects, who may present with breathlessness, poor
feeding and failure to thrive in infancy. Patients with smaller defects may be asymptomatic. Four different septal
defects exist, with perimembranous most common, outlet, atrioventricular, and muscular less commonly.[5]

Signs and symptoms[edit]

Ventricular septal defect is usually symptomless at birth. It usually manifests a few weeks after birth.

Symptoms[edit]

VSD is an acyanotic congenital heart defect, aka a Left-to-right shunt, so there are no signs of cyanosis in the
early stage. However, uncorrected VSD can increase pulmonary resistance leading to the reversal of the shunt
and corresponding cyanosis.

Signs[edit]

Pansystolic (Holosystolic) murmur along lower left sternal border(depending upon the size of the
defect) +/- palpable thrill (palpable turbulence of blood flow). Heart sounds are normal. Larger VSDs may
cause a parasternal heave, a displaced apex beat (the palpable heartbeat moves laterally over time, as
the heart enlarges). An infant with a large VSD will fail to thrive and become sweaty and tachypnoeic
(breathe faster) with feeds.[6]
The restrictive VSDs (smaller defects) are associated with a louder murmur and more palpable thrill (grade IV
murmur). Larger defects may eventually be associated with pulmonary hypertension due to the increased blood
flow. Over time this may lead to an Eisenmenger phenomenon: the original VSD operating with a left-to-right
shunt, now becomes a right-to-left shunt because of the increased pressures in the pulmonary vascular bed.

CAUSES: The cause of VSD (ventricular septal defect) includes the incomplete looping of the heart during
days 24-28 of development. Faults with NKX2.5 gene can cause this.

Treatment[edit]

A nitinol device for closing muscular VSDs, 4 mm diameter in the centre. It is shown mounted on the catheter into which it
will be withdrawn during insertion.

Most cases do not need treatment and heal at the first years of life. Treatment is either conservative or surgical.
Smaller congenital VSDs often close on their own, as the heart grows, and in such cases may be treated
conservatively. Some cases may necessitate surgical intervention, i.e. with the following indications:

1. Failure of congestive cardiac failure to respond to medications

2. VSD with pulmonic stenosis

3. Large VSD with pulmonary hypertension

4. VSD with aortic regurgitation

For the surgical procedure, a heart-lung machine is required and a median sternotomy is
performed. Percutaneous endovascular procedures are less invasive and can be done on a beating heart, but
are only suitable for certain patients. Repair of most VSDs is complicated by the fact that the conducting
system of the heart is in the immediate vicinity.
Ventricular septum defect in infants is initially treated medically with cardiac glycosides (e.g., digoxin 10-
20 g/kg per day), loop diuretics (e.g., furosemide 13 mg/kg per day) and ACE inhibitors(e.g., captopril 0.5
2 mg/kg per day).

Surgical technique for Repair of Perimembranous VSD[edit]

a) Surgical closure of a Perimembranous VSD is performed on cardiopulmonary bypass with ischemic arrest.
Patients are usually cooled to 28 degrees. Percutaneous Device closure of these defects is rarely performed in
the United States because of the reported incidence of both early and late onset complete heart block after
device closure, presumably secondary to device trauma to the AV node.

b) Surgical exposure is achieved through the right atrium. The tricuspid valve septal leaflet is retracted or
incised to expose the defect margins.

c) Several patch materials are available, including native pericardium, bovine pericardium, PTFE (Gore-Tex or
Impra), or Dacron.

d) Suture techniques include horizontal pledgeted mattress sutures, and running polypropylene suture.

e) Critical attention is necessary to avoid injury to the conduction system located on the left ventricular side of
the interventricular septum near the papillary muscle of the conus.

f) Care is taken to avoid injury to the aortic valve with sutures.

g) Once the repair is complete, the heart is extensively deaired by venting blood through the aortic cardioplegia
site, and by infusing Carbon Dioxide into the operative field to displace air.

h) Intraoperative transesophageal echocardiography is used to confirm secure closure of the VSD, normal
function of the aortic and tricuspid valves, good ventricular function, and the elimination of all air from the left
side of the heart.

i) The sternum, fascia and skin are closed, with potential placement of a local anesthetic infusion catheter
under the fascia, to enhance postoperative pain control.

j) A video of Perimembranous VSD repair, including the operative technique, and the daily postoperative
recovery, can be seen here: VSD Repair, Perimembranous Ventricular Septal Defect
Epidemiology and Etiology[edit]

VSDs are the most common congenital cardiac anomalies. They are found in 30-60% of all newborns with a
congenital heart defect, or about 2-6 per 1000 births. During heart formation, when the heart begins life as a
hollow tube, it begins to partition, forming septa. If this does not occur properly it can lead to an opening being
left within the ventricular septum. It is debatable whether all those defects are true heart defects, or if some of
them are normal phenomena, since most of the trabecular VSDs close spontaneously.[7] Prospective studies
give a prevalence of 2-5 per 100 births of trabecular VSDs that closes shortly after birth in 80-90% of the cases.
[8][9]

Congenital VSDs are frequently associated with other congenital conditions, such as Down syndrome.[10]

A VSD can also form a few days after a myocardial infarction[11] (heart attack) due to mechanical tearing of
the septal wall, before scar tissue forms, when macrophages start remodeling the dead heart tissue.

Patent ductus arteriosus

From Wikipedia, the free encyclopedia

Patent ductus arteriosus

Classification and external resources

Heart cross-section with PDA

Patent ductus arteriosus (PDA) is a congenital disorder in the heart wherein a neonate's ductus
arteriosus fails to close afterbirth. Early symptoms are uncommon, but in the first year of life include increased
work of breathing and poor weight gain. With age, the PDA may lead to congestive heart failure if left
uncorrected. The ductus arteriosus is a normal fetal blood vessel that closes soon after birth. In a PDA, the
vessel does not close and remains "patent" (open) resulting in irregular transmission of blood between two of
the most important arteries close to the heart, the aorta and the pulmonary artery. PDA is common in neonates
with persistent respiratory problems such as hypoxia, and has a high occurrence in premature children. In
hypoxic newborns, too little oxygen reaches the lungs to produce sufficient levels of bradykinin and subsequent
closing of the DA. Premature children are more likely to be hypoxic and thus have PDA because of their
underdeveloped heart and lungs.

A PDA allows a portion of the oxygenated blood from the left heart to flow back to the lungs by flowing from the
aorta (which has higher pressure) to the pulmonary artery. If this shunt is substantial, the neonate becomes
short of breath: the additional fluid returning to the lungs increases lung pressure to the point that the neonate
has greater difficulty inflating the lungs. This uses more calories than normal and often interferes with feeding in
infancy. This condition, as a constellation of findings, is calledcongestive heart failure.

In some cases, such as in transposition of the great vessels (the pulmonary artery and the aorta), a PDA may
need to remain open. In this cardiovascular condition, the PDA is the only way that oxygenated blood can mix
with deoxygenated blood. In these cases, prostaglandins are used to keep the DA open.

Signs and symptoms[edit]

While some cases of PDA are asymptomatic, common symptoms include:

tachycardia

respiratory problems

dyspnea - shortness of breath

continuous machine-like heart murmur

cardiomegaly - enlarged heart

left subclavicular thrill

bounding pulse
 widened pulse pressure

patients typically present in good health, with normal respirations and heart rate. If the ductus is
moderate or large, widened pulse pressure and bounding peripheral pulses are frequently present,
reflecting increased left ventricular stroke volume and diastolic runoff of blood into the initially lower-
resistant pulmonary vascular bed. Prominent suprasternal and carotid pulsations may be noted secondary
to increased left ventricular stroke volume.

poor growth[1]

differential cyanosis, i.e. cyanosis of the lower extremities but not of the upper body.

Diagnosis[edit]

Phonocardiograms from normal and abnormal heart sounds

PDA is usually diagnosed using non-invasive techniques. Echocardiography, in which sound waves are used to
capture the motion of the heart, and associated Doppler studies are the primary methods of detecting
PDA. Electrocardiography (ECG), in which electrodes are used to record the electricalactivity of the heart, is
not particularly helpful as there are no specific rhythms or ECG patterns which can be used to detect PDA. [citation
needed]

A chest X-ray may be taken, which reveals the overall size of neonate's heart (as a reflection of the combined
mass of the cardiac chambers) and the appearance of the blood flow to the lungs. A small PDA most often
shows a normal sized heart and normal blood flow to the lungs. A large PDA generally shows an enlarged
cardiac silhouette and increased blood flow to the lungs.

Normal anatomy[edit]

In the developing fetus, the DA is the vascular connection between the pulmonary artery and the aortic
arch that allows most of the blood from the right ventricle to bypass the fetus' fluid-filled compressed lungs.
During fetal development, this shunt protects the right ventricle from pumping against the high resistance in the
lungs, which can lead to right ventricular failure if the DA closes in-utero.

When the newborn takes its first breath, the lungs open and pulmonary vascular resistance decreases. After
birth, the lungs release bradykinin to constrict the smooth muscle wall of the DA and reduce bloodflow through
the DA as it narrows and completely closes, usually within the first few weeks of life. In most newborns with
a patent ductus arteriosus the blood flow is reversed from that of in utero flow, i.e. the blood flow is from the
higher pressure aorta to the now lower pressure pulmonary arteries.

In normal newborns, the DA is substantially closed within 1224 hours after birth, and is completely sealed after
three weeks. The primary stimulus for the closure of the ductus is the increase in neonatal blood oxygen
content. Withdrawal from maternal circulating prostaglandins also contributes to ductal closure. The residual
scar tissue from the fibrotic remnants of DA, called the ligamentum arteriosum, remains in the normal adult
heart.

Treatment[edit]

Neonates without adverse symptoms may simply be monitored as outpatients, while symptomatic PDA can be
treated with both surgical and non-surgical methods.[2] Surgically, the DA may be closed by ligation (though
support in premature infants is mixed),[3] wherein the DA is manually tied shut, or with intravascular coils or
plugs that leads to formation of a thrombus in the DA. This was first performed in humans by Robert E. Gross.
[citation needed]

Because Prostaglandin E1 is responsible for keeping the ductus patent, NSAIDS (inhibitors of prostaglandin
synthesis) such as indomethacin or a special form of ibuprofen have been used to help close a PDA.[1][4] This is
an especially viable alternative for premature infants.[citation needed]

In certain cases it may be beneficial to the neonate to prevent closure of the ductus arteriosus [citation needed]. For
example, in transposition of the great vessels, a PDA may prolong the newborn's life until surgical correction is
possible. The ductus arteriosus can be induced to remain open by administering prostaglandin analogs such
as alprostadil or misoprostol (prostaglandin E1analogs)[citation needed].

More recently, PDAs can be closed by percutaneous interventional method. [citation needed] Via the femoral vein or
femoral artery, a platinum coil can be deployed via a catheter, which induces thrombosis (coil embolization).
Alternatively, a PDA occluder device (AGA Medical)[citation needed], composed of nitinol mesh, is deployed from the
pulmonary artery through the PDA. The larger skirt of the device sits on the aortic side while the ampulla of the
device hugs the walls of the PDA, with care taken to avoid occlusion of the pulmonary arterial lumen by the
device[citation needed]. These methods permit closure without open heart surgery.

Prevention[edit]

There is evidence to suggest that giving indomethacin on the first day of life, prophylactically to all preterm
infants (less than 37 weeks gestation) reduces the risk of developing a PDA (relative risk 0.29 95% CI 0.22,
0.38) and the complications associated with PDA. There is also a decreased need for surgical intervention to
treat PDA in premature infants prophylactically treated with indomethacin (relative risk of 0.51 95%CI 0.37,
0.71). Complications of PDA include intraventricular hemorrhage which can lead to severe brain damage.
There is not evidence however to show that giving indomethacin prophylactically improves survival for these
infants (RR 0.96; 95% CI 0.81, 1.12). There is also no significant evidence to suggest prophylactic
indomethacin decreases long-term disability (cerebral palsy, visual impairment, hearing impairment, decreased
cognitive performance) rates.[5]

Etiology[edit]

A PDA can be idiopathic (i.e. without an identifiable cause), or secondary to another condition. Some common
contributing factors in humans include:

Preterm birth

Congenital rubella syndrome

Chromosomal abnormalities such as Down syndrome

Prognosis[edit]

Without treatments, the disease may progress from left-to-right (noncyanotic heart) shunt to right-to-left shunt
(cyanotic heart) called Eisenmenger's syndrome. Also, a long-term effect would be pulmonary hypertension,
which can lead to needing a heart and/or lung transplant.
 History[edit]

Robert E. Gross, MD performed the first successful ligation of a patent ductus arteriosus on an eight year old
girl at Children's Hospital Boston in 1938.

Atrioventricular canal
From Wikipedia, the free encyclopedia

The proper development of the Atrioventricular canal into its prospective components (The heart septum and
associated valves) to create a clear division between the four compartments of the heart and ensure proper
blood movement through the heart, are essential for proper heart function. When this process does not happen
correctly, a child will develop atrioventricular canal defectwhich occurs in 2 out of every 10,000 births. It also
has a correlation with Down Syndrome because 20% of children with Down Syndrome suffer from
atrioventricular canal disease as well. This is a very serious condition and surgery is necessary within the first
six months of life for a child. [1] Half of the children who are untreated with this condition die during their first
year due to heart failure of pneumonia.[2]

Atrioventricular canal defect is a combination of abnormalities of the heart and is present at birth. There is a
problem when there are holes present in the walls that separate chambers (septum), as well as when valves
are incorrectly constructed. There are other names for these heart abnormalities such as endocardial cushion
defects or atrioventricular septal defect[3]

Contents

[hide]

1 Development

2 Clinical relevance

o 2.1 Atrioventricular canal defect

3 See also

4 References
Development[edit]

This a photo of the basic anatomical structures of the heart. Take note of how during "normal" heart development all four
chambers are separated and the mitral and tricupsid valves are properly developed.

In a normal healthy heart there are 4 chambers. This consists of right and left atria, and right and left ventricles.
The Right atria and right ventricle's function is to pump blood to the lungs while the left atria and left ventricles
pump blood to the rest of the body. There are valves in place that inhibit back-flow between these chambers. [3]

Clinical relevance[edit]

Atrioventricular canal defect[edit]

This is an echocardiography of "Complete" Atriventricular Canal Disorder. There is a clear absence of lower septum that
would separate all four chambers of the heart

Main article: atrioventricular canal defect

This defect is developed because of the improper formation of the endocardial cushions, and their job is to
separate the different parts of the heart during development when they fuse. It is strongly associated
with Down's syndrome. The structures that develop from the fusion of the endocardial cushions are:
 The Atrial septum- this structure divides the left and right atrium

The Ventricular septum-this structure divides the left and right ventricles.

The Mitral Valve and tricuspid valve - these valves are formed by the proper division of an early
common valve being separated into two.[4]

Atrioventricular canal defect may be divided into partial or complete forms. In the partial form, openings
between the left and right atria and improper formation of the mitral valve exist. In the complete form, there is
free movement in all chambers because there is a large hole where the atria and ventricles meet, and instead
[3]
of there being two valves there is one common valve.

Surgery is usually conducted in-between the 3rd and 6th month of life, and with this condition the earlier the
better. Usually, intracardiac repair is completed which is when they close the holes in the septum and they
make two new atrioventricular valves that is available from the underdeveloped common valve leaflet. [2]

Pulmonary atresia is a congenital malformation of the pulmonary valve in which the valve orifice fails to
develop. The valve is completely closed thereby obstructing the outflow of blood from the heart to
the lungs. The pulmonary valve is located on the right side of the heart between the right
ventricle and pulmonary artery. In a normal functioning heart, the opening to the pulmonary valve has
three flaps that open and close like one way doors. As these flaps open and close they allow blood to flow
forward into the pulmonary artery and on to the lungs where the blood becomes oxygenated, and prevent
backward flow into the right ventricle. With the disease pulmonary atresia, the flap-like openings are
completely covered by a layer of tissue, thus preventing the ability of blood flow to the lungs to become
oxygenated. The body requires oxygenated blood for survival. Pulmonary atresia is not threatening to a
developing fetus however, because the mother's placenta provides the needed oxygen since the baby's
lungs are not yet functional. Once the baby is born its lungs must now provide the oxygen needed for
survival, but with pulmonary atresia there is no opening on the pulmonary valve for blood to get to the
lungs and become oxygenated and the only source of pulmonary blood flow is a patent ductus arteriosus.
Due to this, the newborn baby is blue in color and pulmonary atresia can usually be diagnosed within
hours or minutes after birth.

Classification[edit]

There are two types of pulmonary atresia.

Pulmonary Atresia with Intact Ventricular Septum (PA-IVS)

PA-IVS is a rare congenital lesion. This lesion can be diagnosed during the fetal stage of life by using fetal
echocardiography, which is a test that uses sound waves to look at the structure of an unborn baby's
heart. PA-IVS involves complete blockage of the pulmonary valve located on the right side of the heart.
This blockage thus prevents the flow of blood to the lungs. Because of this lack of blood flowing through
the right side of the heart, the structures on that side, such as the pulmonary valve and the tricuspid
valve, are abnormally small. The genetic cause of PA-IVS is unknown. It is rare, occurring in around 4-6
cases per every 100,000 live births.[1]

Pulmonary atresia with Ventricular Septal Defect (PA-VSD)

This lesion is identified by underdevelopment of the right ventricle. The Ventricular Septal Defect (VSD) is
a second opening in the ventricular wall, which provides a way out for blood in the right ventricle. When
this second opening does not exist, very little blood goes to the right ventricle, which is what causes it to
be underdeveloped in PA-IVS. This defect can also be determined before birth. Out of all congenital
cardiac malformations, it is estimated that PA-VSD occurs in 2.5-3.4% of the cases. The genetic cause of
PA-VSD is not known; it is found however, that children whose parents have PA-VSD are at a higher risk
for congenital heart lesions.

Cause[edit]

Doctors are unsure of the cause of congenital heart defects, but there are some medical conditions that
have been found to increase the risk of having a baby with a heart defect such as congenital heart
disease in the mother, father, brother, or sister of the baby, a diabetic mother, use of drugs or alcohol or
over the counter prescriptions during pregnancy. These conditions do not mean that the baby will
definitely be born with a heart defect, but that it runs a higher chance. Sometimes babies are born without
any of these conditions; the cause is unknown.

Treatment[edit]

At first, the child will need to be admitted to the intensive care unit and possibly placed on oxygen and
a ventilator that will help the child breathe. Also, IV medications that assist the heart and lung function
may be given. An IV medication called prostaglandin E1 is used for treatment of pulmonary atresia, as it
stops the ductus arteriosus from closing, allowing mixing of the pulmonary and systemic circulations. But
prostaglandin E1 can be dangerous as it can cause apnea. Another example of preliminary treatment
is heart catheterization to evaluate the defect or defects of the heart; this procedure is much more
invasive. Ultimately, however, the patient will need to have a series of surgeries to improve the blood flow
permanently. The first surgery will likely be performed shortly after birth. A shunt can be created between
the aorta and the pulmonary artery to help increase blood flow to the lungs. As the child grows, so does
the heart and the shunt may need revised in order to meet the body's requirements.

The type of surgery recommended depends on the size of the right ventricle and the pulmonary artery.

If they are normal in size and the right ventricle is able to pump blood, open heart surgery can be
performed to make blood flow through the heart in a normal pattern.
If the right ventricle is small and unable to act as a pump, doctors may perform another type of operation
called the Fontan procedure. In this three-stage procedure, the right atrium is disconnected from the
pulmonary circulation. The systemic venous return goes directly to the lungs, by-passing the heart.

Another treatment option involves the electrosurgical puncture of the atretic valve using a wire introduced
into the patient percutaneously. The puncture is then dilated using a balloon catheter to allow blood flow
from the right ventricle into the pulmonary artery.[2]

Prognosis[edit]

The outcome varies for every child. If the condition is left uncorrected it may be fatal, but the prognosis
has greatly improved over the years for babies with pulmonary atresia. Some factors that affect how well
the child does include how well the heart is beating, the condition of the blood vessels that supply the
heart, and how leaky the other heart valves are. Most cases of pulmonary atresia can be helped with
surgery. If the patient's right ventricle is exceptionally small, many surgeries will be needed in order to
help stimulate normal circulation of blood to the heart.

If uncorrected, babies with this type of congenital heart disease may only survive for the first few days of
life while the fetal shunts between left and right circulations remain patent. However, there are cases of
uncorrected Pulmonary Atresia in which the baby has survived.

Many children with pulmonary atresia will go on to lead 'normal' lives. Patients are usually seen regularly
throughout their lifetime by a cardiologist to be sure that their heart is functioning properly. They have an
increased risk of endocarditis.

Pulmonary atresia (PA) is a heart defect that occurs due to abnormal development of
the fetal heart during the first eight weeks of pregnancy.

Pulmonary atresia means that there is an abnormal development of the pulmonary

valve. The pulmonary valve is found between the right ventricle and the pulmonary
artery, which is the large artery that goes to the lungs. It has three leaflets that function
like a one-way door, allowing blood to flow forward into the pulmonary artery and to the
lungs, but not backward into the right ventricle.

With pulmonary atresia, problems with the valve prevent the leaflets from opening;
therefore, blood cannot flow forward from the right ventricle to the lungs.

Often, if blood is blocked from exiting the pulmonary valve, there is a second opening in
the ventricular wall. The ventricular wall is the wall of heart muscle that separates the
left ventricle from the right ventricle of the heart. This opening is called a ventricular
septal defect (VSD).

There may also be a second opening, or hole, between the two upper chambers of the
heartthe left and right atria. This defect is called an atrial septal defect (ASD). These
holes allow blood in the obstructed right ventricle a way out of the heart. The blood then
ultimately crosses to the left side of the heart and is pumped out to the body.
 This situation cannot support life, because the blood never makes it to the lungs to
become oxygenated, and oxygen-poor (blue) blood cannot meet the body's demands.

Sometimes, newborns will rely on a connection between the aorta and the pulmonary
artery, called the ductus arteriosus. That allows some of the oxygen-poor (blue) blood to
bypass the blocked right ventricle and get to the lungs. This ductus arteriosus is
persistent from normal fetal circulation, and unfortunately, this ductus arteriosus
normally closes within a few hours or days after birth.

Because of the low amount of oxygen provided to the body, pulmonary atresia is a heart
problem that can ultimately result in cyanosis, or a blue color to the skin from lack of
oxygen.

What causes pulmonary atresia?

The problem occurs as the heart is forming during the first eight weeks of fetal
development.

Some congenital heart defects may have a genetic link, either occurring due to a defect
in a gene, a chromosome abnormality, or environmental exposure, causing heart
problems to occur more often in certain families. Most of the time, this heart defect
occurs sporadically (by chance), with no clear reason for its development.

What are the symptoms of pulmonary atresia?

Symptoms can be noted shortly after birth or several weeks later as the ductus
arteriosus closes. The most obvious symptom is blue, or cyanotic, skin in a newborn.

The following are the most common symptoms of pulmonary atresia. However, each
child may experience symptoms differently. Symptoms include:

Rapid breathing

Difficulty breathing

Poor feeding

Lethargy

Pale, cool, or clammy skin

Blue color of the lips or skin

The symptoms of pulmonary atresia may resemble other medical conditions or heart
problems. Always consult your child's physician for a diagnosis.
 How is pulmonary atresia diagnosed?

A pediatric cardiologist and/or a neonatologist may be involved in your child's care. A

pediatric cardiologist specializes in the diagnosis and medical management of
congenital heart defects, as well as heart problems that may develop later in childhood.
A neonatologist specializes in illnesses affecting newborns, both premature and full-
term.

Cyanosis is a major indication that there is a problem with your newborn. Your child's
physician may have also heard a heart murmur during a physical examination.

Diagnostic testing for congenital heart disease varies by the child's age, clinical
condition, and institutional preferences. Some tests that may be recommended include
the following:

Chest X-ray. A diagnostic test which uses X-ray beams to produce images of
internal tissues, bones, and organs onto film.

Electrocardiogram (ECG or EKG). A test that records the electrical activity of

the heart, shows abnormal rhythms (arrhythmias or dysrhythmias), and detects heart
muscle stress.

Echocardiogram (echo). A procedure that evaluates the structure and function

of the heart by using sound waves recorded on an electronic sensor that produce a
moving picture of the heart and heart valves.

Cardiac catheterization. A cardiac catheterization is an invasive procedure

that gives very detailed information about the structures inside the heart. Under
sedation, a small, thin, flexible tube (catheter) is inserted into a blood vessel in the
groin, and guided to the inside of the heart. Blood pressure and oxygen measurements
are taken in the four chambers of the heart, as well as the pulmonary artery and aorta.
Contrast dye is also injected to more clearly visualize the structures inside the heart.

Treatment for pulmonary atresia

Specific treatment for pulmonary atresia will be determined by your child's physician.

Your child will most likely be admitted to the intensive care unit (ICU) or special care
nursery once symptoms are noted. Initially, your child may be placed on oxygen, and
possibly even on a ventilator, to assist his or her breathing. IV medications may be
given to help the heart and lungs function more efficiently.

Other important aspects of initial treatment include the following:

 A cardiac catheterization procedure can be used as a diagnostic procedure, as
well as an initial treatment procedure for some heart defects. A cardiac catheterization
procedure will usually be performed to evaluate the defect(s), and the amount of blood
that is able to get to the lungs to be come oxygenated.

As part of the cardiac catheterization, a procedure called balloon atrial

septostomy may be performed to improve mixing of oxygen-rich (red) blood and
oxygen-poor (blue) blood between the right and left atria.

o A special catheter with a balloon in the tip is used to create an opening in

the atrial septum (wall between the left and right atria).

o The catheter is guided through the foramen ovale (a small opening

present in the atrial septum that closes shortly after birth) and into the left atrium.

o The balloon is inflated.

o The catheter is quickly pulled back through the hole, into the right atrium,
and a hole is created, allowing blood to mix between the atria.

An IV medication called prostaglandin E1 may also be given to keep the ductus

arteriosus from closing.

These interventions will allow time for your baby to stabilize his or her blood while more
definite repair is planned.

Surgical repair. Ultimately, surgery is necessary to improve blood flow to the

lungs on a permanent basis. The exact type of surgery needed depends on a number of
factors, including the size of the right ventricle and whether there is a communication
between the right and left ventricles (a ventricular septal defect or VSD). If there is a
VSD, then the operation may involve closure of the VSD and placement of a conduit
from the right ventricle to the pulmonary artery. This allows blood to leave the right
ventricle through this conduit into the lungs. If there is no VSD, then a series of three
operations are usually recommended and performed shortly after birth. In this series of
operations, blood flow is redirected to the lungs and the body with various surgical
connections. The first operation is placement of a Blalock-Taussig shunt (or BT shunt)
that allows blood to flow to the lungs after the patent ductus arteriosus closes. The
second operation is a Glenn procedure, where the superior vena cava is connected
directly to the right lung artery. The third and final operation is a Fontan
procedure, where the inferior vena cava is connected to the right lung artery.
 Postoperative care for your child

After surgery, infants will return to the ICU to be closely monitored during recovery.

While your child is in the ICU, special equipment will be used to help him or her recover,
and may include the following:

Ventilator. A machine that helps your child breathe while he or she is under
anesthesia during the operation. A small, plastic tube is guided into the windpipe and
attached to the ventilator, which breathes for your child while he or she is too sleepy to
breathe effectively on his or her own. After a pulmonary atresia, children will benefit
from remaining on the ventilator overnight or even longer so they can rest.

Intravenous (IV) catheters. Small, plastic tubes inserted through the skin into
blood vessels to provide IV fluids and important medicines that help your child recover
from the operation.

Arterial line. A specialized IV placed in the wrist or other area of the body where
a pulse can be felt, that measures blood pressure continuously during surgery and while
your child is in the ICU.

Nasogastric (NG) tube. A small, flexible tube that keeps the stomach drained
of acid and gas bubbles that may build up during surgery.

Urinary catheter. A small, flexible tube that allows urine to drain out of the
bladder and accurately measures how much urine the body makes, which helps
determine how well the heart is functioning. After surgery, the heart will be a little
weaker than it was before, and, therefore, the body may start to hold onto fluid, causing
swelling and puffiness. Diuretics may be given to help the kidneys remove excess fluid
from the body.

Chest tube. A drainage tube may be inserted to keep the chest free of blood
that would otherwise accumulate after the incision is closed. Bleeding may occur for
several hours, or even a few days after surgery.

Heart monitor. A machine that constantly displays a picture of your child's

heart rhythm, and monitors heart rate, arterial blood pressure, and other values.

Your child may need other equipment not mentioned here to provide support while in
the ICU, or afterwards. The hospital staff will explain all of the necessary equipment to
you.
 Your child will be kept as comfortable as possible with several different medications;
some relieve pain, and some relieve anxiety. The staff will also ask for your input on
how best to soothe and comfort your child.

After discharge from the ICU, your child will recuperate in another hospital unit before
going home. You will learn how to care for your child at home before your child is
discharged. Your child may need to take medications for a while. The staff will give you
written instructions regarding medications, activity limitations, and follow-up
appointments before your child is discharged.

Infants who spent a lot of time on a ventilator, or who were fairly ill while in the ICU,
may have trouble feeding initially. These babies may have an oral aversion; they might
equate something placed in the mouth, such as a pacifier or bottle, with a less pleasant
sensation, such as being on the ventilator. Some infants are just tired, and need to build
their strength up before they will be able to learn to bottle-feed. Strategies used to help
infants with nutrition include the following:

High-calorie formula or breast milk. Special nutritional supplements may be

added to formula or pumped breast milk that increase the number of calories in each
ounce, thereby allowing your baby to drink less and still consume enough calories to
grow properly.

Supplemental tube feedings. Feedings given through a small, flexible tube

that passes through the nose, down the esophagus, and into the stomach, that can
either supplement or take the place of bottle feedings. Infants who can drink part of
their bottle, but not all, may be fed the remainder through the feeding tube. Infants who
are too tired to bottle feed at all may receive their formula or breast milk through the
feeding tube alone.

Caring for your child at home following PA surgical repair

Pain medications, such as acetaminophen or ibuprofen, may be recommended to keep

your child comfortable. Your child's physician will discuss pain control before your child
is discharged from the hospital.

If any special treatments are to be given at home, the nursing staff will ensure that you
are able to provide them, or a home health agency may assist you.

You may receive additional instructions from your child's physicians and the hospital
staff.
Long-term outlook after pulmonary atresia surgical repair

The outlook varies from child to child. Follow-up care at a center offering pediatric
congenital cardiac care should be carried out regularly. It is not unexpected for multiple
reoperations to be performed to replace conduits or revise a palliation.

After each operation, your infant will need to be followed by a pediatric cardiologist, who
will make adjustments to medications, assist you with feeding problems, measure
oxygen levels, and determine when it is time for the next operation.

There is significant risk for progressive development of complications, such as heart

failure, dysrhythmias, and protein-losing enteropathy (liver congestion).

Pregnancy and other noncardiac surgeries pose major risks and require careful
evaluation and discussion with a congenital cardiologist.

Regular follow-up care at a center offering pediatric or adult congenital cardiac care
should continue throughout the individuals lifespan.

Consult your child's physician regarding the specific outlook for your child.

Pulmonary atresia
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Pulmonary atresia is a form of heart disease that occurs from birth (congenital heart disease), in
which the pulmonary valve does not form properly. The pulmonary valve is an opening on the right side of
the heart that regulates blood flow from the right ventricle (right side pumping chamber) to the lungs.

In pulmonary atresia, a solid sheet of tissue forms where the valve opening should be, and the valve
stays closed. Because of this defect, blood from the right side of the heart cannot go to the lungs to pick
up oxygen.

Causes

As with most congenital heart diseases, there is no known cause of pulmonary atresia. The condition is
associated with another type of congenital heart defect called a patent ductus arteriosus (PDA).

Persons with pulmonary atresia may also have a poorly developed tricuspid valve. They may also have
an underdeveloped right ventricle and abnormal blood vessels feeding the heart.

Pulmonary atresia may occur with or without a ventricular septal defect (VSD).
 If the person does not have a VSD, the condition is called pulmonary atresia with intact
ventricular septum (PA/IVS).

If the person has both problems, the condition is called pulmonary atresia with VSD. This is an
extreme form of tetralogy of Fallot.

Although both conditions are called pulmonary atresia, they are actually different defects.

Symptoms

Symptoms usually occur in the first few hours of life, although it may take up to a few days.

Symptoms may include:

Bluish colored skin (cyanosis)

Fast breathing

Fatigue

Poor eating habits (babies may get tired while nursing or sweat during feedings)

Shortness of breath

Exams and Tests

The health care provider will use a stethoscope to listen to the heart and lungs. Persons with a PDA have
a heart murmur that can be heard with a stethoscope.

The following tests may be ordered:

Chest x-ray

Echocardiogram

Electrocardiogram (ECG)

Heart catheterization

Pulse oximetry - shows the amount of oxygen in the blood

Treatment

A medicine called prostaglandin E1 is usually used to help the blood move (circulate) into the lungs. This
medicine keeps a blood vessel open between the pulmonary artery and aorta. The vessel is called a
patent ductus arteriosus (PDA).

Other treatments include:

A thin, flexible tube (heart catheterization) to repair the problem

Open heart surgery to repair or replace the valve, or to place a tube between the right ventricle
and the pulmonary (lung) arteries

Reconstructing the heart as a single ventricle (for some patients)

Heart transplant

Outlook (Prognosis)

Most cases can be helped with surgery. However, how well a baby does depends on:

The size and connections of the pulmonary artery (the artery that takes blood to the lungs)

How well the heart is beating

How much the other heart valves are leaking

Outcomes can vary because of the different forms of this defect. A baby may need only a single
procedure, or could need three or more surgeries and have only a single working ventricle.

Possible Complications

Delayed growth and development

Seizures

Stroke

Infectious endocarditis

Heart failure

Death
When to Contact a Medical Professional

Call your health care provider if the baby has:

Problems breathing

Skin or nails that appear blue (cyanosis)

Prevention

There is no known way to prevent this condition.

All pregnant women should receive routine prenatal care. Many congenital defects can be discovered on
routine ultrasound examinations.

If the defect is found before birth, medical specialists (such as a pediatric cardiologist, cardiothoracic
surgeon, and neonatologist) can be present at the birth, and ready to help as needed. This preparation
can mean the difference between life and death for some babies.

Epidemiology
Frequency

The best estimates of the relative frequency of pulmonary atresia with ventricular septal defect are 2.5-
3.4% of all congenital cardiac malformations. Pulmonary atresia with ventricular septal defect is slightly
more prevalent in males than in females.

Pathophysiology
In pulmonary atresia with ventricular septal defect, the extent of pulmonary artery development
determines the clinical presentation and the surgical options available. Pulmonary artery atresia may be
local only, with involvement of the pulmonary valve and the proximal portion of the pulmonary trunk, or it
may involve a longer segment. The right and left pulmonary arteries may communicate freely (ie,
confluence) or may not communicate (ie, nonconfluence). Pulmonary circulation may be supplied by a
patent ductus arteriosus (PDA), systemic-to-pulmonary collaterals, or plexuses of bronchial and pleural
arteries.

The pathology of intrapulmonary arteries depends on the pulmonary blood flow and the patency of the
ductus. If the ductus is large and supplies confluent pulmonary arteries, the blood flow and the
intrapulmonary arteries of both lungs are normal. If collaterals are multiple and the ductus is congenitally
absent, abnormal intrapulmonary arborization (ie, stenosis of unbranched and intrapulmonary arteries)
and pulmonary hypertension are present.

Collateral arteries most commonly arise from the thoracic aorta and less commonly arise from subclavian
arteries, internal mammary arteries, intercostal arteries, or the abdominal aorta. Rarely, the collateral
arteries arise from coronary arteries. In 60% of patients, the collateral arteries are stenosed at the aortic
end or at intrapulmonary sites, and stenosis tends to progress over time.
 The ventricular septal defect may be membranous or infundibular, is usually very large, and rarely is
obstructed by membranous tissue. In 50% of patients, a secundum-type atrial septal defect (ASD) or a
patent foramen ovale (PFO) is also present. In 26-50% of patients, the aorta arises predominantly from
the RV and a dilated right-sided aortic arch may be present.

The RV and, to a lesser extent, the right atrium usually are moderately to markedly hypertrophied and
dilated. The left atrium and left ventricle (LV) are usually normal. The coronary arteries are usually normal,
although anomalies have been observed, such as a high origin of the coronary ostia, coronary arteryto
pulmonary artery fistulae,[1] and transposition anatomy with the right coronary artery originating from the
left anterior aortic sinus and transversing the right ventricular infundibulum. Other associations include
tricuspid atresia or stenosis, complete atrioventricular (AV) canal, complete or corrected transposition of
the great arteries, left superior vena cava, anomalies of the coronary sinus, dextrocardia, and asplenia or
polysplenia syndrome.

Classification

Type A: Pulmonary blood flow is provided by native pulmonary arteries.

Type B: Pulmonary blood flow is supplied by native pulmonary arteries and by major
aortopulmonary collateral arteries.
Type C: Pulmonary blood flow is provided by major aortopulmonary collateral arteries.
Presentation
The age at presentation may vary depending on the amount of pulmonary blood flow. However, the great
majority of patients present in the newborn period after the closure of the ductus arteriosus. If collateral
vessels are well developed, presentation may be delayed, although rarely.

The vast majority of patients present with cyanosis and hypoxia. Hypoxia is usually severe and is present
when the entire pulmonary flow is reduced and a closing ductus arteriosus is the only source of
pulmonary blood flow. If systemic collateral arteries are well developed or if the PDA is wide open,
hypoxia is not severe in neonates. Patients may present with progressive hypoxia later because growth
outstrips the pulmonary blood flow.

Rarely, an infant with a large PDA or well-developed systemic collateral arteries may present at age 4-6
weeks with heart failure with increased pulmonary blood flow and minimal cyanosis. This heart failure
may be very difficult to control medically. Paroxysms of dyspnea and squatting occasionally occur in older
children.

Hemoptysis may occur as a result of rupture of extensive systemic-to-pulmonary collateral arteries.

Important and recurrent infections can occur because of immunodeficiency, especially if associated with
DiGeorge syndrome. Survival to adulthood has been described in a few patients with well-developed
collateral arteries.

Growth and development are usually delayed secondary to cyanosis or congestive heart failure (CHF).

Central (ie, perioral) cyanosis is usually mild at birth, but it becomes very severe with the closure of the
PDA. Cyanosis may fluctuate for the first few days because the ductus arteriosus may constrict and relax
intermittently. The patient may have anomalies of the face, palate, and ears as described in
velocardiofacial syndrome. Peripheral pulses are usually normal in neonates and remain normal in
cyanotic infants. In infants with wide-open PDAs, well-developed systemic collateral arteries, or surgically
created shunts, pulses may become pronounced after 4-6 weeks because of a wide pulse pressure.
 Signs of heart failure are rare. Heart pulsation is most prominent at the left lower sternal border. Heart
size is usually normal. A prominent a wave in the jugular pulse may be found. The following may be
observed on auscultation:

S1 is normal; S2 (ie, aortic valve closure) is always single and often accentuated. A grade 3/6
systolic murmur usually is audible along the lower left sternal border.
A continuous murmur is best heard over the upper chest in the presence of a PDA.
If systemic-to-pulmonary collateral arteries are present, continuous murmurs may be diffusely
audible over the entire chest and back.
In some patients with severe cyanosis, no murmur can be heard.
An early diastolic murmur of aortic regurgitation may be noted.

Distinguishing characteristics for the diagnosis of pulmonary atresia with ventricular septal defect can be
divided into 2 major groups, as follows:

Decreased pulmonary blood flow in a neonate with cyanosis

o Severe tetralogy of Fallot
o Transposition of the great arteries with pulmonary stenosis
o Tricuspid atresia
o A double-outlet RV with severe pulmonary stenosis
o A single ventricle with severe pulmonary stenosis
o Total anomalous pulmonary venous connection with pulmonary venous obstruction
Normal or increased pulmonary blood flow in a neonate with minimal cyanosis with or without
heart failure
o Ventricular septal defect
o PDA
o AV canal defect
o A double-outlet RV without significant pulmonary stenosis
o A single ventricle without significant pulmonary stenosis
o Persistent truncus arteriosus
o Total anomalous pulmonary venous connection without pulmonary venous obstruction

Consult a pediatric cardiologist, a pediatric cardiothoracic surgeon, and a geneticist.

Indications
Criteria for complete surgical repair of pulmonary atresia with ventricular septal defect (PA-VSD) are as
follows:

If central pulmonary arteries are present, their central area must be more than 50% of normal for
the patient's age and body surface area.
The pulmonary arteries must supply at least 10 segments, the equivalent of one lung.
If a single pulmonary artery is present, it must be normal in size and reach all segments of that
lung.
Contraindications
Contraindications for complete surgical repair of pulmonary atresia with ventricular septal defect include
(1) hypoplastic or absent central pulmonary arteries and (2) inadequate peripheral arborization of
pulmonary arteries.
 Laboratory Studies
No laboratory or blood tests are available to confirm pulmonary atresia with ventricular septal
defect (PA-VSD).
Pulse oximetry can assist the diagnosis of cyanosis, especially in patients with dark skin and
anemia (>5 mg/dL of reduced hemoglobin is required).
An ABG assessment can reveal hypoxemia and hypocarbia without any significant improvement
with hyperoxia, favoring a diagnosis of cyanotic congenital heart disease.
Reactive polycythemia and coagulation defects may be evident from the results of hematologic
studies.
Because, in some cases, pulmonary atresia with ventricular septal defect is associated with
DiGeorge syndrome and velocardiofacial syndrome, genetic evaluation, including a fluorescent in situ
hybridization (FISH) test, may be required.
Imaging Studies
Chest radiography
A boot-shaped heart (coeur en sabot) is observed. It occurs secondary to an upturned
cardiac apex caused by right ventricular (RV) hypertrophy and concavity in the region of the main
pulmonary artery, which is produced by underdevelopment of the subpulmonary infundibulum.
The heart size is usually normal or slightly enlarged, most often with an RV configuration.
The main pulmonary arterial shadow normally depicted on chest radiography is absent.
The pulmonary vascular markings have a heterogeneous reticular pattern in the presence
of collateral arteries from the systemic arteries.
Approximately 50% of patients have a right aortic arch with a large aorta.
The lung field is oligemic in patients with very small collateral arteries.
Lung fields may be flooded if the patient has a large patent ductus arteriosus (PDA) with
normally developed central pulmonary arteries or well-developed systemic collateral arteries.
Echocardiography
Parasternal long-axis scans reveal a large aortic valve overriding a malaligned ventricular
septal defect.
Position of malalignment of the ventricular septal defect (membranous or infundibular)
and a blind hypoplastic RV infundibulum is easily observed using parasternal cross-sectional
echocardiography.
Atrial septal defects (ASDs) and other muscular ventricular septal defects can be
detected.
Scans from the suprasternal notch and high parasternal windows usually can provide
important information regarding the size of the proximal pulmonary arteries and the presence of
confluence. These views can also help define the side of the aortic arch and assess the patency of the
ductus arteriosus.
A right-sided aortic arch is frequently defined using the suprasternal notch view.
Defining all the collateral arteries with echocardiography is difficult.
Short-axis parasternal and subcostal views are used to detect coronary artery
abnormalities.

MRI: MRI is a less invasive technique used to help define the surgically relevant pulmonary artery
anatomy, but MRI images are inadequate for defining peripheral pulmonary arterial distribution.

RV hypertrophy and right-axis deviation are the rule on echocardiography findings. Right atrial
hypertrophy also is present.
In a small subgroup of patients with increased pulmonary blood flow, combined ventricular
hypertrophy with left atrial enlargement may be present.
 Diagnostic Procedures
Cardiac catheterization and angiography help delineate the size and distribution of the true pulmonary
arteries and the collateral arteries.

Right atrial pressure is normal unless tricuspid incompetence is present.

Pressures in the RVs are at a systemic level because of the nonrestricted ventricular septal
defect.
The pulmonary artery cannot be manipulated through the right side.
Aortic pulse pressure is normal or wide, depending on the presence of a large PDA or collateral
arteries.
True pulmonary arterial resistance is normal.
Medical Therapy
In patients with pulmonary atresia with ventricular septal defect (PA-VSD) a ductal-dependent circulation,
prostaglandin E2 is often required to keep the ductus arteriosus open in the early neonatal period until
surgery can be performed. A neonate who is ill may require fluid and acidosis management, but
mechanical ventilation is rarely needed.

Medical treatment with digitalis, diuretics, and other agents may be indicated in patients with congestive
heart failure (CHF) resulting from increased pulmonary blood flow. Phlebotomy to relieve the adverse
effects of extreme polycythemia in very hypoxic patients is rarely performed. In patients with CHF and
increased work of breathing, a high-energy diet is required. Rarely, a patient may require placement of a
nasogastric tube to achieve the goals of energy intake.

Surgical Therapy
Various options are available, depending on the anatomy of the individual patient.

Palliative surgery

If the atresia is limited to the pulmonary valve (eg, imperforate pulmonary valve, membranous pulmonary
atresia), the valve can be perforated percutaneously using special devices designed for this specific
purpose, such as a needle or a radiofrequency ablation catheter. Then, after the perforation is done, the
valve is dilated with a balloon catheter. Stents can be placed in stenosed aortopulmonary collateral
arteries in patients with hypoplastic pulmonary arteries.

Palliative extracardiac systemic-to-pulmonary shunts can be placed to promote growth of pulmonary

arteries. Direct aortopulmonary shunts (eg, Waterston shunt, Pott shunt) were used in the past but,
subsequently, were found to create severe distortion, scarring, interruption of the pulmonary arteries, and,
on occasion, pulmonary hypertension. Thus, the use of these shunts has fallen into disfavor. Currently,
the modified Blalock-Taussig shunt is used most commonly and is connected from the subclavian or
innominate artery to the pulmonary artery (when anatomy permits). In recent years, a direct right ventricle
to pulmonary arteries shunt has been placed with good results.

Valveless conduits or homografts may be used to connect the right ventricle (RV) to the pulmonary artery.
This may promote the growth of pulmonary arteries.
 In infants with CHF caused by excessive aortopulmonary collateral arteries, flow can be reduced by
performing surgical interruption or by judicious banding or percutaneous coil occlusion of selected
systemic arterial collaterals.

Complete surgical repair

The objective of complete repair is to create an unrestricted continuity between the RV outflow tract and
the pulmonary arterial tree using nonvalved or valved conduits. Subsequently, all extracardiac sources of
pulmonary blood flow need to be ligated. The atrial septal defects (ASDs) and ventricular septal defects
need to be closed. An important goal is to achieve a satisfactory ratio between the peak systolic
pressures in the RV and the left ventricle (LV).

Various approaches have been devised to achieve a complete surgical repair, including the following:

If a patient meets all the criteria for complete repair, single-stage unifocalization of pulmonary
blood supply and complete intracardiac repair is the procedure of choice.
Single-stage unifocalization and postponement of ventricular septal defect closure to a second
operation is an option.
Sequential unilateral unifocalization followed by intracardiac repair is preferred in some patients.

Heart catheterization

More recently, new techniques and devices are being used to treat stenoses and insufficiency of the right
ventricletopulmonary artery conduits and/or homografts in these patients. After complete surgical repair
of the condition, patients require close follow-up and, on occasion, angioplasties and stent placement to
overcome stenotic segments. In current practice, valved stents can be inserted during a heart
catheterization, without the need to open the chest, in the presence of severe pulmonary valve
insufficiency or stenosis. These percutaneous valves can be implanted using fluoroscopic guidance.

Heart-lung transplantation

In patients with completely atretic main, left, and right pulmonary arteries, heart-lung transplantation is a
viable option.

Complications of surgery include the following:

In the unifocalization procedure, severe airflow limitation occurs after the unifocalization surgery
because of tracheobronchial epithelial ischemia resulting from interruption of the tracheobronchial blood
supply. This complication significantly contributes to early postoperative morbidity and mortality rates.
Aortic regurgitation or aortic root dilation may occur.
Restenoses of the shunts and neopulmonary arteries may occur, and subsequent interventions
may be required.
Complications
Possible complications of pulmonary atresia with ventricular septal defect (PA-VSD) include the following:

Congestive heart failure (CHF)

Erythrocytosis
Infective endocarditis
 Brain abscess
Delayed growth and puberty
Arrhythmias and sudden death
Outcome and Prognosis
Patients may require repeated surgeries for a complete repair of pulmonary atresia with ventricular septal
defect (PA-VSD). Educate family members regarding congenital heart disease and how to perform
cardiopulmonary resuscitation (CPR). Genetic counseling for future pregnancies is necessary.

Coarctation of the aorta

Coarctation of the aorta, or aortic coarctation, is a congenital condition whereby the aorta narrows in the
area where the ductus arteriosus inserts. The word coarctation means narrowing. Coarctations are most
common where the aorta the major artery leading away from the heart arches toward the abdomen and
legs. Other cardiac defects may also occur when coarctation is present, typically occurring on the left side of
the heart. When a patient has a coarctation, the left ventricle has to work harder. Since the aorta is narrowed,
the left ventricle must generate a much higher pressure than normal in order to force enough blood through the
aorta to deliver blood to the lower part of the body. If the narrowing is severe enough, the left ventricle may not
be strong enough to push blood through the coarctation, thus resulting in lack of blood to the lower half of the
body. Some signs that can lead to a coarctation have been linked to things like Turner syndrome, bicuspid
aortic valve, and other family heart conditions.

Types

There are three types:[1]

1. Preductal coarctation: The narrowing is proximal to the ductus arteriosus. severe coarctation can be
life-threatening. Preductal coarctation results when an intracardiac anomaly during fetal life decreases
blood flow through the left side of the heart, leading to hypoplastic development of the aorta. This is
the type seen in approximately 5% of infants with Turner Syndrome.[2][3]

2. Ductal coarctation: The narrowing occurs at the insertion of the ductus arteriosus. This kind usually
appears when the ductus arteriosus closes.

3. Postductal coarctation: The narrowing is distal to the insertion of the ductus arteriosus. Even with an
open ductus arteriosus, blood flow to the lower body can be impaired. This type is most common in
adults. It is associated with notching of the ribs (because of collateral circulation), hypertension in the
upper extremities, and weak pulses in the lower extremities.
 Signs and symptoms

In mild cases, children may show no signs or symptoms at first and their condition may not be diagnosed until
later in life. Some children born with coarctation of the aorta have other heart defects, too, such as aortic
stenosis, ventricular septal defect, patent ductus arteriosus or mitral valve abnormalities.

Coarctation is about twice as common in boys as it is in girls.

Symptoms may be absent with mild narrowings (coarctation). When present, they include:

Difficulty breathing, poor appetite or trouble feeding, failure to thrive. Later on, children may develop symptoms
related to problems with blood flow and an enlarged heart. They may experience dizziness or shortness of
breath, faint, chest pain, abnormal tiredness or fatigue, headaches, or nosebleeds. They have cold legs and
feet or have pain in their legs with exercise

In more severe cases, Arterial hypertension in the arms with low blood pressure in the lower extremities is
classic. In the lower extremities, weak pulses in the femoral arteries and arteries of the feet are found.

The coarctation typically occurs after the left subclavian artery. However, if situated before it, blood flow to the
left arm is compromised, a difference between the normal radial pulse in the right arm and the delayed femoral
pulse in the legs may be apparent.

Imaging and diagnosis

With imaging, resorption of the lower part of the ribs may be seen, due to increased blood flow over
the neurovascular bundle that runs there. Post-stenotic dilation of the aorta results in a classic 'figure 3 sign'
on x-ray. The characteristic bulging of the sign is caused by dilatation of the aorta due to an indrawing of
the aortic wall at the site of cervical rib obstruction, with consequent post-stenotic dilation.

When the esophagus is filled with barium, a reverse 3 or E sign is often seen

Echocardiography: It delineates intracardiac anatomy and allows assessment of associated

significant intracardiac anomalies.

Coarctation of the aorta can be accurately diagnosed with magnetic resonance angiography , in untreated
coarctation, blood often reaches the lower body through collaterals, e.g. internal thoracic arteries via the
 subclavian arteries and hypertrophy of the left ventricle is present. Those can be seen on MR, CT
or angiography.

Arteries can be checked using a CT angiogram. This test is very easy on the patient because it is a minimally
invasive procedure. The first step in the process is having a dye injected into the patient to help highlight the
arteries for the CT scanner.

An MRI scan is a test that uses a magnetic field and pulses of radio wave energy to make pictures. This will
reveal the location of the coarctation of the aorta and determine whether it affects other blood vessels in the
body.

Cardiac catheterization is an invasive imaging procedure that is a tool for evaluating heart functions. A long,
narrow tube is inserted. The introducer sheath is typically inserted into the patients arm or leg. The catheter is
positioned through the patients blood vessel until it reaches the coronary arteries, a contrast dye is injected
though the tip of the catheter while x-rays are taken to follow the dye through the chambers of the heart and
arteries. This part of the procedure is called the coronary angiogram. This is an interventional procedure that
opens up the coronary artery to increase the blood flow to the heart. The contrast material injected into the
arteries that help produce images of the heart help locate narrowed or blocked areas in arteries around the
heart. There are other ways to produce images such as intra-vascular ultrasound (IVUS) and fractional flow
reserve (FFR).

Treatment

Treatment is conservative if asymptomatic, but may require surgical resection of the narrow segment if there
is arterial hypertension.

Prostaglandin E1 (0.05-0.15 mcg/kg/min) is infused intravenously to open the ductus

arteriosus.
Ventilatory assistance is provided to patients with markedly increased work of breathing.
Infusion of inotropic drugs (dopamine, dobutamine, epinephrine) is useful when
ventricular dysfunction is present, especially with hypotension.
Preoperative hypertension can be effectively treated using beta-blockers.
ABGs are tested to monitor acidosis.

There are several open-heart surgical techniques to repair aortic coarctation. The
options include:
 Resection with end-to-end anastomosis. This method involves removing the narrowed
segment of the aorta (resection) followed by connecting the two ends of the aorta together
(anastomosis).

Patch aortoplasty. Your doctor may treat your coarctation by cutting across the
constricted area of the aorta and then attaching a patch of synthetic material to widen the
blood vessel. Patch aortoplasty is useful if the coarctation involves a long segment of the
aorta.

Left subclavian flap angioplasty. A portion of the left subclavian artery, the blood
vessel that delivers blood to your left arm, may be used to expand the narrowed area of the
artery.

Bypass graft repair. This technique involves bypassing the narrowed area by inserting
a plastic tube called a graft between the portions of the aorta.

Balloon angioplasty and stenting

Balloon angioplasty is an option for initially treating aortic coarctation or for treating re-
narrowing (re-coarctation) that has occurred after surgery. During this procedure a thin
flexible tube (catheter) is inserted into an artery in the groin and threads it up through
the blood vessels to the heart. An uninflated balloon is placed through the opening of
the narrowed aorta. When the balloon is inflated, the aorta widens and blood flows more
easily. In some cases, a mesh-covered hollow tube called a stent is inserted to keep the
narrowed part of the aorta open.

Complications and prognosis

The most common long-term complication of coarctation of the aorta is high blood
pressure. Although your blood pressure usually falls after the aortic coarctation has
been repaired, it may still remain higher than normal. Occasionally, the segment of the
aorta that has been repaired will become weak and bulge (aortic aneurysm) and may
eventually rupture. In some cases, the coarctation will recur, possibly even years after
treatment, but it's possible to have additional surgeries or procedures to correct the re-
narrowing.
Post Procedure Life[edit]

Mortality Data[edit]

Looking at a study conducted by the Divisions of Pediatric Cardiology at the University of Minnesota School of
Medicine, University of Connecticut Medical School, and University of Michigan where research was done on
252 survivors of the coarctation procedure, the age of the patient at the time of surgery is crucial in their
longevity. Patients with the greatest chance of survival were those administered the procedure at very young
ages, with children between the ages one and five having the lowest mortality rate. A further breakdown of the
relationship between mortality rate and certain age groups proves to be a major indicator of the importance of
early detection and diagnosis. Ninety-five percent of the 252 patients were still alive at ten years post-surgery,
eighty-nine percent at twenty years, eighty-two percent at thirty years, and seventy-nine percent at forty years.
The causes of late death vary but the most common cause was coronary artery disease. At the mean age of
fifty-three years, ten patients were diagnosed and died from this disease. All of these patients were older than
ten years of age when the initial coarctation procedure occurred. Seven patients died during a second cardiac
operation: aortic valve replacement caused three patients to die, recoarctation surgery led to two patients'
deaths, and mitral valve operation caused two others to die. In seven different patients sudden death occurred
and of these seven patients, six were older than ten years of age at the time of the initial coarctation repair.
Ruptured aortic aneurysm caused the death of six subjects; five occurred from ascending aortic dissection and
rupture, while the last patient died from an aneurism occurring at the site of the original repair (Rene M. et al.)

Cause of Late Death No.

Coronary artery disease 10

Second cardiac operation 7

Aortic dissection 6

Sudden unexplained 7
Automobile accident 3

Other 7

Unknown 5

Other=Suicide, endocarditis, cardiomyopathy, alcohol, cancer, autoimmune deficiency syndrome; and prostate
surgery.

Side Effects[edit]

Hypertension is defined when a patient's blood pressure in the arm exceeds 140/90 mmHg under normal
conditions. This is a severe problem for the heart and can cause many other complications. In a study of 120
coarctation repair recipients done in Groningen, The Netherlands, twenty-nine patients (25%) experienced
hypertension in the later years of life due to the repair. While hypertension has many different factors that lead
to this stage of blood pressure, people who have had a coarctation repair regardless of the age at which the
operation was performed are at much higher risk than the general public of hypertension later in life.
Undetected chronic hypertension can lead to sudden death among coarctation repair patients, at higher rates
as time progresses.

Angioplasty is a procedure done to dilate an abnormally narrow section of a blood vessel to allow better blood
flow. This is done in a cardiac catheterization laboratory. Typically taking two to three hours, the procedure may
take longer but usually patients are able to leave the hospital the same day. After a coarctation repair 20-60%
of infant patients may experience reoccurring stenosis at the site of the original operation. This can be fixed by
either another coarctation or by the procedure of choice among cardiologists; angioplasty.[13]

Coronary artery disease, otherwise simply known as heart disease, is a major issue for patients who have
undergone a coarctation repair. Many years after the procedure is done, heart disease not only has an
increased chance of affecting coarctation patients, but also progresses through the levels of severity at an
alarmingly increased rate. In a study conducted by Mare Cohen, MD, et al., one fourth of the patients who
experienced a coarctation died of heart disease, some at a relatively young age (Cohen, Marc, MD et al.) (G Di
Salvo et al.)
Clinical criteria are used in most studies when defining recurrence of coarctation (recoarctation) when blood
pressure is at a difference of >20 mmHg between the lower and upper limbs. This procedure is most common
in infant patients and is uncommon in adult patients. In a study conducted by Koller et al., 10.8% of infant
patients underwent recoarctations at less than two years of age while another 3.1% of older children received a
recoarctation (Michael Giuffre et al.)

Patients who have had a coarctation of the aorta are likely to have bicuspid aortic valve disease. Between 20%
and 85% of patients are affected with this disease. Bicuspid aortic valve disease is a big contributor to cardiac
failure, which in turn makes up roughly 20% of late deaths to coarctation patients (Michael Giuffre et al.)

Followup[edit]

Leaving the hospital after a coarctation is only one step in a lifelong process. Just because the coarctation was
fixed does not mean that the patient is cured. It is extremely important to visit the cardiologist on a regular
basis. Depending on the severity of the patient's condition, which is evaluated on a case-by-case level, visiting
a cardiologist can be a once a year surveillance check up. Keeping a regular schedule of appointments with a
cardiologist after the coarctation is complete helps increase the chances of survivability for the patients. [14]

History[edit]

An anecdotal history statement describes the first diagnosed case of the coarctation of the Aorta in Julia the
daughter of the French poet Alphonse de Lamartine after the autopsy in 1832 in Beirut, the reference
manuscript still exists in one of the Maronite monasteries in Mount Lebanon.

Background

Coarctation of the aorta (CoA) is a relatively common defect that accounts for 5-8% of all congenital heart
defects. Coarctation of the aorta may occur as an isolated defect or in association with various other
lesions, most commonly bicuspid aortic valve and ventricular septal defect (VSD). The diagnosis of
coarctation of the aorta may be missed unless an index of suspicion is maintained, and diagnosis is often
delayed until the patient develops congestive heart failure (CHF), which is common in infants,
or hypertension, which is common in older children. This article discusses the pathology, pathophysiology,
clinical features, noninvasive and invasive evaluation, and therapy in patients with coarctation of the
aorta.

Pathologic anatomy

Coarctation of the aorta may be defined as a constricted aortic segment that comprises localized medial
thickening, with some infolding of the medial and superimposed neointimal tissue. [1] The localized
constriction may form a shelflike structure with an eccentric opening or may be a membranous curtainlike
structure with a central or eccentric opening. The coarctation may be discrete, or a long segment of the
aorta may be narrowed; the former is more common.
In the past, coarctation of the aorta has been described as preductal (or infantile) type or postductal (or
adult) type, depending on whether the coarctation segment is proximal or distal to the ductus arteriosus,
respectively. However, a closer examination of the anatomy suggests that all coarctations are juxtaductal.

The classic coarctation of the aorta is located in the thoracic aorta distal to the origin of the left subclavian
artery at about the level of the ductal structure. However, rarely, a coarcted segment is present in the
lower thoracic or abdominal aorta. In such instances, the coarcted segment may be long and fusiform with
irregular lumen; many consider these to be inflammatory or autoimmune in origin, and they may be
variants of Takayasu arteritis.

Dilatation of the descending aorta immediately distal to the coarctation segment (poststenotic dilatation) is
usually present. A jet lesion on the wall of the aorta distal to the coarctation site may also be present.
Varying degrees of hypoplasia of the isthmus of the aorta (the portion of the aorta between the origin of
the left subclavian artery and ductus arteriosus) are present in most patients with thoracic coarctation; this
hypoplasia may be significant in symptomatic coarctation of the neonate and infant; in children and adults,
the isthmus may have only mild narrowing. The transverse aortic arch (the arch between the origin of the
right innominate artery and the left subclavian artery) is also hypoplastic in symptomatic neonates and
infants. Collateral vessels that connect arteries from the upper part of the body to the vessels below the
level of coarctation may be seen; these may be present as early as a few weeks to a few months of life.

The most commonly associated clinically significant defects include patent ductus arteriosus, VSD, and
aortic stenosis. The earlier the infant presents, the more likely a significant associated defect is
present. Bicuspid aortic valve may be seen in nearly two thirds of infants with coarctation of the aorta,
whereas only 30% of those who present in childhood have such an anomaly.

Mitral valve anomalies, although less common than those of the aortic valve, are also associated with
coarctation of the aorta. Sometimes, coarctation of the aorta is a complicating feature of a more complex
cyanotic heart defect, such astransposition of the great arteries, Taussig-Bing anomaly, double-inlet left
ventricle, tricuspid atresia with transposition of the great arteries, and hypoplastic left heart syndrome.

Aortic coarctation is extremely rare in patients with severe right ventricular outflow tract obstructions such
as tetralogy of Fallot and pulmonary atresia with intact ventricular septum. Some patients with coarctation
of the aorta may have cerebral aneurysms, predisposing them to cerebrovascular accidents with severe
hypertension later in life. Coarctation of the aorta is the most common cardiac defect associated
with Turner syndrome.

Pathogenesis

The exact mechanism by which aortic coarctation is produced is not clearly understood. The most
commonly invoked hypotheses include hemodynamic and ectopic ductal tissue theories. In the
hemodynamic theory, an abnormal preductal flow or abnormal angle between the ductus and aorta that
increases right-to-left ductal flow and decreases isthmic flow potentiates development of coarctation.
Postnatal spontaneous closure of the ductus arteriosus completes the development of aortic obstruction. [2,
3]

A high incidence of coarctation of the aorta in patients with congenital heart defects and decreased
antegrade aortic flow in utero and virtual absence of CoA in patients with right heart obstructions lends
credence to the hemodynamic theory. Abnormal extension of ductal tissue into the aorta (ectopic ductal
tissue)[4, 5] has been postulated to create the coarctation shelf and, with ductal closure, development of
aortic obstruction. This theory, however, does not explain the variable degrees of isthmus and aortic arch
hypoplasia associated with coarctation of the aorta.
Epidemiology

Frequency

United States

Coarctation of the aorta is a common defect and occurs in 6-8% of patients with congenital heart disease.
[13, 14]
However, coarctation may be found more frequently in infants who present with symptoms prior to
age one year.[11]

International

The prevalence of coarctation of the aorta appears to be lower (< 2%) in Asian countries than in
European and North American countries.[15]

Mortality/Morbidity

Past autopsy studies suggest that the mortality rate in patients in whom coarctation of the aorta is not
surgically repaired is 90% by age 50 years, with a mean age of 35 years. [16] In the current era, coarctation
of the aorta mortality is often determined by patient age, patient size, and associated major
cardiovascular anomalies.

Associated problems that may contribute to death or morbidity include hypertension, intracranial
hemorrhage, aortic rupture or dissection, endocarditis, and CHF.

Race

No definitive racial differences have been documented in coarctation of the aorta, although some authors
have suggested that coarctation of the aorta is less common in Asians. [15]

Sex

The male-to-female ratio is 2:1, although this ratio is not valid in abdominal coarctation of the aorta, in
which this rare lesion predominantly affects females. The ratio of abdominal-to-thoracic coarctation is
approximately 1:1000. The male preponderance observed in older patients is not seen in infants with
coarctation of the aorta.

Age

Generally, patients with coarctation of the aorta present early in life with CHF or later in life with
hypertension. Studies continue to document that coarctation of the aorta is often missed in the first year of
life,[17, 18] and the median age of referral to a pediatric cardiologist in one study was 5 years.

Physical
As with history, physical examination may conveniently separate patients into 2 groups: those
who present early with heart failure and those who present later with hypertension.
 Early presentation
o Neonates may be found to have tachypnea, tachycardia, and increased
work of breathing and may even be moribund with shock. Keys to the diagnosis
include blood pressure (BP) discrepancies between the upper and lower
extremities and reduced or absent lower extremity pulses to palpation. However,
when the infant is in severe heart failure, all pulses are diminished. Upon
treatment for heart failure, prominent brachial pulses with weak or nonpalpable
femoral arterial pulses may be discerned. Diminished pulses on examination
should never be disregarded, since the digits appreciate the rate of change in BP,
which may be diminished in ductally dependent coarctation, although the
measured BP may not show discrepancies. In patients with an aberrant origin of
the right subclavian artery from the aorta distal to the obstruction, such
discrepancies in BP may not be present, although lower extremity pulses are
diminished versus the carotid pulses.
o Differential cyanosis (pink upper extremities with cyanotic lower
extremities) may occur when right-to-left shunt across a patent ductus arteriosus
provides flow to the lower body. Although often not obvious to the eye,
differential cyanosis may be documented based on preductal and postductal
pulse oximetry measurements and careful inspection. However, in the presence
of lesions with large left-to-right shunt (eg, VSD), pulmonary artery saturations
may approximate aortic saturations with less obvious differential oximetric
findings. Reversed differential cyanosis (upper body cyanosis with normal lower-
body oxygen saturation) may occur with transposition of the great arteries,
patent ductus arteriosus, and pulmonary hypertension, resulting in right-to-left
ductal shunting.
o In patients with low cardiac output and ventricular dysfunction, pulses
may be diminished diffusely, and BP gradients may seem minimal. Thus, in
addition to coarctation, the differential diagnosis of perinatal circulatory
insufficiency always includes left ventricular (LV) outflow obstruction,
including aortic valve stenosis, subaortic stenosis, andsupravalvar aortic stenosis,
as well as severe mitral stenosis or insufficiency.
o The murmur associated with coarctation of the aorta may be
nonspecific yet is usually a systolic murmur in the left infraclavicular area and
under the left scapula. Additional murmurs that result from the presence of
associated abnormalities, such as VSD or aortic valve stenosis, may also be
detected. An ejection click may signify the presence of a bicuspid aortic valve,
whereas a gallop rhythm may indicate ventricular dysfunction.
Late presentation
o Older infants and children may be referred for evaluation of
hypertension or murmur. Hypertension in a fussy infant or a child may be
attributed to agitation; thus, comparing BP readings in all the 4 extremities is
important. Occasionally, the left arm pressure is lower than the right arm
pressure if the origin of the left subclavian artery is involved in the coarctation.
Similarly, anomalous origin of the right subclavian artery (below the level of
coarctation) may produce decreased or absent right brachial pulse. Careful
simultaneous palpation of upper and lower extremity pulses may help confirm
suspected coarctation.
o In older children, adolescents, and adults, coarctation of the aorta is
best diagnosed clinically based on simultaneous palpation of femoral and
brachial pulses. Blood pressure in both arms and one leg must be determined; a
 pressure difference of more than 20 mm Hg in favor of the arms may be
considered evidence of coarctation of the aorta.
o A murmur in the left infraclavicular area and under the left scapula
may be systolic, but the murmur may also sound continuous in the presence of
multiple collateral vessels or, occasionally, severe coarctation. An ejection click
may be audible when an associated bicuspid aortic valve and a murmur of aortic
stenosis or insufficiency are present. Similarly, a murmur of mitral stenosis or LV
outflow tract obstruction may also occur. A gallop rhythm may occur in the
presence of a hypertrophic noncompliant LV.
o Other findings on physical examination may include abnormalities of
blood vessels in the retina and a prominent suprasternal notch pulsation. A thrill
may be present in the suprasternal notch or on the precordium in the presence of
significant aortic valve stenosis. In the rare case of abdominal coarctation, an
abdominal bruit may be noted.
Causes
Numerous theories have been proposed for the etiology of coarctation of the aorta, including
postnatal ductal constriction,[2, 3] translocation of ductal tissue onto the aorta,[4, 5] and a theory that alterations
in intrauterine blood flow cause altered flow through the aortic arch and result in the substrate for
coarctation.[2]Coarctation of the aorta manifests when the ductus closes starting at the pulmonary end,
with gradual involution of ductal tissue toward the aorta.
Similar to most forms of congenital heart disease (CHD), the etiology of coarctation of the aorta
may be explained by multifactorial inheritance hypothesis. [22] The prevalence of coarctation of the aorta in
genetic abnormalities such as Turner syndrome (45,X), is as high as 15-20%. Familial patterns of
inheritance of coarctation have been reported, as well as for other left heart obstructive lesions. An
increase in seasonal occurrence of coarctation of the aorta is reported in September and November.
Laboratory Studies
The following studies may be indicated in coarctation of the aorta (CoA):

Laboratory studies in neonatal patients who present in shock include the

following:
o Septic workup includes blood, urine, and cerebral spinal fluid (CSF)
cultures.
o Electrolyte levels, BUN, creatinine, and glucose concentrations should
be tested.
o Measure arterial blood gases and serum lactate levels.
Laboratory studies in older patients who present with hypertension include
urinalysis, electrolyte levels, BUN, creatinine, and glucose concentrations.
Imaging Studies
Chest radiography
Radiography in patients with early onset of coarctation of the aorta
may reveal cardiomegaly, pulmonary edema, and other signs of congestive heart
failure (CHF).
Radiography in patients with late onset of coarctation of the aorta may
reveal cardiomegaly. An inverted "3" sign of the barium-filled esophagus or a "3"
sign on a highly penetrated chest radiograph (frontal view) may be visualized. Rib
notching secondary to collateral vessels may also be seen.
 Echocardiography: Echocardiography delineates intracardiac anatomy and
allows assessment of associated significant intracardiac anomalies. The
suprasternal notch 2-dimensional echocardiographic view allows evaluation of the
aortic arch to assess the transverse aortic arch, isthmus, and severity of
coarctation. Doppler echocardiography is used to measure the gradient at the site
of coarctation and to identify the pattern of diastolic runoff typically seen in patients
with severe obstruction.
Instantaneous peak pressure gradients across the aortic coarctation can be
estimated with a modified Bernoulli equation, as follows: P = 4 (V 2 V 2)P is the
2 1

peak instantaneous gradient, and V and V are the peak flow velocities in the
2 1

descending aortic, distal to coarctation (continuous-wave Doppler) and proximal to

the coarctation (pulsed Doppler), respectively. The calculated gradient usually
overestimates the measured blood pressure gradient. Presence of pan-diastolic flow
indicates significant obstruction. Inclusion of duration-related Doppler flow
parameters in the gradient calculation may improve the accuracy of Doppler
prediction of coarctation gradient.[23]
When aortic arch cannot be adequately evaluated, abdominal aortic Doppler
parameters may help in the diagnosis. [24] Absence of early diastolic reversal along
with corrected pulse delay of 2.8 microseconds 1/2 or more may best predict
significant obstruction.
MRI and CT are useful in older or postoperative patients to assess residual
arch obstruction, arch hypoplasia, or formation of aneurysms (see image below). [25,
26]
Ultrafast CT scanning is preferable if multiple surgical clips or a stent is present in

the area of coarctation. Aortic coarctation visualized by aortic

angiography. Aortic coarctation visualized by MR imaging.

Other Tests
Electrocardiography
 ECG in the neonate or infant with early onset of coarctation of the
aorta may reveal right ventricular rather than left ventricular (LV) hypertrophy. The
reasons for right ventricular preponderance in the face of LV outlet obstruction are
mentioned in Pathophysiology.
ECG findings in patients with late onset of coarctation of the aorta may
be normal or may reveal LV hypertrophy and may show signs of LV ischemia or
strain. Sometimes, LV hypertrophy may manifest as increased S waves in leads
V and V , the so-called posterobasal LV hypertrophy.
5 6

Preductal and postductal pulse oximetry readings may show evidence of

ductal right-to-left shunting, especially in the neonate.
Procedures
Cardiac catheterization
Cardiac catheterization and selective cineangiography may not be
required for diagnosis; however, they allow evaluation of the severity of
coarctation, anatomic nature of the aortic obstruction (discrete vs long segment),
and arch anatomy, including hypoplasia of the transverse arch or isthmus.
Cardiac catheterization helps confirm the diagnosis when
echocardiography findings are not completely clear.
Cardiac catheterization allows the evaluation of intracardiac anatomy
and the contribution of associated lesions to the overall hemodynamic
disturbance.
Cardiac catheterization is a prerequisite for intervention in the form of
either balloon angioplasty or stent implantation in native or recurrent coarctation.
When catheterization is performed, elevations of left ventricular and
ascending aortic peak systolic pressures with a peak-to-peak systolic pressure
gradient across the coarcted segment are usually found. A peak-to-peak gradient
in excess of 20 mm Hg is generally considered indicative of significant obstruction.
However, the magnitude of the gradient is not necessarily indicative of the degree
of narrowing because the gradient depends on not only the extent of aortic
narrowing but also the size and number of collateral vessels. In addition, cardiac
output and the state of ductus arteriosus, particularly in the neonate and young
infant, also determine the pressure gradient.
Selective aortic root or aortic arch angiography is necessary to clearly
demonstrate the aortic narrowing. Aortography is useful in demonstrating the type
of aortic coarctation (diffuse, long segment, aortic kinking [pseudocoarctation]);
extent of collateral circulation; the size of ductus arteriosus, if patent; and the
presence and degree of hypoplasia of transverse aortic arch and aortic isthmus,
especially in neonates. If thoracic coarctation is not demonstrated despite clinical
features of coarctation or if neurofibromatosis is suspected, abdominal
aortography may be needed to demonstrate (or exclude) abdominal coarctation.
LV angiography is particularly useful in neonates and infants who
demonstrate ventricular septal defects (VSDs) and in evaluating their function.
Histologic Findings
Coarctation of the aorta results from marked ridgelike thickening of the media of the aortic wall
opposite the insertion of the patent ductus arteriosus or ligamentum arteriosum.
Intima in this area may be thin initially but may thicken over time.
This ridge or shelf becomes an obstruction when the patent ductus involutes and when ductal
tissue in the wall of the aorta involutes.
 Medical Care
Early presentation of coarctation of the aorta (CoA)
Treatment in patients with congestive heart failure (CHF) includes the use of diuretics and
inotropic drugs.
Prostaglandin E1 (0.05-0.15 mcg/kg/min) is infused intravenously to open the ductus
arteriosus.
Ventilatory assistance is provided to patients with markedly increased work of breathing.
Infusion of inotropic drugs (dopamine, dobutamine, epinephrine) is useful when
ventricular dysfunction is present, especially with hypotension.
A Foley catheter is inserted to monitor renal perfusion and urine output.
An umbilical artery catheter may be placed in neonates to assess the response to
prostaglandin infusion with regard to improving lower-body blood flow.
Patients stabilized by the above interventions are better candidates for surgical or
catheter intervention.
In the presence of associated defects, the significance of coarctation on the clinical
course of the patient should be assessed with echo-Doppler and/or catheterization and angiographic
studies. If the coarctation has a significantly adverse effect on the physiology of the associated defects,
and consequently the clinical status, the coarctation should be initially relieved with surgery or balloon
angioplasty and the patient reassessed with regard to need for intervention for the associated defects.
Based on the authors' experience and that of others, the aortic obstruction is usually a major
contributing factor for the symptomatology, and relief of the obstruction may postpone or avert the need
for additional surgical intervention for the associated cardiac defects. [27, 28]
Late presentation of coarctation of the aorta
Treatment of hypertension
The goal should be to reduce upper extremity hypertension, but remember that
vigorous attempts to achieve normal upper extremity blood pressure (BP) may result in inadequate
lower-body perfusion. Beta-blocker therapy prior to surgery may reduce the severity of postoperative
hypertension, although most patients with preoperative hypertension require at least transient
postoperative therapy. Remember that relieving the aortic obstruction promptly rather that attempting
to treat hypertension with antihypertensive medications is better.[1]
Postoperative hypertension can be treated short-term with vasodilators, such as
sodium nitroprusside, and intravenous beta-blockers, such as esmolol. When longer-term
antihypertensive therapy is required, beta-blockers may be continued, and if no residual arch
obstruction exists, ACE inhibitors or angiotensin II antagonists (pediatric dosing not established for
angiotensin II antagonists) may be added if hypertension persists despite beta-blocker therapy.
Guidelines regarding beta-adrenergic receptor blockers have been established. [29]
A recent study concluded that data is not sufficient to discourage or recommend
the use of beta-blockers in children with CHF.[30]
Evaluate associated abnormalities, such as aortic stenosis, subaortic stenosis, or mitral
valve disease.
Evaluate adequacy of collateral blood vessels to assess the safety of surgical
intervention.

There are several open-heart surgical techniques to repair aortic coarctation. Your
doctor can discuss with you which type is most likely to successfully repair your or your
child's condition. The options include:

Resection with end-to-end anastomosis. This method involves removing the narrowed
segment of the aorta (resection) followed by connecting the two ends of the aorta together
(anastomosis).
 Patch aortoplasty. Your doctor may treat your coarctation by cutting across the
constricted area of the aorta and then attaching a patch of synthetic material to widen the
blood vessel. Patch aortoplasty is useful if the coarctation involves a long segment of the
aorta.

Left subclavian flap angioplasty. A portion of the left subclavian artery, the blood
vessel that delivers blood to your left arm, may be used to expand the narrowed area of the
artery.

Bypass graft repair. This technique involves bypassing the narrowed area by inserting
a plastic tube called a graft between the portions of the aorta.

Neonatal jaundice or Neonatal hyperbilirubinemia, or Neonatal icterus (from the Greek

word ), attributive adjective: icteric, is a yellowing of the skin and other tissues of a
newborn infant. A bilirubin level of more than 85 mol/l (5 mg/dL) manifests
clinical jaundice in neonateswhereas in adults a level of 34 mol/l (2 mg/dL) would look icteric. In
newborns, jaundice is detected by blanching the skin with digital pressure so that it reveals underlying
skin and subcutaneous tissue.[1] Jaundiced newborns have an apparent icteric sclera, and yellowing of the
face, extending down onto the chest.

In neonates, the dermal icterus is first noted in the face and as the bilirubin level rises proceeds caudal to
the trunk and then to the extremities.[2]This condition is common in newborns affecting over half (5060%)
of all babies in the first week of life.[3]

Notoriously inaccurate rules of thumb have been applied to the physical exam of the jaundiced infant.[citation
needed]
Some include estimation of serumbilirubin based on appearance. One such rule of thumb includes
infants whose jaundice is restricted to the face and part of the trunk above theumbilicus, have
the bilirubin less than 204 mol/l (12 mg/dL) (less dangerous level). Infants whose palms and soles are
yellow, have serum bilirubin level over 255 mol/l (15 mg/dL) (more serious level). Studies have shown
that trained examiners assessment of levels of jaundice show moderate agreement with icterometer
bilirubin measurements.[2] In infants, jaundice can be measured using invasive or non-invasive methods.
In non-invasive methods, Ingram icterometers and transcutaneous bilirubinometers are used.

Physiological jaundice[edit]
Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their
first week. This common condition is called physiological jaundice. This pattern ofhyperbilirubinemia has
been classified into two functionally distinct periods.

Phase one

1. Term infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204 mol/l
(12 mg/dL).

2. Preterm infants - jaundice lasts for about two weeks, with a rapid rise of serum bilirubin up to
255 mol/l (15 mg/dL).
Phase two - bilirubin levels decline to about 34 mol/l (2 mg/dL) for two weeks, eventually
mimicking adult values.

1. Preterm infants - phase two can last more than one month.

2. Exclusively breastfed infants - phase two can last more than one month.
Causes[edit]
Mechanism involved in physiological jaundice are mainly:

Relatively low activity of the enzyme glucuronosyltransferase which normally

converts unconjugated bilirubin to conjugated bilirubin that can be excreted into the gastrointestinal
tract.[4] Before birth, this enzyme is actively down-regulated, since bilirubin needs to remain
unconjugated in order to cross the placenta to avoid being accumulated in the fetus. [5] After birth, it
takes some time for this enzyme to gain function.

Shorter life span of fetal red blood cells,[4] being approximately 80 to 90 days in a full term infant,
[6]
compared to 100 to 120 days in adults.

Relatively low conversion of bilirubin to urobilinogen by the intestinal flora, resulting in relatively
high absorption of bilirubin back into the circulation
Background

Jaundice is the most common condition that requires medical attention in newborns. The yellow coloration
of the skin and sclera in newborns with jaundice is the result of accumulation of unconjugated bilirubin. In
most infants, unconjugated hyperbilirubinemia reflects a normal transitional phenomenon. However, in
some infants, serum bilirubin levels may excessively rise, which can be cause for concern because
unconjugated bilirubin is neurotoxic and can cause death in newborns and lifelong neurologic sequelae in
infants who survive (kernicterus). For these reasons, the presence of neonatal jaundice frequently results
in diagnostic evaluation.

Neonatal jaundice may have first been described in a Chinese textbook 1000 years ago. Medical theses,
essays, and textbooks from the 18th and 19thcenturies contain discussions about the causes and treatment
of neonatal jaundice. Several of these texts also describe a lethal course in infants who probably had Rh
isoimmunization. In 1875, Orth first described yellow staining of the brain, in a pattern later referred to as
kernicterus.
 Pathophysiology

Neonatal physiologic jaundice results from simultaneous occurrence of the following 2 phenomena:

Bilirubin production is elevated because of increased breakdown of fetal erythrocytes. This is the
result of the shortened lifespan of fetal erythrocytes and the higher erythrocyte mass in neonates.
Hepatic excretory capacity is low both because of low concentrations of the binding protein
ligandin in the hepatocytes and because of low activity of glucuronyl transferase, the enzyme
responsible for binding bilirubin to glucuronic acid, thus making bilirubin water soluble (conjugation).

Bilirubin is produced in the reticuloendothelial system as the end product of heme catabolism and is
formed through oxidation-reduction reactions. Approximately 75% of bilirubin is derived from hemoglobin,
but degradation of myoglobin, cytochromes, and catalase also contributes. In the first oxidation step,
biliverdin is formed from heme through the action of heme oxygenase, the rate-limiting step in the
process, releasing iron and carbon monoxide. The iron is conserved for reuse, whereas carbon monoxide
is excreted through the lungs and can be measured in the patient's breath to quantify bilirubin production.

Next, water-soluble biliverdin is reduced to bilirubin, which, because of the intramolecular hydrogen
bonds, is almost insoluble in water in its most common isomeric form (bilirubin IX Z,Z). Because of its
hydrophobic nature, unconjugated bilirubin is transported in the plasma tightly bound to albumin. Binding
to other proteins and erythrocytes also occurs, but the physiologic role is probably limited. Binding of
bilirubin to albumin increases postnatally with age and is reduced in infants who are ill.

The presence of endogenous and exogenous binding competitors, such as certain drugs, also decreases
the binding affinity of albumin for bilirubin. A minute fraction of unconjugated bilirubin in serum is not
bound to albumin. This free bilirubin is able to cross lipid-containing membranes, including the blood-brain
barrier, leading to neurotoxicity. In fetal life, free bilirubin crosses the placenta, apparently by passive
diffusion, and excretion of bilirubin from the fetus occurs primarily through the maternal organism.

When it reaches the liver, bilirubin is transported into liver cells, where it binds to ligandin. Uptake of
bilirubin into hepatocytes increases with increasing ligandin concentrations. Ligandin concentrations are
low at birth but rapidly increase over the first few weeks of life. Ligandin concentrations may be increased
by the administration of pharmacologic agents such as phenobarbital.

Bilirubin is bound to glucuronic acid (conjugated) in the hepatocyte endoplasmic reticulum in a reaction
catalyzed by uridine diphosphoglucuronyltransferase (UDPGT). Monoconjugates are formed first and
predominate in the newborn. Diconjugates appear to be formed at the cell membrane and may require the
presence of the UDPGT tetramer.

Bilirubin conjugation is biologically critical because it transforms a water-insoluble bilirubin molecule into a
water-soluble molecule. Water-solubility allows conjugated bilirubin to be excreted into bile. UDPGT
activity is low at birth but increases to adult values by age 4-8 weeks. In addition, certain drugs
(phenobarbital, dexamethasone, clofibrate) can be administered to increase UDPGT activity.

Infants who have Gilbert syndrome or who are compound heterozygotes for the Gilbert promoter and
structural mutations of the UDPGT1A1 coding region are at an increased risk of significant
hyperbilirubinemia. Interactions between the Gilbert genotype and hemolytic anemias such as glucose-6-
phosphatase dehydrogenase (G-6-PD) deficiency, hereditary spherocytosis, or ABO hemolytic disease
also appear to increase the risk of severe neonatal jaundice.
Further, the observation of jaundice in some infants with hypertrophic pyloric stenosis may also be related
to a Gilbert-type variant. Genetic polymorphism for the organic anion transporter protein OATP-2
correlates with a 3-fold increased risk for developing marked neonatal jaundice. Combination of
the OATP-2 gene polymorphism with a variant UDPGT1A1 gene further increases this risk to 22-fold.
Studies also suggest that polymorphisms in the gene for glutathione-S-transferase (ligandin) may
contribute to higher levels of total serum bilirubin.

Thus, some interindividual variations in the course and severity of neonatal jaundice may be explained
genetically. As the impact of these genetic variants is more fully understood, development of a genetic
test panel for risk of severe and/or prolonged neonatal jaundice may become feasible.

Once excreted into bile and transferred to the intestines, bilirubin is eventually reduced to colorless
tetrapyrroles by microbes in the colon. However, some deconjugation occurs in the proximal small
intestine through the action of B-glucuronidases located in the brush border. This unconjugated bilirubin
can be reabsorbed into the circulation, increasing the total plasma bilirubin pool. This cycle of uptake,
conjugation, excretion, deconjugation, and reabsorption is termed 'enterohepatic circulation'. The process
may be extensive in the neonate, partly because nutrient intake is limited in the first days of life,
prolonging the intestinal transit time.

In mother-infant dyads who are experiencing difficulties with the establishment of breast feeding,
inadequate fluid and nutrient intake often leads to significant postnatal weight loss in the infant. Such
infants have an increased risk of developing jaundice through increased enterohepatic circulation, as
described above. This phenomenon is often referred to as breastfeeding jaundice and is different from
the breast milk jaundice described below.

Certain factors present in the breast milk of some mothers may also contribute to increased enterohepatic
circulation of bilirubin (breast milk jaundice). -glucuronidase may play a role by uncoupling bilirubin from
its binding to glucuronic acid, thus making it available for reabsorption. Data suggest that the risk of
breast milk jaundice is significantly increased in infants who have genetic polymorphisms in the coding
sequences of the UDPGT1A1 or OATP2 genes. Although the mechanism that causes this phenomenon is
not yet agreed on, evidence suggests that supplementation with certain breast milk substitutes may
reduce the degree of breast milk jaundice (see Other therapies).

Neonatal jaundice, although a normal transitional phenomenon in most infants, can occasionally become
more pronounced. Blood group incompatibilities (eg, Rh, ABO) may increase bilirubin production through
increased hemolysis. Historically, Rh isoimmunization was an important cause of severe jaundice, often
resulting in the development of kernicterus. Although this condition has become relatively rare in
industrialized countries following the use of Rh prophylaxis in Rh-negative women, Rh isoimmunization
remains common in developing countries.

Nonimmune hemolytic disorders (spherocytosis, G-6-PD deficiency) may also cause increased jaundice,
and increased hemolysis appears to have been present in some of the infants reported to have developed
kernicterus in the United States in the past 10-15 years. The possible interaction between such conditions
and genetic variants of the Gilbert and UDPGT1A1 genes, as well as genetic variants of several other
proteins and enzymes involved in bilirubin metabolism, is discussed above.

These discoveries also highlight the challenges involved in the common use of the terms physiologic
jaundice and pathologic jaundice. Although physiologic jaundice is a helpful concept from a didactic
perspective, applying it to an actual neonate with jaundice is more difficult.
Consider the following metaphor: Think of total serum bilirubin in neonatal jaundice as a mountain
covered by a glacier. If a measurement of the height of the mountain is taken when standing on the
summit, the amount of rock and the amount of ice that comprise this measurement is unclear. The same
is true for many total serum bilirubin values obtained in neonatal jaundice. An underpinning of physiologic
processes and pathological process (eg, Rhesus incompatibility) may clearly contribute to the
measurement. However, how much of the measured total value comes from each of these components is
unclear. Also, because genetic variants in bilirubin metabolism are only exceptionally pursued in the
diagnostic work-up of infants with jaundice, their possible contribution to the measured total serum
bilirubin is usually unknown.

Epidemiology

Frequency

United States

Neonatal hyperbilirubinemia is extremely common because almost every newborn develops an

unconjugated serum bilirubin level of more than 30 mol/L (1.8 mg/dL) during the first week of life.
Incidence figures are difficult to compare because authors of different studies do not use the same
definitions for significant neonatal hyperbilirubinemia or jaundice. In addition, identification of infants to be
tested depends on visual recognition of jaundice by health care providers, which varies widely and
depends both on observer attention and on infant characteristics such as race and gestational age.

With the above caveats, epidemiologic studies provide a frame of reference for estimated incidence. In
1986, Maisels and Gifford reported 6.1% of infants with serum bilirubin levels of more than 220 mol/L
(12.9 mg/dL).[1] In a 2003 study in the United States, 4.3% of 47,801 infants had total serum bilirubin levels
in a range in which phototherapy was recommended by the 1994 American Academy of Pediatrics (AAP)
guidelines, and 2.9% had values in a range in which the 1994 AAP guidelines suggest considering
phototherapy.[2]

International

Incidence varies with ethnicity and geography. Incidence is higher in East Asians and American Indians
and lower in blacks. Greeks living in Greece have a higher incidence than those of Greek descent living
outside of Greece.

Incidence is higher in populations living at high altitudes. In 1984, Moore et al reported 32.7% of infants
with serum bilirubin levels of more than 205 mol/L (12 mg/dL) at 3100 m of altitude. [3]

A study from Turkey reported significant jaundice in 10.5% of term infants and in 25.3% of near-term
infants.[4] Significant jaundice was defined according to gestational and postnatal age and leveled off at 14
mg/dL (240 mol/L) at 4 days in preterm infants and 17 mg/dL (290 mol/L) in the term infants.

Studies seem to suggest that some of the ethnic variability in the incidence and severity of neonatal
jaundice may be related to differences in the distribution of the genetic variants in bilirubin metabolism
discussed above.[5, 6]

Mortality/Morbidity
 Kernicterus occurs in 1.5 of 100,000 births in the United States. Death from physiologic neonatal jaundice
per se should not occur. Death from kernicterus may occur, particularly in countries with less developed
medical care systems. In one small study from rural Nigeria, 31% of infants with clinical jaundice tested
had G-6-PD deficiency, and 36% of the infants with G-6-PD deficiency died with presumed kernicterus
compared with only 3% of the infants with a normal G-6-PD screening test result. [7]

Race

The incidence of neonatal jaundice is increased in infants of East Asian, American Indian, and Greek
descent, although the latter appears to apply only to infants born in Greece and thus may be
environmental rather than ethnic in origin. Black infants are affected less often than white infants. For this
reason, significant jaundice in a black infant merits a closer evaluation of possible causes, including G-6-
PD deficiency. In 1985, Linn et al reported on a series in which 49% of East Asian, 20% of white, and 12%
of black infants had serum bilirubin levels of more than 170 mol/L (10 mg/dL). [8]

The possible impact of genetic polymorphisms on ethnic variation in incidence and severity should be
recognized. Thus, in a study of Taiwanese infants, Huang et al reported that neonates who carry the 211
and 388 variants in the UGT1A1 andOATP2 genes and who are breastfed are at particularly high risk for
severe hyperbilirubinemia.[5]

Sex

Risk of developing significant neonatal jaundice is higher in male infants. This does not appear to be
related to bilirubin production rates, which are similar to those in female infants.

Age

The risk of significant neonatal jaundice is inversely proportional to gestational age.

CLINICAL PRESENTATION

History
Presentation and duration of neonatal jaundice

Typically, presentation is on the second or third day of life.

Jaundice that is visible during the first 24 hours of life is likely to be nonphysiologic; further
evaluation is suggested.
Infants who present with jaundice after 3-4 days of life may also require closer scrutiny and
monitoring.
In infants with severe jaundice or jaundice that continues beyond the first 1-2 weeks of life, the
results of the newborn metabolic screen should be checked for galactosemia and
congenital hypothyroidism, further family history should be explored (see below), the infant's weight curve
should be evaluated, the mother's impressions as far as adequacy of breastfeeding should be elicited,
and the stool color should be assessed.

Family history
 Previous sibling with jaundice in the neonatal period, particularly if the jaundice required
treatment
Other family members with jaundice or known family history of Gilbert syndrome
Anemia, splenectomy, or bile stones in family members or known heredity for hemolytic disorders
Liver disease

History of pregnancy and delivery

Maternal illness suggestive of viral or other infection

Maternal drug intake
Delayed cord clamping
Birth trauma with bruising

Postnatal history

Loss of stool color

Breastfeeding
Greater than average weight loss
Symptoms or signs of hypothyroidism
Symptoms or signs of metabolic disease (eg, galactosemia)
Exposure to total parental nutrition

Physical
Neonatal jaundice first becomes visible in the face and forehead. Identification is aided by pressure on the
skin, since blanching reveals the underlying color. Jaundice then gradually becomes visible on the trunk
and extremities. This cephalocaudal progression is well described, even in 19th-century medical texts.
Jaundice disappears in the opposite direction. The explanation for this phenomenon is not well
understood, but both changes in bilirubin-albumin binding related to pH and differences in skin
temperature and blood flow have been proposed.[9, 10] This phenomenon is clinically useful because,
independent of other factors, visible jaundice in the lower extremities strongly suggests the need to check
the bilirubin level, either in the serum or noninvasively via transcutaneous bilirubinometry.

In most infants, yellow color is the only finding on physical examination. More intense jaundice may be
associated with drowsiness. Brainstem auditory-evoked potentials performed at this time may reveal
prolongation of latencies, decreased amplitudes, or both.

Overt neurologic findings, such as changes in muscle tone, seizures, or altered cry characteristics, in a
significantly jaundiced infant are danger signs and require immediate attention to prevent kernicterus. In
the presence of such symptoms or signs, effective phototherapy should commence immediately without
waiting for the laboratory test results (see Laboratory Studies). The potential need for exchange
transfusion should not preclude the immediate initiation of phototherapy.[11, 12]

Hepatosplenomegaly, petechiae, and microcephaly may be associated withhemolytic anemia, sepsis, and
congenital infections and should trigger a diagnostic evaluation directed towards these diagnoses.
Neonatal jaundice may be exacerbated in these situations.
 Causes
Physiologic jaundice is caused by a combination of increased bilirubin production secondary to
accelerated destruction of erythrocytes, decreased excretory capacity secondary to low levels of ligandin
in hepatocytes, and low activity of the bilirubin-conjugating enzyme uridine
diphosphoglucuronyltransferase (UDPGT).

Pathologic neonatal jaundice occurs when additional factors accompany the basic mechanisms described
above. Examples include immune or nonimmune hemolytic anemia, polycythemia, and the presence of
bruising or other extravasation of blood.

Decreased clearance of bilirubin may play a role in breast feeding jaundice, breast milk jaundice, and in
several metabolic and endocrine disorders.

Risk factors include the following:

Race: Incidence is higher in East Asians and American Indians and is lower in African Americans.
Geography: Incidence is higher in populations living at high altitudes. Greeks living in Greece
have a higher incidence than those living outside of Greece.
Genetics and familial risk: Incidence is higher in infants with siblings who had significant neonatal
jaundice and particularly in infants whose older siblings were treated for neonatal jaundice. Incidence is
also higher in infants with mutations/polymorphisms in the genes that code for enzymes and proteins
involved in bilirubin metabolism, and in infants with homozygous or heterozygous glucose-6-
phosphatase dehydrogenase (G-6-PD) deficiency and other hereditary hemolytic anemias.
Combinations of such genetic variants appear to exacerbate neonatal jaundice. [13, 5, 14, 6]
Nutrition: Incidence is higher in infants who are breastfed or who receive inadequate nutrition.
The mechanism for this phenomenon may not be fully understood. However, when inadequate feeding
volume is involved, increased enterohepatic circulation of bilirubin probably contributes to prolonged
jaundice. Recent data have shown that breast milk jaundice correlates with higher levels of epidermal
growth factor, both in breast milk and in infants' serum. [15] Data suggest that the difference between
breastfed and formula-fed infants may be less pronounced with some modern formulas. However,
formulas containing protein hydrolysates have been shown to promote bilirubin excretion.
Maternal factors: Infants of mothers with diabetes have higher incidence. Use of some drugs may
increase the incidence, whereas others decrease the incidence.
Birthweight and gestational age: Incidence is higher in premature infants and in infants with low
birthweight.
Congenital infection
Laboratory Studies
Bilirubin measurement may include the following:

Transcutaneous bilirubinometry can be performed using handheld devices that incorporate

sophisticated optical algorithms. Use of such devices has been shown to reduce the need for blood
sampling in infants with jaundice.[16] However, they cannot be used to monitor the progress of
phototherapy.[17]
Transcutaneous bilirubinometry performs better than visual assessment. The latter is not a
reliable technique for estimating levels of bilirubin, [18] but the complete absence of jaundice as judged by
the eye in good lighting conditions has quite high accuracy as far as predicting which infants are unlikely
to develop high total serum bilirubin levels.[19]
In infants with mild jaundice, transcutaneous bilirubinometry may be all that is needed to assure
that total bilirubin levels are safely below those requiring intervention.
 In infants with moderate jaundice, transcutaneous bilirubinometry may be useful in selecting
patients who require phlebotomy or capillary blood sampling for serum bilirubin measurement.
In infants with extreme jaundice, transcutaneous bilirubinometry may be a useful tool to fast-track
such infants to rapid and aggressive therapy.
Usually, a total serum bilirubin level test is the only one required in an infant with moderate
jaundice who presents on the typical second or third day of life without a history and physical findings
suggestive of a pathologic process. Measurement of bilirubin fractions (conjugated vs unconjugated) in
serum is not usually required in infants who present as described above. However, in infants who have
hepatosplenomegaly, petechiae, thrombocytopenia, or other findings suggestive of hepatobiliary
disease, metabolic disorder, or congenital infection, early measurement of bilirubin fractions is
suggested. The same may apply to infants who remain jaundiced beyond the first 7-10 days of life, and
to infants whose total serum bilirubin levels repeatedly rebound following treatment.

Additional studies may be indicated in the following situations:

Infants who present with jaundice on the first or after the third day of life
Infants who are anemic at birth
Infants who otherwise appear ill
Infants in whom serum bilirubin levels are elevated enough to trigger treatment
Infants in whom significant jaundice persists beyond the first 2 weeks of life
Infants in whom family, maternal, pregnancy, or case histories suggest the possibility of a
pathologic process
Infants in whom physical examination reveals findings not explained by simple physiologic
hyperbilirubinemia

In addition to total serum bilirubin levels, other suggested studies may include the following, particularly if
the rate of rise or the absolute bilirubin concentration is approaching the need for phototherapy:

Blood type and Rh determination in mother and infant

Direct antiglobulin test (DAT) in the infant (direct Coombs test)
Hemoglobin and hematocrit values
Serum albumin levels: This appears to be a useful adjunct in evaluating risk of toxicity levels
because albumin binds bilirubin in a ratio of 1:1 at the primary high-affinity binding site.
Nomogram for hour-specific bilirubin values: This is a useful tool for predicting, either before or at
the time of hospital discharge, which infants are likely to develop high serum bilirubin values. Infants
identified in this manner require close follow-up monitoring and repeated bilirubin measurements. The
predictive ability has been shown both for bilirubin values measured in serum and for values measured
transcutaneously. The nomogram has also been shown to work well for DAT-positive infants with AB0
incompatibility.[20] A positive DAT test result did not add any value to the clinical management of these
infants beyond that already obtained by an hour-specific bilirubin value plotted onto the nomogram.
Measurement of end-tidal carbon monoxide in breath: End-tidal carbon monoxide in breath
(ETCO) may be used as an index of bilirubin production. Measurement of ETCO may assist in
identifying individuals with increased bilirubin production and, thus, at increased risk of developing high
bilirubin levels. An apparatus has been developed that makes measuring ETCO simple (CO-Stat End
Tidal Breath Analyzer; Natus Medical Inc).
Peripheral blood film for erythrocyte morphology
Reticulocyte count
Conjugated bilirubin levels: Measuring bilirubin fractions may be indicated in the circumstances
described above. Note that direct bilirubin measurements are often inaccurate, are subject to significant
interlaboratory and intralaboratory variation, and are generally not a sensitive tool for
diagnosingcholestasis unless repeated measurements confirm the presence of an elevated conjugated
bilirubin.
 Liver function tests: Aspartate aminotransferase (ASAT or SGOT) andalanine
aminotransferase (ALAT or SGPT) levels are elevated in hepatocellular disease. Alkaline phosphatase
and -glutamyltransferase(GGT) levels are often elevated in cholestatic disease. A -GT/ALAT ratio of
more than 1 is strongly suggestive of biliary obstruction. However, it does not distinguish between
intrahepatic and extrahepatic cholestasis.
Tests for viral and/or parasitic infection: These may be indicated in infants with
hepatosplenomegaly, petechiae, thrombocytopenia, or other evidence of hepatocellular disease.
Reducing substance in urine: This is a useful screening test for galactosemia, provided the infant
has received sufficient quantities of milk.
Blood gas measurements: The risk of bilirubin CNS toxicity is increased in acidosis,
particularly respiratory acidosis.
Bilirubin-binding tests: Although they are interesting research tools, these tests have not found
widespread use in clinical practice. Although elevated levels of unbound ("free") bilirubin are associated
with an increased risk of bilirubin encephalopathy, unbound bilirubin is but one of several factors that
mediate/modulate bilirubin toxicity.
Thyroid function tests
Imaging Studies
Ultrasonography: Ultrasonography of the liver and bile ducts is warranted in infants with laboratory or
clinical signs of cholestatic disease.

Radionuclide scanning: A radionuclide liver scan for uptake of hepatoiminodiacetic acid (HIDA) is
indicated if extrahepatic biliary atresia is suspected. At the author's institution, patients are pretreated with
phenobarbital 5 mg/kg/d for 3-4 days before performing the scan.

Other Tests
Auditory and visually evoked potentials are affected during ongoing significant jaundice; however, no
criteria have been established that allow extrapolation from evoked potential findings to the risk of
kernicterus. Data suggest that the probability of a bilateral "refer" on an automated auditory brainstem
response (AABR) study increases with unbound bilirubin concentrations. [21] Because unbound bilirubin
concentrations may be more closely correlated with bilirubin neurotoxicity, a "refer" finding may indicate
an increased risk of bilirubin neurotoxicity. A "refer" AABR result obtained shortly after admission of an
infant with significant jaundice seems to argue for immediate and aggressive treatment.

Brainstem auditory-evoked potentials should be obtained in the aftermath of severe neonatal jaundice to
exclude sensorineural hearing loss. In physiologic jaundice, the auditory-evoked potential returns to
normal with the resolution of hyperbilirubinemia. However, in patients with significant neonatal jaundice or
kernicterus, the auditory-evoked potential and functional hearing may remain abnormal.

The phonetic characteristics of the infant's cry are changed in significant neonatal jaundice; however,
computerized analyses of these phonetic characteristics are not used in clinical practice.

Histologic Findings
Organs, including the brain, are yellow in any individual with significant jaundice; however, the yellow
color does not always indicate CNS toxicity. This distinction was not always clearly understood in older
descriptions of so-called "low-bilirubin kernicterus." At present, this has contributed to confusion and
uncertainty regarding therapeutic guidelines and intervention levels.
 See Kernicterus for a more detailed description.

Medical Care
Phototherapy, intravenous immune globulin (IVIG), and exchange transfusion are the most widely used
therapeutic modalities in infants with neonatal jaundice.

Phototherapy

Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia. This therapeutic
principle was discovered rather serendipitously in England in the 1950s and is now arguably the most
widespread therapy of any kind (excluding prophylactic treatments) used in newborns.

Phototherapy is effective because 3 reactions can occur when bilirubin is exposed to light, as follows:

Initially, photooxidation was believed to be responsible for the beneficial effect of phototherapy.
However, although bilirubin is bleached through the action of light, the process is slow and is now
believed to contribute only minimally to the therapeutic effect of phototherapy.
Configurational isomerization is a very rapid process that changes some of the predominant
4Z,15Z bilirubin isomers to water-soluble isomers in which one or both of the intramolecular bonds are
opened (E,Z; Z,E; or E,E). In human infants, the 4Z,15E isomer predominates, and, at equilibrium
conditions, the isomer constitutes about 20-25% of circulating bilirubin after a few hours of phototherapy.
This proportion is not significantly influenced by the intensity of light. Data have shown that formation of
photoisomers is significant after as little as 15 minutes of phototherapy.
Structural isomerization consists of intramolecular cyclization, resulting in the formation of
lumirubin. This process is enhanced by increasing the intensity of light. During phototherapy, lumirubin
may constitute 2-6% of the total serum bilirubin concentration.

The photoisomers of bilirubin are excreted in bile and, to some extent, in urine. The half-life of lumirubin in
serum is much shorter than that in E isomers, and lumirubin is the primary pigment found in bile during
phototherapy.

Bear in mind when initiating phototherapy that lowering of the total serum bilirubin concentration may be
only part of the therapeutic benefit. Because photoisomers, by virtue of their water-soluble nature, should
not be able to cross the blood-brain barrier, phototherapy may reduce the risk of bilirubin-induced
neurotoxicity as soon as the lights are turned on. At any given total serum bilirubin concentration, the
presence of 20-25% of photoisomers means that only 75-80% of the total bilirubin may be present in a
form that can enter the brain. Please note that although theoretically coherent, no experimental data
support this speculation.

Phototherapy can be administered in a number of ways. To understand the benefits and limitations of the
various approaches, some basic principles regarding wavelength and types of light are discussed below
with comments and suggestions regarding each system.

First, wavelength must be considered. Bilirubin absorbs light primarily around 450-460 nm. However, the
ability of light to penetrate skin is also important; longer wavelengths penetrate better. Thus, lamps with
output predominantly in the blue region of the spectrum (460-490 nm) are probably most effective. In
practice, light is used in the white, blue, turquoise, and green wavelengths.
 Second, a dose-response relationship may be observed between the amount of irradiation and reduction
in serum bilirubin up to an irradiation level of 30-40 W/cm 2/nm. Many older phototherapy units deliver
much less energy, some at or near the minimally effective level, which appears to be approximately 6
W/cm2/nm. On the other hand, newer phototherapy units, when properly configured and with the use of
reflecting blankets and curtains may deliver light energy above the 40 W/cm 2/nm suggested to be the
saturation level.

Third, the energy delivered to the infant's skin decreases with increasing distance between the infant and
the light source. This distance should not be greater than 50 cm (20 in) and can be less (down to 10 cm)
provided the infant's temperature is monitored.

Fourth, the efficiency of phototherapy depends on the amount of bilirubin that is irradiated. Irradiating a
large skin surface area is more efficient than irradiating a small area, and the efficiency of phototherapy
increases with serum bilirubin concentration.

Fifth, the nature and character of the light source may affect energy delivery. Irradiation levels using
quartz halide spotlights are maximal at the center of the circle of light and decrease sharply towards the
perimeter of the circle. Large infants and infants who can move away from the circle's center may receive
less efficient phototherapy.

Although green light theoretically penetrates the skin better, it has not been shown unequivocally to be
more efficient in clinical use than blue or white light. Because green light makes babies look sick and is
unpleasant to work in, green light has not gained widespread acceptance.

Blue fluorescent tubes are widely used for phototherapy. Narrow-spectrum blue lamps (special blue)
appear to work best, while ordinary blue fluorescent lamps are probably equivalent to standard white
daylight lamps. Blue lights may cause discomfort in hospital staff members, which can be ameliorated by
mixing blue and white tubes in the phototherapy unit.

White (daylight) fluorescent tubes are less efficient than special blue lamps; however, decreasing the
distance between infants and lamps can compensate for the lower efficiency. Use of reflecting materials
also helps. Thus, in developing countries where the cost of special blue lamps may be prohibitive,
efficient phototherapy is accomplished with white lamps.

White quartz lamps are an integral part of some radiant warmers and incubators. They have a significant
blue component in the light spectrum. When used as spotlights, the energy field is strongly focused
towards the center, with significantly less energy delivered at the perimeter, as discussed above.

Quartz lamps are also used in single or double banks of 3-4 bulbs attached to the overhead heat source
of some radiant warmers. The energy field delivered by these is much more homogeneous than that of
spotlights, and the energy output is reasonably high. However, because the lamps are fixed to the
overhead heater unit, the ability to increase energy delivery by moving lights closer to infants is limited.

Fiberoptic light is also used in phototherapy units. These units deliver high energy levels, but to a limited
surface area. Efficiency may be comparable to that of conventional low-output overhead phototherapy
units but not to that of overhead units used with maximal output. Drawbacks of fiberoptic phototherapy
units include noise from the fan in the light source and decrease of delivered energy with aging and/or
breakage of the optic fibers. Advantages include the following:

Low risk of overheating the infant

No need for eye shields
 Ability to deliver phototherapy with the infant in a bassinet next to the mother's bed
Simple deployment for home phototherapy
The possibility of irradiating a large surface area when combined with conventional overhead
phototherapy units (double/triple phototherapy)

Light-emitting diode (LED) lights are found in some newer phototherapy units. Advantages include low
power consumption, low heat production, and a much longer life span of the light-emitting units (20,000
hours) compared with older light sources. Blue LED lights have a narrow spectral band of high-intensity
light that overlaps the absorption spectrum of bilirubin. Trials comparing LED phototherapy to other light
sources were recently reviewed by the Cochrane Collaboration and by Tridente and DeLuca. The authors
of these reviews conclude that the efficacy of LED lights in reducing total serum bilirubin levels is
comparable to that of conventional light sources (fluorescent or halogen lamps). [22, 23] However, further
studies are needed to evaluate the comparable efficacy of LED lights in infants with hemolytic jaundice or
with severe hyperbilirubinemia.

"Double" and "triple" phototherapy, which implies the concurrent use of 2 or 3 phototherapy units to treat
the same patient, has often been used in the treatment of infants with very high levels of serum bilirubin.
The studies that appeared to show a benefit with this approach were performed with old, relatively low-
yield phototherapy units. Newer phototherapy units provide much higher levels of irradiance, which may in
fact be close to the apparent saturation level of bilirubin photoisomerization. Whether double or triple
phototherapy also confers a benefit with the newer units, has not been tested in systematic trials.

The purpose of treating neonatal jaundice is to avoid neurotoxicity. Thus, indications for treatment have
been based on clinical studies of infants who developed kernicterus. Historical data, much of which was
derived from infants with hemolytic jaundice, appeared to suggest that total serum bilirubin levels greater
than 350 mol/L (20 mg/dL) were associated with increased risk of neurotoxicity, at least in full-term
infants.

As treatment of premature infants became more widespread and increasingly successful during the last
half of the 20th century, autopsy findings and follow-up data suggested that immature infants were at risk
of bilirubin encephalopathy at lower total serum bilirubin levels than mature infants. Treatment was
initiated at lower levels for these infants.

Until the 1940s, a truly effective treatment was not available. At that time, exchange transfusion was
shown to be feasible and was subsequently used in the treatment of Rh-immunized infants with severe
anemia, hyperbilirubinemia, or hydrops. However, exchange transfusion is not without risk for the infant,
and only with the discovery of phototherapy did neonatal jaundice start to become an indication for
treatment on a wider scale. Once phototherapy was shown to be a rather innocuous treatment, lights
were turned on at lower serum bilirubin values than those that had triggered exchange transfusion.

Exchange transfusion became the second-line treatment when phototherapy failed to control serum
bilirubin levels. However, data have shown that treatment with IVIG in infants with Rh or ABO
isoimmunization can significantly reduce the need for exchange transfusions. [24, 25] At the author's
institution, a tertiary center where exchange transfusions used to be frequent, only 0-2 such procedures
per year are performed, and IVIG has replaced exchange transfusion as the second-line treatment in
infants with isoimmune jaundice.[26]

Clearly, the scientific data on which current therapeutic guidelines are based have very significant
shortcomings. Unfortunately, because the endpoint of bilirubin neurotoxicity is permanent brain damage, a
randomized study to reassess the guidelines is ethically unthinkable.
In most neonatal wards, total serum bilirubin levels are used as the primary measure of risk for bilirubin
encephalopathy. Numerous people would prefer to add a test for serum albumin at higher bilirubin levels
because bilirubin entry into the brain, a sine qua non for bilirubin encephalopathy, increases when the
bilirubin-albumin ratio exceeds unity. Tests for bilirubin-albumin binding or unbound bilirubin levels are
used by some but have failed to gain widespread acceptance. New analytical tools for measurement of
unbound bilirubin have greatly simplified the process, but the effect on clinical practice remains to be
seen.

Numerous guidelines for the management of neonatal jaundice have been published, and even more
appear to be in local use without submission for critical review. In a survey published in 1996, the author
analyzed clinical practices in this field based on responses from 108 neonatal intensive care units
(NICUs) worldwide.[27] The survey revealed a significant disparity in guidelines.

The image below shows a box-and-whisker plot of the range of serum bilirubin values that trigger
phototherapy and exchange transfusion, respectively, in these NICUs. Evidently, an infant might receive
an exchange transfusion in one NICU for a serum bilirubin level that would not trigger phototherapy in
many other NICUs. This disparity illustrates how difficult it has been to translate clinical data into sensible
treatment guidelines.

The graph represents indications for phototherapy and exchange transfusion in

infants (with a birthweight of 3500 g) in 108 neonatal ICUs. The left panel shows the range of indications for phototherapy,
whereas the right panel shows the indications for exchange transfusion. Numbers on the vertical axes are serum bilirubin
concentrations in mg/dL (lateral) and mmol/L (middle). In the left panel, the solid line refers to the current recommendation of
the American Academy of Pediatrics (AAP) for low-risk infants, the line consisting of long dashes (- - - - -) represents the
level at which the AAP recommends phototherapy for infants at intermediate risk, and the line with short dashes (-----)
represents the suggested intervention level for infants at high risk. In the right panel, the dotted line (......) represents the
AAP suggested intervention level for exchange transfusion in infants considered at low risk, the line consisting of dash-dot-
dash (-.-.-.-.) represents the suggested intervention level for exchange transfusion in infants at intermediate risk, and the line
consisting of dash-dot-dot-dash (-..-..-..-) represents the suggested intervention level for infants at high risk. Intensive
phototherapy is always recommended while preparations for exchange transfusion are in progress. The box-and-whisker
plots show the following values: lower error bar = 10th percentile; lower box margin = 25th percentile; line transecting box =
median; upper box margin = 75th percentile; upper error bar = 90th percentile; and lower and upper diamonds = 5th and
95th percentiles, respectively.

In 2004, the AAP published new guidelines for the management of hyperbilirubinemia in healthy full-term
newborns.[28] These guidelines have been plotted on the image above.

The 2004 AAP guidelines represent a significant change from the 1994 guidelines. [28] Thus, the emphasis
on preventive action and risk evaluation is much stronger. An algorithm aids in the assessment of risk and
the decision about further management and follow-up (see the image below). The committee that wrote
the guidelines has carefully assessed the strength of the scientific evidence on which the guidelines are
based.
 Algorithm for the management of jaundice in the newborn nursery.

Practitioners in North America are advised to follow the 2004 AAP guidelines. However, clinicians in
different ethnic or geographic regions should tailor these guidelines as pertinent to their own populations
and must consider factors that are unique to their medical practice settings. Such factors may include
racial characteristics, prevalence of congenital hemolytic disorders, and environmental concerns. At
present, the wisest course of action may be to apply local guidelines that have been successful in the
prevention of kernicterus. Please note that the AAP guidelines do not provide guidance for treatment of
jaundice in the smaller and more premature/immature infants.

With this background and the clear understanding that this is meant only as an example, the image below
shows the chart currently in use in most pediatric departments in Norway. These guidelines are the result
of a 2006 consensus in the Neonatal Subgroup of the Norwegian Pediatric Society. The similarities
between the Norwegian chart and the 2004 AAP guidelines are apparent.

Guidelines for management of neonatal jaundice currently in use in most pediatric

departments in Norway. The guidelines were based on previously used charts and were created through a consensus
process in the Neonatal Subgroup of the Norwegian Pediatric Society. These guidelines were adopted as national at the fall
meeting of the Norwegian Pediatric Society. The reverse side of the chart contains explanatory notes to help the user
implement the guidelines. A separate information leaflet for parents was also created.

The Norwegian chart suggests intervention limits for premature/immature infants. For infants of less than
1000 gram birthweight, these guidelines propose starting phototherapy at 100 mol/L (6 mg/dL) at age 24
hours, increasing gradually to 150 mol/L (8.8 mg/dL) at age 4 days, and remaining steady thereafter at
that level. This compares with a range of 85 mol/L (5 mg/dL) to 171 mol/L (10 mg/dL) used in a
Neonatal Research Network (NRN) phototherapy trial in infants of less than 1000 gram birthweight. The
intervention level depended on postnatal age and whether the infant was allocated to conservative or
aggressive phototherapy.[29]

In a post hoc analysis of the NRN data, which compared infants who had not received any phototherapy
with those who had received such treatment, the subgroup of infants with birthweights of 501-750 grams
who had not received any phototherapy had a significantly higher rate of mental developmental index of
less than 50.[30] However, it should be noted that in the original trial analysis, mortality in the aggressive
 phototherapy group at 501-750 gram birthweight was 5 percentage points higher than in the conservative
group, which, although not significant, appeared to offset the possible developmental gain in survivors. [29]

Key points in the practical execution of phototherapy include maximizing energy delivery and the available
surface area. Also consider the following:

The infant should be naked except for diapers (use these only if deemed absolutely necessary
and cut them to minimum workable size), and the eyes should be covered to reduce risk of retinal
damage.
Check the distance between the infant's skin and the light source. With fluorescent lamps, the
distance should be no greater than 50 cm (20 in). This distance may be reduced down to 10-20 cm if
temperature homeostasis is monitored to reduce the risk of overheating. Note that this does not apply to
quartz lamps.
Cover the inside of the bassinet with reflecting material; white linen works well. Hang a white
curtain around the phototherapy unit and bassinet. These simple expedients can multiply energy
delivery by several fold.
When using spotlights, ensure that the infant is placed at the center of the circle of light, since
photoenergy drops off towards the circle's perimeter. Observe the infant closely to ensure that the infant
doesn't move away from the high-energy area. Spotlights are probably more appropriate for small
premature infants than for larger near-term infants.
Older data suggested that phototherapy was associated with increased insensible water loss;
therefore, many clinicians have routinely added a certain percentage to the infant's estimated basic fluid
requirements. Newer data suggest that if temperature homeostasis is maintained, fluid loss is not
significantly increased by phototherapy. At the author's institution, routine fluid supplementation for
infants under phototherapy is no longer recommended. Rather, the infant is monitored for weight loss,
urine output, and urine specific gravity. Fluid intake is adjusted accordingly. In infants who are orally fed,
the preferred fluid is milk because it serves as a vehicle to transport bilirubin out of the gut.
Timing of follow-up serum bilirubin testing must be individualized. In infants admitted with extreme
serum bilirubin values (>500 mol/L or 30 mg/dL), monitoring should occur every hour or every other
hour. Reductions in serum bilirubin values of 85 mol/L/h (5 mg/dL/h) have been documented under
such circumstances. In infants with more moderate elevations of serum bilirubin, monitoring every 6-12
hours is probably adequate.
Expectations regarding efficacy of phototherapy must be tailored to the circumstances. In infants
in whom serum bilirubin concentrations are still rising, a significant reduction of the rate of increase may
be satisfactory. In infants in whom serum bilirubin concentrations are close to their peak, phototherapy
should result in measurable reductions in serum bilirubin levels within a few hours. In general, the
higher the starting serum bilirubin concentration, the more dramatic the initial rate of decline.
Discontinuation of phototherapy is a matter of judgment, and individual circumstances must be
taken into consideration. In practice, phototherapy is discontinued when serum bilirubin levels fall 25-50
mol/L (1.5-3 mg/dL) below the level that triggered the initiation of phototherapy. Serum bilirubin levels
may rebound after treatment has been discontinued, and follow-up tests should be obtained within 6-12
hours after discontinuation.
Indications for prophylactic phototherapy are debatable. Phototherapy probably serves no
purpose in an infant who is not clinically jaundiced. In general, the lower the serum bilirubin level, the
less efficient the phototherapy. It seems more rational to apply truly effective phototherapy once serum
(and skin) bilirubin has reached levels at which photons may do some good.
Wherever phototherapy is offered as a therapeutic modality, a device for measuring the irradiance
delivered by the equipment used should be readily at hand. This assists in configuring the phototherapy
set-up to deliver optimal efficiency. Some recommend this routinely, every time phototherapy is initiated,
and use this as a tool to focus staff attention on maximizing energy delivery.

Generally, phototherapy is very safe and may have no serious long-term effects in neonates; however, the
following adverse effects and complications have been noted:
 Insensible water loss may occur, but data suggest that this issue is not as important as previously
believed. Rather than instituting blanket increases of fluid supplements to all infants receiving
phototherapy, the author recommends fluid supplementation tailored to the infant's individual needs, as
measured through evaluation of weight curves, urine output, urine specific gravity, and fecal water loss.
In the NRN phototherapy trials in premature infants of less than 1000 gram birthweight, mortality
was increased by 5 percentage points in the subgroup of 501-750 gram birthweight receiving
aggressive phototherapy.[29] Although not significant, it should be noted that the study was underpowered
for this analysis, and a negative effect of aggressive phototherapy on the smallest and most immature
infants cannot be ruled out with certainty.
Phototherapy may be associated with loose stools. Increased fecal water loss may create a need
for fluid supplementation.
Retinal damage has been observed in some animal models during intense phototherapy. In an
NICU environment, infants exposed to higher levels of ambient light were found to have an increased
risk of retinopathy. Therefore, covering the eyes of infants undergoing phototherapy with eye patches is
routine. Care must be taken lest the patches slip and leave the eyes uncovered or occlude one or both
nares.
The combination of hyperbilirubinemia and phototherapy can produce DNA-strand breakage and
other effects on cellular genetic material. In vitro and animal data have not demonstrated any implication
for treatment of human neonates. However, because most hospitals use (cut-down) diapers during
phototherapy, the issue of gonad shielding may be moot.
Skin blood flow is increased during phototherapy, but this effect is less pronounced in modern
servocontrolled incubators. However, redistribution of blood flow may occur in small premature infants.
An increased incidence ofpatent ductus arteriosus (PDA) has been reported in these circumstances.
The appropriate treatment of PDA has been reviewed.[31]
Hypocalcemia appears to be more common in premature infants under phototherapy lights. This
has been suggested to be mediated by altered melatonin metabolism. Concentrations of certain amino
acids in total parenteral nutrition solutions subjected to phototherapy may deteriorate. Shield total
parenteral nutrition solutions from light as much as possible.
Regular maintenance of the equipment is required because accidents have been reported,
including burns resulting from a failure to replace UV filters.

Intravenous immune globulin

In recent years, IVIG has been used for numerous immunologically mediated conditions. In the presence
of Rh, ABO, or other blood group incompatibilities that cause significant neonatal jaundice, IVIG has been
shown to significantly reduce the need for exchange transfusions.

The 2004 AAP guidelines suggest a dose range for IVIG of 500-1000 mg/kg. [28]

The author routinely uses 500 mg/kg infused intravenously over a period of 2 hours for Rh or ABO
incompatibility when the total serum bilirubin levels approach or surpass the exchange transfusions limits.
The author has, on occasion, repeated the dose 2-3 times. In most cases, when this is combined with
intensive phototherapy, avoiding exchange transfusion is possible. In the authors' institution, with about
750 NICU admissions per year, the use of exchange transfusions has decreased to 0-2 per year following
the implementation of IVIG therapy for Rh and ABO isoimmunization. [26] The author does not use IVIG in
the presence ofhydrops. Anecdotally, IVIG appears less likely to be successful when the infant is anemic
(Hb < 10 g/dL).

Exchange transfusion

Exchange transfusion is indicated for avoiding bilirubin neurotoxicity when other therapeutic modalities
have failed or are not sufficient. In addition, the procedure may be indicated in infants with
erythroblastosis who present with severe anemia, hydrops, or both, even in the absence of high serum
bilirubin levels.

Exchange transfusion was once a common procedure. A significant proportion was performed in infants
with Rh isoimmunization. Immunotherapy in Rh-negative women at risk for sensitization has significantly
reduced the incidence of severe Rh erythroblastosis. Therefore, the number of infants requiring exchange
transfusion is now much smaller, and even large NICUs may perform only a few procedures per year.
ABO incompatibility has become the most frequent cause of hemolytic disease in industrialized countries.

Early exchange transfusion has usually been performed because of anemia (cord hemoglobin < 11 g/dL),
elevated cord bilirubin level (>70 mol/L or 4.5 mg/dL), or both. A rapid rate of increase in the serum
bilirubin level (>15-20 mol/L /h or 1 mg/dL/h) was an indication for exchange transfusion, as was a more
moderate rate of increase (>8-10 mol/L/h or 0.5 mg/dL/h) in the presence of moderate anemia (11-13
g/dL).

The serum bilirubin level that triggered an exchange transfusion in infants with hemolytic jaundice was
350 mol/L (20 mg/dL) or a rate of increase that predicted this level or higher. Strict adherence to the
level of 20 mg/dL has been jocularly referred to as vigintiphobia (fear of 20).

Currently, most experts encourage an individualized approach, recognizing that exchange transfusion is
not a risk-free procedure, that effective phototherapy converts 15-25% of bilirubin to nontoxic isomers,
and that transfusion of a small volume of packed red cells may correct anemia. Administration of IVIG
(500 mg/kg) has been shown to reduce red cell destruction and to limit the rate of increase of serum
bilirubin levels in infants with Rh and ABO isoimmunization (see above).

Current AAP guidelines distinguish between 3 risk categories: low, intermediate, and high. [28] These
correspond to 3 levels of suggested intervention, which increase from birth and plateau at age 4 days.
Naturally, intervention levels associated with exchange transfusion are higher than those of phototherapy.
Intensive phototherapy is strongly recommended in preparation for an exchange transfusion. In fact,
intensive phototherapy should be performed on an emergency basis in any infant admitted for
pronounced jaundice; do not await laboratory test results in these cases. Phototherapy has minimal side
effects, whereas the waiting period for laboratory test results and blood for exchange can take hours and
could constitute the difference between intact survival and survival with kernicterus. If phototherapy does
not significantly lower serum bilirubin levels, exchange transfusion should be performed.

Many believe that hemolytic jaundice represents a greater risk for neurotoxicity than nonhemolytic
jaundice, although the reasons for this belief are not intuitively obvious, assuming that total serum bilirubin
levels are equal. In animal studies, bilirubin entry into or clearance from the brain was not affected by the
presence of hemolytic anemia.

The technique of exchange transfusion, including adverse effects and complications, is discussed
extensively elsewhere. For more information, please consult Hemolytic Disease of Newborn.

Management of infants with extreme jaundice

Numerous cases have been reported in which infants have been readmitted to hospitals with extreme
jaundice. In some cases, significant delays have occurred between the time the infant was first seen by
medical personnel and the actual commencement of effective therapy.[32]

Any infant who returns to the hospital with significant jaundice within the first 1-2 weeks of birth should be
immediately triaged with measurement of transcutaneous bilirubin. High values should result in immediate
initiation of treatment. If such a measuring device is not available, or if the infant presents with any kind of
neurological symptoms, the infant should be put in maximally efficient phototherapy as an emergency
procedure, preferably by fast-tracking the infant to a NICU. Waiting for laboratory results is not necessary
before instituting such therapy because no valid contraindications to phototherapy are possible in this
scenario. Plans for an exchange transfusion do not constitute an argument for delaying or not performing
phototherapy. Immediate benefit may be obtained within minutes, as soon as conversion of bilirubin into
water-soluble photoisomers is measurable (see discussion above).

The need for intravenous hydration in such infants has been discussed. In the absence of clinical signs of
dehydration, no evidence suggests that overhydration is helpful. If the infant is dehydrated, hydration
should be given as clinically indicated. However, if the infant is able to tolerate oral feeding, oral hydration
with a breast milk substitute is likely to be superior to intravenous hydration because it reduces
enterohepatic circulation of bilirubin and helps "wash" bilirubin out of the bowel.

Every hospital in which babies are delivered, or which has an emergency department in which infants
may be seen, should develop a protocol and triage algorithm for rapid evaluation and management of
jaundiced infants. The objective of such a protocol should be rapid recognition of risk severity and
reduction in the time to initiate appropriate treatment.

Infants admitted with signs of intermediate to advanced acute bilirubin encephalopathy (ABE) are in
urgent need of treatment because reversibility may be possible, even in such cases. The term "crash-cart
approach" has been used as a recommendation in such cases. The author, together with other European
colleagues, has published a series that included 6 patients with signs of ABE who were urgently managed
and appear to have escaped neurologic sequelae.[33]

In a review of the Kernicterus Registry, full recovery was noted in 8 of 11 cases treated with a crash-cart
approach, which included effective phototherapy plus exchange transfusion; full recovery was not noted in
cases in which delays had occurred.[32] In the Kernicterus Registry, reversal was not observed in cases
treated with only phototherapy; the authors strongly recommend that exchange transfusion be performed
in such cases.[32] In the European study, reversal was also seen in 2 patients who did not receive
exchange transfusion.[33] In one of these cases, IVIG was used in lieu of exchange transfusion; in the other
case, intensive phototherapy and intravenous albumin were used.

Other therapies

In infants with breast milk jaundice, interruption of breastfeeding for 24-48 hours and feeding with breast
milk substitutes often helps to reduce the bilirubin level. Evidence suggests that the simple expedient of
supplementing feeds of breast milk with 5 mL of a breast milk substitute reduces the level and duration of
jaundice in breast milkfed infants. Because this latter intervention causes less interference with the
establishment of the breastfeeding dyad, the author prefers to use this approach rather than complete
interruption of breast feeding in most cases.

Oral bilirubin oxidase can reduce serum bilirubin levels, presumably by reducing enterohepatic circulation;
however, its use has not gained wide popularity. The same may be said for agar or charcoal feeds, which
act by binding bilirubin in the gut. Bilirubin oxidase is not available as a drug, and for this reason, its use
outside an approved research protocol probably is proscribed in many countries.

Prophylactic treatment of Rh-negative women with Rh immunoglobulin has significantly decreased the
incidence and severity of Rh-hemolytic disease.
 Diet
Breastfeeding concerns associated with neonatal jaundice are as follows:

Incidence and duration of jaundice have increased as breastfeeding has become more popular.
The factors in breast milk that contribute to this phenomenon are unclear. In selected infants,
interruption of breastfeeding and its replacement for 24-48 hours by a breast milk substitute may be
indicated. This decision should always be discussed in person with the mother before implementation.
The author's practice is now to first perform a trial of 5 mL of a hydrolyzed formula given after each
breast meal. The author typically tries this for at least 1-2 days, with follow-up of bilirubin values. Only if
this is unsuccessful does the author occasionally attempt interruption of breast feeding.
With increasing emphasis on breastfeeding, some new mothers may have difficulty admitting
(even to themselves) to a lack of success in establishing lactation. Occasionally, infants of breastfeeding
mothers are admitted to hospitals with severe jaundice. They typically weigh significantly less than their
birthweight at a time when they should have regained and surpassed that weight. Presumably, the
process is one of increased enterohepatic circulation, as bilirubin is left longer in the proximal gut for
lack of milk to bind it and carry it onward and out. The author refers to this condition as lack-of-breast-
milk jaundice. These infants may respond dramatically to phototherapy plus oral feedings of milk ad
libitum.
Medication Summary
Medications are not usually administered in infants with physiologic neonatal jaundice. However, in
certain instances, phenobarbital, an inducer of hepatic bilirubin metabolism, has been used to enhance
bilirubin metabolism. Several studies have shown that phenobarbital is effective in reducing mean serum
bilirubin values during the first week of life. Phenobarbital may be administered prenatally in the mother or
postnatally in the infant.

In populations in which the incidence of neonatal jaundice or kernicterus is high, this type of
pharmacologic treatment may warrant consideration. However, concerns surround the long-term effects of
phenobarbital on these children. Therefore, this treatment is probably not justified in populations with a
low incidence of neonatal jaundice. Other drugs can induce bilirubin metabolism, but lack of adequate
safety data prevents their use outside research protocols.

Intravenous immunoglobulin (IVIG) at 500 mg/kg has been shown to significantly reduce the need for
exchange transfusions in infants with isoimmune hemolytic disease. [26] The mechanism is unknown but
may be related to the way the immune system handles red cells that have been coated by antibodies.
Published experience is still somewhat limited, but administration of immunoglobulin does not appear to
be likely associated with greater risks for the infant than an exchange transfusion.

A new therapy currently under development consists of inhibition of bilirubin production through blockage
of heme oxygenase. This can be achieved through the use of metal mesoporphyrins and protoporphyrins.
Apparently, heme can be directly excreted through the bile; thus, inhibition of heme oxygenase does not
result in accumulation of unprocessed heme. This approach may virtually eliminate neonatal jaundice as
a clinical problem. However, before the treatment can be applied on a wide scale, important questions
regarding the long-term safety of the drugs must be answered. Also, in light of data suggesting that
bilirubin may play an important role as a free radical quencher, a more complete understanding of this
putative role for bilirubin is required before wholesale inhibition of its production is contemplated.

Phototherapy for Jaundice

Background
Jaundice refers to the yellow appearance of the skin that occurs with the deposition of bilirubin in the
dermal and subcutaneous tissue. Normally in the body, bilirubin is processed through the liver, where it is
conjugated to glucuronic acid by the enzyme uridine diphosphate glucuronyl transferase (UGT) 1A1. This
conjugated form of bilirubin is then excreted into the bile and removed from the body via the gut. When
this excretion process is low following birth, does not work efficiently, or is overwhelmed by the amount of
endogenously produced bilirubin, the amount of bilirubin in the body increases, resulting in
hyperbilirubinemia and jaundice.

Jaundice occurs in as many as 60% of all normal newborns within the first week of life. [1] Jaundice in the
newborn can occur from an underlying pathological condition, such as isoimmune hemolysis or an RBC
enzyme deficiency. However, it is more commonly due to the normal physiological inability of the newborn
infant to process bilirubin adequately due to the combined effects of increased RBC turnover and a
transient deficit in bilirubin conjugation in the liver.[1] This type of nonpathologic jaundice is referred to as
physiologic jaundice of the newborn.[2]

In most infants with physiologic jaundice, bilirubin concentrations do not rise to a point that requires
treatment. However, in some infants with exaggerated physiologic jaundice, and in many infants with
pathologic jaundice, bilirubin in the blood reaches very high concentrations that put the infant at risk for
acute and chronic bilirubin encephalopathy (kernicterus). In these cases, treatment aimed at decreasing
bilirubin concentration is required in order to avoid kernicterus. Etiologies of hyperbilirubinemia in
newborns are provided in the image below.

Causes of hyperbilirubinemia in newborn infants. Adapted from Maisel MJ. Neonatal

Jaundice. Pediatrics in Review. 2006; 27: p. 445.

Effective treatments to decrease bilirubin levels in infants with severe jaundice include phototherapy and
exchange transfusion.

The effect of light on jaundice in neonates, and the ability of light to decrease serum bilirubin levels, was
first described by Cremer et al in 1958.[3] This observation led to the development of light sources for use
in the treatment of infants with hyperbilirubinemia, a treatment now referred to as phototherapy. Since its
inception, phototherapy has been effectively used as a relatively inexpensive and noninvasive method of
treating neonatal hyperbilirubinemia. The decline in the number or exchange transfusions in recent years
is, at least in part, likely a direct reflection of the effectiveness of phototherapy at treating
hyperbilirubinemia. In modern neonatal ICUs (NICUs) exchange transfusions are rare and are only used
as a rescue therapy to avoid kernicterus in newborns with severe jaundice when phototherapy is
inadequate.

At its most basic, phototherapy refers to the use of light to convert bilirubin molecules in the body into
water soluble isomers that can be excreted by the body. The absorption of light by normal bilirubin
(4Z,15Z-bilirubin) results in the creation of 2 isomeric forms of bilirubin: structural isomers and
configurational isomers. The main structural isomer of bilirubin is Z-lumirubin. The main configurational
isomer of bilirubin is 4Z,15 E -bilirubin. Configurational isomerization is reversible, and structural
isomerization is irreversible. Both the configurational and structural isomers of bilirubin are less lipophilic
than normal bilirubin and can be excreted into bile without undergoing glucuronidation in the liver. Some
of the configurational isomers of bilirubin, however, revert back to the native form after excretion into bile
and can be reabsorbed via enterohepatic circulation in the gut. Structural bilirubin isomers, like Z-
lumirubin, can also be excreted in the urine.

The absorptions of light by bilirubin also results in the generation of excited-state bilirubin molecules that
react with oxygen to produce colorless oxidation products, or photooxidation products. This process
occurs more slowly than configurational or structural isomerization. Photooxidation products are primarily
excreted in the urine. The image below provides a schematic of the conversion of normal bilirubin to
configurational isomers, structural isomers, and photooxidation products and the respective routes of
excretion from the body.

Mechanism of phototherapy: Blue-green light in the range of 460-490 nm is most

effective for phototherapy. The absorption of light by the normal bilirubin (4Z,15Z-bilirubin) generates configuration isomers,
structural isomers, and photooxidation products. The 2 principal photoisomers formed in humans are shown. Configurational
isomerization is reversible and much faster than structural isomerization. Structural isomerization is slow and irreversible.
Photooxidation occurs more slowly than both configurational and structural isomerization. Photooxidation products are
excreted mainly in urine. Adapted from Maisel MJ, McDonagh AD. Phototherapy for Neonatal Jaundice. N Engl J Med.
2008;358:920-928.

Indications
Prior studies have shown that approximately 5-40 infants per 1,000 in the United States require
phototherapy in the newborn nursery, and an equal number require readmission to the hospital for
phototherapy after discharge from the nursery.[1]The specific total serum bilirubin concentration at which
phototherapy should be initiated varies and depends on several factors, including the total serum bilirubin
level, the infants gestational age, age of the infant in hours at the time of testing, and any individual risk
factors for hyperbilirubinemia.

Risk factors for the development of severe hyperbilirubinemia and kernicterus include isoimmune
hemolytic disease, glucose-6-phosphate deficiency, asphyxia, significant lethargy, temperature instability,
sepsis, acidosis, and hypoalbuminemia (< 3g/dL).[4] To aid physicians in the decision on when to initiate
phototherapy, the American Academy of Pediatrics Subcommittee on Hyperbilirubinemia developed
guidelines on the management of hyperbilirubinemia in newborns 35 or more weeks gestation. [4] This
guideline includes an algorithm for the management of jaundice in the newborn nursery as well as
guidelines for the initiation of phototherapy based on total serum bilirubin levels, gestational age, age of
the infant in hours, and individual risk factors.

No evidence-based guidelines are available on the indication for phototherapy in premature infants less
than 35 weeks gestation. However, several commonly used reference texts provide tables. [5, 6] A
commonly used rule of thumb in the NICU is to start phototherapy when the total serum bilirubin level is
greater than 5 times the birth weight. Thus, in a 1-kg infant, phototherapy is started at a bilirubin level of 5
mg/dL; in a 2-kg infant, phototherapy is started at a bilirubin level of 10mg/dL and so on.

This article discusses the clinical procedure for providing phototherapy for neonatal jaundice.

Contraindications
Few contraindications to phototherapy are recognized. These include the concomitant use of
photosensitizing medications, a diagnosis of congenital erythropoietic porphyria, or a family history of
porphyria.[1] Infants with cholestatic jaundice and direct hyperbilirubinemia who are exposed to
phototherapy may experience a dark, gray-brown discoloration of the skin, commonly known as bronze-
baby syndrome. The etiology of this discoloration is unknown but is possibly due to porphyrin
accumulation. The skin discoloration that occurs with bronze-baby syndrome is transient and disappears
with the discontinuation of phototherapy.[1] The presence of direct hyperbilirubinemia is not a
contraindication to phototherapy.[4]

Technical Considerations
Phototherapy Dose

The effectiveness of phototherapy at converting bilirubin into configurational isomers, structural isomers,
and photooxidation products is determined by the dose of phototherapy provided to the infant. The dose
of phototherapy depends on several factors, including the spectral wave length of light, the spectral
irradiance delivered to the infants skin, and the total spectral power (average spectral irradiance
delivered across the surface area of the infant). Factors that affect phototherapy are described in the
image below.

Factors that affect phototherapy: The 3 factors that affect the dose of phototherapy
include the irradiance of light used, the distance from the light source, and the amount of skin exposed. Standard
phototherapy is provided at an irradiance of 8-10 microwatts per square centimeter per nanometer (mW/cm2 per nm).
Intensive phototherapy is provided at an irradiance of 30 mW/cm2 per nm or more (430490 nm). For intensive
phototherapy, an auxiliary light source should be placed under the infant. The auxiliary light source could include a fiber-optic
pad, a light-emitting diode (LED) mattress, or a bank of special blue fluorescent tubes. Term and near-term infants should
receive phototherapy in a bassinet and the light source should be brought as close as possible to the infant, typically within
10-15 cm. However, if halogen or tungsten lights are used, providers should follow the manufacturer recommendation on the
distance of the light from the infant to avoid overheating. Preterm infant can be treated in an incubator, but the light rays from
the phototherapy device should be perpendicular to the surface of the incubator to minimize light reflectance. Adapted from
Maisel MJ, McDonagh AD. Phototherapy for Neonatal Jaundice. N Engl J Med. 2008;358:920-928.

Light in the blue region of the spectrum, near 460 nm, is most strongly absorbed by bilirubin. However,
only light that penetrates the skin and is absorbed by bilirubin provides the needed photochemical effect.
Tissue penetration increases as the wavelength of the light increases. Thus, one must balance the use of
a higher wavelength of light, which more readily penetrates tissue, with the use of a wavelength that is
more readily absorbed by bilirubin, which may penetrate less deeply. With this in mind, light in the 460-
490 nm wavelength is probably the most effective for use during phototherapy.[1]
Spectral irradiance is measured in watts per centimeter, or microwatts per square centimeter per
nanometer (mW/cm2 per nm) over a wavelength band. Higher spectral irradiance results in a more rapid
decline in the bilirubin levels.[7] Spectral irradiance increases as the distance from the light source to the
infants skin deceases.[4] Different phototherapy devices deliver significantly different levels of irradiance.
The American Academy of Pediatrics defines standard phototherapy as 8-10 mW/cm 2 per nm and
intensive phototherapy as more than 30 mW/cm 2 per nm in the 430-490 nm band.[4]

Spectral power increases as the amount of skin exposed to phototherapy increases. Ways to increase
surface area exposure include removal of clothing and increasing the number of lights/lighting devices
used to deliver phototherapy. Infants receiving phototherapy should be left only in their diaper, allowing
adequate surface area exposure for phototherapy. The use of lights both above and below an infant
effectively doubles the area of exposure. Several manufacturers produce fiberoptic pads that can be
placed under the infant. The Bili Bassinet (Olympic Medical; Seattle, WA) is one commercial device that
provides special blue fluorescent tubes that emit light in the 460-490 nm wavelength, both above and
below the infant.

The dose of phototherapy, in mW/cm2 per nm, should be measured during phototherapy using a
commercially available radiometer. These devices typically measure the spectral irradiance of
phototherapy in the 425-475 or 400-480nm band wavelength. The radiometer used to measure irradiance
should be the one recommended by manufacturer of the light source. Due to variance in the strength of
phototherapy over the surface of the infant, and because measurements of spectral irradiance can differ
greatly depending on where on the infant the measurement is made, taking several measures in different
locations on the infant and averaging the values is important. [4]

Complication Prevention
Eye protection should be placed on all infants receiving phototherapy. The need for eye protection is
based on animal data that phototherapy may be damaging to the retina. [8] Various commercially available
infant eye shields are available for use. In addition to eye shields, many centers also prescribe lubricating
eye drops (carboxymethylcellulose sodium) for infant receiving phototherapy. The infant's temperature
should be closely monitored while receiving phototherapy. This is especially important in infant under
halogen lights because these emit significant amounts of heat and can cause hyperthermia. Unclothed
infants in basinets under fluorescent or light-emitting diode (LED) devices are at risk for hypothermia,
especially if they are in an area with a low ambient temperature. Premature infants and infants unable to
maintain body temperature in a basinet should be placed on a radiant warmer or in an isolette while
receiving phototherapy in order to maintain normothermia.

The use of photosensitizing medications should be avoided while infants are receiving phototherapy.
Medications used in the newborn period that have been linked to phototoxic reactions include
nonsteroidal anti-inflammatory drugs (ibuprofen), diuretics (furosemide, hydrochlorothiazide), and certain
antibiotics (doxycycline, tetracycline, ciprofloxacin, ofloxacin, levofloxacin, and sulfonamides). In general,
however, photosensitivity from medications are most likely to occur after exposure to light in the UV-A
(320- 400 nm) and UV-B (290-302 nm) ranges.[9] Because phototherapy does not produce significant UV-A
or UV-B light, phototoxic reactions in infants receiving these medications are rare

Outcomes
Phototherapy has been safely used for the treatment of neonatal jaundice for over 40 years.
Complications from phototherapy are rare and generally mild. The two most notable complications include
increased insensible water loss and cutaneous reactions in infants with cholestatic jaundice receiving
phototherapy.

Phototherapy with halogen spot lights can increase cutaneous blood flow and increase insensible water
loss through the skin. This is especially important in premature infants whose skin barrier function is
compromised due to immaturity and is more permeable to water. Contemporary studies in premature
infants undergoing phototherapy with halogen spot lights have shown transepidermal water loss
increases of 20-26%, despite constant temperature and relative humidity.[8, 10] Phototherapy is thought to
increases skin blood flow by a mechanism known as photorelaxation. [11] The pathway of this mechanism is
not completely understood but is believed to be caused by S-nitrosothiols mediated nitric oxide release. [12]

Due to this increase in insensible water loss, recommendations have been made to increase maintenance
fluid by 10 mL/kg/d in premature infants exposed to conventional phototherapy.[12] Additional intravenous
fluids are not required in term infants who are maintaining adequate oral intake. [4] Increases in
transepidermal water loss in premature infants have not been documented with LED-based phototherapy.
[1]

A dark, greyish-brown discoloration of the skin may develop in infants with cholestatic jaundice and direct
hyperbilirubinemia exposed to phototherapy. This reaction is commonly referred to as bronzed-baby
syndrome. This discoloration of the skin is transient and resolves with cessation of phototherapy.[1] Bolus
and purpuric reactions of the skin have also been reported in infants with severe cholestatic jaundice
receiving phototherapy. This is thought to be due to sensitization by accumulation of porphyrins.

Patient Preparation
Positioning

Infants receiving phototherapy should be placed lying flat on a radiant warmer or in a bassinet. Small or
premature infants can remain in an infant incubator during phototherapy. The infant should be naked with
the exception of eye protection and a diaper to maximize the surface area of skin exposed to light. The
phototherapy device should be placed at the side of the infants bed with the light shining on the infant
and covering as much surface area as possible.

When fluorescent tubes or LED devices are used, the infant should be placed as close as possible to the
light source, typically within 10 cm.[4] This increases the spectral irradiance of the light delivered. Halogen-
based devices emit greater amounts of heat than fluorescent or LED devices and therefore need to be
positioned at a greater distance from the infant. Providers should follow the manufacturers
recommendations on how far to position the halogen light source from the infant.

Fiberoptic pads can be positioned directly underneath the infant to provide an additional source of
phototherapy. The fiberoptic pads do not emit significant heat. Due to their relatively hard surface,
phototherapy pads should be used with caution in extremely low birth weight infants or other infants who
are at risk for skin break down from pressure sores.

If phototherapy is provided through the top of an infant, incubator the light source should be kept
perpendicular to the surface of the isolette to decrease light reflectance off the plastic, which diminishes
the amount of light that reaches the infant inside the isolette. In cases of severe hyperbilirubinemia, white
towels or aluminum foil can be placed around the interior of the bassinet to reflect light back on the infant
and increase surface area exposure.
 Monitoring & Follow-up
Monitoring of serial bilirubin values in infants on phototherapy is important to confirm that the therapy is
effective. With intensive phototherapy (>30 mW/cm 2per nm), a decrease in bilirubin concentration by 30-
40% can be expected within the first 24 hours.[4] The most significant drop in bilirubin concentration is
typically seen within the first 4-6 hours of phototherapy.[4] Thus, bilirubin concentrations are typically
checked prior to the start of phototherapy, after 4-6 hours of phototherapy to confirm effectiveness, and
then repeated at 12-24 hour intervals until levels are low enough to stop phototherapy. Although no
standard is noted for the discontinuation of phototherapy, current guidelines suggest stopping
phototherapy on infants 35 or more weeks gestation at birth readmitted after their birth hospitalization
when the levels of total bilirubin fall below 13-14 mg/dL. [4]

For infants with hemolytic disease, and in those younger than 3-4 days, a rebound bilirubin should be
checked within 24 hours after discontinuation of phototherapy.[4] This 24-hour rebound bilirubin check can
also be considered in infants 35 or more weeks gestation at birth with nonhemolytic jaundice who are
readmitted with hyperbilirubinemia.[4]

No evidenced-based guidelines to indicate when phototherapy should be discontinued in premature

infants. In general, phototherapy is stopped when the total serum bilirubin level is several points lower
than when it was started. Most practitioners routinely check a rebound bilirubin in all premature infants
within 24-48 hours after discontinuation of phototherapy, or sooner if a hemolytic process is present.

Approach Considerations
Determine if the infant requires phototherapy based on the infant total serum bilirubin level, the
gestation age, hours of life, and individual risk factors using established guidelines form the American
Academy of Pediatrics.[4]
Place infant on warmer or in bassinet with diaper on and eye protection in place.
Position phototherapy device at bedside with lights set at recommended distance from the infant.
For fluorescent and LED lights, this is as close as possible to the infants skin, typically less than 10 cm.
[4]
If using a halogen spot light, the light should be kept at the manufacturer recommended distance to
avoid overheating.
Turn on the phototherapy lights.
Direct light towards the infant with exposure of maximal surface area. If halogen spotlights are
used, more than one light may be required to cover the entire infant with light. This is typically done with
one light directed at the chest and head, with the second directed at the abdomen and legs.
Measure the spectral irradiance of the phototherapy setup with a commercially available
radiometer in several areas over the surface of the infant and average the results. [4] See the image below.

neoBLUE light-emitting diode (LED) phototherapy radiometer.

 Follow serial bilirubin levels to ensure the phototherapy is effectively decreasing the bilirubin
level.
Intermittently repeat measurements of the spectral irradiance and maintain the lights in the proper
position to provide maximum benefit.

Device Summary
Several devices can be used to provide phototherapy. These include tungsten-halogen lamps, fluorescent
tubes, fiberoptic systems, and gallium nitride LED lights. All these devices are capable of emitting light in
the 430-490 nm band at standard spectral irradiance levels of 8-10 mW/cm 2 per nm. However, when
intensive phototherapy is required either special blue fluorescent tubes or specially designed LED
devices should be used because these are the only devices that can reliably provide more than 30
mW/cm2 per nm in the 430-490 nm band.[4]

Halogen-based phototherapy lamps

Halogen-based phototherapy lamps, or spotlights, use a commercially available tungsten- halogen light
bulb and direct a strong beam of white/yellow light towards the infant. These devices are typically free-
standing on a pole, or available as part of a radiant warmer. Halogen-based spot lights are the most heat
producing of all the available phototherapy lights. Care must be taken not to place the devices closer to
the infant than recommended by the manufacturer to avoid overheating the infant. Additionally, due to the
associated heat output, halogen lights may result in increased insensible water loss in infants receiving
phototherapy.

See the image below.

Infant under Ohmeda halogen lamp with eye protection.

Fluorescent tubes

Fluorescent tubes used to deliver phototherapy have been classified as daylight, blue, and special
blue. A commercially available daylight tube is the F20T12/D (General Electric, Westinghouse, Sylvania).
A commercially available blue florescent tube is the F20T12/B (General Electric, Westinghouse,
Sylvania). Special blue fluorescent tubes include those labeled TL52/20W (Philips, Endhoven, The
Netherlands) or F20T12/BB (General Electric, Westinghouse, Sylvania).

In prior clinical studies, only the special blue fluorescent tubes were able to reliably emit light at more than
30 mW/cm2 per nm in the 430-490 nm band.[13] Special blue tubes are most effective because they emit
light in the blue-green spectrum, which penetrates skin well and is maximally absorbed by bilirubin.
Fluorescent tubes are typically housed in a commercially available device which holds 4-8 tubes that are
24 inches. The device is typically attached to a pole and the height of the lighting device can be adjusted
up and down. One commercially available device, the Bili Bassinet (Olympic Medical; Seattle, WA),
contains special blue fluorescent tubes in a housing both above and below the infant.

Fiberoptic phototherapy

Fiberoptic phototherapy devices deliver light form a high intensity lamp to a fiberoptic blanket. These
BiliBlanket devices are typically used in conjunction with overhead halogen, fluorescent, or LED systems.
These devices are also commonly used to provide home phototherapy. A disadvantage of using fiberoptic
pads is that they cover a fairly small surface area. Therefore, 2-3 pads may be needed to provide
effective phototherapy.[13] This is one reason why home phototherapy is reserved only for use in low-risk
infants with total bilirubin levels 2-3 mg/dL lower than that recommended for intensive phototherapy.[4] See
the image below.

Infant under neoBLUE phototherapy light and lying on fiberoptic phototherapy

blanket.

LED phototherapy systems

LED phototherapy systems, which use gallium nitride LEDs, are the newest devices used to provide
phototherapy. Gallium nitride LEDs emit high-intensity light in the blue-green portion of the spectrum
within a narrow wavelength (460-485 nm).[14] LEDs offer some advantages to other phototherapy sources.
Their narrow wavelength of emission is close to the wavelength at which light is maximally absorbed by
bilirubin. Additionally, the spectral quality of the LED device can be customized by the use of varying
proportions of blue, blue-green, and green LEDs. Also, LEDs generate less heat than either halogen or
fluorescent lamps, and can thus be positioned very close to the skin without significant risk of overheating
or burns.

Prior studies have shown that using an array of 600, 3-mm blue LEDs, at a short distance from an infant
can achieve an irradiance of more than 200 mW/cm 2 per nm.[14] Specially designed LED systems, such as
the neoBLUE LED Phototherapy system (Natus Inc; San Carlos, CA), are recommended by the American
Academy of Pediatrics for use during intensive phototherapy.[4] See the image below.

neoBLUE light-emitting diode (LED) phototherapy system.

Jaundice
Over 50% of all newborn infants become visibly jaundiced. This is
because:

there is marked physiological release of haemoglobin from

the breakdown of red cells because of the high Hb
concentration at birth (Fig. 10.19)
the red cell life span of newborn infants (70 days) is
markedly shorter than that of adults (120 days)
hepatic bilirubin metabolism is less efficient in the first few
days of life.
 Figure 10.19 The breakdown product of haemoglobin is unconjugated bilirubin
(indirect bilirubin

Neonatal jaundice is important as:

it may be a sign of another disorder, e.g. haemolytic

anaemia, infection, metabolic disease, liver disease.
unconjugated bilirubin can be deposited in the brain,
particularly in the basal ganglia, causing kernicterus.

Kernicterus
Figure 10.20 Postmortem brainstem and cerebellum showing kernicterus with
yellow bilirubin staining of

This is the encephalopathy resulting from the deposition of unconjugated

bilirubin in the basal ganglia and brainstem nuclei (Fig. 10.20). It may
occur when the level of unconjugated bilirubin exceeds the albumin-
binding capacity of bilirubin of the blood. As this free bilirubin is fat-
soluble, it can cross the bloodbrain barrier. The neurotoxic effects vary
in severity from transient disturbance to severe damage and death. Acute
manifestations are lethargy and poor feeding. In severe cases, there is
irritability, increased muscle tone causing the baby to lie with an arched
back (opisthotonos), seizures and coma. Infants who survive may
develop choreoathetoid cerebral palsy (due to damage to the basal
ganglia), learning difficulties and sensorineural deafness. Kernicterus
used to be an important cause of brain damage in infants with severe
rhesus haemolytic disease, but has become rare since the introduction of
prophylactic anti-D immunoglobulin for rhesus-negative mothers.
However, a few cases continue to occur, especially in slightly preterm
infants (3537 weeks), which has led NICE to issue guidelines on the
management of neonatal jaundice.

Clinical evaluation

Babies become clinically jaundiced when the bilirubin level reaches

about 80 mol/L. Management varies according to the infants
gestational age, age at onset, bilirubin level and rate of rise, and the
overall clinical condition.

Age at onset
Table 10.2 Causes of neonatal jaundice

The age of onset is a useful guide to the likely cause of the jaundice
(Table 10.2).

Jaundice <24 h of age

Jaundice starting within 24 h of birth usually results from haemolysis.

This is particularly important to identify as the bilirubin is unconjugated
and can rise very rapidly and reach extremely high levels.

Haemolytic disorders

Rhesus haemolytic disease Affected infants are usually identified

antenatally and monitored and treated if necessary (see Ch. 9). The
birth of a severely affected infant, with anaemia, hydrops and
hepatosplenomegaly with rapidly developing severe jaundice, has
become rare. Antibodies may develop to rhesus antigens other than D
and to the Kell and Duffy blood groups, but haemolysis is usually less
severe.

ABO incompatibility This is now more common than rhesus

haemolytic disease. Most ABO antibodies are IgM and do not cross the
placenta, but some group O women have an IgG anti-A-haemolysin in
the blood which can cross the placenta and haemolyse the red cells of a
group A infant. Occasionally, group B infants are affected by anti-B
haemolysins. Haemolysis can cause severe jaundice but it is usually less
severe than in rhesus disease. The infants haemoglobin level is usually
normal or only slightly reduced and, in contrast to rhesus disease,
hepatosplenomegaly is absent. The direct antibody test (Coombs test),
which demonstrates antibody on the surface of red cells, is positive. The
jaundice usually peaks in the first 1272 h.

G6PD deficiency (see Ch. 22) Mainly in people originating in the

Mediterranean, Middle-East and Far East or in African-Americans.
Mainly affects male infants , but some females develop significant
jaundice. Parents of affected infants should be given a list of drugs to be
avoided, as they may precipitate haemolysis.

Spherocytosis This is considerably less common than G6PD

deficiency (see Ch. 22). There is often, but not always, a family history.
The disorder can be identified by recognising spherocytes on the blood
film.

Congenital infection

Jaundice at birth can also be from congenital infection. In this case, the
bilirubin is conjugated and the infants have other abnormal clinical
signs, such as growth restriction, hepatosplenomegaly and
thrombocytopenic purpura.

Jaundice at 2 days to 2 weeks of age

Physiological jaundice

Most babies who become mildly or moderately jaundiced during this

period have no underlying cause and the bilirubin has risen as the infant
is adapting to the transition from fetal life. The term physiological
jaundice can only be used after other causes have been considered.

Breast milk jaundice

Jaundice is more common and more prolonged in breast-fed infants. The

hyperbilirubinaemia is unconjugated. The cause is multifactorial but
may involve increased enterohepatic circulation of bilirubin.

Dehydration

In some infants, the jaundice is exacerbated if milk intake is poor from a

delay in establishing breast-feeding and the infant becomes dehydrated.
Breast-feeding should be continued, although the bilirubin level would
fall if it were interrupted. In some infants, intravenous fluids are needed
to correct dehydration.

Infection

An infected baby may develop an unconjugated hyperbilirubinaemia

from poor fluid intake, haemolysis, reduced hepatic function and an
increase in the enterohepatic circulation. If infection is suspected,
appropriate investigations and treatment should be instigated. In
particular, urinary tract infection may present in this way.

Other causes

Although jaundice from haemolysis usually presents in the first day of

life, it may occur during the first week. Bruising and polycythaemia
(venous haematocrit is >0.65) will exacerbate the infants jaundice. The
very rare CriglerNajjar syndrome, in which the enzyme glucuronyl
transferase is deficient or absent, may result in extremely high levels of
unconjugated bilirubin.
 The causes and management of jaundice at >2 weeks of age
(persistent neonatal jaundice), (3 weeks if preterm), are different and are
considered separately below.

Severity of jaundice

Jaundice can be observed most easily by blanching the skin with ones
finger. The jaundice tends to start on the head and face and then spreads
down the trunk and limbs. If the baby is clinically jaundiced, the
bilirubin should be checked with a transcutaneous bilirubin meter or
blood sample. It is easy to underestimate in Afro-Caribbean, Asian and
preterm babies, and a low threshold should be adopted for measuring
the bilirubin of these infants. A high transcutaneous bilirubin level must
be checked with a blood laboratory measurement. It is now
recommended in the UK that all babies should be checked clinically for
jaundice in the first 72 h of life, whether at hospital or home, and if
clinically jaundiced, a transcutaneous measurement made.

Rate of change

The rate of rise tends to be linear until a plateau is reached, so serial

measurements can be plotted on a chart and used to anticipate the need
for treatment before it rises to a dangerous level.

Gestation

Preterm infants are more susceptible to damage from raised bilirubin, so

the intervention threshold is lower.

Clinical condition

Infants who experience severe hypoxia, hypothermia or any serious

illness may be more susceptible to damage from severe jaundice. Drugs
which may displace bilirubin from albumin, e.g. sulphonamides and
diazepam, are therefore avoided in newborn infants.
Management

Poor milk intake and dehydration will exacerbate jaundice and should be
corrected, but studies have failed to show that routinely supplementing
breast-fed infants with water or dextrose solution reduces jaundice.
Phototherapy is the most widely used therapy, with exchange transfusion
for severe cases.

Phototherapy

Light (wavelength 450 nm) from the bluegreen band of the visible
spectrum converts unconjugated bilirubin into a harmless water-soluble
pigment excreted predominantly in the urine. It is delivered with an
overhead light source placed the optimal distance above the infant to
achieve high irradiance. Although no long-term sequelae of phototherapy
from overhead light have been reported, it is disruptive to normal
nursing of the infant and should not be used indiscriminately. The
infants eyes are covered, as bright light is uncomfortable. Phototherapy
can result in temperature instability as the infant is undressed, a macular
rash and bronze discoloration of the skin if the jaundice is conjugated.

Continuous multiple (intensive) phototherapy is given if the

bilirubin is rising rapidly or has reached a high level.

Exchange transfusion

Exchange transfusion is required if the bilirubin rises to levels which are

considered potentially dangerous. Blood is removed from the baby in
small aliquots, (usually from an arterial line or the umbilical vein) and
replaced with donor blood (via peripheral or umbilical vein). Twice the
infants blood volume (2 80 ml/kg) is exchanged. Donor blood should
be as fresh as possible and screened to exclude CMV, hepatitis B and C
and HIV infection. The procedure does carry some risk of morbidity and
mortality.
 Phototherapy has been very successful in reducing the need for
exchange transfusion. In infants with rhesus haemolytic disease or ABO
incompatibility unresponsive to intensive phototherapy, intravenous
immunoglobulin reduces the need for exchange transfusion.

There is no bilirubin level known to be safe or which will definitely

cause kernicterus. In rhesus haemolytic disease, it was found that
kernicterus could be prevented if the bilirubin was kept below
340mol/L (20 mg/dl). As there is no consensus among paediatricians
in the UK on the bilirubin levels for phototherapy and exchange
transfusion, guidelines have been published by NICE to ensure uniform
practice.

Jaundice at >2 weeks of age

Jaundice in babies more than 2 weeks old (3 weeks if preterm), is called

persistent or prolonged neonatal jaundice. The key feature is that it may
be caused by biliary atresia, and it is important to diagnose biliary atresia
promptly, as delay in surgical treatment adversely affects outcome
(see Ch. 20 for further details).

However, in most infants with persistent neonatal jaundice, the

hyperbilirubinaemia is unconjugated, but this needs to be confirmed on
laboratory testing.

In prolonged unconjugated hyperbilirubinaemia:

Breast milk jaundice is the most common cause, affecting

up to 15% of healthy breast-fed infants; the jaundice gradually
fades and disappears by 45 weeks of age.
Infection, particularly of the urinary tract, needs to be
considered.
Congenital hypothyroidism may cause prolonged jaundice
before the clinical features of coarse facies, dry skin, hypotonia
and constipation become evident. Affected infants should be
identified on routine neonatal biochemical screening (Guthrie
test).

Conjugated hyperbilirubinaemia (>25 mol/L) is suggested by the baby

passing dark urine and unpigmented pale stools. Hepatomegaly and
poor weight gain are other clinical signs that may be present. Its causes
include neonatal hepatitis syndrome and biliary atresia, with improved
prognosis of biliary atresia with early diagnosis (see Ch. 20 for further
details).

Summary