EDITOR SPEAKS

Vol. 8 Editor-in-Chief Sectional Editor Issue 3 & 4 April - September 2009 Dr. Vinay Aggarwal Dr. Parkash Gera Editorial Board Dr. Vijay Agarwal Atul Gandotra Dr. Sharda Jain Dr. Rajiv Gupta Dr. Deepak Pande Dr. Vineet Jain Dr. Hariharan Mr. S.K. Singhal Design and Layout Photographer Dr. Ashok Grover Dr. Madhumita Puri Dr. B.K. Gupta Dr. S. Arul Rhaj Dr. Yogesh Jhamb Dr. Neeraj Jain Dr. Atul Jain Ms. Tabassum Mr. Mukesh Kapoor

Pregnancy is an occasion to rejoice for the family as it heralds the beginning of a new generation, a continuation of the family-line. As a result, any mention of a medical disorder during pregnancy causes a lot of anxiety - both to expectant mother and her family members. Unfortunately, the perinatal mortality of the mother as well as the newborn is reasonably high in our country. Many questions are asked by the couple and their relatives from the attending doctors, eg, is there a hereditary disease in the family or has the pregnant women got heart disease, hypertension, diabetes, thyroid disorders, bronchial asthma or infection like tuberculosis. There are other issues to name a few are those that concern the hospital where the patient will deliver the baby and whether it is well equipped to resuscitate the patient in the event of acute disorders like thromboembolism or dialytic support for it is equipped with renal disorders. Some concerns relate to the unborn child regarding normalcy of the baby, effect of medications administered impacting the fetus, the line of action to be taken in the event of an emergency, and so on. The answers to such questions are not straight forward all the time. Pregnancy causes considerable alteration in the physiology of a woman and management of medical problems has to be charted out with great care. It is mandatory that the attending physician has complete knowledge of functional, physiological, hemodyanamic, endocrinological and morphological changes associated with normal pregnancy. Evaluation of these functions should take into account expected levels during gestation and the clinician should avoid comparing the measured values with reported normal values obtained in non pregnant woman. Success of feto-maternal medicine can be achieved only by the team work - of obstetricians, pediatricians, and physicians, as well as experts in imaging science and laboratory medicine. In most of high risk pregnancies good antenatal care and close monitoring of the problems arising during labour and after, provides rewarding results. It has been increasingly felt that to institute appropriate co-ordination amongst specialists from various medical fields, a the specialty of pregnancy medicine should be started. Keeping the above problems, issues and concerns in mind, we at Pushpanjali Crosslay Hospital are planning to start a pregnancy medicine clinic in near future, to provide state-of-the-art care to pregnant woman with medical disorders. This volume of Medi-focus is a collective effort of authors to cover the clinical approach and management of some of the common medical disorders in pregnancy, with a view to give our readers an insight into the medical challenges faced in day-to-day practice. Dr. Parkash Gera
Head, Department of Medicine Pushpanjali Crosslay Hospital

CONTENTS
1. Normal Physiology of Pregnancy 2. Resuscitation of a Pregnant Patient 4. Hypertension in Pregnancy 3 7 13

3. Venous Thromboembolism and Pregnancy 11 5. Current Guidelines for the Management 17 of Asthma During Pregnancy 6. Gestational Diabetes 21 7. Thyroid Diseases in Pregnancy 25 8. Maturing of Medical Aesthetics - 28 Restylane- Tissue 9. Cardiomyopathy in Pregnancy 35 10. Acute Renal Failure in Pregnancy 39 11. TB in Pregnancy 45 12. Maternal Medication: Curing Mother, 49 Protecting Fetus 13. Events and Initiatives 53 14. Guidelines for submission of 59 Manuscripts

Owned, Edited, Printed and Published by Dr. Vinay Aggarwal for and on behalf of Pushpanjali Medical Publications Pvt. Ltd., A-14, Pushpanjali, Vikas Marg Extn., Delhi-110092 Printed at Kumar Offset Printer, 381, Patparganj Industrial Area, Delhi - 110 092 All disputes to be settled in Delhi Courts only.

All rights reserved. No responsibility is taken for returning unsolicited manuscripts unless a self-addressed stamped envelope is enclosed. Views expressed in articles in Pushpanjali Medi-Focus do not necessarily reflect those of the editorial board.

1 Vol. 8, Issue 3 & 4, April - September 2009

Normal Physiology of Pregnancy

Rini Goyal
The physiological adaptations of pregnancy are profound. Many of these could be perceived as abnormal in the non-pregnant woman. Cardiovascular changes include substantive increase in blood volume and cardiac output which may mimic thyrotoxicosis. On the other hand, these same adaptations may lead to ventricular failure if there is an underlying heart disease. Thus, these physiological changes can be misinterpreted as pathological and can also unmask or worsen pre-existing disease. Virtually every organ system undergoes changes that can alter the diagnostic criteria and treatment of diseases Reproductive tract: Uterus progressively enlarges and increases in bulk. Hyperplasia of uterine muscles increases its weight from approximately 60 gm to 900 gms at term. The cervix undergoes pronounced softening and Table 1: Hemodynamic changes in late pregnancy Constituents Cardiac output (litre/min) Stroke volume (ml) Pulse rate /min Arterial blood pressure mmHg Femoral venous pressure Non pregnant 4.5 6.5 70 110-120/65-80 8-10 cm water Pregnancy near term 5.3 (40 weeks) 6.0 (32 weeks) 75 (40 weeks ) 85 Same 20 cm water Changes +30% Rise Rise May have midpregnancy drop Rise way to thick pale yellow colostrum in later pregnancy. Montgomery tubercles appear and keep the areola and the nipple healthy. Skin: Myriad skin pigmentations take place. Primary and secondary areola occurs in the first and second trimester respectively along with nipple darkening. Chloasma (on face) and linea nigra (on abdomen) make an appearance along with striae gravidarum. These appear to be under the control of melanocyte stimulating factors and Adrenocorticotropic hormone (ACTH). Cardiovascular system: This system is put to extra work during pregnancy mainly as a result of growth of fetus, feto placental unit and increase in body vascular beds and metabolism. Plasma volume increases (30- 50 %), and red cell volume increases by 5 10 %. These changes are depicted in Table 1.

cyanosis due to increased vascularity and hyperplasia of cervical glands. Ovulation ceases in pregnancy and the maturation of new follicles is suspended. The corpus luteum continues to grow instead of degenerating and enlarges to 2.5 cm at the end of second month then it becomes cystic and wanes by the end of third month. Vagina, fallopian tubes, broad and round ligaments all show increased vascularity and hypertrophy.
Rini Goyal Consultant Deptt. Obs. & Gynae

Blood changes: Substantial blood changes occur throughout pregnancy as outlined in Table 2. Respiratory changes: During pregnancy the breathing becomes diaphragmatic as the movement of the diaphragm increases (Table 3). Urinary system: A remarkable number of changes are observed in the urinary system as a result of pregnancy as depicted in Table 4. Gastrointestinal tract: The gums may become vascular during pregnancy as often there is bleeding while brushing the teeth. Pyrosis (heartburn) is common. Atony of smooth muscles of alimentary tract results in delayed emptying of stomach and better absorption from

Breasts: The breasts enlarge with prominent nipples and increased pigmentation. Estrogen and progesterone mediated ductal and alveolar proliferation takes place. The sticky discharge from the nipple in the initial months gives 3

Pushpanjali Crosslay Hospital Ghaziabad (NCR)

Vol. 8, Issue 3 & 4, April - September 2009

Table 2: Blood Changes During Late Pregnancy Constituents Blood volume(ml) Plasma volume (ml) Red cell volume (ml) Total haemoglobin (gm) Hb in gm% in peripheral blood Hematocrit (%) Total protein (gm) Plasma protein (gm %) Albumin (gm%) Globulin (gm %) Table 3: Changes in the Respiratory System Constituents Respiratory rate / min Tidal volume (ml) Vital capacity (ml) O2 consumption Arterial PO2 Arterial PCO2 Arterial blood PH Venous blood PH 95 mmHg 38 mmHg 7.40 7.35 Non-pregnant 16 500 3200 Pregnancy near term 18 700 3300 Increased 105 mmHg 30 mmHg 7.40 7.38 Change Slight rise >40% Unaltered >20% Increase Fall Unaltered Slight rise Nonpregnant 4000 2500 1400 475 12.5 40 180 7 4.3 2.7 Pregnancy near term 5000 3500 1550 Up to 560 11 38 230 5.8 3 3 Change +25% +30-40% +10% Up to +20% -12% Slight fall Rise Fall Fall Rise

intestine often leads to constipation. Bile stasis associated with increased cholesterol saturation contributes towards increased prevalence of cholesterol stones in multiparous women. Liver shows no histological changes, however, some of the laboratory Table 4: Renal Changes in Normal Pregnancy Alteration Increased renal size Dilation of pelvis, calyces, and ureters

test to evaluate hepatic function yields appreciably different results during normal pregnancy. There is a rise in globulin, fibrinogen and alkaline phosphatase progressively to term. There is no change in bilirubin and transaminases.

Clinical relevance Renal length approximately 1cm greater Postpartum decreases in size should not be on radiographs mistaken for parenchymal loss Resembles hydronephrosis on ultrasound Not to be mistaken for obstructive uropathy; or IVP (more marked on right ) retained urine leads to collection error ; upper urinary tract infections are more virulent ; may be responsible for distention syndrome ; elective pyelography should be deferred to at least 2 weeks postpartum Glomerular filtration rate and renal Serum creatinine and urea nitrogen values plasma flow increase ~50% decrease during normal gestation; 0.8mg /dl ( 72mol/l) creatinine already suspect; protein, amino acid, and glucose excretion - all increase Renal bicarbonate threshold decreases; Serum bicarbonate and PCO2 are 4-5meq/L progesterone stimulates respiratory and 10mmHg lower, respectively, in normal, center gestation; a PCO2 of 40 mmHg already represents CO2 retention Osmoregulation altered: osmotic thresholds for AVP release and thirst decrease; hormonal disposal rates increase Serum osmolality decreases 10mosm/l (serum Na ~ 5 Eeq/L ) during normal gestation; increased metabolism of AVP may cause transient diabetes insipidus in pregnancy

Increased renal hemodynamics

Changes in acid base metabolism

Renal water handling

4 Vol. 8, Issue 3 & 4, April - September 2009

Endocrine system Pituitary gland - maternal pituitary gland enlarges during pregnancy. Pituitary growth hormone decreases to 150ng/ml at term. Pituitary prolactin plasma level increases to 150 g/ml at term. Oxytocin level rises from mean 10.5 pg/ml at 9th week to mean 74.2 pg/ml at 38th week. Thyroid gland - the gland enlarges during pregnancy. The basal metabolic rate increases to 30% at later weeks of pregnancy. Protein bound iodine (PBI) content of blood rises from 4-8g percent to 6-11g percent during pregnancy. Serum TSH, free T4, free T3 levels remain normal during pregnancy. Thyroid binding globulin is elevated

Parathyroid - the glands show hyperplasia and parathyroid hormone level rise. Adrenal cortex - maternal plasma cortisol level rises from 10 g to 30 g percent throughout pregnancy. Serum aldosterone level rises from 5 to 50 g percent during pregnancy. Metabolic changes: In response to the increased demands of the rapidly growing fetus and placenta, the pregnant woman undergoes metabolic changes as depicted briefly in the following Tables 4 & 5. Other systems Musculoskeletal system: Progressive lordosis, increased mobility of sacroiliac, sacrococcygeal and pubic joints is characteristic of pregnancy. Eyes: intraocular pressure and corneal sensitivity decrease with slight increase in corneal thickness. Central nervous system: There are often problems with attention, concentration and memory. Sleep disturbances appear as early as 12 weeks and extend into postpartum period and may contribute to the post partum blues and even frank depression.

Table 4: Analysis of Weight Gain based on Physiological Events in Pregnancy {cumulative increase in weight (g)} Tissues and fluids 10 weeks 5 20 30 140 45 100 0 310 650 20 weeks 300 170 350 320 180 600 30 2,050 40,00 30 weeks 1,500 430 750 600 360 1,300 80 3,480 8,500 40 weeks 3,400 650 800 970 405 1,450 1,480 3,345 12,500

Fetus Placenta Amnionic fluid Uterus Breasts Blood Extravascular fluid Maternal sources (fat) Total

References 1. Clark SL, Cotton DB, Lee W, et al. Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 1989;161:143942 2. Dinn RB, Harris A, Marcus PS. Ocular changes in pregnancy. Obstet Gynecol Surv 2003; 58: 137144.

Table 5: Changes in Metabolic Products Constituents Non-pregnant Pregnancy near term Changes

Blood glucose (mg%)

Fasting 80-100 postprandial below 110 mg% 700 140 180 15-40 0.6-0.7

Fall by 10 mg% Below 110 mg% 20-25 mg% during 1000 250 250 9-25 0.6-1 6l increase

With rise of first 2 hours

Blood total lipids (mg%) Blood triglyceride (mg%) Blood cholesterol (mg%) Blood urea (mg%) Blood creatinine (mg%) Body water Plasma sodium (mmol/l) Plasma potassium (mmol/l) Plasma bicarbonate

Rise Rise Rise Fall Fall Rise 3% fall 3% fall Fall

132-144 3.3-4.7 26 mmol/l 5

Reduced Reduced 22 mmol/l

Vol. 8, Issue 3 & 4, April - September 2009

Resuscitation of A Pregnant Patient

Amit Gupta
Although pregnancy and delivery are usually safe for mother and her newborn child, serious maternal complications, including cardiac arrest, can occur in the prenatal, intrapartum and postpartum periods. Cardiac arrest occurs only about once in every 30,000 late pregnancies1, but survival from such an events is exceptional. Most deaths are from acute causes, with many mothers receiving some form of resuscitation. However, the number of indirect deaths that is, deaths from medical conditions exacerbated by pregnancy is greater than that of deaths from conditions that arise from pregnancy itself. Factors peculiar to pregnancy that weigh the balance against survival include anatomical changes that make it difficult to maintain a clear airway and perform intubation, pathological changes such as laryngeal edema, physiological factors such as increased oxygen consumption, and an increased likelihood of pulmonary aspiration2. In the third trimester, the most important factor is compression of the inferior vena cava and impairment of venous return by the gravid uterus when the woman lies supine3. These difficulties may be exaggerated by obesity. All staff directly or indirectly concerned with obstetric care need to be trained in resuscitation. Key points During resuscitation there are two patients, mother and fetus. The best hope of fetal survival is maternal survival. Consider the physiologic changes due to pregnancy Interventions to prevent arrest1 Place the patient in the left lateral position Give 100% oxygen Establish IV access and give a fluid bolus Consider reversible causes of cardiac arrest and identify any preexisting medical conditions that may be complicating the resuscitation. arrest, but this should not delay other treatments. 1. Excess magnesium sulfate Iatrogenic overdose is possible in women with ecclampsia, particularly if the woman becomes oliguric Administration of calcium gluconate (1 amp/ 1 g) is the treatment of choice. Pregnant women may experience acute coronary syndromes, typically in association with other medical conditions. Because fibrinolytics are relatively contraindicated in pregnancy, percutaneous coronary intervention is the reperfusion strategy of choice for ST-elevation myocardial infarction. 2. Pre-eclampsia/eclampsia Pre-eclampsia/eclampsia develops after the 20th week of gestation and can produce severe HTN and ultimate diffuse organ system failure. If untreated it may result in maternal and fetal morbidity and mortality. 3. Life-threatening pulmonary embolism and stroke Successful use of fibrinolytics for a massive, life-threatening pulmonary embolism and ischemic stroke has been reported in pregnant women. 4. Trauma and drug overdose Pregnant women are not exempt from the accidents and mental illnesses Domestic violence also increases during pregnancy; in fact, homicide and suicide are leading causes of mortality during pregnancy. 5. Aortic dissection Pregnant women are at increased risk for spontaneous aortic dissection. Resuscitation of the pregnant women in cardiac arrest Modifications of Basic Life Support General measures At a gestational age of 20 weeks, the pregnant uterus can press against the inferior vena cava and the aorta, impeding venous return and cardiac output. Uterine obstruction of venous return can produce pre-arrest hypotension or shock and in the critically ill patient may precipitate arrest. It also limits the effectiveness of chest compressions. The gravid uterus may be shifted away from the IVC and aorta by placing in LUD or by

Differential diagnosis Same reversible causes of cardiac arrest that occur in non-pregnant women can occur during pregnancy. Providers should be familiar with pregnancy specific disease and procedural complications Use of abdominal US should be considered in detecting possible causes of the cardiac 7 Vol. 8, Issue 3 & 4, April - September 2009

Amit Gupta Consultant and Head Deptt. of Critical Care and Emergency Medicines Pushpanjali Crosslay Hospital Ghaziabad (NCR)

pulling the gravid uterus to the side. This may be accomplished manually or by placement of a rolled blanket or other object under the right hip and lumbar area. Airway Hormonal changes promote insufficiency of the gastro esophageal sphincter, increasing the risk of regurgitation. Apply continuous cricoid pressure during positive-pressure ventilation for any unconscious pregnant woman. Secure the airway early in resuscitation Use an ETT 0.5 to 1mm smaller in internal diameter than that used for a non-pregnant woman. Breathing Hypoxemia can develop rapidly because of decreased functional residual capacity and increased oxygen demand, so be prepared to support oxygenation and ventilation. Ventilation volumes may need to be reduced because the mothers diaphragm is elevated. Circulation Perform chest compressions higher slightly above the center of the sternum. To adjust for the elevation of the diaphragm and abdominal contents. Vasopressor agents, including epinephrine and vasopressin, will decrease blood flow to the uterus. But since there are no alternatives, indicated drugs should be used in recommended doses. Defibrillation Defibrillate using standard ACLS defibrillation doses. There is no evidence that shocks from a direct current defibrillator have adverse effects on the heart of the fetus. If fetal or uterine monitors are in place, remove them before delivering shocks. Emergency Cesarean Delivery for the Pregnant Woman in Cardiac Arrest CRP leader should consider the need for ER cesarean delivery as soon as a pregnant woman develops cardiac arrest. The best survival rate for infants >24 to 25 weeks in gestation occurs when the delivery of the infant occurs no more than 5 minutes after the mothers heart stops beating. This typically requires that the provider begin the delivery about 4 minutes after cardiac arrest. Delivery of the baby empties the uterus, relieving both the venous obstruction and the aortic compression. Delivery also allows access to the infant so that newborn resuscitation can begin. It is important to remember that one will both mother and infant if one cannot restore blood flow to the mothers heart. Decision making for emergency cesarean delivery Consider gestational age Although the gravid uterus reaches a size that will begin to compromise aortocaval blood flow at approximately 20 weeks of gestation, fetal viability begins at approximately 24 to 25 weeks. Portable ultrasonography, may aid in determination of gestational age and positioning, but the use of US should not delay the decision to perform delivery. Gestational age <20 weeks Need not be considered because this size gravid uterus is unlikely to significantly compromise maternal cardiac output. 8 Vol. 8, Issue 3 & 4, April - September 2009

Gestational age approximately 20 to 23 weeks Perform to enable successful resuscitation of the mother, not the survival of the delivered infant, which is unlikely at this gestational age. Gestational age >24 weeks Perform to save the life of both the mother and infant4. The following can increase the infants chance for survival: Short interval between the mothers arrest and the infants delivery No sustained prearrest hypoxia in the mother Minimal or no signs of fetal distress before the mothers cardiac arrest Aggressive and effective resuscitative efforts for the mother Delivery to be performed in a medical center with a neonatal intensive care unit Consider the professional setting5 Are appropriate equipment and supplies available? Is emergency hysterotomy within the rescuers procedural range of experience and skills? Are skilled neonatal/pediatric support personnel available to care for the infant, especially if the infant is not full term? Are obstetric personnel immediately available to support the mother after delivery? Summary6 Successful resuscitation of a pregnant woman and survival of the fetus require prompt and excellent CPR with some modifications in techniques. By the 20th week of gestation, the gravid uterus can compress the IVC and aorta, obstructing venous return and arterial blood flow. Rescuers can relieve this compression by positioning the woman on her side or by pulling the gravid uterus to the side. Defibrillation and medication doses used for resuscitation of the pregnant woman are the same as those used for other adults Rescuers should consider the need for emergency cesarean delivery as soon as the pregnant woman develops cardiac arrest. Rescuers should be prepared to proceed if the resuscitation is not successful within 4 minutes. References 1. Cardiac Arrest Association with Pregnancy. Circulation 2005; 112; IV-150-IV-153; 2005. American Heart association. 2. Ueland K, Novy MJ, Peterson EN, Metcalfe J. Maternal cardiovascular dynamics. IV. The influence of gestational age on the maternal cardiovascular response to posture and exercise. Am J Obstet Gynecol. 1969 Jul 15;104(6):856864. 3. Kerr MG, Scott DB, Sameul E. Studies of the inferior vena cava in late pregnancy. Br Med J. 1964 Feb 29;1(5382):532533. 4. Marx GF. Cardiopulmonary resuscitation of late-pregnant women. Anesthesiology. 1982 Feb;56(2):156. 5. Varma, R. (2004). Resuscitation in pregnancy article omitted several points. BMJ 328: 168-169 6. Morris S and Stacey M. ABC of Resuscitation: Resuscitation in pregnancy, BMJ. 2003 November 29; 327(7426): 12771279.

Venous Thromboembolism and Pregnancy

Neelesh Goyal and Parkash Gera
Venous thromboembolism (VTE) is a potentially life threatening condition, it includes two interrelated but distinct clinical entities, deep vein thrombosis (DVT) and pulmonary embolism (PE). This is often a silent yet potentially fatal disease. Despite the availability of effective prophylactic and therapeutic options venous thromboembolism continues to be under diagnosed and under treated. It is more complex to diagnose VTE in pregnant women. The incidence is estimated at 0.76 to 1.72 per 1000 pregnancies, which is four times as great a risk in non-pregnant woman. Delayed diagnosis, inadequate treatment and thromboprophylaxis lead to more mortality in pregnancy as compared with non-pregnant patients in whom successful strategies have been developed. Risk factors 1. Pregnancy is a hypercoagulable state due to increased fibrin, decreased fibrinolytic activity and changes in coagulation factors, protein C and S. 2. Reduction in venous flow by 50% in lower limbs from 20-25 weeks of pregnancy lasting 6 weeks into pueperium. 3. Others factors include diabetes, cardiac disease, lupus, smoking, multiple pregnancies, age more than 35 years, obesity and LSCS (especially emergency LSCS). Diagnosis of thromboembolism Clinical suspicion is of paramount importance and as the usual signs like leg swelling, tachypnea, tachycardia and dyspnea are common in pregnancy, only 10% patients turn out to have PE. Since sudden death is not uncommon in thromboembolism, it is acceptable to investigate all patients presenting with signs suggestive of PE. Treatment with low molecular weight heparin (LMWH) or unfractionated heparin (UH) is warranted till the results of investigations are known or the treatment is strongly contraindicated. Compression ultrasonography (CUSG): It is highly sensitive for symptomatic proximal DVT and is the investigation of choice in pregnancy but is less sensitive for calf and iliac vein thrombosis. The need for high pressure 11 Vol. 8, Issue 3 & 4, April - September 2009 to compress the femoral vein at the groin or absence of flow on Doppler study is suggestive of iliac vein thrombosis. Magnetic resonance direct thrombus imaging (MRDTI): This has no radiation effect on the fetus and is very sensitive and specific for the diagnosis of iliac vein thrombosis. CT scanning (Risk to fetus needs to be considered) or pulsed Doppler study can be used in the absence of MRDTI. D-Dimer: To be used in addition to other tests as its level rises with normal pregnancy. However negative test done with highly specific assay in the first and second trimester has a negative predictive value of 100%. So, a negative test is useful if the CUSG is normal whereas a positive D-Dimer would require further testing. Ventilation perfusion scanning (VP Scan): patient with normal CUSG and X-ray chest may be taken up for VP scanning or CT pulmonary angiography (CTPA), if clinical suspicion is high. VP scan delivers more radiation to fetus than CTPA, but CTPA carries 13% more maternal breast cancer risk. Management in pregnancy Unfractionated heparin or LMWH is only used, as warfarin causes warfarin embroyopathy. Both kinds of heparin do not cross the placenta and do not affect the fetus adversely. Unfractionated heparin has been replaced by LMWH as it has reduced episodes of side effects and there is no need of monitoring. Management of isolated calf vein thrombosis is controversial but as the iliofemoral thrombosis originates from calf veins, all symptomatic patients should receive LMWH in full doses Vena caval filters are reserved for the patients in whom heparin is contraindicated or the thromboembolism occurs within 2 weeks of delivery. Daily once dosing is practiced by many clinicians but twice daily dosing is recommended due to altered pharmacokinetics in pregnancy. Cutaneous allergic reactions are rare and are more common with long term use. Foundaparinux can be used in patients with cross reactivity among many LMWH (category B in pregnancy). Bed rest is advisable only in phlegmasia.

Neelesh Goyal Consultant Physician Deptt. of Medicine Pushpanjali Crosslay Hospital Ghaziabad (NCR) Parkash Gera Head, Deptt. of Medicine Pushpanjali Crosslay Hospital Ghaziabad (NCR)

Clinical features S/O DVT Start LMWH Compression USG Negat VE Positive

Clinical features S/O PE Start LMWH Compression USG

Negative

D-Dimer Positive Negative

Continue LMWH

X-ray Chest

Asthma/other ABN

Normal

Clinical follow up S/O ILIAC vein thrombosis

CTPA

CTPA/VP Scan

Yes

No Repeat Comp. USG in 5-6 D

MRDTI

or

Positive

Normal Resart LMWH

Normal

Positive

No Result/high Suspicion

Pulsed Doppler/ CT ILIAC veins

Clinical follow UP

Continue LMWH Pulmonary angiography Serial Comp, USG, MRDTI, Pulsed doppler

Anticoagulants in labor and delivery Current Guidelines spinal anesthesia can be given 12 hours after last dose of prophylactic low molecular weight heparin and 24 hours after the last dose of therapeutic low molecular weight heparin Intravenous unfractionated heparin should be stopped 6 hours before the neuraxial blockade and a normal PTT should be present. Once in established labor, LMWH should be stopped. Unfractionated heparin is usually instituted in the last few weeks of pregnancy but meticulous control of APTT is required. Resume prophylactic LMWH after 12 hours of delivery in absence of active bleeding and removal of epidural catheter. Therapeutic doses need to wait for at least 24 hours post operatively. LMWH or warafarin can be continued thereafter for at least 6 months. Management of embolism in late pregnancy and labor: Give supplemental oxygen to maintain SPO2 at > 95% Intravenous heparin Temporary vena caval filter in hemodynamically stable patient Stop (reverse with protamine) heparin at the onset of labor Do not do LSCS in fully anticoagulated patient. Massive PE with fetal compromise needs complex management which may include cardiopulmonary bypass, surgical embolectomy with LSCS followed by clot fragmentation and venacaval filter. 12 Vol. 8, Issue 3 & 4, April - September 2009

Thromboprophylaxis in pregnancy and puerperium Risk of recurrent thromboembolism is higher in pregnancy and more so in puerperium. Graduated compression stockings are recommended. LMWH is used for 6 weeks postpartum Aspirin is not recommended All antepartum women with a history of 2 or more episode of thromboembolism and with thrombophilias should receive LMWH. Individual decision can be taken in women with single episode or low risk thrombophilia or morbidly obese or confined to bed. Thromboprophylaxis after LSCS: Thromboembolism is uncommon after LSCS but can be fatal Low risk = LSCS for uncomplicated pregnancy with no other risk factor threat with early ambulation. Moderate risk = Age >35 years, obesity BMI >30, parity >3, gross varicose veins, current infection, pre-eclampsia, immobility PO >4 days. High risk: = Presence of two of above risk factors, caesarian hysterectomy, previous DVT, known thrombophilia, LMWH plus stockings. Duration of therapy is to be individualized and depending on the indication, it can be continued for up to 6 weeks post OP.

Hypertension In Pregnancy
KP Singh and DP Dubey
Hypertensive disorders in pregnancy are among the major causes of maternal mortality along with thromboembolism, hemorrhage, and nonobstetric injuries. Maternal diastolic BP of >110 mmHg is associated with an increased risk for placental abruption and fetal growth restriction. Pre-eclamptic disorders cause most of the morbidity due to chronic hypertension during pregnancy. Serious maternal complications include eclamptic seizures, intra-cerebral hemorrhage, pulmonary edema due to capillary leak of myocardial dysfunction, acute renal failure due to vasospasm, proteinuria greater than 4-5 g/d, hepatic swelling with or without liver dysfunction and disseminated intravascular coagulation and/or consumptive coagulopathy, which is rare. Fetal complications include abruption placentae, intra-uterine growth restriction, premature delivery and intrauterine fetal death. Hypertensive disorders during pregnancy are classified into four categories, as recommended by the National High Blood Pressure Programme working group on high blood pressure in pregnancy. 1. Chronic hypertension 2. Gestational hypertension 3. Pre-eclampsia superimposed on chronic hypertension 4. Pre-eclampsia Investigations CBS Note of caution if platelet count is <150,000/l 75% are secondary to dilutional thrombocytopenia of pregnancy; Table 1: Hypertension in Pregnancy
Chronic hypertension Gestational hypertension KP Singh
Consultant Physician

24% due to pre-eclampsia; 1% not related to pregnancy. Platelet count <100,000/l suggests preeclampsia or ITP. KFT LFT Urine R/E if proteinuria present do 24hour proteinuria and spot urine protein/ creatinine ratio. Serum uric acid -- >5mg/mL is non-specific marker of tubular dysfunction in preeclampsia PT, aPTT and INR abnormal in DIC or if liver enzymes are abnormal and/or decreased platelet count ECG LVH seen in chronic hypertension EEG, if seizures occur For HELLP syndrome, check for hemolysis, elevated liver enzymes, low platelets

Differential diagnosis Diabetes mellitus Disseminated intravascular coagulation (DIC) Hypertensive encephalopathy Acute glomerulonephritis Hemolytic uremic syndrome Malignant hypertension Thyroid disorders - hyper/hypo/Hashimotos thyroiditis Hypercoagulable syndromes, like antiphospholipid syndrome, protein C and protein S deficiency Systemic Lupus Erythematosus

Hypertension (blood pressure >140 mm of Hg systolic or >90 mmHg diastolic) present before pregnancy or diagnosed before the 20th week of gestation. New hypertension with BP > 140/90mm of Hg on two separate accessions, without proteinura, arising denovo after 20 weeks of pregnancy; BP normalize by 12 weeks postpartum. Increased BP above patients baseline, change in proteinuria or evidence of end-organ function.

Deptt. of Medicine Pushpanjali Crosslay Hospital Ghaziabad (NCR) DP Dubey

Consultant Physician

Preeclampsia superimposed on chronic hypertension Preeclampsia

Deptt. of Medicine Pushpanjali Crosslay Hospital Ghaziabad (NCR)

Proteinuria (>3.0gm over 24 hours or 2+/4+ on two separate urine samples) in addition to new hypertension, edema no longer included in this diagnosis. When proteinuria is absent, disease suspected with increased BP associated with headache, blurred vision, abdominal pain, low platelet count or abnormal liver enzyme levels.

13 Vol. 8, Issue 3 & 4, April - September 2009

Table 2: Difference between preeclampsia and chronic hypertension

Features Age (years) Parity Onset Preeclampsia Young (20 years) Primigravida After 20 weeks of pregnancy Sudden Chronic hypertension Older (>30 years) Multigravida Before 20 weeks of pregnancy Gradual

Management Though methyldopa remains the most popular and acceptable antihypertensive in hypertension with pregnancy, excluding ACE inhibitors (ACEI) and angiotensin receptor blocker (ARB), all antihypertensive drugs are used in the belief that the mother should be protected and that the fetus should not suffer any hemodynamic shift. Among beta-blockers, Labetalol has been a preferred choice, although Metaprolol and Atenolol also have a good safety profile. For managing eclampsia, adequate care of gestational hypertension is needed with extra caution to avoid volume overload as pulmonary edema is the most common cause of maternal mortality. Cerebral hemorrhage is another common cause. Magnesium sulphate has shown good results for prevention and treatment of eclamptic seizures. Delaying pregnancy until after the teenage years and better prenatal care remains the key to prevent pre-eclampsia. A low dose of aspirin has also been found useful in prevention, according to some studies. Others Care of diet moderate salt restriction, activity bed rest, Fetal monitoring to be done.

Weight gain and edema Systolic blood pressure Fundoscopic examination Proteinuria Plasma uric acid Blood pressure after delivery

<160 mmHg

>160mmHg

Spasm, edema

Anteriovenous nicking exudates Absent Normal Normal

Present Increased Normal

14 Vol. 8, Issue 3 & 4, April - September 2009

Current Guidelines for the Management of Asthma During Pregnancy

Ashok Grover and Pankaj N Choudhary
Adapted from: Current Guidelines for the Management of Asthma during Pregnancy, Immunology and Allergy Clinics of North America, Volume 26; Number 1; February 2006 Asthma is the most common, potentially serious medical problem that complicates pregnancy. Studies have shown that pregnant asthmatic women have an increased risk of adverse perinatal outcomes, whereas controlled asthma is associated with reduced risks. Managing asthma during pregnancy is unique because the effect of the illness and the treatment on the developing fetus as well as the patient needs to be considered. Prevalence of Asthma during Pregnancy Previous estimates of asthma prevalence during pregnancy were between 4% and 7%. Many of these reports were from retrospective data, rather than being based on nationally representative sample. Recently, Kwon and colleagues reviewed U.S. national health surveys spanning 1997 to 2001. The aim was to determine more definitively the prevalence of asthma in pregnant women ages 18 to 44 years. Time trends also were examined using health surveys form 1976 to 1980 and 1988 to 1994. They found that asthma affected between 3.7% and 8.4% of pregnant women in the United States between 1997 and 2001. There was a twofold increase in the prevalence of asthma (from 2.9% to 5.8%) between 1976 and 1980 and 1988 and 1994. This study supports initial prevalence estimated, but also suggests that they may have been conservative. More importantly, this study supports the observation that asthma affects more pregnant women each year. Effects of Uncontrolled Asthma on Pregnancy Observations that support the hypothesis that uncontrolled asthma increased perinatal risks, whereas controlled asthma reduces these risks form an important basis for the management recommendations in this article. Studies have shown that better controlled asthma (defined by lack of acute episodes or higher maternal pulmonary function) leads to improved intrauterine growth (measured by birth weight or ponderal indices. In contrast patients who have daily asthma symptoms are at increased risk for intrauterine growth retardation and preeclampsia. 17 Vol. 8, Issue 3 & 4, April - September 2009 Asthma Management during Pregnancy I: Non-pharmacological therapy The general principles of asthma management during pregnancy do not differ substantially from the management of non-pregnant asthmatics. The ultimate goal for the pregnant asthmatic is to have no limitation of activity, minimal chronic symptoms, no exacerbations, normal pulmonary function, and minimal adverse effects of medications. It is the clinicians job to provide optimal therapy to maintain asthma control that improves maternal quality of life and allows for normal fetal maturation. Assessment and monitoring: Objective assessments and monitoring should be performed on a monthly basis. Including pulmonary function testing (ideally spirometry), detailed symptom history (symptom frequency, nocturnal asthma, interference with activities, exacerbations, and medication use), and physical examination with specific attention paid to auscultation of the lungs. Thirty percent of subjects whose asthma is mild, switch categories during pregnancy to moderate or severe groups. Thus, pregnant asthmatic patients, even those who have mild or well during controlled disease, need to be monitored closely during pregnancy. It is also observed that patients with FEY1 of less than 80% predicted are at increased risk of asthma morbidity and pregnancy complications. Home peak flow monitoring is a valuable tool in managing the pregnant asthmatic that have moderate to severe disease. Since asthma has been associated with IUGR and preterm birth, it is useful to establish pregnancy dating accurately by a first trimester ultrasound. Patients should be instructed to be attentive to fetal activity. Some women may benefit from additional evaluation of fetal activity and growth by serial ultrasound examinations. According to current guidelines, exacerbation is a candidate for antenatal surveillance. There should be open lines of communication with the patients obstetricians should be involved in asthma care and should obtain information on asthma status during prenatal visits. Avoidance of asthma triggering factors: Avoidance of asthma triggers, such as animal dander, tobacco smoke, and pollutions, is important because exposure may lead to increased asthma symptoms and the potential

Ashok Grover Senior Consultant Internist

Deptt. of Medicine Pushpanjali Crosslay Hospital Ghaziabad (NCR)

Pankaj N Choudhary Consultant Physician

Deptt. of Medicine Pushpanjali Crosslay Hospital Ghaziabad (NCR)

need for more medication. Often, allergen immunotherapy is effective for those patients in whom symptoms and the potential need for more medication. Often, allergen immunotherapy is effective for those patients in whom symptoms persist, despite optimal environmental control and proper drug therapy. Allergen immunotherapy can be continued carefully during pregnancy in patients who are deriving benefit, who are not experiencing systemic reactions, and who are receiving maintenance doses. Benefit-risk considerations do not generally favor beginning immunotherapy during pregnancy for must patients because of the undefined propensity for systemic reactions, the increased likelihood of systemic reactions during initiation of immunotherapy, the latency of immunotherapy effect, and the frequent difficulty in acting - agonist of choice during pregnancy because it has been available for a longer period of time in India. Other medication: The 1993 report recognized the use of nebulized ipratropium in women who presented with acute asthma who do not improve substantially with the first inhaled - agonist treatment. Since then, there have been no further published data on anticholinergics in pregnancy, but this recommendation is maintained in the updated guidelines. Other medications are recommended only as an alternative, but not preferred, choices during pregnancy. These include cromolyn (for mild persistent asthma), theophylline (for mild persistent asthma or as add-on therapy to inhaled corticosteroids), and zafirlukast or montelukast (for mild persistent asthma or as add-on therapy to inhaled corticosteroids). The serum concentrations of theophylline need to be monitored closely and low-dose therapy is recommended with maintenance serum levels targeted at 5 to 12 g/mL. II. Pharmacological Therapy Many pregnant asthmatic women require medications to control their asthma. Current guidelines recommend a generalized stepwise approach (Table 1) in achieving and maintaining asthma control. Table 1: Comparatively safe drugs in pregnancy Category Mild intermittent Mild persistent Step therapy Inhaled - agonist as needed Low-dose inhaled corticosteroid Alternative cromolyn, leukotriene receptor antagonist, or theophylline Low-dose inhaled corticosteroid and long-acting - agonist o r medium-dose inhaled corticosteroid o r (if needed) medium-dose inhaled corticosteroid A lternative: low-dose or (if needed) medium-dose inhaled corticosteroid and either theophylline or leukotriene receptor antagonist High-dose inhaled corticosteroid and, if needed, oral corticosteroids Alternative: High-dose inhaled corticosteroid and theophylline 18 Vol. 8, Issue 3 & 4, April - September 2009

The number and dose of medications used are increased as necessary and decreased when possible. Decreasing doses should be done carefully because this may lead to an exacerbation of symptoms. Current guidelines suggest that it may be prudent to postpone attempts at reducing therapy that is controlling the patients asthma until after the infants birth. The classification of asthma severity as outlined in the current guidelines also may help to predict asthma morbidity during pregnancy. Schatz and colleagues reported that asthma morbidity (hospitalizations, office visits, oral corticosteroid use) correlated closely with asthma classification applied to the subjects at entry (ie, subjects who had mild asthma experienced fewer hospitalizations, unscheduled visits, oral corticosteroid courses, and total exacerbations than those who had moderate asthma; subjects who had severe asthma at entry experienced the greatest risk of asthma morbidity during pregnancy). Management of Acute Exacerbations A recent multicenter study reported that 20% of women who have persistent asthma experienced an unscheduled predicting which asthmatic patients will benefit from immunotherapy. Smoking should be discouraged strongly, and all patients should try to avoid environmental tobacco smoke exposure as much as possible. Morbidity during pregnancy that is due to smoking may be independent of, and additive to, morbidity that is due to asthma. Patient education: Patient education is very important during pregnancy. The patient must understand the potential adverse effects of uncontrolled asthma on the well-being of the fetus, and that treating asthma with medications is safer than increased asthma symptoms that may lead to maternal and fetal hypoxia. Above all, the mother-to-be should be able to recognize symptoms of worsening asthma and be able to treat them appropriately. Correct inhaler technique should be assured, and the patient also should understand how she can reduce her exposure to, or control those, factors that exacerbate her asthma. The 1993 report of NAEPP recommended that controller therapy for moderate asthma (which included what was later defined as mild or moderate persistent asthma) be initiated with cromolyn because of its safety profile. Since then, strong evidence demonstrates that cromolyn is not as effective as inhaled corticosteroids for treatment of persistent asthma, and new information regarding the safety of inhaled corticosteroids has been published. Therefore, inhaled steroids are recommended as the preferred controller therapy for all levels of persistent asthma. Two equal treatment options are recommended for moderate persistent asthma: a combination of low-dose inhaled corticosteroids plus a long-acting a-2 agonist, or medium-dose inhaled corticosteroids. Treatment Effectiveness of Inhaled Corticosteroids during Pregnancy Inhaled corticosteroids are well documented to prevent asthma exacerbations in nonpregnant women. This also is true in the pregnant population as reported by Stenius-Aarniala and colleagues. They found a higher incidence of asthma

Moderate persistent

Severe persistent

exacerbations in those who were not treated initially with inhaled corticosteroid in comparison with patients who had been on an inhaled corticosteroid from the beginning of pregnancy. In addition, two randomized controlled trials during pregnancy support the efficacy of inhaled steroids during pregnancy. First, a prospective randomized controlled trial studied 72 pregnant asthmatics who presented to an emergency department or prenatal clinic with an asthma exacerbation. There was a 55% reduction in exacerbations and readmissions in women who were given inhaled beclomethasone dipropionate with oral corticosteroids and a-2 agonists compared with women who were treated with oral corticosteroids and a-2 agonists alone. Second, a prospective, double-blind, double placebo-controlled randomized clinical trial that was published recently by Dombrowski and colleagues compared the efficacy of inhaled beclomethasone dipropionate with oral theophylline for the prevention of asthma exacerbations during pregnancy. There was no significant difference in the proportion of asthma exacerbations among the 194 women who used beclomethasone dipropionate. This study supports previous guidelines that inhaled corticosteroids are the therapy of choice for persistent asthma during pregnancy. Choice of Specific Medications Inhaled corticosteroids: In 1993, the Working Group on Asthma and pregnancy stated that corticosteroids are the most effective anti-inflammatory drugs for the treatment of asthma. At that time, beclomethasone dipropionate, triamcinolone, and flunisolide were recognized as treatment options; there was the most experience during pregnancy with beclomethasone dipropionate. Therefore, it was recommended as the inhaled corticosteroid of choice at that time. Publications since then have supported the overall safety of inhaled corticosteroid use in pregnancy; the most safety data are available for inhaled budesonide. Thus, in the current guidelines, budesonide is the preferred inhaled corticosteroid during pregnancy The recent guidelines emphasize that there are no data to suggest that other inhaled corticosteroids are less safe during pregnancy. Thus, if a pregnant asthmatic woman is using an alternative inhaled corticosteroid before pregnancy and her asthma is well controlled, it would not be unreasonable to continue it through the pregnancy. Oral corticosteroids: Data regarding the use of systemic corticosteroids during pregnancy have not been totally reassuring. Recent available human studies include a metaanalysis of 6 cohort studies by Park- Wyllie and colleagues evaluating the relationship between corticosteroid use during pregnancy and congenital malformations, and four case-control studies evaluating the potential relationship between systemic corticosteroid use during pregnancy and oral clefts. They found that while there was no definite increased risk of total congenital malformations, there was a statistically significant increased risk of oral clefts in infants of mothers treated with corticosteroids during the first trimester. Other adverse outcomes that recently were associated with systemic corticosteroid use during pregnancy include pre19 Vol. 8, Issue 3 & 4, April - September 2009

eclampsia, low birth weight, and preterm delivery. The available data make it difficult to separate the effects of the corticosteroids on these outcomes from the effects of severe or uncontrolled asthma. It must be stressed that the potential risks of oral corticosteroid use during pregnancy must be balanced against the risks to the mother and infant of poorly managed severe disease, which include maternal mortality, fetal mortality, or both. The current recommendations support the use of oral corticosteroids when indicated for the long-term management of severe asthma or for severe exacerbations during pregnancy. Short-acting bronchodilators: The 1993 guidelines did not make a recommendation regarding a specific short-acting inhaled beta2 agonist for use during pregnancy. Based on the data that have been published since then, albuterol is recommended as the inhaled, short-acting beta-2 agonist of choice during pregnancy. Long-acting agonists: Since 1993, two long-acting inhaled bronchodilators have become available-salmeterol and formoterol. There are few published data regarding the safety of these drugs during pregnancy. The new guidelines recommend salmeterol as the long for asthma during pregnancy. Such exacerbations can compromise fetal well-being; therefore, aggressive home management of acute symptoms needs to be reviewed with pregnant asthmatic patients. Above all, pregnant asthmatic patients should be taught to recognize the early signs and symptoms of exacerbations. The current recommendations for home and emergency department management of asthma exacerbations in pregnant asthmatic women are not different from the EPR-2 recommendations in non-pregnant asthmatic women that were published previously. These guidelines are reviewed in detail elsewhere in this issue. Management of Asthma during Labor and Delivery Only approximately 10% to 20% of women develop an exacerbation of asthma during labor and delivery. Nonetheless asthma medications should be continued during labor and delivery. If a systemic steroid has been used in the previous month, then stress-dose steroid should be administered during labor to prevent maternal adrenal crisis. Practitioners should be aware the potential side effects that labor medications that are used commonly may have on asthma. For instance, prostaglandin F2 alpha and methylergonovine, which are used for postpartum hemorrhage, can include bronchospasm. Prostaglandin E2 and magnesium sulfate may be used safely in asthmatic patients. Maternal and fetal hypoxia due to asthma during labor and deliver can be managed medically. It is rarely necessary to perform an emergent caesarean section. Summary Over the past few years, much has been learned that is relevant to the management of asthma in pregnancy. Although the studies that were reviewed herein provide more insight into the mechanisms that are involved and the treatment of asthma during pregnancy, there are more questions to be answered. It is hoped that the updated guidelines, which address the safely to contemporary asthma medications during pregnancy, will be a helpful resource in the treatment of our pregnant asthmatic patients.

Gestational Diabetes
Vipin Mishra
Gestational Diabetes Mellitus (GDM) is the first detection of Diabetes Mellitus during pregnancy in women previously not known to have Diabetes. Some of these cases definitely have undiagnosed Diabetes earlier which gets detected during pregnancy. Previously diagnosed cases of Diabetes are referred to as Pre GDM. Gestational diabetes generally has few symptoms and it is most commonly diagnosed by screening during pregnancy. Gestational diabetes affects 5-10% of pregnancies, depending on the population studied. No specific cause has been identified, but it is believed that the hormones produced during pregnancy have profound anti-Insulin action, leading toimpaired glucose tolerance and Diabetes. Those women who develop Diabetes definitely have a compromised beta cell function and are therefore high risk subjects for future development of full fledged Type 2 Diabetes. Babies born to mothers with gestational diabetes are at increased risk of problems like being large for gestational age (which may lead to delivery complications), low blood sugar, and jaundice. Gestational diabetes is a treatable condition and women who have adequate control of glucose levels can effectively decrease these risks. Children born to mothers with Gestational Diabetes are prone to developing childhood obesity, with type 2 diabetes later in life. Most patients respond well to just lifestyle management are treated only with diet modification and moderate exercise but some take anti-diabetic drugs, including insulin. Pathophysiology The exact mechanisms underlying gestational diabetes are not well understood. The hallmark of GDM is increased insulin resistance. Pregnancy hormones, especially Progesterone and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor. The interference probably occurs both at the receptor as well as the post receptor level of cell signaling pathway. Since insulin promotes passage of glucose into most cells, insulin resistance prevents glucose from entering the cells properly. As a result, high levels of 21 Vol. 8, Issue 3 & 4, April - September 2009 glucose develop in the blood. More than normal amounts of insulin are needed to overcome this resistance. In a normal uncomplicated pregnancy, bout 1.5-2.5 times more insulin is produced as compared to normal non-pregnant condition. Insulin resistance is a normal phenomenon that develops in the second trimester of pregnancy, and progresses thereafter to levels seen in nonpregnant patients with type 2 diabetes. It is thought to provide sufficient glucose supply to the growing fetus. Women with GDM have an insulin resistance they cannot compensate with increased production in the -cells of the pancreas. Placental hormones, and to a lesser extent increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol and progesterone are the main culprits, but human placental lactogen, prolactin and estradiol also contribute. Occurenec of GDM means that the patient has inherent Insulin resistance and beta cell defect, the two components causing Type2 Diabetes Mellitus. Risk factors C ommon risk factors for developing gestational diabetes are as follows - 1. Previous diagnosis of gestational diabetes or pre-diabetes, impaired glucose tolerance, or impaired fasting glucose 2. Family history revealing a first degree relative with type 2 diabetes 3. Maternal age - a womans risk for GDM increases as she gets older (especially for women over 35 years of age) 4. Ethnic background (those with higher risk include African-Americans, AfroCaribbeans, Native Americans, Hispanics, Pacific Islanders, and people originating from the Indian subcontinent) 5. Being overweight, obese or severely obese increases the risk by a factor 2.1, 3.6 and 8.6, respectively. 6. Previous pregnancy which resulted in a child with a high birth weight (>90th centile, or >4000 g (8 lbs 12.8 oz)) 7. Previous poor obstetric history

Vipin Mishra Senior Consultant and Head Deptt. of Endocrinology

Pushpanjali Crosslay Hospital Ghaziabad (NCR)

I n addition to this, stastics shows a double risk of GDM in smokers. Polycystic ovarian syndrome is also a risk factor. Some studies have looked at more controversial potential risk factors, such as short stature. About 40-60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women. Typically women with gestational diabetes exhibit no symptoms (another reason for universal screening), but some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, fungal infections and blurred vision. Screening and diagnosis A number of screening and diagnostic tests have been used to look for high levels of glucose in plasma or serum in defined situations. One approach is to perform diagnostic test only on those subjects who show positive on screening test. Alternatively, a more definite diagnostic test can be used directly at the first antenatal visit in high-risk patients (for example in those with polycystic ovarian syndrome or obesity). N on-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with oral glucose load. A blood glucose levels is studied either at fasting, 2 hours after a meal, or simply at any random time. In contrast challenge tests involve drinking a glucose solution and measuring glucose concentration thereafter in the blood. In the United States, most obstetricians prefer universal screening with a screening glucose tolerance test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. Non-challenge blood glucose tests W hen a plasma glucose level is found to be higher than 126 mg/ dl (7.0 mmol/l) after fasting, or over 200 mg/dl (11.1 mmol/l) on any occasion, and if this is confirmed on a subsequent day, the diagnosis of GDM is made, and no further testing is required. These tests are typically performed at the first antenatal visit. They are patient-friendly and inexpensive, but have a lower sensitivity of diagnosis. Screening glucose challenge test T he screening glucose challenge test is typically performed between 2428 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). It involves drinking a solution containing 50 grams of glucose, and measuring blood glucose levels 1 hour later. If the cut-off point is set at 140 mg/ dl (7.8 mmol/l), 80% of women with GDM will be detected. If this threshold for further testing is lowered to 130 mg/dl, 90% of GDM cases will be detected, but there will also be more women who will be subjected to a consequent OGTT unnecessarily. Oral glucose tolerance test (OGTT) O GTT should ideally be performed in the morning after an overnight fast of between 8 and 14 hours. During the three previous days the subject must have an unrestricted diet 22 Vol. 8, Issue 3 & 4, April - September 2009

(containing at least 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated during the test and should not smoke throughout the test. The test involves drinking a solution containing 100 gms of glucose, and drawing blood to measure glucose levels at the start and on hourly intervals thereafter. Following are the values which the American Diabetes Association considers to be abnormal during the 100 g of glucose OGTT: Fasting blood glucose level 95 mg/dl 1 hour blood glucose level 180 mg/dl 2 hour blood glucose level 155 mg/dl 3 hour blood glucose level 140 mg/dl Complications G DM poses some risk to mother and child. This risk is largely related to high blood glucose levels and its consequences. The risk increases with higher blood glucose levels. Treatment resulting in better control of these levels can reduce many of the risks of GDM considerably. The two main risks GDM causes to the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic) and small for gestational age. Macrosomia in turn increases the risk of forceps deliveries or problems during vaginal delivery. Macrosomia may affect 12% of normal women compared to 20% of patients with GDM. Neonates are also at an increased risk of hypoglycemia, jaundice, polycythemia and hypocalcemia and hypomagnesemia. GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis. U nlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first trimester. There are conflicting reports on whether GDM can cause congenital malformations. It is also unclear at the moment whether women with GDM have a higher risk of preeclampsia. The best policy is however to treat GDM as and when it is detected to maintain sugar levels in the ideal range. Prognosis G estational diabetes generally resolves after delivery of the baby. Based on different studies, the chances of developing GDM in a subsequent pregnancy are between 30 and 80%, depending on ethnic background. A second pregnancy within 1 year of the previous pregnancy has a relatively higher chance of recurrence. Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. The risk is highest in women who needed insulin treatment, had antibodies associated with diabetes (such as antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2), women with more than two previous pregnancies,

and women who were obese (in order of importance). Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years. Depending on the population studied, the diagnostic criteria and the length of follow-up, the risk can vary enormously. The risk appears to be highest in the first 5 years, reaching a plateau thereafter. Treatment T he goal of treatment is to reduce the risks of GDM for mother and child. Scientific evidence is beginning to suggest that controlling glucose levels can result in significantly less serious fetal complications (such as macrosomia) and increased maternal quality of life. Unfortunately, treatment of GDM is also accompanied by more infants admitted to neonatal wards and more inductions of labour, with no proven decrease in cesarean section rates or perinatal mortality. These findings are still recent and controversial. C ounseling before pregnancy and multidisciplinary management are important for good pregnancy outcomes. Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy. A ny diet needs to provide sufficient calories for pregnancy, with the exclusion of simple carbohydrates. The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources (low glycaemic index foods). Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more. Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM. S elf monitoring can be accomplished using a glucometer. Compliance with these glucometer systems can be low. Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows: F asting capillary blood glucose levels <100 mg% 1 hour postprandial capillary blood glucose levels <145 mg% 2 hour postprandial blood glucose levels <120 mg% R egular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period. If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might become necessary. Insulin is the best medicine to be used when lifestyle modification in itself is insufficient to control glycemia. When required Insulin can usually be given in the form of two doses of premixed 30/70 Insulin, one dose before breakfast and the other before dinner. Starting dose of Insulin should be around 0.1 to 23 Vol. 8, Issue 3 & 4, April - September 2009

0.2 units per kg body weight. So, for a fifty kg lady the starting Insulin dose may be 510 units per day. It should then be adjusted according to the blood glucose values done 3-5 times in a day by glucometer. Two thirds of the total daily dose should be given in the morning before breakfast and one third in the evening before dinner. If fluctuations in sugar values are dramatic or the overall control is bad, patient may be switched over to MSI regimen i.e. three doses of regular insulin, one before each meal plus an intermediate acting insulin before dinner. Unless there is hypoglycemia or ketonuria, Insulin doses should be altered at five to seven days interval to achieve ideal fasting and 2 hour post meal sugar values. Because of lack of safety reports, Insulin analogues are not recommended in pregnancy. Care must be exercised to avoid low blood sugar levels (hypoglycemia) due to excessive insulin injections. T here is some evidence that certain oral glycemic agents might be safe in pregnancy, or at least, are significantly less dangerous to the developing fetus than poorly controlled diabetes. However, few studies have been performed as of this time and this is not a generally accepted treatment. These agents may be used in research settings, or if the patient needs intervention but refuses insulin therapy, and is aware of the risks. Glibenclamide, a second generation sulfonylurea, has been shown to be an effective alternative to insulin therapy. Metformin has also been shown to be effective and safe during pregnancy. Treatment of polycystic ovarian syndrome with Metformin during pregnancy has been noted to decrease GDM levels. A recent randomized controlled trial of metformin versus insulin showed that women preferred metformin tablets to insulin injections, and that metformin is safe and equally effective as insulin. Severe neonatal hypoglycemia was less common in insulin-treated women, but preterm delivery was more common. Almost half of patients did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight. There remains a possibility of long-term complications from metformin therapy, although follow-up at the age of 18 months of children born to women with polycystic ovarian syndrome and treated with metformin revealed no developmental abnormalities. If diet, exercise, and oral medication are inadequate to control glucose levels, insulin therapy may become necessary. T he development of macrosomia can be evaluated during pregnancy by using sonography. Women who use insulin, with a history of stillbirth, or with hypertension are managed like women with overt diabetes. Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child. A repeat OGTT should be carried out 24 months after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised. Women who had GDM during pregnancy must be serious about managing their lifestyle and controlling weight throughout life.

Thyroid Diseases in Pregnancy

Vipin Mishra
Normal changes in thyroid function associated with Pregnancy P regnancy is normally associated with profound changes in almost every system of the body. Endocrine system is one of the most severely affected systems during pregnancy. There are lot of changes that occur in the functions of the thyroid gland during normal pregnancy. For this reason laboratory tests of thyroid function must be interpreted with great caution during pregnancy. Changes in thyroid function occur basically because of two factors. Firstly, because of human chorionic gonadotropin (HCG), a pregnancy related hormone secreted from the placenta, and secondly, due to high levels of estrogen that occur during pregnancy. HCG is a natural thyroid gland stimulant and causes enlargement of the size of thyroid gland and enhancement of hormone synthesis. As a result of this, TSH levels may reduce slightly during the first trimester. The levels of FT3 and FT4 however remain normal. In the second and third trimesters TSH levels also remain in the normal range (Table 1). High level of estrogen is a hallmark of normal pregnancy. Table 1: Values of thyroid hormone indices during normal pregnancy
1st Trimester TSH Free T4 Free T3 Total T4 Total T3 Normal or decreased Normal Normal High High 2nd Trimester Normal Normal Normal High High 3rd Trimester Normal Normal Normal High High

E xcept during the first trimester, the growing foetus is not totally dependent on the mothers thyroid hormones. The foetus starts making its own thyroid hormones by the end of the first trimester. For this reason mild untreated maternal hypothyroidism has only minimal or negligible effects on the brain and physical development of the foetus. Maternal thyroid hormones do cross the placenta and so does the maternal iodine. The foetus is dependent on the mother for iodine supply. Maternal intake of 200 micrograms of iodine per day is sufficient to provide for all the foetal needs. Excessive maternal iodine intake may lead to development of goiter in the foetus because of the Wolf Chaikoff Effect (Iodide Effect). Sometimes this goiter may be big enough to cause birth asphyxia to the baby. Hypothyroidism and Pregnancy H ypothyroidism during pregnancy is a common occurrence. The most common situation is development of pregnancy in a diagnosed case of hypothyroidism who is on optimum or even sub-optimum replacement therapy with Levothyroxine. Alternatively it can start for the first time during pregnancy. The most common cause of hypothyroidism during pregnancy or even otherwise, is Hashimotos thyroiditis. After introduction of iodized salt in India, iodine deficiency has almost been totally eradicated. Risks of hypothyroidism to the mother U ntreated, or inadequately treated, hypothyroidism can cause several maternal problems including anemia, myopathy (muscle pain, weakness), congestive heart failure, preeclampsia, placental abnormalities, low birth weight infants, and postpartum hemorrhage. Occurrence of these complications is related to the severity of hypothyroidism. Most women with mild hypothyroidism may have minimal or no symptoms. In mild hypothyroidism, symptoms due to thyroid disease may be mistaken for those caused by pregnancy itself. Risks of maternal hypothyroidism to the baby U ntreated hypothyroid patients often develop infertility. As and when pregnancy develops, untreated hypothyroidism can lead to miscarriage, threatened abortion, and small size baby (Intra Uterine Growth Retardation). All these complications can be totally avoided by proper treatment with replacement doses of Levothyroxine.

As an estrogen effect, amount of thyroid hormone binding proteins in the serum get increased and likewise the total thyroid hormone levels in the blood also get increased. About 98% of the thyroid hormones in the blood are bound to these proteins. Levels of Free T3 and Free T4, the active forms of the hormones, however remain unaffected. Observation of normal TSH, normal FT4 and normal FT3 rule out any inherent thyroid gland disease.
Vipin Mishra Senior Consultant and Head Deptt. of Endocrinology

Pushpanjali Crosslay Hospital Ghaziabad (NCR)

T hyroid gland size increases during pregnancy. This increase in size is much more prominent in the presence of nutritional iodine deficiency. In the iodine sufficient areas the increase in thyroid gland size is not more than 10 15% and is not clinically discernible. 25

Vol. 8, Issue 3 & 4, April - September 2009

T hyroid hormone plays a crucial role in the brain development of the baby. Babies born to severe untreated hypothyroid mothers have been shown to have defects in brain development. Such defects include lower IQ, cognitive dysfunction, neurological defects or developmental problems. This is especially true for maternal hypothyroidism due to iodine deficiency, as iodine is required as a raw material for thyroid hormone synthesis in the foetus as well. Foetal source of iodine is only maternal iodine ingestion. Even mild untreated maternal hypothyroidism can effect foetal brain development. Screening I n many developed countries neonatal screening for congenital hypothyroidism has been made mandatory. This policy has been successful in avoidance of crippling cretinism in the childhood. Intra-uterine development of the foetus including its brain development is not much deranged even in the presence of congenital hypothyroidism. This is because of the effect of maternal thyroid hormones on foetal development. After birth however, if the situation is not quickly diagnosed, it can cause severe brain and developmental defects. Fast recognition and and treatment of congenital hypothyroidism ensures an almost normal brain and physical development of the baby. T here is however no clear consensus on screening pregnant women for maternal hypothyroidism. Most endocrinologists now prefer a preconception or just after conception thyroid function test. This is especially important for those women who have a goiter, positive family history of thyroid disease or history of treatment for thyrotoxicosis in the past. Once hypothyroidism has been detected and the patient has been put on replacement therapy, or in known hypothyroid women developing pregnancy, FT4 and TSH should be tested every 4-6 weeks throughout pregnancy. This is important because thyroid hormone requirement changes significantly during pregnancy. Accordingly the dose of Levothyroxine should be continuously titrated and adjusted to the changing requirements. Treatment T reatment of hypothyroidism in a pregnant woman is not different from a non-pregnant woman or from a man. The treatment is adequate replacement of thyroid hormone in the form of synthetic Levothyroxine. The dose of Levothyroxine generally increases upto 50 75% during pregnancy. Maximum increases occur in the third trimester of pregnancy. TSH and FT4 estimation should be done at 4-6 weeks interval. Total T3 and T4 are not of any use in pregnancy. Dose of LT4 should be so titrated to keep TSH at around 0.5 to 1.0 IU and FT4 at around the upper end of the normal range. LT4 dose should be ingested by the patient in an empty stomach as the first thing in the morning. After the delivery, doses of LT4 tend to decrease and go back to the pre-pregnancy levels but the time taken in this is highly variable. The dose of LT4 should not be mechanically reduced immediately after delivery. TSH and FT4 estimation at 6-8 week interval should be continued for 6-12 months even after delivery and the LT4 doses should be reduced only when necessitated by the reports. It must be remembered that 6-12 months post partum period is a time of enhanced thyroid autoimmunity. Many a times the mild problems during pregnancy worsen in this period. This is the importance of continued monitoring of thyroid hormones in the post partum period. Many women are given iron preparations during pregnancy. Care should be 26 Vol. 8, Issue 3 & 4, April - September 2009

exercised in separating Levothyroxine from iron by at least four hours. Iron hampers the absorption of Levothyroxine. Hyperthyroidism and Pregnancy P regnancy may sometimes be complicated by hyperthyroidism (Thyrotoxicosis). Pregnancy may develop to a pre-existing hyperthyroid patient taking anti-thyroid treatment. Alternatively and less commonly hyperthyroidism may develop for the first time during pregnancy. Around 80 90% of such cases of hyperthyroidism with pregnancy have Graves Disease. Other less common causes of thyrotoxicosis during pregnancy include Hyperemesis Gravidarum and toxic thyroid nodule. Hyperemesis Gravidarum is associated with high levels of HCG which is a thyroid stimulant. Thyrotoxicosis presents with classical symptoms of heat intolerance, weakness, anxiety and eye signs. Clinical suspicion is not difficult and diagnosis is clinched by hormonal levels. FT4 and FT3 are increased and TSH is depressed. Radioactive thyroid scan is contraindicated during pregnancy. Radioactive iodine may get concentrated in the foetal thyroid gland causing congenital hypothyroidism. H yperthyroidism can affect the mother in many ways. It can cause infertility and miscarriage if and when pregnancy develops. Alternatively it can also lead to early labour and sometimes a very serious condition of pre-eclampsia. Inadequately treated Graves disease can generate into a very serious and life threatening condition of Thyroid Storm. Graves Disease tends to exacerbate in the first trimester of pregnancy and in the post partum period. It tends to remit or reduce in severity in the third trimester of pregnancy. Effects of Graves Disease on the baby Maternal Graves Disease can affect the baby in three possible ways 1. Uncontrolled maternal hyperthyroidism: Uncontrolled maternal hyperthyroidism can give rise to fetal tachycardia, small for gestational age babies, prematurity, stillbirths and possibly congenital malformations. This is an important reason to treat hyperthyroidism in the mother. It is also possible that it affects the mental functions, personality and attitude of the baby as well. 2. Extremely igh evels f hyroid timulating mmunogloblulins h l ot s i (TSI): Graves disease is an autoimmune disorder caused by the production of antibodies that stimulate thyroid gland referred to as thyroid stimulating immunoglobulins (TSI). These antibodies do cross the placenta and can interact with the babys thyroid. Although uncommon (2-5% of cases of Graves disease in pregnancy), high levels of maternal TSIs, have been known to cause fetal or neonatal hyperthyroidism. Fortunately, this typically occurs only when the mothers TSI levels are very high (many times above normal). It is however a self limiting condition and passes off in a short time (few weeks) after birth. 3. In the mother with Graves disease consuming antithyroid drug therapy, fetal hyperthyroidism due to the mothers TSI is rare, since the antithyroid drugs also cross the placenta. Of potentially more concern to the baby is the mother with prior treatment for Graves disease (for example radioactive iodine or surgery) who no longer requires antithyroid drugs. In this situation the foetus may get affected either by the residual TSI in mothers blood or the residual radioactivity.

Anti-thyroid drug therapy (ATD) C arbimazole, Methimazole and Propylthiouracil (PTU) are the ATDs available in India for the treatment of hyperthyroidism. All these drugs cross the placenta and can potentially impair the babys thyroid function and cause fetal goiter. Conventionally, PTU has been the drug of choice for treatment of maternal hyperthyroidism, possibly because transplacental passage may be less than with the other drugs. Many studies have shown that all the three drugs are safe to use during pregnancy. It is recommended that the lowest possible dose of ATD be used to control maternal hyperthyroidism to minimize the development of hypothyroidism in the baby or neonate. Neither drug appears to increase the general risk of birth defects. Overall, the benefits to the baby of treating a mother with hyperthyroidism during pregnancy outweigh the risks if therapy is carefully monitored. Treatment strategies M ild hyperthyroidism (slightly elevated thyroid hormone levels, minimal symptoms) can be monitored closely without therapy as long as both the mother and the baby are doing well. When hyperthyroidism is severe enough to require therapy, antithyroid medications are the treatment of choice, with PTU being the conventional drug of choice. The goal of therapy is to keep the mothers free T4 and free T3 levels in the high-normal range on the lowest dose of antithyroid medication. Targeting this range of free hormone levels will minimize the risk to the baby of developing hypothyroidism or goiter. Maternal hypothyroidism must always be avoided. Therapy should be closely monitored during pregnancy. This is ideally done by following thyroid function tests (TSH and free thyroid hormone levels) monthly. I f for some reason the anti thyroid drugs cannot be used (i.e.

those who develop an allergic reaction to the drugs), and whose disease is reasonably severe, surgery is an acceptable alternative. Surgical removal of the thyroid gland is only very rarely recommended in the pregnant woman due to the risks of both surgery and anesthesia to the mother and the baby. R adioiodine is contraindicated to treat hyperthyroidism during pregnancy since it readily crosses the placenta and is taken up by the babys thyroid gland. This can cause destruction of the gland and result in permanent hypothyroidism. B eta-blockers can be used during pregnancy to help treat significant palpitations and tremor due to hyperthyroidism. They should be used sparingly due to reports of impaired fetal growth associated with long-term use of these medications. Typically, these drugs are only required until the hyperthyroidism is controlled with anti-thyroid medications and they should be used in the minimum possible doses. Natural course of Graves Disease after delivery T here is a general tendency of Graves Disease to worsen in the postpartum period, usually in the first 3 months after delivery. Higher doses of anti-thyroid medications are frequently required during this time. As usual, close monitoring of thyroid function tests is necessary. T he mother with Graves disease, who is being treated with anti-thyroid drugs, can breastfeed her infant. PTU is the drug of choice because it is highly protein bound. Consequently, lower amounts of PTU cross into breast milk compared to other anti thyroid drugs. It is important to note that the new born will require periodic assessment of his/her thyroid function to ensure maintenance of normal thyroid status.

27 Vol. 8, Issue 3 & 4, April - September 2009

Maturing of Medical Aesthetics Restylane - Tissue

Dinesh Bhargava
Restylane is a natural building block haluronic acid molecule, as the bases of a larger molecule which provides for a long term survival of the material in the tissue. Since it is a natural body constituent, the concerns about allergies do not exist. With the introduction of Restylane in the market, the use of Hyaluronic based filler has grown with leaps and bounds, filling not just the tissue deficit but also a human need in our society. The large molecules of Hyaluronic acid are metabolized by the tissue enzymes hyaluronidase over a period of several months and lose all the substance in about 9-12 months. This process is very gradual and the patient, who has enjoyed the benefits of the treatment will often come back for a touch up in about 6 months time. The treatment at comeback requires less than the original amount of injectable to refreshen looks. Restylane helps erase the early signs of aging with a simple injection that leads to immediate correction and therefore very dramatic in its appeal. This is achieved by correcting: - nasolabial folds, - depressed scars, - contour deformities, - thinning lips, and by - creating a prominent lip line for a voluptuous appearance. The procedure is simple but does require a degree of appropriate planning and execution to achieve good results. If you are concerned about the facial lines, find out if this procedure is for you and how you can benefit from it. Call us at A New Image, Center for Aesthetic Surgery and Medicine 0 120 4173181 Let us help you create A New Image for you

Dinesh Bhargava A New Image Center for Aesthetic Surgery & Medicine Pushpanjali Crosslay Hospital Ghaziabad (NCR)

28 Vol. 8, Issue 3 & 4, April - September 2009

Cardiomyopathy in Pregnancy
D Singhania and Meenakshi Aggarwal

Introductions One of the important causes of mortality in pregnancy is dilated cardiomyopathy associated with pregnancy. Traditionally, dilated cardiomyopathy which evolves between the last month of pregnancy and first 5 months post partum and presents as heart failure is known as Peripartum cardiomyopathy (PPCM)1. Elkayam et al2 described pregnancy associated cardiomyopathy in to early and late. Early Cardiomyopathy is term used by them for cardiomyopathy occurring earlier than the traditional criteria, ie, earlier then third trimester and late they used to describe traditional PPCM. PPCM is a very high risk condition and is recognized as a complication of pregnancy since 18th century3. Ritchie4 described heart failure in late pregnancy. Clinical and pathogenic features of dilated and nonischemic cardiomyopathy were described in 1937 by Gauley et al5. Another form of cardiomyopathy is hypertrophic cardiomyopathy. This is again of two varieties obstructive or nonobstructive. In this form of cardiomyopathy myocardium gets hypertrophied and may obstruct blood flow in systole. The pregnancy and delivery are usually accomplished without difficulty in this provided one keeps a check on factors which can increase the obstruction for example hypotension, blood loss, cardiac stimulation, fatigue and violent expulsive effort. This is usually managed with beta blockers and diuretics. In view of the high risk nature of PPCM this article focuses only on dilated cardiomyopathy in pregnancy (PPCM). Diagnostic criteria for peripartum cardiomyopathy (Demakis, et al 1971)1 1. Heart failure symptoms presenting in last month of pregnancy or within 5 months of delivery. 2. No other etiology for the heart failure is established. 3. Evidence of left ventricular dysfunction (ie, left ventricular ejection fraction <45%) or combination of Echo (M Mode) fractional shortening <30% and end diastolic dimension >2.7cm/m2. Incidence PPCM is more common in African population but is known to occur in all geographical areas and incidence may vary up to 1 in 3000 to 15000 pregnancies6,7. 35 Vol. 8, Issue 3 & 4, April - September 2009

Etiology of PPCM is unknown; currently more and more evidences suggest that PPCM is actually a type of myocarditis arising from an infectious, autoimmune, or idiopathic process. Etiology Exact etiology of PPCM is unknown. Initially it was thought to be a variant of dilated Cardiomyopathy but now it is considered as a separate entity because of its timing and prognosis. It presents in the last trimester usually and complete recovery is seen in up to 30% patients whereas in idiopathic dilated cardiomyopathy recovery is rare. Various hypotheses have been put forward to explain the etiology and pathogenesis of PPCM. Myocarditis as a cause of PPCM was first suggested by Gouley et al5. Melvin et al8 found myocarditis on endomyocardial biopsy in three patients of PPCM. They also noted that prednisone and azathioprin treatment improved the patients clinically which also corresponded with improvement in repeat biopsy. Various viral genomes (parvovirus B19, human herpes virus 6, EpsteinBarr virus and human cytomegalovirus) have also been implicated, but still further studies are needed to establish relationship between the presence of viral genomic material to prognosis and treatment. Other commonly accepted hypothesis is decreased immunity during pregnancy. Some authors have suggested decreased ability of a pregnant mother to clear antigens that enter the maternal circulation because of decreased humoral immunity. Abnormal response to hemodynamic stress of pregnancy, apoptosis9,10, cytokine-mediated inflammation11,12, malnutrition particularly selenium deficiency13, excessive salt consumption, excessive prolactin production14, increased adrenergic tone and myocardial ischemia are some other factors which have been hypothesized to cause PPCM. Risk Factors In the absence of a clear-cut etiology various risk factors have been identified which are associated with development of PPCM e.g., advance maternal age, high parity, high gravidity, twin pregnancy, use of tocolytic therapy, African descent, non-Caucasian ethnicity, poverty. Presenting features PPCM presents as features of heart failure,

D Singhania Senior Consultant Cardiologist Puahpanjali Crosslay Hospital Ghaziabad (NCR) Meenakshi Aggarwal Senior resident, Cardiology Pushpanjali Crosslay Hospital Ghaziabad (NCR)

thromboembolism and cardiac arrhythmias Symptoms Dyspnea Orthopnea Paroxysmal nocturnal dyspnea Cough Chest pain Anorexia Fatigue Pedal edema Signs General 1 Jugular venous distention 2. Tachycardia 3. Tachypnea 4. Hepatomegaly 5. Hepatojugular reflux 6. Ascites 7. Peripheral edema 8. Mental status changes 9. Thromboemboli Cardiac 10. Gallop rhythm 11. Mitral regurgitation murmur 12. Loud P2 13. Rales Importance of 2D Echo Doppler in diagnosis ECG is usually non specific; it may show sinus tachycardia, frequent ectopics, atrial arrhythmias, inverted T waves, left ventricular hypertrophy and nonspecific ST-T changes. As these are nonspecific and X-rays are avoided in pregnancy and also many of the symptoms and signs of heart failure are even otherwise present in pregnancy because of volume overload, so 2D Echo Doppler becomes important modality for diagnosing the situation. 2D echo reveals dilated cardiac chambers, LV dysfunction; it also rules out other etiologies like valvular heart disease. Treatment PPCM is managed in the same way as heart failure. But few precautions need to be taken. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy as they can cause birth defects which are otherwise important medications in treating heart failure. They can lead to fetal hypotension, oligohydroamnios, anemia and renal tubular dysplasia. However they can be used safely in post-partum period. In pregnancy main stay of treatment is non-pharmacological management (low sodium diet <4g/d, fluid restriction (<2l/d), moderate daily exercise (i.e., walking) and pharmacological treatment with loop diuretics, digoxin and Beta-blockers. Hydralazine and Nitrates may also be used safely during pregnancy for reducing after load. Newer treatment Certain treatment strategies have been found to be effective in some studies but are still lacking in sufficient evidence to accept 36 Vol. 8, Issue 3 & 4, April - September 2009

them as universal therapies. Pentoxifylline14 Intravenous immunoglobin15 Immunosuppressive therapy16,17 Bromocriptine18 Calcium channel antagonists19 Statins20 Therapeutic apheresis21 Cardiomyoplasty22 Anticoagulant treatment Heparin and low molecular weight heparin can be used for prevention and treatment of thromboembolism during pregnancy. Oral anticoagulants are known to have risk of embryopathies, so are avoided. Cardiac transplant can be offered in advanced cases in countries where cardiac transplant is a feasible option. Duration of treatment Heart failure treatment should be continued for minimum of 6-12 months. It can be stopped in patients after these periods, who have recovered completely (Normalized left ventricular function). Natural course PPCM has a relatively better prognosis than dilated cardiomyopathy with 94% survival rate at 5 years. Poor prognostic factors are: a. Irreversible congestive symptoms even after 6 months of delivery. b. Elevated cardiac troponin-T within 2 weeks of onset c. QRS duration > 120 ms d. Initial LV ejection fraction <30% e. Initial LV end - systolic dimension >5.5 cm f. LV thrombus Even after complete recovery of LV function subsequent pregnancy carries a risk of relapse, very high morbidity and mortality. Subsequent pregnancies should be planned as per the recommendations of Dorbala et al23. LV Function fully recovered LV Function practically recovered LVF function not recovered

Subsequent pregnancy is not contraindicated

Perform dobutamine stress echocardiography

The risk is high and subsequent pregnancy is not recommended.

The patient should be told that, although the risk is low, it is not absent.

If the left ventricular inotropic response to dobutamine is normal, then patients can be counseled as above

If the left ventricular inotropic response to dobutamine is abnormal, than the risk is moderate and pregnancy is not recommended

Conclusion Pregnancy associated dilated cardiomyopathies occurring between last month of pregnancy till 5 months post delivery are known as peripartum Cardiomyopathy. When they present early (before the last month of pregnancy) they are referred as pregnancy associated cardiomyopathy. Etiology of PPCM is still uncertain. In future delineation of molecular and biochemical pathways will guide us in better management of the disease.

References 1. Demakis JG, Rahimtoola SH, Sutton GC, Meadows WR, Szanto PB, Tobin JR, Gunnar RM. Natural course of peripartum cardiomyopathy. Circulation. 1971;44:10531061 Elkayam U, Akhter MW, Singh HS, et al. Peripartum cardiomyopathy: a review. Am J Obstet Gynaecol 1984;148:805-18. Hibbard JU, Lindheimer M, Lang RM. A modified definition for peripartum cardiomyopathy and prognosis based on echocardiography. Obstet Gynecol 1999; 94:311316. Ritchie C. Clinical contribution to the pathology, diagnosis and treatment of certain chronic diseases in the heart. Edinburgh Med Surg J 1849;2:333. Gouley B, McMillan T, Bellet S. Idiopathic myocardial degeneration associated with pregnancy and especially the puerperium. Am J Med Sci. 1937; 19: 185-99. Cunningham F, Pritchard J, Hankins G, et al. Peripartum heart failure: idiopathic cardiomyopathy or compounding cardiovascular events?. Obstet Gynecol. 1986; 67: 157-67. Seftel H, Susser M. Maternity and myocardial failure in African women. Br Heart J. 1961; 23: 43-52. Melvin KR, Richardson PJ, Olsen EG, Daly K, Jackson G. Peripartum cardiomyopathy due to myocarditis. N Engl J Med. 1982;307:731734. Hayakawa Y, Chandra M, Miao W, Shirani J, Brown JH, Dorn II GW, et al. Inhibition of cardiac myocyte apoptosis improves cardiac function and abolishes mortality in the peripartum cardiomyopathy of G{alpha}q transgenic mice. Circulation. 2003;108:30363041. Sliwa K, Skudicky D, Bergemann A, Candy G, Puren A, Sareli P. Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1. J Am Coll Cardiol. 2000;35(3):701705. Bozkurt B, Kribbs SB, Clubb FJ, Michael LH, Didenko VV, Hornsby PJ, et al. Pathophysiologically relevant concentrations of tumor necrosis factor-{alpha} promote progressive left ventricular dysfunction and remodeling in rats. Circulation. 1998;97:13821391. Fett JD, Dowell DL, Carraway RD, Sundstrom JB, Ansari AA. One hundred cases of peripartum cardiomyopathy and counting: what is going on?. Int J Cardiol. 2004;97:571573. Fillmore SJ, Parry EO. The evolution of peripartal heart failure in Zaria. Circulation. 1977;56:10581061. Hilfiker-Kleiner D, Kaminski K, Podewski E, Bonda T, Schaefer A, Sliwa K, et al. A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell. 2007;128:589600. Sliwa K, Skudicky D, Candy G, Bergemann A, Hopley M, Sareli P The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum 37 Vol. 8, Issue 3 & 4, April - September 2009

2.

3.

4.

5.

6.

7. 8.

cardiomyopathy. Eur J Heart Fail 2002; 4:305309. 16. Bozkurt B, Villaneuva FS, Holubkov R, et al. Intravenous immune globulin in the therapy of peripartum cardiomyopathy. J Am Coll Cardiol 1999; 34:177180. 17. Kishimoto C, Shioji K, Kinoshita M, et al. Treatment of acute inflammatory cardiomyopathy with intravenous immunoglobulin ameliorates left ventricular function associated with suppression of inflammatory cytokines and decreased oxidative stress. Int J Cardiol 2003; 91:173178. 18. Zimmermann O, Kochs M, Zwaka TP, et al. Myocardial biopsy based classification and treatment in patients with dilated cardiomyopathy. Int J Cardiol 2005; 104:92100. 19. Fett JD. Inflammation and virus in dilated cardiomyopathy as indicated by endomyocardial biopsy. Int J Cardiol 2006; 112:125126. 20. Hilfiker-Kleiner D, Meyer GP, Schieffer E, et al. Recovery from postpartum cardiomyopathy in 2 patients by blocking prolactin release with bromocriptine. J Am Coll Cardiol 2007; 50:23542355. 21. Yuan Z, Kishimoto C, Shioji K. Beneficial effects of low-dose benidipine in acute autoimmune myocarditis: suppressive effects on inflammatory cytokines and inducible nitric oxide synthase. Circ J 2003; 67:545 550. 22. Li WM, Liu W, Gao C, Zhou BG. Immunoregulatory effects of atorvastatin on experimental autoimmune myocarditis in Lewis rats. Immunol Cell Biol 2006; 84:274280. 23. Dorbala S, Brozena S, Zeb S, et al. Risk stratification of women with peripartum cardiomyopathy at initial presentation: a dobutamine stress echocardiography study. J Am Soc Echocardiogr 2005; 18:45-48

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Acute Renal Failure in Pregnancy

Neeru P Aggarwal and LK Jha

Acute renal failure in pregnancy is associated with significant fetal and maternal mortality. The kidneys undergo marked hemodynamic, renal tubular and endocrine changes during pregnancy. An understanding of anatomical and physiological renal changes in normal pregnancy is essential to understand the ARF in pregnancy. Renal Changes in Normal Pregnancy Alteration Increased renal Size

4. GFR increases by 50% above baseline due to increased renal plasma flow. (45% by 9 weeks and 70% in mid pregnancy). 5. Plasma osmolality reduces in the 1st t trimester and then remains constant during pregnancy. 6. Sodium reabsorption increases (increased GFR Increases filtered sodium load) 7. A relative respiratory alkalosis develops (direct stimulus of respiratory centre).

Manifestation Renal Length 1 cm greater on radiographs Resembles hydronephrosis on ultrasound or IVP (more marked on right)

Clinical Relevance Postpartum decrease in size should not be mistaken for parenchymal loss Not to be mistaken for obstruction uropathy; retained urine leads to collection errors; upper urinary tract infections are more virulent; may be responsible for over-distention syndrome; elective pyelography should be deferred to >12 wk postpartum Serum creatinine and blood urea nitrogen values decrease; >0.8 mg/dL (>72mol/L) creatinine already suspect; protein, amino acid and glucose excretion all increase Serum bicarbonate and Pco2 are 4-5mmol/L and 10 mmHg lower, respectively; a Pco2 of 40mmHg already represents substantial CO2 retention Serum osmolality decrease 10 mOsmol/L (serum Na 5 mEq/ L); increased metabolism of AVP may cause transient diabetes insipid us in pregnancy

Dilation of pelves, calices, and ureters

Increased renal Hemodynamics

Glomerular filtration rate and renal plasma flow increase 35%50%

Changes in acid-base Metabolism

Renal bicarbonate threshold decreases; progesterone stimulates respiratory centre

Renal water handling

Osmoregulation altered (osmotic thresholds for AVP release and thirst decrease; hormonal disposal rates increase)

Renal Physiology in Normal Pregnancy

Neeru P Aggarwal Senior Consultant Nephrologist Deptt. of Nephrology Pushpanjali Crosslay Hospital Ghaziabad (NCR) LK Jha Consultant Nephrologist Deptt. of Nephrology Pushpanjali Crosslay Hospital Ghaziabad (NCR)

1. Early decreases in peripheral vascular resistance lead to lower BP in early pregnancy which When rises gradually to baseline at term 2. Cardiac output increases( 50% above no pregnant baseline) 3. Red cell mass increase (proportionately less then increases in plasma volume, therefore a mild anaemia results). 39

8. Glycosuria develops the maximum tabular transport capacity for glucose reabsorption. 9. Renal size increase with advancing gestation due to dilation of renal collecting system, especially on right side and fluid overload Epidemiology of acute kidney injury Over the last 20 years the incidence of AKI has reduced in developed but less so in developing countries. AKI requiring dialysis now occurs in 1 in 20,000 pregnancies in Europe and North America.

Vol. 8, Issue 3 & 4, April - September 2009

In developing countries, pregnancy continues to cause 20% of total AKI and mortality is as high as 50%. Clinical Feature Causes: They depend on the cause of AKI 1. Pre renal AKI Persistent vomiting, diarrhoea or diuretic therapy. Pre eclampsia Ant partum and post partum haemorrhage 2. Intrinsic renal AKI Acute tubular necrosis Bilateral cortical necrosis Microangiopathy. Acute interstitial nephritis De novo glomerulo nephritis Septicaemia Amniotic fluid embolism 3. Post Renal AKI Uncommon Renal calculi Obstruction by gravid uterus Tubular obstruction Clinical presentation It depends largely on the precipitating cause of AKI. It is Important to establish the presence of: Fever and other systematic symptoms of sepsis. Symptoms of bleeding or other obstetric complications Specific disease associate symptoms eg, - rash in SLE, Joint pains, Vasculitic rash etc. BP May be low in perennial AKI or raised in the presence of PeT or Glomerulonehritis. JVP---may be low due to volume depletion or high when there is establish renal impairment indicating hypervolemia and fluid overload. 1. Acute Tubercular Necrosis in Pregnancy Causes Prolonged Volume depletion Hypertension Vasoconstriction Pre-eclampsia, HELLP syndrome Acute fatty liver of pregnancy Septicemia - Septic abortion - Acute pyelonephritis Prolonged IUD Amniotic fluid embolism 2. Bilateral Cortical necrosis Causes Sustained hypovolenia Hypotension Profound vasoconstriction Septic abortion (20% incidence) 3. Microangiopathetic syndrome in pregnancy Pet/HELLP Syndrome Thrombotic thrombocytopenic purpurea Haemolytic uremic syndrome It occurs in 2nd or 3rd trimester C/F Thrombocytopenia Haemolytic anaemia 40 Vol. 8, Issue 3 & 4, April - September 2009

Fever Renal dysfunction Neurological symptoms hypertension

Lab Investigation Anaemia Thrombocytopenia Schistocytes/fragmented RBCs on blood film Elevated LDH Reduced haptoglobin Impaired renal function Management Cryoprecipitate-poor fresh frozen plasma in non obliguric patients Plasma exchangedaily to remove excess von WF multimers and auto antibodies against the metal protein are ADAMTS13. Blood transfusion wherever required Avoid platelet transfusion unless there is risk of life threatening bleeding. Haemodialysis for patients with significant renal dysfunction. Response to treatment Reduced schistocytes Reduction in LDH Increased platelets counts Out come Increased maternal morbidity and mortality. 4. Acute Interstitial Nephritis It is often due to medication in pregnancy. Drug considered a potential cause of AIN should be discontinued and avoided. Steroid therapy can be necessary. 5. De novo glomerulonephritis Glomerulonephritis can present at any stage during pregnancy. It may be difficult to differentiate from PeT. Presence of sign of other organ involvement, skin lesions and joints pain along with proleinuria and hematuria with or without impaired renal functions thrombocytopenia, edema and hypertension suggest glomerulonephritis. Lupus nephritis in Pregnancy Pregnancy may exacerbate SLE, especially if the disease is active at the time of conception. In later pregnancy it may be difficult to distinguish from PeT. Management of glomerulonephritis in pregnancy It depends on the type of glomerulonephritis and the severity of presentation. Treatment of SLE in pregnancy Coticosteroid Low dose aspirin Immuno suppressive medication Hydroxy chloroquine Antihypertensive Low eg heparin Mycophenolate mofetil is contraindicated in pregnancy

Investigations These are essentially the same for nonpregnant patients, but with particular emphasis on identification of specific causes related to pregnancy. Biochemistry Urea and elctyrolytes Liver function tets Quantification of urinary pretin excertion Blood film, LDH, haptoglobin and platelet count To exclude schistocytes and microangiopathic hemolytic anemia Urate Raised in patients with diagnostic of PeT Immunology screen dsDNA antibodies complemnent levels C3, C4 lupus anticoagulant and anticardiolipin antiboidies ANCA Renal ultrasound scan Diagnosis of urinary tact obstruction may be difficult as dilation of ureter and renal pelvis 9especially on right) is a feature of normal pregnancy Renal biopsy Consider in certain cases if, for example, GN is suspected and results of a biopsy are likely to lead to specific therapy. Indications for renal biopsy in pregnancy Sudden deterioration in renal function before 28 weeks gestation of unknown cause In this situation a biospsymay identify an important reversible pathology and lead to immediate treatment e.g. SLE with lupus nephritis, revel vasculitis. Symptomatic nephrotic syndrome before 28 weeks Renal biopsy may identify a pathology which is treatable such as minimal changes. SLE or a pathology for which you would not initiate further therapy during pregnancy eg, mesangiocapillary glomwerulonephritis. In this way a renal biopsy can also be useful to prevent initiation of potentially toxic empirical treatment with steroids during pregnancy. All other situation Generally, investigation by renal biopsy should be deferred until after delivery but may sometimes be considered in Ist trimester if the result would inform future management decisions. 6. Urinary Tract Obstruction Urolithiasis The patients usually present with repeated urinary tract infections and pain in flanks. Currently however, the placement of ureteral stents under ultrasound guidance, a less invasive technique, has made it possible to mange gravidas through gestation and to defer more definitive surgical procedures until after delivery. Treatment The following are required Prompt identification and correction of volume deplention and electrolyte disturbance; Prompt identification of sepsis with supportive treatment and commencement of broad spectrum and then specific antibiotics Prompt investigation and relief of urinary tract obstruction 41 Vol. 8, Issue 3 & 4, April - September 2009

Discontinuation of medication likely to cause acute interstitial nephritis. Specific therapy for some pathologies, eg, SLE may require Immunosuppressive therapy ;HUS may require fresh frozen plasma and plasma exchange; Close monitoring of all biochemical parameters including urea and electrolytes, acidosis. When AKI occurs in pregnancy one of the most important treatment decisions is whether the outcome would be improved by immediate delivery. Early delivery of the baby The decision to deliver the baby depends upon; 1. Whether the cause of AKI is presumed to be peT, HELLP or acute fatty liver of pregnancy where delivery is often the only way to stop the disease process or when the presences of an ongoing pregnancy prevent administration of the adequate treatment to the mother. 2. The stage of pregnancy .facilitating delivery is relatively easy in later pregnancy >28-32 weeks when the fetus is likely to be viable, but below this level of gestation the pregnancy may be lost if immediate delivery takes place. In this situation if the maternal condition is stable and fetus is viable, a patient with AKI may be given dialysis then a decision may need to be taken regarding maximizing the viability of the fetus versus continuing the pregnancy and risking further deterioration in renal function. This requires close liaison between renal and obstetric teams. Indications for dialysis in pregnancy Volume overload Hyperkalemia Metabolic acidosis Uremia (urea>20mmol/L) There is no clear evidence to indicate the correct time to start dialysis in pregnancy: however, most nephrologists aim to keep the serum urea level <20mmol/L in a pregnant patient. Dialysis modality Both peritoneal dialysis and haemodialysis have been successfully used in pregnancy hemodialy have been successfully used in pregnancy. Haemodialysis is used most frequently and needs to be performed approximately daily to minimize uremia and intradialytic weight gain. Generally six treatments per week (20 hour) are recommended. Care needs to be taken to avoid hypokalemia and excessive fluid removal because hypotension and wide variations in volume status may affect placental perfusion patients may also be anaemic; haemoglobin should be maintained >10g/dl units. Erythropoietin therapy appears safe in pregnancy. Prognosis Outcome depends on the cause of AKI When the cause of AKI is reversible, renal function often recovers in 3-4 weeks. Some patients will require dialysis and other intensive care measure. Unfortunately, bilateral cortical necrosis may also be a consequence and recovery of renal function may then be limited. Full renal recovery is reported in 60% - 90% cases of AKI in pregnancy Follow up Postpartum follow-up of women with AKI in pregnancy is essential. The urgency and duration of follow-up depends on the nature of the AKI. All women in the UK have a 6week postnatal check but women with AkI may need early nephrological review to consider further

investigation, ie, renal biopsy and management of persisting problems. Many medications are changed or omitted during pregnancy eg, ACEIs. A full medication review is required postpartum to consider reintroduction of medications discontinued antenatally . It is important to consider the safety of medications in women who are breastfeeding and advice may be needed from a pharmacist. Future prospects The majority of the available data on renal disease and pregnancy dates from the 1970s and 1980s. There is a need for contemporary data to improve the advice we are able to give to pregnant mothers with renal disease. It will be important that future collaborative studies are established and funded and that information regarding renal disease in pregnancy is accumulated by the National obstetric and renal registries-for example UK CORD (collaboration in renal disease in pregnancy) and the UK transplant pregnancy registry. The royal College of obstetric and gynaecology and NICE are currently reviewing the evidence for treatment of hypertension in pregnancy and will publish their recommendations within the next 12 months.

References 1. Davison JM. Overview: Kidney function in pregnant women. Am Kidney Dis 1987;9:248 2. Dwyer PL, OReilly M. Recurrent urinary tract infection in the female. Curr Opin Obstet Gynecol 2002; 14: 537543 3. Evans R, Fernandez-Perez, Salman S, et al. Sepsis during pregnancy. Crit Care Med 2005. 4. Gammill HS, Jeyabalan A. Acute renal failure in pregnancy Crit Care Med 2005;33 910, Suppl; S372384. 5. Hou S, Firanek C. Management of the pregnant dialysis patient. Adv Renal Replacemnt Therapy 1998;5; 24-30. 6. Johnson J, Feehally J (eds). Renal complications in the Normal Pregnancy. Comprehensive clinical nephrology, 2nd edn. London; Mosby;2003, Chapter 44, pp. 567581. 7. Karumanchi SA, Epstein FH. Renal complications in pregnancy. In :Feehally J. Floege J. Johnson J (eds) Comprehensive Clinical Nephrology, 3rd edn., Philadelphia, PA: Mosby: 2007; chapter 41, pp 483-494

42 Vol. 8, Issue 3 & 4, April - September 2009

TB in Pregnancy
KK Pandey
India accounts for 30% of the burden of all TB cases in the world. More than 80% of the patients are in the economically productive age group of 15-24 years. The disease is responsible for killing more women of reproductive age than all the combined causes of maternal morbidity and gives rise to nearly one-third of the female infertility in the country. The occurrence of pregnancy in patients with tuberculosis is increasing in developed countries. TB is believed to flare by the stress of pregnancy, especially in association with a poor nutritional state, immune-deficiency state or coexistent disease. However, data from San Domingo gave no evidence that pregnancy increased the chance of tuberculosis or of developing postpartum in either HIV positive or negative women. Studies from London showed rates of tuberculosis in the pregnant population to be the seen as in the non-pregnant population. The presentation of tuberculosis in pregnant women is similar to that in non-pregnant women but diagnosis may be delayed by the non-specific nature of early symptoms and the frequency of malaise and fatigue in pregnancy. The most common site in pregnancy is lung and in one study by Good et al clinical presentation in sputum positive cases were cough (74%) weight loss (41%), fever (30%), malaise (30%) or fatigue (30%) and themoptysis (19%); 20% were asymptomatic but all had abnormal radiographs. The diagnosis of pulmonary tuberculosis is also complicated by the fact that women with tuberculosis associated with pregnancy are more likely to post-pone having chest radiography and that investigation of sputum smear negative tuberculosis is more difficulty. The incidence of extra pulmonary tuberculosis in pregnant women is comparable to nonKK Pandey Senior Consultant Reparatory Medicine Metro Hospital and Cancer Institute Delhi

is doubtfully positive, and 7-10 mm is reactive. An increase from under to over 10 mm with an increase of at least 6 mm is consistent with new infection. A negative tuberculin test in pregnancy should not lead to BCG vaccination which, as a live vaccine, is contraindicated in pregnancy. Under RNTCP sputum examination done as per algorithm is the preferred method for diagnosis of pulmonary TB. A chest skiagram performed (after shielding the abdomen), is done if all the three sputum smears are negative and symptoms persist despite giving antibiotics for 1-2 weeks. The presence of suggestive radiographic abnormalities and the medical officers decision to treat with ATT, labels the patient is a smear negative TB case. A pregnant woman with extra pulmonary tuberculosis has constitutional and organ affection system. Treatment The main concern about tuberculosis treatment in pregnancy is the risk of teratogenicity. ATT should be started promptly as untreated disease presents a hazard to the mother and fetus. The same regimen is recommended for use in pregnancy as for the non-pregnant state except for withholding streptomycin. There are no significant animal teratogenicity studies reports of malformation in pregnant women treated with pyrazinamide combinations. Therefore, doubts about the use of pyrazinamide in pregnancy have since been set at rest. Currently, an intermittent regimen under the DOTS strategy of RNTCP is being increasingly used worldwide for pregnant women with TB. Most of the second line TB drugs are teratogenic. Therefore, expectant mothers with MDR-TB should be advised to terminate the pregnancy. Supportive measure during ATT administration includes: A. Intake of pyridoxine with isoniazid during the entire period of therapy to prevent peripheral neuropathy (as being practiced

pregnancy women (5-10%). Tuberculosis testing using purified protein derivative (PPD) is regarded safe in pregnancy. According to ATS-CDSC guidelines an introduction of 0-4 mm is negative, 5-10 mm 45

Vol. 8, Issue 3 & 4, April - September 2009

under the RNTCP). B. Prophylactic vitamin K administration to baby at birth for preventing hemorrhagic disease of the newborn. C. Segregation of the mother from the neonate if she has active and infectious disease (especially MDR-TB) or she is not likely to receive ATT due to maternal non-compliance or has received it only for less than 2 weeks prior to delivery. D. Examination of the contacts of the pregnant womans household. E. Necessary procedural interventions like pleural, ascitic or pericardial tapping intercostal chest drainage tube, etc. Breast feeding The first line antituberculous drugs cross into breast milk in variable amounts. Rifampacin is excreted into breast milk with milk to plasma ratio of 0.2. The amount transferred to the infant (0.05% of maternal dose) does not cause adverse effects. Pyrazinamide excretion into breast milk is minimal (0.3% of the ingested dose reaching to the infant). Streptomycin excreted into breast milk since the drug is poorly absorbed orally.

Ethambutol is excreted into breast milk with approximate milk to serum ratio of 1. Conclusion Due to demographic changes, pregnancy and tuberculosis are seen more frequently in both developing and developed countries. This leads to the need for heightened awareness to consider the diagnosis. Standard short course chemotherapy is recommended but the outcome for both the mother and the fetus is improved by early diagnosis. It is estimated that instances of congenital tuberculosis will increase, particularly in HIV endemic areas.

References 1. P Ormerod. Respiratory diseases in pregnancy: Tuberculosis in pregnancy and the puerperium, Thorax, Jun 2001; 56: 494 - 499. 2. Arora VK and Gupta R. Tuberculosis and pregnancy. Ind J Tub, 2003; 50: 13 16. 3. Good JT, Iseman MD, Davidson PT, et al. Tuberculosis in association with pregnancy. Am J Obstet Gynecol, 1981; 140: 492

46 Vol. 8, Issue 3 & 4, April - September 2009

Maternal Medication: Curing Mother, Protecting Fetus

SK Mittal
Pregnant mothers are as much, (nay more) vulnerable to common medical problems like cold, cough, and fevers, apart from the host of disorders peculiar to pregnancy. Further, many chronic illnesses like hypertension, diabetes, hypothyroidism, and infective hepatitis pose peculiar problems in pregnancy endangering both the mother and the fetus. To compound the problem many medications used quite successfully in non pregnant individuals for these common ailments, have a less-thandesirable safety profile during pregnancy with a great likelihood of causing teratogenic effects on the growing fetus. Uncertainty and anxiety about adverse effects of drugs on the growing fetus has increased several fold since the infamous thalidomide tragedy which resulted in a large number of phocomelic babies being born. Thus, the guiding principle at present is to consider almost all medications to be potentially harmful to the fetus and to avoid all maternal medications unless required. In unavoidable instances, the same should be limited to those drugs proven over years of use in clinical practice as comparatively safe in pregnancy. Table 1: Comparatively safe drugs in pregnancy Antibiotics Antipyretics Antimalarials Anticonvulsants Gastrointestinal drugs Penicillin, ampicillin, erythromycin, cephalexin Paracetamol, aspirin* chloroquine** phenobarbitone, diazepam Metoclopramide, bephenlum hydroxynapthoate, metronidazole* Digoxin, hydralazine, alpha-methyl dopa Insulin barbiturates*, thiouracil, carbimazole*, magnesium sulphate Table 2: Adverse effects of some of the drugs on the fetus Medicines which are definitely harmful Androgens Amphetamine Aminopterin Chlorothiazide Lysergic acid (LSD) Dicoumarol Effect on fetus

Masculinization of female Congenital heart disease Abortion, malformations Thrombocytopenia Chromosomal damage Bleeding, hypoplastic nails

Antithyrioid drug Goitre (iodised) Radioactive iodine Quinine Stilbesterol Tetracycline Streptomycin Trimethadione Thalidomide ACE inhibitors Not specific, but to be avoided Corticosteroids Caffeine Antimetabolites Progesterone Progesterone Propranolol Tolbultamide Vitamin D of use. Such examples being precipitation of diabetes due to beta blockers, increased risk of strokes due to estrogen use in post menopausal Destruction of fetal thyroid Abortion, deafness, thrombocytopenia Adenocarcinoma of uterus Retarded skeletal growth, teeth pigmentation Deafness Multiple malformations, mental retardation Phocomelia, deafness Renal dysgenesis

Cardiovascular

Miscellaneous

SK Mittal Chairman Deptt. of Pediatrics Pushpanjali Crosslay Hospital Ghaziabad (NCR)

While the adverse effects of certain drugs on the fetus are well known and documented (Table 2), the safety of a majority of drugs in pregnancy remain unproven. It is seen that the side effects of many drugs become apparent only after years 49

Vol. 8, Issue 3 & 4, April - September 2009

women, increased risk of ischemic heart disease with use of naproxen, hepatic damage due to prolonged or excessive dose of NSAIDS, and renal damage due to prolonged use of paracetamol. Due to the delayed realization of the adverse reactions of otherwise widely used medicines and as a result of limited post marketing surveillance of maternal medications during pregnancy, it is recommended that prescription of medications during pregnancy is kept to the minimum. In fact, since the maximum teratogenic effects of drugs are likely during the most formative stage of the embryo ie, the first trimester, when many women may not even be aware of their pregnancy status, it is always important to check on the pregnancy status of all women in the child bearing age before giving any medicine.

reaction. As Rabies is a potentially fatal infection, pregnancy is no contraindication for use of the Rabies vaccine, if required Table 3: Vaccines in Pregnancy Contraindicated Live viral vaccine like Measles, MMR Rubella, Varicella, Yellow fever Hepatitis A, Influenza, HPV

Avoidable

To be used with Hepatitis B, Vi antigen typhoid caution Use if indicated Safe Rabies for post exposure prophylaxis TT, DT Immunoglobulin (human origin)

Vaccines (Table 3) are also in a way medicines, albeit preventive, which are required to be used with great caution during pregnancy. In general, live viral vaccines (Measles, MMR, Rubella, Varicella, Yellow fever, etc) are contraindicated during pregnancy as their use is associated with occurrence of viremia in the recipients, which may have teratogenic effects on the fetus, much like that of natural viral infections. Killed viral vaccines such as Influenza vaccine, Hepatitis A vaccine, and HPV vaccine should also be avoided during pregnancy. Recombinant Hepatitis B vaccine can be used cautiously, remaining alert for any possible anaphylactic

for post exposure prophylaxis although it should be avoided for primary prophylaxis. On the other hand, bacterial vaccines available as Toxoids (tetanus, diphtheria, etc) are considered quite safe during pregnancy. Typhoid vaccines are not contraindicated as such, but pyrexia caused by the conventional typhoid vaccine may precipitate labor, so it would be advisable to avoid conventional typhoid vaccine during pregnancy.

50 Vol. 8, Issue 3 & 4, April - September 2009

Pushpanjali Health Care Events and Initiatives

4 April 2009 Fetal Medicine Update
Dr Sharda Jain organized the workshop that was attended by over 60 professionals. The sessions were interactive and highly educative.

26 April 2009 Temporal Bone Dissection Competition

PCH has in the past organized two Temporal Bone Dissection Courses in association with Carlos Foundation, Spain and in the process trained over 18 ENT Surgeons from Northern India. In continuation of this effort, the Association of Otolaryngologists of India, Delhi organized a Temporal Bone Dissection Competition at PCH premises. Four teams of two ENT surgeons from AIIMS, MAMC, Army Hospital R&R and Wellington Hospital participated.

7 April 2009 World Health Day

On the occasion of World Health Day PCH and IMA, East Delhi Branch organized a series of lectures on the theme Save lives and make your hospital safe for medical emergencies. The talks were delivered by Dr PP Singh, Director, Hindu Rao Hospital, Dr Atul Gupta, Sr Anesthesiologist and Dr Amit Gupta, Head, Emergency & Critical Care, PCH.

9 May 2009 Probiotics in Children

Dr SK Mittal with the support of M/s Yakult, India, organized a clinical meeting of pediatricians from East Delhi, Ghaziabad and NOIDA. The theme of the meeting was on the efficacy of Probiotics in Children. M/s Yakult who market a probiotic drink under the brand name Yakult made a presentation on the product that has been recently launched in India. The drink was served to all present in the audience. Yakult was represented by their Managing Director and other senior executives.

Executive Director with Dr Ajay Lekhi & Dr Dinesh Sahai

20-22 May 2009 Medical Preparedness for Emergency Medical Response to CBRN
JPN Apex Trauma Centre, AIIMS organized a 3day training program on Medical Preparedness for Emergency Medical Response to CBRN (acronym for chemical, biological, radiological, and nuclear). Over 50 experts in emergency medicine from across the country deliberated on the proceedings. Dr Amit Gupta, Head, Emergency medicine and Critical care, PCH, presented his understanding of Preventive measures and management of biological disasters including pandemics, which was very well received by the audience.

11 April 2009 Renal Failure in Intensive Care

The lecture session on Renal Failure in Intensive Care was organized by the Dept. of Medicine. Dr Neeru Agarwal, Head, Nephrology, PCH addressed Consultant physicians and General practitioners on the subject. The session was chaired by Dr Dipak Bhalla, Head, Nephrology, Narendra Mohan Hospital.

25 April 2009 Treatment Strategies for HIV-AIDS

A session on Treatment strategies for HIVAIDS was organized by Dr BB Rewari, Prof of Medicine, Jai Parkash Narayan Hospital and NACO. Dr Rewari was supported by Dr Ruby Bansal, an expert on HIV medicine. Dr Prakash Gera chaired the session. 53 Vol. 8, Issue 3 & 4, April - September 2009

24 May 2009 Neonatology Advance Life Support

The Dept of Pediatrics in collaboration with National Neonatology Forum, Delhi under the chairmanship of Dr SK Mittal organized a 1day workshop on Neonatology Advance Life

Expert Panelists conducting open house

Support (NALS). Eminent faculty comprising Prof Vikram Datta, Dr Sugandha Arya, Dr Mamta Jajoo, and Dr Pankaj Gupta deliberated on topics like Endotracheal intubation, Chest compression, and Devices for positive pressure ventilation. Dr Vivek Jain, Neonatolgist, PCH and organizing Secretary NALS played a pivotal role in making the workshop a success.

Dr. Ashok Grover all attentive to Dr. Uma Kumar

5 June 2009 Emergency Medicine

A lecture Session by Dr Deepak Talwar, on Antimicrobial Resistance-Is there light at the end of Tunnel? was organised. Dr. Parkash Gera Chaired the session.

Attentive and interactive audience

30 May 2009 Abdominal Surgery

A seminar on Abdominal Surgery was organized by the Dept of Surgery under the leadership of Dr Lamba and with the guidance of Dr AK Mittal. Dr Amit Gupta of JPN Apex Trauma Centre, AIIMS was the special invitee. Dr Amit dealt on the subject, inviting interest and interaction from attending surgeons and experts of emergency medicine.

Dr. Deepak Talwar brings home a point

17 June 2009 Recombinant factor VII a

Dr Amit Gupta with the support of Novo Nordisk organized a lecture session by Dr Badrinath on Recombinant factor VII a. Consultants from PCH and very senior doctors attending to emergencies were participants.

Dr Lamba addressing the audience

4 June 2009 Recent trends in the Management of Rheumatoid arthritis

On the initiative of the Dept of Medicine, a lecture session on Recent trends in the management of Rheumatoid arthritis was organized. The session was conducted by Dr Uma Kumar, Associate Professor Medicine and Head, Rheumatology Division, AIIMS and was attended by Physicians, Orthopedic surgeons, General practitioners and PCH consultants. 54 Vol. 8, Issue 3 & 4, April - September 2009

Dr Badrinath talking about Recombinant factor

20 June 2009 Preparedness on Pandemic H1N1 Swine Flu

The Dept of Medicine with the support of Sanofi Aventis organized a lecture by Dr Shashi Khare, Director, National Institute of C o m m u n i c a b l e Diseases on P r e p a r e d n e s s on Pandemic H1N1 Swine Flu. Dr Narendra Saini chaired Dr. Shashi Khare talking on Swine Flu management the session. The session was attended by a large number of doctors, paramedics and PCH staff.

2 July 2009 Press Conference on Swine flu

PCH organized a press conference with media fraternity from Ghaziabad on H1N1 Swine flu with a presentation by Dr Narinder Saini. Over 20 heath reporters from print and electronic media attended the c o n f e r e n c e . The press Dr. N. Saini talking to health reporters c o n f e r e n c e was attended by Dr Vinay Aggarwal, Dr PD Garg, Atul Gandotra and supported by Gaurav Pandey and Dhirendra Tiwari.

17 April 2009 Workshop on Breast feeding

Dr Sharda Jain with the active support of her team organized a workshop on breast feeding. The workshop was attended by Doctors and young mothers.

July & CMD look on 2009

Expert Panelists conducting open house

Dr. P. D. Garg makes a point while Dr. N. Saini

31 May 2009 No Tobacco Day

A March from Rajghat to IMA was organized, which was flagged by Ms Nafisa Ali at Rajghat. On this occasion Dr Narinder Saini spoke about the ill-effects of tobacco. Nafisa Ali also expressed her concerns about the ill effects of tobacco. The Galaxy Cancer Institute sponsored No tobacco t-shirts which were distributed to all present.

Dr SK Mittal, Head Dept. of Pediatrics, PCH was honored for his contribution in the field of pediatrics at a glittering function at FICCI.

School Mental Health Program Pushpanjali Crosslay Hospital

The Department of Pediatrics and Department of Mental Health and Psychological Services organized a 1-day workshop on School Mental Health at Sun Valley International School, Sector1, Vaishali. The objective of the program was to sensitize teachers about the various developmental, behavioral and academic difficulties that are commonly seen in children. More than 50 teachers participated. The workshop was chaired by Dr SK Mittal, Head of the Pediatrics Department, who gave an overview on the subject at the beginning of the session. Among the other speakers were Sanjeeta Kundu (Clinical Psychologist), Prerna Duggal (Clinical Psychologist), and Dr Mani Bansal (Speech Therapist). The speakers equipped the teachers with comprehensive screening tools for identifying children with various academic and behavior difficulties, and also discussed the practical strategies on classroom management of such children. The session ended with a Q & A session in which many teachers participated actively. 55

Nafisa Ali speaking to Press

Vol. 8, Issue 3 & 4, April - September 2009

Guidelines for Submission of Manuscripts

You are invited to contribute your articles, case reports, clinical experiences and any other relevant material which is for the benefit of clinical community at large. The articles/ contribution should be sent to: The Editor in-Chief Dr. Vinay Aggarwal & The Editor Dr Ashok Grover PUSHPANJALI MEDICAL PUBLICATIONS PVT. LTD. A-14, Pushpanjali, Vikas Marg Extn. Delhi 110092 E-mail : pmc_pub@hotmail.com pmc_pub@yahoo.co.in Manuscripts can be submitted by e-mail, but it is mandatory that photographs (if any) should be submitted in glossy paper by post. To maintain the uniformity the articles, authors should follow the following pattern: All Manuscripts submitted to Medi-Focus should not have been published in any form in any other publication, and become the property of the publishers. All manuscripts must be accompanied by the following written statement signed by all the authors. The undersigned author (s) certify (ies) that the article is original, is not under consideration by any other journal, and has not been previously published. All copyright ownership of the manuscript entitled (title of article) is hereby transferred to the publishers of Medi-focus. Articles will be edited for style and grammar. Technical jargon is to be kept to a minimum. American spellings are used in the Journal.

Structured Abstract. Should be a factual condensation of the entire work with objective, methods, results, conclusions and should be in one para. The abstract should state the purposes of the study or investigation, basic procedures (selection of study subjects or laboratory animal; Observational and analytical methods), main findings (giving specific data and their statistical significance, if possible), and the principal conclusion. It should emphasize new and important aspects of the study or observations. Clinical Briefs must not exceed 1000 words with one figure and 5-8 references. Text. Authors must consider and follow the format : Introduction, Material and Methods, Results, Discussion, and Conclusion (if necessary). The matter must be written in a manner which is easy to understand, and should be restricted to the topic discussed. Do not use vertical lines or underlining in the text. Acknowledgments should be placed as the last element of the text before references. Abbreviate measurements (cm, ml). Abbreviations should be used sparingly and must be preceded by the full form initially. References. In citing other work, only references consulted in the original should be included. If it is against citation by others this should also be stated. Use the Sequential numbering system. Arrange the reference list in the sequence in which the references are first cited. In the text, references cited should be superscripted and should appear on top of the line after the punctuation. Responsibility for the accuracy and completeness of references lies with the author. References should not exceed 15-20 in number. The Journal follows the Vancouver system of references. References should be numbered and listed consecutively in the order in which they are first cited in the text. Tables should be identified in the text by superior Arabic numerals. The full list of references at the end of the paper should include : names and initials of all authors (unless more than 6, when only the first 3 are given followed by et al); the title of the paper; the journal title abbreviated according to the style of Index Medicus; year of publication; volume number; first and last page numbers. References of books should

Preparation of Manuscripts
Format. The manuscript must not exceed 1012 pages typed in double space (including 1520 references). Number all pages in sequence, beginning with the title page. Submit a copy of all elements arranged as follows: Title Page. This should contain the title of the manuscript (5-6 words title) the names of all authors, and their affiliations, a short title (not more than 20 letters to be used as running head) and at the bottom of the page, institution where the work has been carried out, and the address for all correspondence and reprints, including Fax, Phone and E-mail. 59 Vol. 8, Issue 3 & 4, April - September 2009

give the book title, place of publication, publisher and year; those of multiple authorship should also include the chapter title, first and last page numbers, and names and initials of editors. 1. Mehta MN, Mehta JN. Serum lipids and ABO blood groups in cord blood of neonates. Indian J Pediatr 1984; 51 : 30-43. 2. Smith GDL. Chronic Ear Disease. Edinburgh; Churchill Livingstone, 1980 : 78-81. 3. Malhotra KC. Medicogenetic problems of Indian tribes. In Verma IC, ed. Medical Genetics in India. Vol. 2., Pondicherry; Auroma Enterprises, 1978; 51-55. Papers accepted but not yet published should be included in the references followed by In press. Those in preparation, personal communications and unpublished observations should be referred to as such in the text only. For more detailed information about the Vancouver system, authors should consult Uniform requirements for manuscripts submitted to biomedical journals (Br Med J. 1982; 284 : 1766-70). Legends. A descriptive legend must accompany each illustration and must define all abbreviations used therein. Illustrations and graphs. Submit glossy black and white photographs. The cost reproduction of colour photographs will be borne entirely by the author. Number all illustrations with Arabic numericals (1, 2).

Tables. These must be self-explanatory. The data must be clearly organized and should supplement and not duplicate the text. Explanatory matter should be given as footnotes. Statistical analyses used must be appropriate. Each table must have a title and should be numbered with Arabic numericals (1, 2).

Manuscript Submission Checklist

1. Three copies of manuscript in hard copy 2. Name and address correspondence. of author responsible for

3. Structured Abstract (150-200 words) & 3-5 key words. 4. References, cited consecutively in the text. 5. Three glossy prints for illustrations. 6. Documentation of permission to reuse any previously published material. 7. Covering letter, including statement of originality and signifying approval of final copy by all authors. 8. Upon final acceptance of the manuscript, a CD disk in MS Word should be submitted. The disk should be labeled with the title of article, file name and version used and must contain the final revised manuscript material.

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