SPECIAL TOPICS IN PEDIATRIC NURSING PREMATURE NEONATE

Richard Benedict S. Roxas, R.N, MD, MSc. Physiology (u)

PREMATURE NEONATE
Prematurity refers to the broad category of neonates born at less than 37 weeks' gestational age (GA). Although the estimated date of confinement (EDC) is 40 weeks' GA, the World Health Organization broadened the range of full term to include 37-42 weeks' GA.

Premature newborns have many physiologic challenges when adapting to the extrauterine environment. Serious morbidities occur in extremely low-birth-weight (LBW) infants. The near-term neonate (34-36 weeks' GA) has issues of prematurity that include feeding immaturity, temperature instability, and prolonged jaundice.

ROLE OF PLACENTA
The placenta serves 3 major roles for the fetus: provision of all the nutrients for growth, elimination of fetal waste products, and synthesis of hormones that promote fetal growth. With the exception of most electrolytes, the maternal circulation contains more substrate (eg, blood glucose) than the fetal circulation. In addition, the placenta is metabolically active and consumes glucose. Waste products of fetal metabolism (eg, heat, urea, bilirubin, carbon dioxide) are transferred across the placenta and eliminated by the mother's excretory organs (ie, liver, lung, kidneys, skin). In addition, the placenta acts as a barrier to infection through mucosal macrophages and by allowing transfer of maternal immunoglobulins (Igs, eg, IgG) to the fetus beginning at 32-34 weeks of gestation. Placental dysfunction is involved in the transfer of IgG. Antibacterial activity of the amniotic fluid improves as GA advances.

EXTREMELY LOW BIRTH WEIGHT

Extremely low birth weight (ELBW) is defined as a birth weight less than 1000 g (2 lb, 3 oz). The majority of ELBW infants are also the youngest of premature newborns, usually born at 27 weeks' gestational age or younger. Nearly 1 in 10 infants with low birth weight (<2500 g) are ELBW infants (approximately 32,320 US born ELBW infants in 2003).

Infants born at less than 1500 g are termed very low birth weight (VLBW). Infants whose weight is appropriate for their gestational ages are considered appropriate for gestational age (AGA). Infants who are heavier than expected are large for gestational age (LGA); conversely, those smaller than expected are considered small for gestational age (SGA) and are usually also found to be intrauterine growth restricted (IUGR) prior to birth.

ELBW survival has improved with the widespread use of surfactant agents, maternal steroids, and advancements in neonatal technologies. The minimum age of viability is now as young as 23 weeks, with scattered reports of survivors born at 21-22 weeks' estimated gestational age.

Although the mortality rate has diminished with the use of surfactants, the proportion of surviving infants with severe sequelae, such as chronic lung disease, cognitive delays, cerebral palsy, and neurosensory deficits (ie, deafness and blindness), has not.

ASSESSMENT TOOLS
Confirmation of GA is based on physical and neurologic characteristics. In 1979, the Dubowitz Scoring System for determining GA based on neurologic and physical parameters was revised to include 12 items. The Ballard Scoring System, recently revised again to include extremely LBW infants, remains the main tool clinicians use after delivery to confirm GA by means of physical examination.

Neurologic Criteria include muscle tone of the trunk and extremities and joint mobility. Reassessing the neurologic criteria 18-24 hours after birth is best to allow for recovery from maternal medication (eg, magnesium sulfate, analgesics), which may decrease tone and responsiveness

Preterm infant at 28 weeks' gestation. Note the small amount of ear cartilage and/or flattened pinna

Preterm infant at 33 weeks' gestation. Note the increased cartilage, recoil, and outer ridge curving inward

NOTE & COMPARE

MORBIDITY & MORTALITY

Survivability correlates with gestational age for infants who are appropriately grown (AGA) (13.8% for birth weights <500 g, 51% for birth weights of 500-749 g, 84.5% for birth weights of 750-1000 g in 2002 for the first year of life). ELBW infants are more susceptible to all of the possible complications of premature birth, both in the immediate neonatal period and after discharge from the nursery.

CAUSES
Premature delivery can be the result of preterm labor and PPROM or can occur for maternal indications: Chorioamnionitis

Amniocentesis that demonstrates bacteria, WBCs, and a low glucose concentration confirms the diagnosis of chorioamnionitis and is an indication for delivery. A decrease in the biophysical score or profile in association with chorioamnionitis is associated with fetal infection. Rates of perinatal mortality, neonatal infection, and RDS increase in the presence of maternal fever and chorioamnionitis.

Intrauterine Growth Restriction (10th percentile for birth weight) is significantly associated with perinatal mortality and long-term morbidity. Low Socioeconomic Status: Programs offering additional social support for at-risk pregnant women have not been demonstrated to reduce the numbers of LBW or preterm infants Pregnancy Induced Hypertension

Maternal Diabetes
Pregnancies complicated by diabetes and poor glycemic control are associated with a high incidence of prematurity, macrosomia, malformation, fetal death, and neonatal death. The rate of preterm birth (GA <37 wk) is 20-22% of persons with insulin-dependent diabetes. In women with diabetes diagnosed before pregnancy, the frequency of preeclampsia is increased as the severity of diabetes increases.

Multiple-Gestation Pregnancies
Women with multiple-gestation pregnancies are at high risk of preterm labor and delivery and account for increasing percentage of preterm births and LBW infants. With advances in assisted reproductive technology, multiple-gestation pregnancies have increased. Preterm birth rate for twins has increased from 40.9% in 1981 to 55% in 1997. Multiple births related to infertility treatment have increased dramatically (Fritz, 2002).

 Prepregnancy counseling of prospective parents regarding the risks related to multiple gestations is important. Preterm birth (<35 weeks' GA) occurs in 26% of twins versus in 3% of singletons. Triplet pregnancies are associated with an increased incidence of preterm labor and delivery at a decreased GA and birth weight, as compared with singletons and twins. When the data are controlled for GA, outcomes are similar for singletons, twins, and triplets.

Maternal Age
In women aged 13-15 years, the rate of preterm birth is 5.9%. This rate declines to 1.7% in women aged 18-19 years and 1.1% in women aged 20-24 years. The rate of preterm births increases in pregnancies in which the mother is older than 40 years. The scoring system for the risk of preterm delivery uses a criterion of >40 years of age.

Tobacco Use
Approximately 15-20% of pregnant women smoke tobacco. Tobacco use is a risk factor for placental abruption and accounts as a factor for 15% of preterm births and 20-30% of LBW infants.

DIAGNOSTICS
Initial laboratory testing is performed to identify issues that, if corrected, improve the patient's outcome. Blood Tests Are Performed.
CBC findings may reveal anemia or polycythemia that is not clinically apparent. A high or low WBC count and a number of immature neutrophil types also may be found. An abnormal WBC count may suggest subtle infection. A blood type and antibody testing (Coombs test) are performed to detect blood-group incompatibilities between the mother and infant and to identify antibodies against fetal RBCs. Such incompatibilities increase the risk for jaundice and kernicterus.

Serum Electrolytes Analysis

At birth, most serum electrolyte levels reflect those of the mother. If the mother received magnesium sulfate to inhibit labor, the baby's respiratory effort may be compromised, and the serum magnesium value is elevated. The serum calcium may be low shortly after birth in small preterm babies.

 Immature renal function, as well as limited bone and tissue reserves, result in the need for intravenous replacement of calcium, sodium, potassium, phosphate, and trace minerals in those infants who are taking nothing by mouth. Infants who can tolerate enteric nutrition receive ample electrolyte and minerals from appropriate preterm formulas and fortified human milk. These issues are more acute with decreasing GA. Frequent laboratory determinations of serum sodium, potassium, and glucose in conjunction with monitoring of daily weight and urine output in extremely LBW infants assists the practitioner in determination of fluid requirements.

Serum glucose concentrations must be monitored closely because of the risk of hypoglycemia and hyperglycemia in preterm infants. The baby's GA and other medical conditions dictate the frequency of testing. Metabolic Screening is done.
Every state has a metabolic screening program. All programs include testing of newborn blood spots for a minimum of phenylketonuria, hypothyroidism, and galactosemia. The timing of obtaining the sample varies. In general, false-positive results are most common in preterm babies. Early detection and intervention minimizes the long-term neurologic risk.

Imaging Studies: Imaging studies are specific to the organ system affected.
Chest radiography is performed to assess lung parenchyma in newborns with respiratory distress Cranial ultrasonography is performed to detect occult intracranial hemorrhage in very LBW newborns

MANAGEMENT
Medical Care: Stabilization in the delivery room with prompt respiratory and thermal management is crucial to the immediate and long-term outcome of premature infants, particularly extremely premature infants. Principles of respiratory management are as follows:

Recruit and maintain adequate lung volume or optimal lung volume. In infants with respiratory distress, this step may be accomplished with early continuous positive airway pressure (CPAP) given nasally, by mask (Neopuff), or by using an endotracheal tube when ventilation and/or surfactant is administered. Avoid hyperoxia and hypoxia by immediately attaching a pulse oximeter and keeping the oxygen saturation (SaO2) between 86% and 93% by using an oxygen blender. Prevent barotrauma or volutrauma by using a ventilator that permits measurement of the expired tidal volume and by keeping it 4-7 mL/kg. Administer surfactant early (<2 h of age) when indicated and prophylactically in all extremely premature neonates (<29 wk). Many centers are using early CPAP and a relatively permissive approach to ventilation. Research is needed to provide evidence to support an approach that provides the best outcome.

Thermoregulation
Maintenance of the neutral thermal environment is critical for minimizing stress and optimizing growth of the premature infant. The neutral thermal environment is defined as the environmental temperature in which the neonate maintains a normal temperature and is consuming minimal oxygen for metabolism.

Neonates lose heat by 4 means, as follows: Evaporation: Evaporation is energy consumed by a fluid as it converts from a liquid to gas. This is primarily in the delivery room. Completely drying the infant is of primary importance in prevention of hypothermia. This step can be omitted if other resuscitative measures are taking place. Conduction: This is direct transfer of heat from a warm body to a cool object by contact (eg, placing an infant on a cold scale). Convection: This is the loss of heat from the warm air next to the skin to moving air currents (eg, windchill effect). Double-walled isolettes help to reduce convective heat loss. Radiation: This is the loss of heat that radiates from a warm body to a cool surface (eg, window,

 Preterm infants are relatively unable to compensate for cold stress because of a small amount of subcutaneous tissue (insulation) and decreased brown fat to produce heat. Preterm infants do not shiver. The increased surface area to body mass allows for rapid heat loss, especially from the head.

 Decreased posturing ability further diminishes their ability to compensate. In extremely LBW infants, immature skin further complicates thermoregulation due to increased evaporative water loss. Consequences of cold stress are increased metabolism with loss of weight or failure to gain weight and increased use of glucose with depletion of glycogen stores and hypoglycemia. Metabolic acidosis results in a decreased surfactant production and loss of functional alveolar number, which results in hypoxia. The hypoxia causes pulmonary vasoconstriction, and further hypoxia. Increased oxygen consumption results in hypoxia, anaerobic metabolism, and lactic acid production.

 In the intensive care nursery, radiant decreases heat loss due to conduction, convection, and radiation. With warmers may be used to compensate for heat loss. Incubators are more efficient than radiant warmers because the heated environment radiant warmers, consider using plastic wrap and a humidified environment for extremely LBW infants. New devices function as both an incubator and an overhead warmer to enable access for procedures. In all nurseries, maintain the environmental temperature at >70F (>21C). Temperature maintenance is especially critical during neonatal resuscitation, when the same principles apply.

Skin Care Premature infants have immature skin, a decreased or absent stratum corneum, decreased cohesiveness between skin layers, increased water fixation, and tissue edema. The immature skin integrity leads to easy injury, transdermal absorption of drugs and other materials in contact with the skin and increased risk for infection..

 The National Association of Neonatal Nurses (NANN) and the Association of Women's Health, Obstetric and Neonatal Nu (AWHONN) recommended the following areas of newborn skin care, which are based on clinical and laboratory research. Bathing: Use only water and no soap for infants weighing <1000 g. Decrease the frequency of using cleansers. Only use neutral-pH cleansers. Disinfectants (eg, povidone-iodine, chlorhexidine): Remove completely these agents after the procedure to decrease transdermal absorption. Isopropyl alcohol use is discouraged because it is relatively ineffective as a disinfectant and is drying to the skin. Alcohol burns, and cracked skin can result.

Adhesives: Minimize their use. Use double-backed silk tape versus tape with strong adhesive properties (Elastoplast). Use hydrogel electrodes. Avoid solvents or bonding agents. Transepidermal water loss: Place infants born at 30 weeks' GA in a high-humidity (>70%) environment. Topical solutions: Review ingredients of any topical solution placed on the skin of a preterm infant. Transdermal absorption can occur. Discourage use of solvents for adhesive removal. Pectin barriers (eg, DuoDERM extra thin, Restore extra thin) are recommended: Anchoring devices (umbilical lines) to pectin barriers results in improved skin integrity

Fluid and Electrolyte Management

Preterm infants need intense monitoring of their fluid and electrolytes because of their increased transdermal water loss, immature renal function, and other environmental issues (eg, radiant warming, phototherapy, mechanical ventilation). Expected loss of extracellular water in the first week of life in the term infant is 5% of birth weight, LBW infant is 10% of birth weight, and in the extremely LBW infant is 15-20%. Data curves, which Dancis developed in the 1940s, may be useful in monitoring weight loss in each group of infants.

 The degree of prematurity and the infant's specific medication problems dictate initial fluid therapy. However, the following general principles apply to all preterm infants:
Initial fluids should be a solution of glucose and water. More mature infants can be started at 60-80 mL/kg/day. The most immature infants may need up to 100-150 mL/kg/d Environmental aspects of care, eg, radiant warming, phototherapy, and a nonhumidified environment, increase insensible water loss and the need for fluids. Mechanical ventilation, use of double-walled isolettes, and provision of humidity decrease insensible water loss. The glucose infusion rate (GIR) is usually started at 4-6 mg/kg/min. In general, to obtain this rate, a solution of dextrose 10% in water (D10W) should be used initially. The exception is the extremely LBW infant who should initially be given dextrose 5% in water (D5W) to provide the same GIR and to prevent hyperglycemia.

Electrolytes should not be added until 24 hours of age, when urine output is adequate. Electrolytes and calcium should be monitored at 12-24 hours of age depending on the degree on prematurity and other medical issues. Basal needs are sodium is 2-3 mEq/kg/d, potassium 1-2 mEq/kg/d, and calcium 600 mg/kg/d (as calcium gluconate). Urinary losses, which may increase in the most immature of infants and in those exposed to diuretics, dictate the need for supplemental sodium.

Infants who develop acute tubular necrosis (ATN) should be treated with fluid restriction that equals insensible water loss plus urine output. Additional fluid is administered by closely and frequently monitoring the output and electrolytes during the post-ATN diuretic phase. Hyponatremia and weight gain should be treated with decreasing fluid administration. Monitoring of urinary electrolyte losses is sometimes helpful in replacement therapy.

The patient's weight should be followed up every 24 hours. Results of laboratory monitoring and change in weight dictate changes in fluid and electrolyte support.

Diet: Preterm infants born at <34 weeks of gestation have poor coordination of the suck and swallow reflexes and decreased intestinal motility. Nutrition in the first several days after birth often is provided intravenously. Even the relatively healthy preterm infant may not reach full enteral nutrition until a week or longer after birth. Colostrum:
If available, colostrum is the preferred initial nourishment. Colostrum contains digestible proteins, antibody (secretory immunoglobulin A [IgA]), growth factors, and other components that in the aggregate promote intestinal villous growth and influence the intestinal colonization.

Mature Breast Milk

Mature breast milk replaces transitional milk by 10-12 days after birth. The caloric density varies among mothers based in part on the mother's nutritional status. For extremely LBW infants, breast milk is often inadequate to sustain growth. Most calories are contained in lactose (35%) and fat (50%). In the more preterm infants, lactase activity is low which may contribute to less-than-optimal digestion of lactose and absorption of carbohydrate. This improves with GA. Calcium, sodium, potassium, and trace mineral levels are insufficient to meet the needs of the preterm infant. Therefore, minerals, protein, carbohydrates, and lipids often are added to breast milk to support optimal growth in the form of commercially available breast milk fortifiers. Approximately 120-150 cal/kg/d are required for growth. Small preterm infants with increased metabolic needs due to complications such as bronchopulmonary dysplasia (BPD) may require up to 180 cal/kg/d to grow.

PARENT EDUCATION
Discharge teaching of the premature infant includes the following:
Basic infant care - Bathing, skin care, taking a temperature Infant feeding - Feeding cues, support of breastfeeding Infant safety - Use of car seats, avoiding exposure to a smoky environment Back to sleep - Strategies to help preterm infants return to sleep Illness prevention (handwashing, avoid crowds, prophylaxis against infection with respiratory syncytial virus (RSV) as indicated, immunization schedule When to call healthcare provider - Poor feeding, signs of illness, change in behavior, respiratory distress Specifics related to chronic conditions - For example, use of a nasal canula and home oxygen therapy

COMPLICATIONS
Thermoregulation As a result of a high body surface areatobody weight ratio, decreased brown fat stores, nonkeratinized skin, and decreased glycogen supply, ELBW infants are particularly susceptible to heat loss immediately after birth. Hypothermia may result in hypoglycemia, apnea, and metabolic acidosis. Heat loss can occur in ELBW infants in 4 ways, namely, conduction, convection, evaporation, and radiation. Conduction is the transfer of energy from the molecules of a body to the molecules of a solid object in contact with the body, resulting in heat loss, while convection is the similar loss of thermal energy to an adjacent gas. Evaporative heat loss is the total heat transfer by energy-carrying water molecules from the skin and respiratory tract to the drier environment, while radiant loss is the net rate of heat loss from the body to environmental surfaces not in contact with the body. Extremely preterm infants are especially prone to these losses secondary to the poor barrier provided by their thin, poorly keratinized skin.

Temperature control is paramount to survival and typically is achieved with use of radiant warmers or double-walled incubators. Hypothermia (<35C) has been associated with poor outcome, including chronic oxygen dependency. Immediately after birth, the infant should be dried and placed on a radiant warmer and a hat or another covering should be placed on his or her head. Recent studies have shown that placing a plastic film over the baby immediately after drying can further minimize evaporative and convective heat losses.

For transport to the neonatal intensive care unit (NICU) from the delivery room, the infant should be covered with either warmed blankets or cellophane wrap. For transport of more than very short distances, the infant should be placed in a double-walled, heated incubator. The delivery room and NICU should be kept warm to aid in the prevention of hypothermia in the preterm infant. Architectural designs should facilitate adjacent location of delivery rooms and NICUs or at least provide separately heated resuscitation rooms. Although chemical heating pads commonly are used to provide a warm surface on which to place the baby, the unregulated heat source may burn the very fragile skin of the ELBW infant and are not recommended.

Hypoglycemia Fetal euglycemia (maintenance of normal blood glucose levels) is maintained during pregnancy by the mother via the placenta. ELBW infants have difficulty maintaining glucose levels within reference range after birth, when the maternal source of glucose has been lost. In addition, ELBW infants are usually under increased stress compared with their term counterparts, and they have insufficient levels of glycogen stores. Preterm infants are generally considered hypoglycemic when whole-blood glucose levels are lower than 45 mg/dL.

Because symptoms of hypoglycemia (seizures, jitteriness, lethargy, apnea, poor feeding) may be less obvious in preterm infants, hypoglycemia may only be detected on routine sampling. One form of accepted treatment consists of an immediate intravenous dextrose infusion of 2 mL/kg of 10% dextrose-in-water solution (200 mg/kg) followed by a continuous intravenous infusion of dextrose at 6-8 mg/kg/min to maintain a constant supply of glucose for metabolic needs and to avoid further hypoglycemia. Rapid infusion of glucose concentrations greater than 10% should be avoided because of the hyperosmolarity of the solution and risk of cerebral hemorrhage.

Hyperbilirubinemia Most ELBW infants develop clinically significant hyperbilirubinemia (jaundice) requiring treatment. Hyperbilirubinemia develops as a result of increased red blood cell turnover and destruction in the context of an immature liver that has physiologically impaired conjugation and elimination of bilirubin. In addition, most preterm infants have reduced bowel motility due to inadequate oral intake, which delays elimination of bilirubin-containing meconium, coupled with increased enterohepatic circulation of conjugated bilirubin that enters the intestinal tract. These complications of extreme prematurity, in addition to typical conditions that cause jaundice (eg, ABO incompatibility, Rh disease, sepsis, inherited diseases), is thought to place these infants at higher risk for kernicterus at levels of bilirubin far below those in more mature infants, although specific serum bilirubin levels that are safe versus toxic have never been elucidated.

Kernicterus occurs when free, unconjugated bilirubin crosses the blood-brain barrier (BBB) and stains the basal ganglia, pons, and cerebellum; diminished protein status and the occurrence of acidosis in ELBW infants may potentiate the proportion of unbound bilirubin available to cross the BBB. Infants with kernicterus who do not die may have sequelae such as deafness, mental retardation, and cerebral palsy. Phototherapy is used to decrease bilirubin levels to prevent the elevation of unconjugated bilirubin to levels that cause kernicterus. Special blue-green lamps with wavelengths of 420-475 nm are used to break down unconjugated bilirubin to the more water-soluble product lumirubin via photoisomerization and photooxidation through the skin. This product can then be eliminated in bile and urine. The fluorescent bulbs are positioned at 50 cm above the infant with the rate of bilirubin reduction being directly proportional to the light intensity. Clinical studies have shown maximum effectiveness when the intensity of the light exceeds 12-15 W/cm2.

Newer phototherapy lights have been developed in recent years that decrease the amount of insensible water loss due to photo-induced vasodilatation. In extremely premature infants, insensible water loss can still be significant, and careful attention must be paid to fluid balance. As with the older models, the infant's eyes should be covered with patches to avoid exposure to the blue light. White light phototherapy is not as effective. Fiberoptic blankets may be used, although some concerns exist regarding skin burns from the devices.

While phototherapy of ELBW infants is initiated at birth at some institutions, others start phototherapy when the bilirubin value approaches 50% of the birth weight value (eg, 4 mg/dL in an 800-g infant). Use of prophylactic phototherapy has not been shown to decrease the peak level of total serum bilirubin (TSB) or the duration of phototherapy. If the level of bilirubin does not decrease satisfactorily with phototherapy, exchange transfusion is the next therapeutic option. Exchange transfusion should be considered in ELBW infants if the level of bilirubin approaches 10 mg/dL (or 10 mg/dL/kg). In otherwise healthy term infants, exchange transfusion is not considered until the bilirubin level approaches greater than 25 mg/dL and the infant has failed a trial of phototherapy. In exchange transfusions, almost 90% of the infant's blood is replaced with donor blood, and, if performed correctly, the bilirubin level usually falls to 50-60% of the preexchange level. Complications of exchange transfusion include electrolyte abnormalities (eg, hypocalcemia, hyperkalemia), acidosis, thrombosis, sepsis, and bleeding

Infection Infection remains a major contributing factor to the morbidity and mortality of ELBW infants and can present at any point in the clinical course. Early-onset infection (occurring within the first 72 h of life) may present with immediate respiratory distress shortly after birth or after an asymptomatic period. No matter the timing of presentation, the sequence of events leading to early-onset infection begins with colonization of the maternal genital tract. Late infections typically occur after the first week of life and result from endogenous hospital flora (nosocomial). Signs of infection are myriad, may be nonspecific, and include temperature instability (hypothermia or hyperthermia), tachycardia, decreased activity, poor perfusion, apnea, bradycardia, feeding intolerance, increased need for oxygen or higher ventilatory settings, and metabolic acidosis. Laboratory studies may include complete blood count with differential, blood culture, cerebrospinal fluid culture, urine culture, and cultures from indwelling foreign bodies, such as central lines or endotracheal tubes.

The most common causes of early sepsis in the immediate newborn period are group B streptococci (GBS) and Escherichia coli. Nosocomial sources of infection include coagulase-negative staphylococci (CoNS) and Klebsiella and Pseudomonas species, which may be resistant to the antibiotics typically started for early-onset sepsis, necessitating a different treatment regimen. Fungi, most commonly Candida albicans, are frequently a cause of late-onset sepsis in the ELBW infant and may manifest with the above-mentioned symptoms and with thrombocytopenia, particularly if the infant has been exposed to broad-spectrum antibiotics. Indolent late-onset sepsis may be related to CoNS, but fulminant late-onset clinical sepsis is more commonly secondary to gram-negative organisms. Late-onset sepsis is especially common in ELBW infants who have indwelling catheters, and it may occur in as many as 40% of these infants.

In most institutions, first-line therapy in infants with early sepsis is with ampicillin and gentamicin or a thirdgeneration cephalosporin. Vancomycin should be reserved for proven CoNS infections and organisms resistant to other agents to prevent the emergence of resistant organisms. Vancomycin and a third-generation cephalosporin often are used to treat late-onset sepsis and may be adjusted based on sensitivity patterns of positive cultures. Therapy with amphotericin commonly is initiated in infants with proven or suspected fungal infections, although fluconazole is frequently used as an alternative first-line therapy. Cultures should dictate antibiotic management whenever possible to help prevent increased resistance.

Respiratory Distress Syndrome and Chronic Lung Disease An early complication of extreme prematurity is respiratory distress syndrome (RDS) caused by surfactant deficiency. Clinical signs include tachypnea (>60 breaths/min), cyanosis, chest retractions, nasal flaring, and grunting. Untreated RDS results in increasing difficulty in breathing and increasing oxygen requirement over the first 24-72 hours of life. Chest radiographs reveal a uniform reticulogranular pattern with air bronchograms. As a result of surfactant deficiency, the alveoli collapse, causing a worsening of atelectasis, edema, and decreased total lung capacity. Surfactants decrease the surface tension of the smaller airways so that the alveoli or the terminal air sacs do not collapse, which results in less need for supplemental oxygen and ventilatory support. The incidence of RDS is inversely proportional to gestational age, with an incidence of 60% at 29 weeks' gestation. RDS affects about 40,000 infants in the United States annually, with most ELBW infants being affected. Common complications include air leak syndromes, chronic lung disease (CLD), and retinopathy of prematurity (ROP). Surfactant agents may be administered as prophylaxis or as rescue intervention after RDS. Prophylactic use in infants younger than 28 weeks' gestation has been shown to decrease short-term ventilatory needs; neither strategy has resulted in a decreased incidence of CLD/BPD.

Synthetic surfactants currently on the market lack the proteins found in animal-derived surfactants and may not be as effective as the latter. Newer synthetic surfactants with a synthetic surfactant protein analog are being tested. The incidence of RDS in preterm infants has been significantly reduced with the use of antenatal steroids to promote lung maturityan additive effect was seen with the use of both antenatal steroids and early surfactant treatment. The use of antenatal steroids also has been linked to a reduction in the incidence of clinically significant patent ductus arteriosus (PDA) and severe intraventricular hemorrhage (IVH), but concerns have surfaced regarding neurodevelopmental sequelae of repeated antenatal courses of steroids. In the last decade, surfactants have been widely used to treat RDS, and it was suggested that surfactants should be administered routinely as prophylaxis in infants younger than 30 weeks' gestation. However, this results in unnecessary treatment in some infants. A shift in practice is occurring, and fewer infants are being intubated immediately after birth, making prophylactic treatment with surfactant impossible. Infants who are not immediately intubated usually are maintained with nasal continuous positive airway pressure (CPAP), which has been shown to improve endogenous surfactant production. These infants are intubated and given surfactant only if they fail the initial trial of CPAP, as evidenced by increasing PaCO2, increasing respiratory distress, or persistently high oxygen requirement.

If used as prophylactic treatment, surfactants should be administered as soon after birth as possible. When administered as rescue treatment, a reasonable approach is to treat most infants as soon as clinical signs of RDS appear, or if the respiratory picture does not improve after the initial resuscitation. A major morbidity of premature birth is CLD (or bronchopulmonary dysplasia [BPD]), which is defined as receiving supplemental oxygen or ventilatory support at 36 weeks' postmenstrual age. This definition has relatively replaced the former definition of oxygen dependence beyond 28 days of age. BPD is a staged disease that was originally described by Northway et al in 1967 as the clinical sequelae of prolonged ventilation associated with radiographic and pathologic findings; it is the result of abnormal reparative processes in response to injury and inflammation

Intraventricular hemorrhage A hemorrhage in the brain that begins in the periventricular subependymal germinal matrix can progress into the ventricular system causing intraventricular hemorrhage (IVH). Both incidence and severity of IVH are inversely related to gestational age. ELBW babies are at particular risk for IVH because development of the germinal matrix typically is incomplete and the protective cerebral autoregulation present in older babies has not yet developed. Any event that results in disruption of vascular autoregulation can cause IVH, including hypoxia, ischemia, rapid fluid changes, and pneumothorax. Presentation can be asymptomatic or catastrophic, depending on the degree of the hemorrhage. Symptoms include apnea, hypertension or hypotension, sudden anemia, acidosis, changes in muscular tone, and seizures. The most commonly used system classifies IVH into 4 grades, as follows: Grade I - Germinal matrix hemorrhage Grade II - IVH without ventricular dilatation Grade III - IVH with ventricular dilatation Grade IV - IVH with extension into the parenchyma IVH is diagnosed using cranial ultrasonography. Since most IVHs occur within 72 hours of delivery, neurosonograms are usually performed on ELBW infants during the first week after birth and serially thereafter depending on clinical scenario. Use of antenatal steroids decreases incidence of IVH, and treatment consists of supportive care. Progressive intraventricular dilatation and hydrocephalus may necessitate surgical diversion of accumulating CSF. Early administration of indomethacin may reduce the incidence of grades III and IV IVH when used prophylactically in ELBW infants but may adversely affect urine output and platelet function, and it has not been shown to improve neurodevelopmental function at age 2 years. Prognosis is correlated with the grade of IVH. The outcome in infants with grades I and II is good; as many as 40% of infants with grade III IVH have significant cognitive impairment, and as many as 90% of infants with grade IV IVH have major neurologic sequelae. Prevention of preterm birth is the most effective method of preventing IVH. The risk of IVH is higher in infants who are transported after birth, underlining the need for preterm births to occur at tertiary centers specializing in high-risk deliveries. Adequate resuscitation is paramount, and hypocarbia and hypoxia should be avoided. Maintenance of adequate mean arterial pressure and avoiding elevations in cerebral blood flow as much as possible are vital. Multiple clinical trials have been undertaken to determine the effect of various medications, either antenatally or perinatally, on incidence of IVH. One trial demonstrated a decrease in the incidence of severe grades of IVH but no difference in neurodevelopmental outcomes at age 18-24 months with the use of postnatal indomethacin. Because of the potentially serious complications of indomethacin, the question of using such an approach remains unanswered.