Extremely low birth weight (ELBW) is defined as a birth weight less than 1000 g ( 2 lb , 3 oz ). ELBW infants also represent the youngest of premature newborns, born at 27 weeks' gestational age or younger. Nearly 1 in 10 infants with low birth weight (< 2500 g ) are ELBW infants (27,988 births in the United States in 1997). ELBW survival has improved with the widespread use of surfactant agents and maternal steroids, treatments that have lowered the minimum age of viability to as young as 23 weeks.

Mortality and morbidity:

Survivability correlates with gestational age (11.6% for birth weights < 500 g , 50.7% for birth weights of 500- 749 g , 83.9% for birth weights of 750- 1000 g ). Although black infants comprise 15.5% of live births in the United States, they account for 36.8% of babies with birth weights less than 1000 g . 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. Although the mortality rate has diminished with the use of surfactants, the proportion of surviving infants with severe sequelae, such as mental retardation, cerebral palsy, and deafness, has not.

Clinical features:

Thermoregulation

As a result of a high body surface area–to–body weight ratio, decreased brown fat stores, and decreased glycogen supply, ELBW infants are particularly susceptible to heat loss immediately after birth. Hypothermia may result in hypoglycemia, apnea, and metabolic acidosis. ELBW infants can lose heat in 4 ways, namely, via radiation, conduction, convection, and evaporation. Radiation occurs when the infant loses heat to a colder object, conduction occurs when the infant loses heat through contact with a surface, convection occurs when the infant loses heat to the surrounding air, and evaporation occurs when heat is lost through water dissipation.

Temperature control is paramount to survival and typically is achieved with use of radiant warmers or double-walled incubators. Immediately after birth, the infant should be dried and placed on a radiant warmer and a hat or another covering should be placed on its head. Hypothermia (< 35°C ) has been associated with poor outcome, including chronic oxygen dependency.

During transport from the delivery room to the neonatal intensive care unit, care should be taken to cover the baby, either with warmed blankets or with cellophane wrap, to help the infant retain body heat. The infant should be placed in a double-walled heated incubator during transport. The delivery room and the neonatal intensive care unit also should be kept warm to prevent hypothermia in the infant. Future architectural designs should facilitate adjacent location of delivery rooms and neonatal intensive care units or at least provide separately heated resuscitation rooms.

Hypoglycemia

Fetal euglycemia is maintained during pregnancy by the mother via the placenta. However, ELBW infants have difficulty maintaining glucose levels within reference range after birth, at which time the maternal source of glucose is lost. In addition, ELBW infants are usually under stress and have insufficient levels of glycogen stores. In the preterm infant, hypoglycemia usually is diagnosed when whole blood glucose levels are lower than 20-40 mg/dL. In a recent review, Cornblath et al also recommended that a glucose concentration of less than 45 mg/dL be used as a screening or treating level in preterms infants. Symptoms may be present but may not be as obvious as those in a more mature infant (seizures, jitteriness, lethargy, apnea, poor feeding).

Thus, hypoglycemia often may be discovered only after routine serum dextrose sampling. One form of accepted treatment consists of an immediate intravenous glucose infusion of 2 mL/kg of 10% dextrose-in-water solution (200 mg/kg) followed by a continuous infusion of dextrose at 6-8 mg/kg/min to maintain a constant supply of glucose for metabolic needs and to avoid hypoglycemia.

Fluids and electrolytes

Fluid and electrolyte management must be closely controlled because disturbances may result in or exacerbate morbidities, such as patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), and chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD). Compared to full-term newborns, ELBW infants have proportionally more fluid in the extracellular fluid compartment than the intracellular compartment. They also have a larger proportion of total body weight composed of water. During the early days after birth, diuresis may result in a 10-20% weight loss, which can be exacerbated by iatrogenic causes, such as radiant warmers and phototherapy.

ELBW infants also have compromised renal function stemming from a decreased glomerular filtration rate; a decreased ability to reabsorb bicarbonate, secrete potassium, and other ions; and a relative inability to concentrate urine. In addition, they reabsorb creatinine via the tubules following birth and, thus, serum creatinine levels are elevated for at least the first 48 hours of life, especially in ELBW infants, and do not reflect renal function for the first few days following birth. Fluid status is commonly monitored with daily (or sometimes twice daily) body weights and strict recording of fluid intake and output.

Electrolytes are monitored frequently to maintain homeostasis. ELBW infants are prone to nonoliguric hyperkalemia, defined as a serum potassium level greater than 6.5 mmol/L, which has been associated with cardiac arrhythmias and death. Omar et al concluded that prenatal administration of steroids prevented nonoliguric hyperkalemia in ELBW infants, and they speculated that prenatal use of steroids induced up-regulation of cell membrane sodium-potassium-ATP activity in the fetus.

Nutrition

Initiating and maintaining growth of ELBW infants is a continuing challenge. Infants commonly are weighed daily, and body length and head circumference usually are measured weekly to track growth. The growth rate often lags because of complications such as hypoxia and sepsis. Concern that early feeding may be a risk factor for necrotizing enterocolitis (NEC) often deters initiation of enteral feeding. Parenteral nutrition may provide the greater source of energy in ELBW infants in the first few weeks after birth.

ELBW infants have high energy requirements because of their greater growth rate. Heat loss from the skin also raises energy needs. ELBW infants expend 60-75 kcal/kg/d and need at least 120 kcal/kg/d to achieve the desired growth rate of 15 g/kg/d. Current common practice in the early days after birth calls for most energy to be provided in the form of parenteral glucose and lipids. ELBW infants may tolerate a glucose infusion rate of 6-8 mg/kg/min, but hyperglycemia may be a common and serious complication early after birth.

Lipid intake may vary from 1-4 g/kg/d of 20% lipid emulsion, as tolerated. Since ELBW infants lose at least 1.2 g/kg/d of endogenous protein, they require at least that amount of amino acids and 30 kcal/kg/d to maintain protein homeostasis. They also need such essential amino acids as cysteine and may require glutamine, found in human breast milk but not always present in parenteral nutrition mixtures. Trace minerals, such as iron, iodine, zinc, copper, selenium, and fluorine, are beneficial as well. Early evidence suggests that chromium, molybdenum, manganese, and cobalt may need to be added to the nutritional regimen, especially in ELBW infants who require long-term parenteral nutrition.

Enteral feeding often is begun when the infant is medically stable, using small-volume trophic feeding (approximately 10 mL/kg/d) to stimulate the gastrointestinal tract and prevent mucosal atrophy. Prolonged use of parenteral nutrition may result in cholestasis and elevated triglyceride levels. To reduce these complications, weekly laboratory tests usually are obtained to evaluate liver function, alkaline phosphatase, and triglyceride levels. Bolus feedings every 2-4 hours may begin as early as day 1. If tolerated, as evidenced by minimal gastric residuals and clinical stability, feeding may increase to 10-20 mL/kg/d, although feeding practices vary widely. Although bolus feeding may appear to be more physiologically appropriate, infants who do not tolerate the volume of the bolus may be fed continuously.

Breast milk is considered by some to be the best choice for enteral feeding and has been suggested to have protective effects against NEC. Breast milk must be fortified with calcium and phosphorus to promote proper bone growth. Low birth weight infants have a high need for macronutrients and micronutrients that approaches intrauterine needs; at the same time, the functionally immature gastrointestinal tract precludes adequate enteral intake. Despite its many immunologic and nutritional advantages, an exclusive diet of unsupplemented breast milk may provide insufficient quantities of energy, protein, calcium, and phosphorous to support the goals of intrauterine bone mineralization and growth rates in small premature infants.

Human milk may be supplemented by adding liquid or powder commercially available fortifiers, premature infant formulas, modular supplements, or vitamin/mineral supplements. Commercially available multinutrient fortifiers include Enfamil Human Milk Fortifier (Mead Johnson Nutritionals; Evansville, Indiana) or Similac Human Milk Fortifier (Ross Products, Abbott Laboratories; Columbus, Ohio), both of which are powders. Similac Natural Care Liquid Fortifier (Ross Products), which is a liquid, is also available.

Comparisons of the nutrient content and source of macronutrients of these fortifiers have been published. Potential complications of human milk fortifiers include nutrient imbalance, increased osmolarity, and bacterial contamination. A number of specially formulated preterm formulas are available that have been shown to promote proper growth, as well. Caloric density usually is increased when a full feeding volume is achieved and the infant is no longer on intravenous supplementation.

Hyperbilirubinemia

Most ELBW infants develop clinically significant typically unconjugated or indirect hyperbilirubinemia requiring treatment. Hyperbilirubinemia develops as a result of increased red blood cell turnover and destruction, an immature liver that is impaired during conjugation and elimination of bilirubin, and reduced bowel motility, which delays elimination of bilirubin-containing meconium. These manifestations of extreme prematurity in addition to typical conditions that cause jaundice (eg, ABO incompatibility, Rh disease, sepsis, inherited diseases) place these infants at higher risk for kernicterus at levels of bilirubin far below those in more mature infants. Kernicterus occurs when unconjugated bilirubin crosses the blood-brain barrier and stains the basal ganglia, pons, and cerebellum. 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. Phototherapy, which uses special blue lamps with wavelengths of 420-475 nm, breaks down unconjugated bilirubin to a more water-soluble product via photoisomerization and photooxidation through the skin. Then, this product can be eliminated in bile and urine. The fluorescent bulbs are positioned at 50 cm above the infant with a resulting intensity of 6-12 m W/cm 2 . Tan has shown that the rate of bilirubin reduction is proportional to the light intensity. Phototherapy causes an increase in insensible water loss, so the amount of fluid intake typically should be increased. The infant's eyes are covered with patches to avoid exposure to blue light.

While phototherapy is initiated at birth of ELBW infants 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). If the level of bilirubin does not decrease satisfactorily with phototherapy, exchange transfusion is another option. If the level of bilirubin approaches 10 mg/dL (or 10 mg/dL/kg), exchange transfusion can begin to be considered in ELBW infants. In otherwise healthy term infants, exchange transfusion is not considered until the bilirubin level approaches 25 mg/dL.

In exchange transfusions, almost 90% of the infant's blood is replaced with donor blood, and the bilirubin level falls to 50-60% of the preexchange level. Complications include electrolyte abnormalities (hypocalcemia, hyperkalemia), acidosis, thrombosis, sepsis, and bleeding.

Respiratory distress syndrome

An early complication of extreme prematurity is respiratory distress syndrome (RDS), which is caused by surfactant deficiency. Clinical signs include tachypnea (>60 breaths/min), cyanosis, chest retractions, nasal flaring, and grunting. Untreated RDS results in increased difficulty in breathing and an increased oxygen requirement over the first 24-72 hours of life. Chest radiographs reveal a uniform reticulogranular pattern with air bronchograms. Since the incidence of RDS correlates with the degree of prematurity, most ELBW infants are affected. 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.

Common complications include air leak syndromes, CLD, and retinopathy of prematurity (ROP). Surfactant agents may be administered as prevention or prophylactic treatment or as rescue intervention after hyaline membrane disease (HMD) is established. Synthetic surfactants lack the proteins found in animal-derived surfactants and may not be as effective as the latter.

Available evidence based on cost analysis and clinical outcome suggests that surfactants should be administered routinely as prophylaxis in infants younger than 30 weeks' gestation. When used as prophylactic treatment, surfactants should be administered as soon after birth as possible. When administered as rescue treatment, a reasonable guideline is to administer surfactants when the infant reaches an arterial-to-alveolar (a/A) oxygen ratio of 0.22 or less. Typically, this is seen in an infant who requires greater than 35% oxygen to maintain a PaO 2 of 50- 80 mm Hg.

A major morbidity of premature birth is CLD, which is defined as receiving supplemental oxygen at 36 weeks' postmenstrual age, which has become more frequently accepted than the former definition of oxygen dependence beyond age of 28 days. BPD is included in the spectrum of CLD and was originally described by Northway et al in 1967 as the clinical sequelae of prolonged ventilation associated with radiographic and pathologic findings.

Lemons et al looked at the outcomes of 4438 infants in the National Institutes of Child Health and Human Development Neonatal Research Network (NICHD) registry with birth weights between 501- 1500 g born from 1995-1996. They found that 52% of the infants in the 501- to 750-g group had CLD and 34% of the infants in the 751- to 1000-g group also were affected. Hack et al, looking at 333 ELBW infants born from 1992-1995 also found that of the 241 infants who survived to 20 months' corrected age, 40% (89) had CLD. CLD is also a risk factor for poor neurodevelopmental outcome. The exact reason is not clear but appears to be related to poor growth and prolonged episodes of hypoxia, which may contribute to neuronal injury.

Apnea of prematurity (AOP) is common in ELBW infants and is defined as cessation of breathing, typically lasting 15-20 seconds, with or without bradycardia or cyanosis. The incidence is inversely correlated with gestational age and weight. As many as 90% of infants weighing less than 1000 g at birth have AOP. Apnea can be caused by decreased central respiratory drive, which causes what is termed central apnea. Apnea also can be caused by an obstruction in which no nasal airflow occurs despite initiation of respiration, by a combination of central and obstructive apnea, or by mixed apnea, in which a lack of central respiratory stimulation is followed by airway obstruction.

In addition, apnea can be caused by hypoxia, sepsis, hypoglycemia, neurologic lesions, seizures, and temperature irregularities. Apnea is diagnosed clinically and can be detected via use of cardiorespiratory monitors and pulse oximetry. A pneumogram can be used to illustrate the number and severity of the apneic episodes, with or without bradycardia, in conjunction with a continuous electrocardiogram reading. Treatment of AOP includes nasal continuous positive airway pressure (CPAP) and use of pharmacologic agents, such as theophylline and caffeine citrate. Caffeine appears to be more effective in stimulating the central nervous system and has a wider therapeutic range than theophylline, and caffeine causes less tachycardia than theophylline. Theophylline is more efficacious than caffeine as a bronchodilator and diuretic.

Premature infants who are believed to have AOP at the time of discharge may be sent home with an apnea monitor. In one study, as many as 40% of babies born weighing less than 750 g went home with a monitor; however, the use of home apnea monitors remains controversial. AOP often persists beyond 40 weeks' corrected age, which is longer than was previously believed. AOP does not appear to be related to an increased incidence of sudden infant death syndrome.

Patent ductus arteriosus

In the fetus, the ductus arteriosus is a conduit between the left pulmonary artery and the aorta that results in shunting of blood past the lungs. In full-term newborns, the PDA typically closes within 48 hours of birth because of oxygen-induced prostaglandin production, which constricts the ductus. However, as many as 80% of ELBW infants have a clinically significant PDA, resulting in a left-to-right shunt that causes a variety of symptoms, including a loud systolic murmur, widened pulse pressures, bounding pulses, hyperactive precordium, increased effort to breathe, and, because of a net decrease in systemic cardiac output due to left-to-right shunting, decreased urine output, feeding intolerance, and hypotension. Diagnosis typically is confirmed using echocardiography, and treatment includes decrease of fluid intake, indomethacin administration, and surgical ligation, if necessary.

Indomethacin is used prophylactically at some institutions and is administered in the first 24 hours of life to close a PDA in anticipation of the deleterious effects of a continued PDA in an ELBW infant. Some evidence suggests that prophylactic use of indomethacin has led to decreased symptomatic PDAs and PDA ligations in ELBW infants. Concerns regarding indomethacin and its effects on cerebral and renal blood flow have led to the investigation of the role of intravenous ibuprofen as an agent to close a PDA in preterm infants.

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 infection that occurs during the first 3-4 days of life is believed to result from maternal factors, particularly if chorioamnionitis was diagnosed prenatally. Late nosocomial infections typically occur after the first week of life and result from endogenous hospital flora. 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), Escherichia coli, and Listeria monocytogenes . Nosocomial sources of infection include coagulase-negative staphylococci (CoNS), and Klebsiella and Pseudomonas species, which may necessitate a different antibiotic regimen than antibiotics typically started after birth for suspected sepsis. CoNS and fungi, most commonly Candida albicans, are causes of late-onset sepsis and may manifest with the above-mentioned symptoms and with thrombocytopenia. Importantly, fulminant late-onset clinical sepsis rarely is caused by CoNS and 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 third-generation 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. Therapy with amphotericin commonly is initiated in infants with fungal infections. Cultures should dictate antibiotic management whenever possible.

Necrotizing enterocolitis

NEC is a disease of the premature gastrointestinal tract that represents injury to the intestinal mucosa and vasculature. Incidence of NEC is associated with decreasing gestational age, and it is a dreaded complication of premature birth. NEC accounts for 7.5% of all neonatal deaths. Risk factors include asphyxia or any ischemic insult to the gastrointestinal blood supply. The role of enteral feeding is controversial. Breast milk may have a protective effect but has not been shown to prevent NEC.

Presenting symptoms may be vague and include apnea, bradycardia, and abdominal distention. These symptoms can quickly progress to indicators of increasing sepsis, such as large gastric residuals, metabolic acidosis, and lethargy. Radiographic findings include stacked bowel loops, pneumatosis intestinalis (presence of gas in the bowel wall), portal venous gas, and free air, which indicates perforation of the bowel and is an ominous sign of impending deterioration. NEC usually presents close to the time that the infant is taking full enteral feedings, usually between the second and third weeks of life.

NEC is commonly managed with antibiotics, elimination of oral intake, gastric decompression by nasogastric tube, and supportive measures to correct complications such as metabolic acidosis, thrombocytopenia, and hypotension. Surgical intervention may be necessary if evidence of perforation exists (presence of free air on radiographs) or medical treatment fails. Long-term complications include those related to bowel resection (short gut syndrome), bowel strictures, and risk of abdominal adhesions.

Spontaneous bowel perforation often occurs in the first week of life, presenting earlier than a typical case of NEC. Stark et al showed a strong interaction between postnatal use of dexamethasone and indomethacin on incidence of perforation (19%) in ELBW infants in a trial designed to determine if a 10-day course of postnatal dexamethasone would reduce the risk of CLD or death.

Intraventricular hemorrhage

A hemorrhage in the brain that begins in the periventricular subependymal germinal matrix can progress into the ventricular system. 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. 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. One commonly used system classifies IVH into 4 grades, as follows:

IVH is diagnosed using cranial ultrasound, which usually is performed on ELBW infants during the first week after birth, since most IVHs occur within 72 hours of delivery. Use of antenatal steroids decreases incidence of IVH, and treatment consists of supportive care. Early administration of indomethacin also reduces the risk of IVH when used prophylactically in ELBW infants but may affect urine output and platelet function adversely. 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.

The recent Trial of Indomethacin Prophylaxis in Prematurity (TIPP) demonstrated a decrease in the incidence of severe grades of IVH but no difference in neurodevelopmental outcomes at age 18-24 months. Thus, the question of using such an approach remains unanswered. The use of antenatal steroids has been associated with a decreased incidence of IVH in ELBW infants.

Periventricular leukomalacia

Periventricular leukomalacia (PVL) is defined as damage to white matter that results in severe motor and cognitive deficits in ELBW infants who survive. PVL occurs most often at the site of the occipital radiation at the trigone of the lateral ventricles and around the foramen of Monro. The origin of PVL is believed to be multifactorial; the injury possibly results from episodes of fluctuating cerebral blood flow, which are caused by prolonged episodes of systemic hypertension or hypotension. PVL has been linked to periods of hypocarbic alkalosis. Recently, PVL also has been associated with chorioamnionitis. PVL is diagnosed using brain ultrasound in patients aged 4-6 weeks, and it occurs in 10-15% of ELBW infants. The presence of PVL, particularly cystic PVL, is associated with an increased risk of cerebral palsy; spastic diplegia is the most common outcome.

Follow-up:

Nearly all ELBW infants require neurodevelopmental follow-up monitoring to track their progress and to identify disorders that were not apparent during the hospital stay. These infants typically have complicated medical courses and often go home with multiple treatments and medications. In addition to monitoring their immediate medical needs upon discharge, evaluation of cognitive development, vision and hearing ability, and neurodevelopmental progress is important.

As many as 48% of ELBW infants have some type of major neurosensory or neurodevelopmental impairment. Infants with grade III or IV IVH or infants with PVL (cysts in brain parenchyma, typically seen on routine brain ultrasound /images in infants aged 4-6 wk) are at the greatest risk for mental retardation. Other risk factors for developmental disabilities include meningitis, asphyxia, delayed head growth, and CLD.

Saigal et al investigated the long-term academic and social outcomes of ELBW infants born from 1977- 1982 in Ontario , Canada . ELBW infants performed more poorly at psychometric testing at age 8 years and continued to do so into their adolescence. When the birth weights were stratified, the cohort with birth weights less than 750 g performed worse than the heavier ELBW cohort (750- 1000 g ), but both groups still required more remedial resources than the control group of term children. However, although this group of children were reported by their parents to have more frequent and more complex limitations to daily functioning, the children and their parents rated the quality of life of the children to be fairly high.

Vision

Retinopathy of prematurity (ROP) is a disease of a premature retina that has not yet fully vascularized. Changes in oxygen exposure have been postulated to cause a disruption in the natural course of vascularization and may result in abnormal growth of blood vessels, which can result in retinal detachment and blindness. All infants with birth weights less than 1000 g should undergo an eye examination by an experienced pediatric ophthalmologist at age 4-6 weeks and, depending on the results, at least every 2 weeks thereafter until the retina is fully vascularized.

If ROP is present, its stage and location dictate management, which can range from repeat examinations 1 week later to laser surgery or cryotherapy. The presence of plus disease, or tortuosity of the retinal vessels, is a poor prognostic sign and requires immediate treatment. Infants with ROP are also at greater risk for sequelae, such as myopia, strabismus, and amblyopia. ELBW infants without ROP should have a follow-up eye examination at age 6 months.

Hearing

All infants should undergo hearing examinations prior to discharge, using either evoked otoacoustic emissions or brainstem auditory evoked potentials. ELBW infants are at higher risk for hearing impairment because of their low birth weights. Other risk factors include meningitis, asphyxia, exchange transfusions, and administration of ototoxic drugs such as gentamicin. In addition, ELBW infants should undergo repeat hearing examinations at age 6 months.

Other therapy

For problems with cognitive and neurodevelopmental development, physical and occupational therapy and early intervention development programs should be some of the options available. Such programs should be coordinated with the infant's pediatrician and with the follow-up care clinic. As an increasing number of babies are born and continue to survive with birth weights less than 1000 g ; optimizing their chances for a healthy productive life is important.

Medical and legal pitfalls:

As the number of ELBW infants increased in the postsurfactant era, so did questions regarding ethical, economic, and legal dilemmas surrounding the care of the infants. The United States is no longer alone in confronting neonatal-perinatal medical, legal, and ethical issues.

Management of anticipated delivery of an ELBW infant and subsequent care require the clinician to make decisions "in the moment of clinical truth." Pellegrino successfully argues that morally defensible difficult decisions must be made with available information and focus on "the morally right and good thing to do in this patient." Information regarding mortality, morbidity, and prognosis changes with time. Using the best information available, the clinician should manage the situation while taking into account the family's wishes and "what is in the best interest of the patient." When resolving bioethical dilemmas facing families and clinicians, the physician must address issues of futility, extension of the dying process, respect for the dignity of life, and pain and suffering. From a legal standpoint in the United States , government regulations exist based on child abuse laws enforced by individual states.

The question of what to do in the case of extreme prematurity ( < 23 wk) is a difficult one. Gestational age, which typically is based on the mother's recount of her last menstrual period, can differ from the actual gestational age by as much as 2 weeks, even when the latest ultrasound technology is used. Most centers do not have minimum birth weight criteria for resuscitation, and often a "trial of life" may be discussed with the parents before the birth so that the infant can be resuscitated and evaluated for viability after birth. Discussions about treatment or withdrawal of support are often necessary when the family and medical team agree that continuation of medical treatment is not in the infant's best interest.

Naturally, these circumstances raise numerous ethical, moral, and legal issues and sometimes generate more questions than answers. Bioethics consultants and multidisciplinary ethics committees discuss such issues and arrive at recommendations for clinicians and families.

A 1987 California study calculated that the average cost per first-year survivor in infants in neonatal intensive care units with birth weights less than 750 g was $273,900; for those who weighed 750- 999 g , average cost was $138,800. However, the overall percentage of costs for infants who died, usually within the first 3 days of life, was small. Hospital bills continue to rise as a result of advancing technology and may rise even higher if the child needs any type of rehabilitation or follow-up care. The infant's family undergoes severe emotional and financial stress with the birth of an extremely premature infant, and they often are confused, angry, and frustrated by resulting issues. In addition, society in general is affected by these infants, some of whom are significantly cognitively or physically impaired and require lifelong public assistance.