Incidence

The reported incidence of spontaneous twinning is highest among blacks and East Indians, followed by northern European whites, and is lowest in the Asian races. Specific rates are 1/56 in Belgium, 1/70 among American blacks, 1/86 in Italy, 1/88 among American whites, 1/130 in Greece, 1/150 in Japan, and 1/300 in China. Differences in the incidence of twins mainly involve fraternal (polyovular) dizygotic twins. Triplets are estimated to occur in 1 in 86² pregnancies and quadruplets in 1 in 86³ pregnancies in the USA. The incidence of monozygotic twins (3-5/1,000) is unaffected by racial or familial factors. The incidence of twins detected by ultrasonography at 12 wk of gestation (3-5%) is much higher than that occurring later in pregnancy; the vanishing twin syndrome results in a singleton fetus. Although the incidence of spontaneous multifetal gestation has been stable over the years, the overall incidence of multifetal gestation is increasing as a result of treatment of infertility with ovarian stimulants (clomiphene, gonadotropins) and in vitro fertilization. Twins account for about 2.5% of births but about 20% of very low birthweight (VLBW) infants.

Etiology

The occurrence of monovular twins appears to be independent of genetic influence. Polyovular pregnancies are more frequent beyond the 2nd pregnancy, in older women, and in families with a history of polyovular twins. They may result from simultaneous maturation of multiple ovarian follicles, but follicles containing two ova have been described as a genetic trait leading to twin pregnancies. Twin-prone women have higher levels of gonadotropin. Polyovular pregnancies occur in many women treated for infertility.

Conjoined twins (Siamese twins—incidence 1/50,000) probably result from relatively late monovular separation, as does the presence of two separate embryos in one amniotic sac. The latter condition has a high fatality rate owing to obstruction of the circulation secondary to intertwining of the umbilical cords. The prognosis for conjoined twins depends on the possibility of surgical separation, which in turn depends on the extent to which vital organs are shared. The site of connections varies: thoraco-omphalopagus (28% of conjoined twins), thoracopagus (18%), omphalopagus (10%), craniopagus (6%), and incomplete duplication (10%). Difficult-to-separate conjoined twins have occasionally survived to adulthood. Most conjoined twins are female.

Superfecundation, or fertilization of an ovum by an insemination that takes place after one ovum has already been fertilized, and superfetation, or fertilization and subsequent development of an embryo when a fetus is already present in the uterus, have been proposed as uncommon explanations for differences in size and appearance of certain twins at birth.

A prenatal diagnosis of pregnancy with twins is suggested by a uterine size that is greater than that expected for gestational age, auscultation of two fetal hearts, and elevated maternal serum α-fetoprotein or human chorionic gonadotropin levels, and it is confirmed by ultrasonography. Ninety percent of twins are detected before delivery.

Monozygotic Versus Dizygotic Twins

Identifying twins as monozygotic or dizygotic (monovular or polyovular) is important because studying monozygotic twins is useful in determining the relative influence of heredity and environment on human development and disease. Twins of widely discrepant size are usually monochorionic. Twins not of the same sex are dizygotic. In twins of the same sex, zygosity should be determined and recorded at birth through careful examination of the placenta. Detailed blood typing, gene analysis, or tissue (HLA) typing can also be used to determine zygosity. Monozygotic twins may have physical and cognitive differences because their in utero environment may be different; differences may exist in the mitochondrial genome, in post-translational gene product modification, and in the epigenetic modification of nuclear genes in response to environmental factors.

Prognosis

Most twins are born prematurely, and maternal complications of pregnancy are more common than with single pregnancies. The risk for twins is most often associated with twin-twin transfusion, assisted reproductive technology, and early-onset discordant growth. Although monochorionic twins have a significantly higher perinatal mortality, there is no significant difference between the neonatal mortality rates of twin births and single births in comparable weight and gestational age groups (Fig. 91-2). Because most twins are premature, their overall mortality is higher than that of single-birth infants. The perinatal mortality of twins is about four times that of singletons. Monoamnionic twins have an increased likelihood of entangling the cords, which may lead to asphyxia. Theoretically, the 2nd twin is more subject to anoxia than the 1st because the placenta may separate after birth of the 1st twin and before birth of the 2nd. In addition, delivery of the 2nd twin may be difficult because it may be in an abnormal presentation (breech, entangled), uterine tone may be decreased, or the cervix may begin to close after the 1st twin’s birth. The mortality for multiple gestations with four or more fetuses is excessively high for each fetus. Because of this poor prognosis, selective fetal reduction (with transabdominal intrathoracic fetal injection of KCl) to two to three fetuses has been offered as a treatment option. Monozygotic twins have an increased risk of one twin dying in utero. The surviving twin has a greater risk for cerebral palsy and other neurodevelopmental sequelae.

Figure 91-2 Mortality, all discharges, The neonatal mortality rate for all babies who died during the original hospitalization at each week of gestational age is given. The bars on the left represent singletons; the middle bars represent twins, and the bars on the right represent triplets. There are no differences among singleton births, twin births, and triplet births. EGA, estimated gestational age.

(From Garite TJ, Clark RH, Elliott JP, et al: Twins and triplets: the effect of plurality and growth on neonatal outcome compared with singleton infants, Am J Obstet Gynecol 191:700–707, 2004.)

Treatment

Prenatal diagnosis enables the obstetrician and pediatrician to anticipate the birth of infants who are at high risk because of twinning. Close observation is indicated during labor and in the immediate neonatal period so that prompt treatment of asphyxia or fetal transfusion syndrome can be initiated. The decision to perform an immediate blood transfusion in a severely anemic “donor twin” or to perform a partial exchange transfusion of a “recipient twin” must be based on clinical judgment.

Definitions

Liveborn infants delivered before 37 wk from the 1st day of the last menstrual period are termed premature by the World Health Organization. LBW (birthweight of 2,500 g or less) is due to prematurity, poor intrauterine growth (IUGR, also referred to as SGA), or both. Prematurity and IUGR are associated with increased neonatal morbidity and mortality. Ideally, definitions of LBW for individual populations should be based on data that are as genetically and environmentally homogeneous as possible. As previously mentioned, Figure 91-1 presents variations in mortality based on birthweight, gestational age, and gender.

Incidence

There is an increasing percentage of deaths in children <5 yr of age that occur in the neonatal period. Approximately 57% of deaths in this age group occur within the 1st mo of life, of which approximately 36% are attributable to premature birth. In 2008, 8.2% of liveborn neonates in the USA weighed <2,500 g; the rate for blacks was almost twice that for whites. Over the past 2 decades, the LBW rate has increased primarily because of an increased number of preterm births. Women whose 1st births are delivered before term are at increased risk for recurrent preterm delivery. Approximately 30% of LBW infants in the USA have IUGR and are born after 37 wk. At LBW rates >10%, the contribution of IUGR increases and that of prematurity decreases. In developing countries, approximately 70% of LBW infants have IUGR. Infants with IUGR have greater morbidity and mortality than do appropriately grown, gestational age–matched infants (see Fig. 91-1). Although U.S. infant mortality rates have fallen since 1971, the ethnic disparity between black infants and white or Hispanic infants remains unchanged. Black infants have higher neonatal mortality rates and comprise a larger percentage of low birthweight births in the USA.

The incidence of preterm births in the USA continues to rise (Fig. 91-3) and is due in part to multiple gestation pregnancies. In single births, the overall incidence has been stable, but premature births due to medically indicated deliveries have increased, whereas premature births due to spontaneous preterm birth or ruptured membranes have declined (Fig. 91-4).

Figure 91-3 Percentage of all births classified as preterm in the USA, 1981-2004.

(From Martin JA, Kochanek KD, Strobino DM, et al: Annual summary of vital statistics—2003, Pediatrics 115:619–634, 2005.)

Figure 91-4 Temporal changes in singleton preterm births overall and temporal changes resulting from ruptured membranes, medically indicated preterm labor, and spontaneous preterm labor in the USA, 1989-2000. A, Rates in each group by year. B, The percentage change in rates relative to 1989.

(Adapted from Ananth CV, Joseph KS, Oyelese Y, et al: Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000, Obstet Gynecol 105:1084–1091, 2005.)

Very Low Birthweight Infants

VLBW infants weigh <1,500 g and are predominantly premature. In the USA in 2008, the VLBW rates were approximately 1.46% overall, 3.01% among blacks, and 1.18% among whites. The VLBW rate is an accurate predictor of the infant mortality rate. VLBW infants account for over 50% of neonatal deaths and 50% of handicapped infants; their survival is directly related to birthweight, with approximately 20% of those between 500 and 600 g and >90% of those between 1,250 and 1,500 g surviving. The VLBW rate has remained unchanged for black Americans but has increased among whites, perhaps because of a rise in multiple births among whites. Perinatal care has improved the rate of survival of VLBW infants. When compared with term infants, VLBW neonates have a higher incidence of rehospitalization during the 1st yr of life for sequelae of prematurity, infections, neurologic complications, and psychosocial disorders.

Factors Related to Premature Birth and Low Birthweight

It is difficult to separate completely the factors associated with prematurity from those associated with IUGR (Chapters 88 and 89). A strong positive correlation exists between both preterm birth and IUGR and low socioeconomic status. Families of low socioeconomic status have higher rates of maternal undernutrition, anemia, and illness; inadequate prenatal care; drug misuse; obstetric complications; and maternal history of reproductive inefficiency (abortions, stillbirths, premature or LBW infants). Other associated factors, such as single-parent families, teenage pregnancies, short interpregnancy interval, and mothers who have borne more than four previous children, are also encountered more frequently in such families. Systematic differences in fetal growth have also been described in association with maternal size, birth order, sibling weight, social class, maternal smoking, and other factors. The degree to which the variance in birthweight among various populations is due to environmental (extrafetal) rather than genetic differences in growth potential is difficult to determine.

The etiology of preterm birth is multifactorial and involves a complex interaction between fetal, placental, uterine, and maternal factors (Table 91-3).

Premature birth of infants whose LBW is appropriate for their preterm gestational age is associated with medical conditions characterized by an inability of the uterus to retain the fetus, interference with the course of the pregnancy, premature rupture of the amniotic membranes or premature separation of the placenta, multifetal gestation, or an undetermined stimulus to effective uterine contractions before term.

Overt or asymptomatic bacterial infection (group B streptococci, Listeria monocytogenes, Ureaplasma urealyticum, Mycoplasma hominis, Chlamydia, Trichomonas vaginalis, Gardnerella vaginalis, Bacteroides spp.) of the amniotic fluid and membranes (chorioamnionitis) may initiate preterm labor. Bacterial products may stimulate the production of local inflammatory mediators (interleukin-6, prostaglandins), which may induce premature uterine contractions or a local inflammatory response with focal amniotic membrane rupture. Appropriate antibiotic therapy reduces the risk of fetal infection and may prolong gestation.

IUGR is associated with medical conditions that interfere with the circulation and efficiency of the placenta, with the development or growth of the fetus, or with the general health and nutrition of the mother (Table 91-4). Many factors are common to both prematurely born and LBW infants with IUGR. IUGR is associated with decreased insulin production or insulin (or insulin-like growth factor [IGF]) action at the receptor level. Infants with IGF-I receptor defects, pancreatic hypoplasia, or transient neonatal diabetes have IUGR. Genetic mutations affecting the glucose-sensing mechanisms of the pancreatic islet cells that result in decreased insulin release (loss of function of the glucose-sensing glucokinase gene) give rise to IUGR.

IUGR may be a normal fetal response to nutritional or oxygen deprivation. Therefore, the issue is not the IUGR but rather the ongoing risk of fetal malnutrition or hypoxia. Similarly, some preterm births signify a need for early delivery from a potentially disadvantageous intrauterine environment. IUGR is often classified as reduced growth that is symmetric (head circumference, length, and weight equally affected) or asymmetric (with relative sparing of head growth) (see Fig. 90-1). Symmetric IUGR often has an earlier onset and is associated with diseases that seriously affect fetal cell number, such as conditions with chromosomal, genetic, malformation, teratogenic, infectious, or severe maternal hypertensive etiologies. It is important to assess gestational age carefully in infants suspected to have symmetric IUGR because incorrect overestimation of gestational age may lead to the diagnosis of symmetric IUGR. Asymmetric IUGR is often of late onset, demonstrates preservation of Doppler waveform velocity to the carotid vessels, and is associated with poor maternal nutrition or with late onset or exacerbation of maternal vascular disease (preeclampsia, chronic hypertension). Problems of infants with IUGR are noted in Table 91-5.

Table 91-5 PROBLEMS OF INFANTS SMALL FOR GESTATIONAL AGE OR WITH INTRAUTERINE GROWTH RETARDATION*

↓, Decreased; ↑, increased.

* Other problems include pulmonary hemorrhage and those common to the gestational age-related risks of prematurity if born at less than 37 wk.

Assessment of Gestational Age at Birth

When compared with a premature infant of appropriate weight, an infant with IUGR has a reduced birthweight and may appear to have a disproportionately larger head relative to body size; infants in both groups lack subcutaneous fat. Neurologic maturity (nerve conduction velocity), in the absence of asphyxia, correlates with gestational age despite reduced fetal weight. Physical signs may be useful in estimating gestational age at birth. Commonly used, the Ballard scoring system is accurate to ±2 wk (Figs. 91-5 to 91-7). An infant should be presumed to be at high risk for mortality or morbidity if a discrepancy exists between the estimation of gestational age by physical examination, the mother’s estimated date of her last menstrual period, and fetal ultrasonographic evaluation.

Figure 91-5 Physical criteria for maturity. The expanded New Ballard score includes extremely premature infants and has been refined to improve accuracy in more mature infants.

(From Ballard JL, Khoury JC, Wedig K, et al: New Ballard score, expanded to include extremely premature infants, J Pediatr 119:417–423, 1991.)

Figure 91-6 Neuromuscular criteria for maturity. The expanded New Ballard score includes extremely premature infants and has been refined to improve accuracy in more mature infants.

(From Ballard JL, Khoury JC, Wedig K, et al: New Ballard score, expanded to include extremely premature infants, J Pediatr 119:417–423, 1991.)

Figure 91-7 Maturity rating. The physical and neurologic scores are added to calculate gestational age.

(From Ballard JL, Khoury JC, Wedig K, et al: New Ballard score, expanded to include extremely premature infants, J Pediatr 119:417–423, 1991.)

Spectrum of Disease in Low-Birthweight Infants

Immaturity increases the severity but reduces the distinctiveness of the clinical manifestations of most neonatal diseases. Immature organ function, complications of therapy, and the specific disorders that caused the premature onset of labor contribute to the neonatal morbidity and mortality associated with premature, LBW infants (Table 91-6). Among VLBW infants, morbidity is inversely related to birthweight. Respiratory distress syndrome is noted in approximately 80% of infants weighing 501-750 g; in 65% of those 751-1,000 g; in 45% of those 1,001-1,250 g; and in 25% of those 1,251-1,500 g. Severe intraventricular hemorrhage (IVH) is noted in approximately 25% of infants weighing 501-750 g; in 12% of those 751-1,000 g; in 8% of those 1,001-1,250 g; and in 3% of those 1,251-1,500 g. Overall, the risk of late sepsis (24%), bronchopulmonary dysplasia (23%), severe IVH (11%), necrotizing enterocolitis (7%), and prolonged hospitalization (45-125 days) is high in VLBW infants. Problems associated with IUGR LBW infants are noted in Table 91-5; these added problems are often superimposed on those noted in Table 91-6 if an infant with IUGR is also premature. Poor postnatal growth is an important problem for both preterm and IUGR infants.

Nursery Care

At birth, the measures needed to clear the airway, initiate breathing, care for the umbilical cord and eyes, and administer vitamin K are the same for immature infants as for those of normal weight and maturity (Chapter 88). Special care is required to maintain a patent airway. Additional considerations are the need for (1) thermal control and monitoring of the heart rate and respiration, (2) oxygen therapy, and (3) special attention to the details of fluid requirements and nutrition. Safeguards against infection can never be relaxed. Routine procedures that disturb these infants may result in hypoxia. The need for regular and active participation by the parents in the infant’s care in the nursery, the need to instruct the mother in at-home care of her infant, and the question of prognosis for later growth and development require special consideration.

Initiation of Feeding

The optimal time to introduce enteral feeding to a sick premature or LBW infant is controversial. Trophic feeding is the practice of feeding very small amounts of enteral nourishment to VLBW preterm infants to stimulate development of the immature gastrointestinal tract. The benefits of trophic feeding include enhanced gut motility, improved growth, decreased need for parenteral nutrition, fewer episodes of sepsis, and shortened hospital stay. Once the infant is stable, small-volume feedings are given in addition to intravenous fluids/nutrition. Feeding is gradually advanced, and parenteral nutrition decreased. This approach may reduce the incidence of necrotizing enterocolitis. The main principle in feeding premature infants is to proceed cautiously and gradually. Careful early feeding of breast milk or formula tends to reduce the risk of hypoglycemia, dehydration, and hyperbilirubinemia without the additional risk of aspiration, provided that there is no indication for withholding oral feedings, such as the presence of respiratory distress or other disorders.

If an infant is well, is making sucking movements, and is in no distress, oral feeding may be attempted, although most infants weighing <1,500 g require tube feeding because they are unable to coordinate breathing, sucking, and swallowing. Intestinal tract readiness for feeding may be determined by active bowel sounds, passage of meconium, and the absence of abdominal distention, bilious gastric aspirates, and emesis. For infants <1,000 g, the initial trophic feedings can be given at 10-20 mL/kg/24 hr as a continuous nasogastric tube drip (or given by intermittent gavage every 2-3 hr) for 5-10 days. If the initial feedings are tolerated, the volume is increased by 20-30 mL/kg/24 hr. Once a volume of 150 mL/kg/24 hr has been achieved, the caloric content may be increased to 24 or 27 kcal/oz. With high caloric density, infants are at risk for dehydration, edema, lactose intolerance, diarrhea, flatus, and delayed gastric emptying with emesis. Intravenous fluids are needed until feedings provide approximately 120 mL/kg/24 hr. The feeding protocol for premature infants weighing >1,500 g is initiated at a volume of 20-30 mL/kg/24 hr with increments in total daily formula volume of 20-30 mL/kg/24 hr. The expected weight increments for premature infants of various birthweights are projected from Figure 91-8. Infants with IUGR may not demonstrate the marked initial weight loss noted in premature infants.

Figure 91-8 Average daily weight vs postnatal age for infants with birthweight ranges of 501-750 g, 751-1,000 g, 1,001-1,250 g, and 1,251-1,500 g (dotted lines), plotted with the curves from Dancis and colleagues for infants with birthweights of 750 g, 1,000 g, 1,250 g, and 1,500 g (solid lines).

(From Wright K, Dawson JP, Fallis D, et al: New postnatal growth grids for very low birth weight infants, Pediatrics 91:922–926, 1993.)

Regurgitation, vomiting, abdominal distention, or gastric residuals from previous feedings should arouse suspicion of sepsis, necrotizing enterocolitis, or intestinal obstruction; these conditions are indications to stop feedings, at least temporarily, and to increase subsequent feedings slowly only as tolerated or to change to intravenous alimentation and evaluate the infant for more serious problems (Chapter 96.2). Weight gain may not be achieved for 10-12 days. Alternatively, in infants whose feeding schedule is advanced successfully in calories or volume, weight gain may appear within a few days.

When tube feeding is used, the contents of the stomach should be aspirated before each feeding. If only air or small amounts of mucus are obtained, the feeding is given as planned. If all or a substantial part of the previous feeding is aspirated, it is advisable to withhold feedings or to reduce the amount of the feeding and proceed more gradually with subsequent increases, depending on the physical findings and other evidence of feeding intolerance.

The digestive enzyme systems of infants older than 28 wk of gestation are mature enough to permit adequate digestion and absorption of protein and carbohydrate. Fat is less well absorbed, primarily because of inadequate amounts of bile salt; unsaturated fats and the fat of human milk are absorbed better than the fat of cow’s milk. The weight gain of infants weighing <2,000 g at birth should be adequate when either human milk or “humanized” milk premature formula (40% casein and 60% whey) with a protein intake of 2.25-2.75 g/kg/24 hr is fed. These two alternatives should provide all amino acids essential for premature infants, including tyrosine, cystine, and histidine. Higher protein intake may be well tolerated and is generally safe, especially in older, rapidly growing infants. Protein intake >4-5 g/kg/24 hr may be hazardous. Although they may promote linear growth, high-protein formulas may cause abnormal plasma aminogram results; elevations in blood urea nitrogen, ammonia, and sodium concentrations; metabolic acidosis (cow’s milk formulas); and untoward effects on neurologic development. Furthermore, the high protein and mineral contents of balanced cow’s milk formulas with a high caloric content constitute a large solute load for the kidneys, a fact important in maintaining water balance, especially in infants with diarrhea or fever.

Breast milk from their mothers is the preferred milk for all infants, including VLBW infants. In addition to nutritional advantages, the benefits of breast milk include protection against a wide range of infections (through both specific and nonspecific anti-infective factors in breast milk and beneficial effects on intestinal flora), a decreased risk of necrotizing enterocolitis in preterm infants, a lower risk of sudden infant death syndrome, and possible long-term effects, including a lower risk of childhood/adolescent obesity and improved neurodevelopmental outcome. Once a premature infant takes 120 mL/kg/24 hr, breast milk fortifiers are added to supplement breast milk with protein, calcium, and phosphorus. If breast milk is unavailable, special preterm formulas should be used.

Properly fed premature infants may have from 1 to 8 daily stools of semisolid consistency; a sudden increase in their number, the appearance of occult or gross blood, or change to a watery consistency is more reason for concern than any arbitrarily stated stooling frequency.

Immaturity of Drug Metabolism

Renal clearance of almost all substances excreted in the urine is diminished in newborn infants, but more so in premature ones. The glomerular filtration rate rises with increasing gestational age; therefore drug dosing recommendations vary with age. Intervals between doses may therefore need to be extended with administration of drugs excreted chiefly by the kidneys. Longer intervals are required for many drugs administered to preterm infants. Drugs that are detoxified in the liver or require chemical conjugation before renal excretion should also be given with caution and in doses smaller than usual.

When possible, blood levels should be determined for potentially toxic drugs, especially if renal or hepatic dysfunction is present. Decisions about the choice and dose of antibacterial agents and the route of administration should be made on an individual basis rather than routinely because of the dangers of (1) development of infections with organisms resistant to antibacterial agents, (2) inhibition of intestinal bacteria that manufacture significant amounts of essential vitamins (vitamin K and thiamine), and (3) harmful interference in important metabolic processes.

Many drugs apparently safe for adults on the basis of toxicity studies may be harmful to newborn infants, especially premature ones. Oxygen and a number of drugs have proved toxic to premature infants in amounts not harmful to term infants (Table 91-7). Thus, administering any drug, particularly in high doses, that has not undergone pharmacologic testing in premature infants should be undertaken carefully after risks have been weighed against benefits.

Table 91-7 POTENTIAL ADVERSE REACTIONS TO DRUGS ADMINISTERED TO PREMATURE INFANTS

Prognosis

Infants born weighing 1,501-2,500 g have a 95% or greater chance of survival, but those weighing still less have significantly higher mortality (see Fig. 91-1). Intensive care has extended the period during which a VLBW infant is at increased risk of dying of complications of prematurity, such as bronchopulmonary dysplasia, necrotizing enterocolitis, and nosocomial infection (Table 91-8). The postdischarge mortality rate of LBW infants is higher than that of term infants during the 1st 2 yr of life. Because many of the deaths are attributable to infection (e.g., respiratory syncytial virus [RSV]), they are at least theoretically preventable. In addition, premature infants have an increased incidence of failure to thrive, sudden infant death syndrome, child abuse, and inadequate maternal-infant bonding. The biologic risk associated with poor cardiorespiratory regulation due to immaturity or complications of underlying perinatal disease and the social risk associated with poverty also contribute to the high mortality and morbidity of these infants. Congenital anomalies are present in approximately 3-7% of LBW infants.

Table 91-8 SEQUELAE OF LOW BIRTHWEIGHT

In the absence of congenital abnormalities, central nervous system injury, VLBW, or marked IUGR, the physical growth of LBW infants tends to approximate that of term infants by the 2nd yr; the approximation occurs earlier in premature infants with larger birth size. VLBW infants may not catch up, especially if they have severe chronic sequelae, insufficient nutritional intake, or an inadequate caretaking environment (see Table 91-8). Infrequently, infants with IUGR (SGA) grow poorly and do not demonstrate catch-up growth. These infants may benefit from recombinant human growth hormone therapy beginning at age 4 yr.

Premature birth in itself may adversely affect later development. The greater the immaturity and the lower the birthweight, the greater the likelihood of intellectual and neurologic deficit; as many as 50% of 500-750 g infants have significant neurodevelopmental impairment (mental retardation, cerebral palsy, blindness, deafness). Small head circumference at birth may be related to a poor neurobehavioral prognosis. Many surviving LBW infants have hypotonia before 8 mo corrected age, which improves by the time they are 8 mo to 1 yr old. This transient hypotonia is not a poor prognostic sign. Thirty percent to 50% of VLBW children have poor school performance at 7 yr of age (repeating of grades, special classes, learning disorders, poor speech and language), despite a normal IQ. Factors posing a risk for poor academic performance include birthweight below 750 g, severe IVH, periventricular leukomalacia, bronchopulmonary dysplasia, cerebral atrophy, posthemorrhagic hydrocephalus, IUGR, low socioeconomic status, and, possibly, low thyroxine levels. Antenatal exposure to magnesium sulfate may have neuroprotective effects and may reduce the incidence of cerebral palsy in high-risk neonates. Adolescents who were VLBW report satisfactory health; 94% are integrated in regular classes despite neurosensory disabilities (hearing, vision, cerebral palsy, cognition) in 24%.

Both premature and IUGR infants are at risk for significant metabolic conditions (obesity, type II diabetes) and cardiovascular disorders (ischemic heart disease, hypertension) as adults. This fetal origins hypothesis of adult morbidities may involve insulin resistance, which may be evident in early childhood.

Predicting Neonatal Mortality

Birthweight and gestational age have traditionally been used as strong indicators for the risk of neonatal death. Indeed, survival at 22 wk of gestation is poor, particularly in those infants requiring aggressive resuscitation in the delivery room. With increasing gestational age, survival rates rise to approximately 15% at 23 wk, 56% at 24 wk, and 79% at 25 wk. The survival of infants of <24 wk gestation, weighing <750 g, and with a 1-min Apgar score <3 is 30%. Antenatal steroids to increase lung maturation, female sex, and singleton pregnancy increase the chance for survival. However, extremely premature infants are also at risk for poor neurodevelopmental outcome.

Birthweight-specific neonatal diseases such as intraventricular hemorrhage, group B streptococcal sepsis/pneumonia, and pulmonary hypoplasia also contribute to a poor outcome. Scoring systems that have been developed take into consideration physiologic abnormalities (hypotension-hypertension, acidosis, hypoxia, hypercapnia, anemia, neutropenia), as in the Score for Neonatal Acute Physiology (SNAP), or clinical parameters (gestational age, birthweight, anomalies, acidosis, Fio₂), as in the Clinical Risk Index for Babies (CRIB). CRIB includes six parameters collected in the 1st 12 hr after birth, and SNAP has 26 variables collected in the 1st 24 hr. Prediction models can be used before birth, but additional data from throughout the hospitalization improve the identification of infants at high risk for death or neurodevelopmental impairment. Combining a physician’s judgment and an objective score may produce a more accurate assessment of the risk of death.

Discharge from the Hospital

Before discharge, a premature infant should be taking all nutrition by nipple, either bottle or breast (Table 91-9). Some medically fragile infants may be discharged home while receiving gavage feedings after the parents have received appropriate training and education. Growth should be occurring at steady increments of approximately 30 g/day. Temperature should be stabile in an open crib. Infants should have had no recent episodes of apnea or bradycardia, and parenteral drug administration should have been discontinued or converted to oral dosing. Stable infants recovering from bronchopulmonary dysplasia may be discharged on a regimen of oxygen given by nasal cannula as long as careful follow-up is arranged with frequent pulse oximetry monitoring and outpatient visits. All infants with birthweight <1,500 g and those with birthweights between 1,500 and 2,000 g with an unstable clinical course requiring oxygen should undergo an eye examination to screen for retinopathy of prematurity. All infants should have a hearing test prior to discharge. In those who had indwelling umbilical arterial catheters, blood pressure should be measured to check for renal vascular hypertension. The hemoglobin level or hematocrit should be determined to evaluate for possible anemia. If all major medical problems have resolved and the home setting is adequate, premature infants may then be discharged when their weight approaches 1,800-2,100 g; close follow-up plus easy access to health care providers is essential for early discharge protocols. Alternatively, if the medical or social environment is not ideal, high-risk neonates who have been transported to neonatal intensive care units and whose major illnesses have resolved may be returned to their hospital of birth for an additional period of hospitalization. Standard vaccinations with full doses should commence after discharge or, if infants are still in the hospital, with vaccines that do not contain live viruses. For RSV prophylaxis, see Chapter 252.

Home Care

While the infant is in the hospital, the mother should receive instruction on how to care for the baby after discharge and should be allowed to provide infant care in the hospital. Ideally, a home care program should include at least one home visit by someone capable of evaluating domestic arrangements and advising about any needed improvements. Early developmental intervention programs focused on parent-infant relationship and/or infant development after discharge improve cognitive development in the short to medium term (up to preschool) but do not improve motor outcomes. However these benefits are not sustained at school age.