Genetic Factors

The occurrence of chromosomal abnormalities, congenital anomalies, inborn errors of metabolism, mental retardation, or any familial disease in blood relatives increases the risk of the same condition in the infant. Because many parents recognize only obvious clinical manifestations of genetically determined diseases, specific inquiry should be made about any disease affecting one or more blood relatives.

Maternal Factors

The lowest neonatal mortality rate occurs in infants of mothers who receive adequate prenatal care and who are 20-30 yr of age. Pregnancies in both teenagers and women older than 40 yr, particularly primiparous women, are at increased risk for intrauterine growth restriction, fetal distress, and intrauterine death. Advanced maternal age increases the risk of both chromosomal and nonchromosomal fetal malformations (Fig. 89-1).

Figure 89-1 Natural birth prevalence of Down syndrome according to maternal age.

(From Wald NJ, Leck I: Antenatal and neonatal screening, ed 2, Oxford, 2000, Oxford University Press.)

Maternal illness (Table 89-2), multiple pregnancies (particularly those involving monochorionic twinning), infections (Table 89-3), and certain drugs (Chapter 90) increase the risk for the fetus. The use of assisted reproductive technology (in vitro fertilization, intracytoplasmic sperm injection) increases the risk of perinatal mortality, infant morbidity, prematurity, low and very low birthweight, and cerebral palsy, largely because of the increase in multiple-fetus pregnancies with such technology; the risks for birth defects are also increased, in part, because of epigenetic effects on gene expression.

Table 89-2 MATERNAL CONDITIONS AFFECTING THE FETUS OR NEONATE

Table 89-3 MATERNAL INFECTIONS AFFECTING THE FETUS OR NEWBORN

Preterm birth is common in high-risk pregnancies (Chapter 91). Factors associated with prematurity, noted in Table 89-1, include biologic markers such as cervical shortening, genital infection, fetal fibronectin in cervicovaginal secretions, serum α-fetoprotein, and preterm premature rupture of membranes (PROM). PROM occurs in 1% of pregnancies but is noted in 30-40% of preterm deliveries, and it is a leading identifiable cause of prematurity. Premature delivery is often difficult to predict.

Polyhydramnios and oligohydramnios indicate high-risk pregnancies. Although the turnover rate of amniotic fluid is rapid, during normal pregnancy the amniotic fluid volume gradually increases at a rate of <10 mL/day until about the 34th wk of pregnancy, after which it slowly diminishes. Volumes vary widely in normal pregnancy; term volume may be 500-2,000 mL. A volume estimated at greater than 2,000 mL in the 3rd trimester constitutes polyhydramnios, and a volume estimated at <500 mL indicates oligohydramnios. Polyhydramnios complicates 1-3%, and oligohydramnios 1-5%, of pregnancies. The ultrasonographic criteria for these diagnoses are based on the amniotic fluid index, which is determined by measuring the vertical diameter of amniotic fluid pockets in four quadrants; an index > 24 cm suggests polyhydramnios, whereas an index < 5 cm suggests oligohydramnios.

Acute polyhydramnios is rare and is usually associated with premature labor and delivery, before 28 wk of gestation. Chronic polyhydramnios is diagnosed in the 3rd trimester from the discrepancy between uterine size and gestational age; it is occasionally not diagnosed until the patient has dysfunctional labor or an abnormally large amount of amniotic fluid is noted during delivery. Polyhydramnios is associated with premature labor, abruptio placentae, multiple congenital anomalies, and fetal neuromuscular dysfunction or obstruction of the gastrointestinal tract that interferes with reabsorption of the amniotic fluid that is normally swallowed by the fetus (Table 89-4). Increased fetal urination or edema formation is also associated with excessive amniotic fluid volume. Ultrasound demonstrates the increased amniotic fluid surrounding the fetus and detects associated fetal anomalies, hydrops, pleural effusions, and ascites. In 60% of patients, no cause is identified. Symptomatic polyhydramnios may be managed by serial amniocenteses or by short-course maternal indomethacin if the problem is due to excessive fetal urination. Treatment is indicated for acute maternal respiratory distress and threatened preterm labor or to provide time for the administration of corticosteroids to enhance fetal lung maturity.

Oligohydramnios is associated with congenital anomalies; intrauterine growth restriction; severe renal, bladder, or urethral anomalies; and drugs that interfere with fetal urination (see Table 89-4). Oligohydramnios becomes most evident after 20 wk of gestation, when fetal urination is the major source of amniotic fluid. Rupture of the membranes is the most common cause of oligohydramnios and must be ruled out if oligohydramnios is suspected, especially if a normal-sized bladder is seen on fetal ultrasound. Oligohydramnios causes fetal compression abnormalities such as fetal distress, clubfoot, spadelike hands, and a flattened nasal bridge. The most serious complication of chronic oligohydramnios is pulmonary hypoplasia. The risk of umbilical cord compression during labor and delivery is increased in pregnancies complicated by oligohydramnios and may be alleviated by saline amnioinfusion. Prophylactic intrapartum amnioinfusion reduces the need for cesarean section and improves Apgar scores.

Antenatal screening can be used to detect a number of disorders, including Down syndrome and other chromosomal abnormalities, neural tube defects and other structural anomalies, Tay-Sachs disease and other metabolic genetic diseases, hemoglobinopathies and other blood disorders, and cystic fibrosis. Screening methods include maternal blood tests, fetal ultrasound, and diagnostic tests on cells or fluid obtained by amniocentesis or chorionic villus sampling and by fetal blood or tissue sampling.

Second-trimester screening (15-18 wk) of maternal serum α-fetoprotein (MSAFP) values is used to screen for open neural tube defects. About 90% of affected pregnancies can be detected by an elevated MSAFP value. Gastroschisis, omphalocele, congenital nephrosis, twins, and other abnormal conditions can also be identified. Low MSAFP is associated with incorrect gestational age estimates, trisomy 18 or 21, and intrauterine growth restriction.

Several effective screening strategies can be used to detect Down syndrome (Fig. 89-2), including a combination of maternal age, nuchal translucency on ultrasound, and a number of serum markers: α-fetoprotein, unconjugated estriol, total human chorionic gonadotropin (HCG), the free β subunit of HCG, inhibin A, and pregnancy-associated plasma protein A. The most effective strategy, the integrated test, combines 1st- and 2nd-trimester screening and can identify 94% of affected pregnancies with a 5% false-positive rate or 85% with a 1% false-positive rate (Chapter 76.1). Absence of the fetal nasal bone is also noted in trisomy 21. Chromosomal analysis of cells obtained by amniocentesis or chorionic villus sampling makes the diagnosis.

Figure 89-2 Rates of detection of Down syndrome and false-positive rates for various screening tests. The triple test includes measurements of serum α-fetoprotein, unconjugated estriol, and human chorionic gonadotropin in the 2nd trimester. The quadruple test includes the measurements of the triple test plus inhibin A in the 2nd trimester. The combined test includes measurements of serum pregnancy-associated plasma protein A, free β subunit of human chorionic gonadotropin (HCG), and nuchal translucency in the 1st trimester. The integrated test includes measurements of serum, α-fetoprotein, unconjugated estriol, HCG, and inhibin A in the 2nd trimester.

(From Wald NJ, Watt HC, Hackshaw AK: Integrated screen for Down syndrome based on tests performed during the first and second trimester, N Engl J Med 341:461–467, 1999.)

A pregnancy should be considered high risk when the uterus is inappropriately large or small. A uterus large for the estimated stage of gestation suggests the presence of multiple fetuses, hydramnios, or an excessively large infant; an inappropriately small one suggests oligohydramnios or poor intrauterine growth. PROM more than 24 hr before delivery carries a risk of fetal infection; it also increases the risk of premature birth. PROM at term usually results in the onset of labor within 48 hr but poses a risk of chorioamnionitis and umbilical cord compression. With PROM before 37 wk, there is a longer latency until labor starts, and its occurrence has the added risks of cord prolapse, oligohydramnios, abruptio placentae, fetal malposition; also, if membrane rupture is present for >7 days in a fetus during the 2nd trimester, pulmonary hypoplasia, uterine-induced deformations, and extremity contractures can develop. Prolonged and difficult labor increases the risk for mechanical and hypoxic damage. A tumultuous short labor with a precipitous delivery increases the risk of birth asphyxia and intracranial hemorrhage. Placental separation at any time before delivery and abnormal implantation or compression of the cord increase the possibility of brain damage from fetal hypoxia; brown or muddy amniotic fluid suggests that meconium has been passed, possibly during an episode of fetal hypoxia.

Although the safety of any type of delivery depends on the skill of the obstetrician, additional hazards accompany particular methods and result from the circumstances that dictated them. The risk of intracranial hemorrhage is greater in infants delivered by vacuum extraction or forceps than in those born unassisted in spontaneous vaginal deliveries. Neonatal deaths after mid-forceps delivery, breech extraction, and version are likely to be related to traumatic intracranial injury.

Infants born by cesarean section present problems possibly related to the unfavorable obstetric circumstance that necessitated the operation. In normal term pregnancies without any indication of fetal distress, surgical delivery through the abdomen carries a greater risk than delivery through the birth canal. Controversy exists regarding the safest type of delivery for a nondistressed, viable immature fetus, especially in a breech presentation; cesarean section may involve less risk than the “stress” of labor and the potentially hypoxic effects of uterine contractions during vaginal delivery. Some term infants in breech position (≈3-4% of term births) that do not assume vertex position after external cephalic version attempts may also benefit from cesarean section. A small percentage of mature infants delivered by cesarean section have some degree of respiratory difficulty for 1-2 days. Although transient tachypnea is the most frequently associated problem, respiratory distress syndrome may develop, particularly in infants born by cesarean section to women who are not in labor, in those with uncertain dates, and in those born to diabetic mothers or after asphyxia. There is no contraindication to a trial of labor after a previous low segment cesarean section, but in women with more than one previous cesarean section, there is an increased risk of uterine rupture. An elective cesarean section should be delayed until ≥39 wk of gestation.

Anesthesia and analgesia affect the fetus as well as the mother; severe maternal hypoxemia secondary to hypoventilation or hypotension resulting from epidural anesthesia may lead to severe fetal hypoxia and shock. Skilled use of medication avoids severe fetal narcosis while securing the benefits of gentle and unhurried delivery. Even skilled administration may result in a mildly depressed infant whose crying and breathing may be delayed 1-2 min and who may be somewhat inactive for several hours.