Managing preterm birth to lower the risk of cerebral palsy

Using the BPP. The biophysical profile has been used to identify fetuses at risk of FIRS in the presence of pPROM. Oligohydramnios—especially when the largest vertical amniotic fluid pocket is smaller than 1 cm—and diminished fetal breathing and body movement are associated with chorioamnionitis and suspected or proven neonatal sepsis. A nonreactive nonstress test is specific but not sensitive.

Although each component of the BPP provides useful information, a BPP score of 7 or lower predicts infection-related outcome much better than any single finding. In a population with an infection-related outcome of 30%, a BPP score of 7 or lower within 24 hours of delivery had a positive predictive value of 95% and a negative predictive value of 97%.¹⁶ A retrospective case-control study found that women who were followed with daily BPP and delivered within 24 hours after a BPP score of 7 or lower on two examinations 2 hours apart had a lower rate of neonatal sepsis than women who were managed expectantly or had a single amniocentesis on admission to the hospital.¹⁷

How management tactics affect neurologic outcome

Options for women in preterm labor with intact membranes or pPROM include antibiotics, antenatal steroids, tocolytics, or early delivery.

Antibiotics in cases of pPROM only

The findings of two large clinical trials powerful enough to evaluate adjunctive antibiotics in women with pPROM are in agreement: Such treatment prolongs the pregnancy briefly (as long as 10 days).^18,19

NICHD-MFMU study. In a trial conducted by the National Institute of Child Health and Human Development Maternal–Fetal Medicine Units (NICHD-MFMU) Research Network, 48 hours of intravenous therapy with ampicillin and erythromycin followed by 5 days of oral amoxicillin and enteric-coated erythromycin given to 614 women between 24 and 32 weeks’ gestation decreased the number of infants who died or suffered a major morbidity, including respiratory distress syndrome, early sepsis, severe IVH, or severe necrotizing enterocolitis.¹⁸

ORACLE I. The results of the larger ORACLE I trial, which included 4,826 women, were less impressive.¹⁹ Patients who developed pPROM before 37 weeks’ gestation received erythromycin, amoxicillin-clavulanic acid, or both, or placebo for up to 10 days. Although antibiotic therapy prolonged pregnancy briefly, it did not have a major impact on neonatal mortality or any major morbidity, including cerebral abnormality on ultrasonography (US). In contrast to the NICHD-MFMU Research Network study, treatment with oral amoxicillin-clavulanic acid increased the risk of necrotizing enterocolitis.

ORACLE II. The ORACLE II trial evaluated the benefit of adjunctive antibiotics for 6,295 women in spontaneous preterm labor before 37 weeks’ gestation who had intact membranes and no evidence of clinical infection.²⁰ The women received erythromycin, amoxicillin-clavulanic acid, or both, or placebo for as long as 10 days. Compared with placebo, none of the antibiotics was associated with a lower rate of the composite primary outcome, which included major cerebral abnormality on US before discharge from the hospital.

Prophylaxis. It has been suggested that antibiotics are more likely to prevent preterm birth if they are given long before contractions start or membranes rupture. Studies of antibiotic prophylaxis to prevent preterm birth and related sequelae don’t support this notion. A Cochrane meta-analysis of six randomized clinical trials involving 2,184 asymptomatic women who received prophylactic antibiotics in the second or third trimester found no reduction in the risk of subsequent preterm birth.²¹ In fact, intervention increased the risk of neonatal sepsis (odds ratio [OR]=8.07, 95% confidence interval [CI], 1.36 to 47.77). Another meta-analysis of the effect of antibiotics on BV during pregnancy drew similar conclusions.²² This analysis of 15 randomized clinical trials with a total of 5,888 patients showed that treating BV did not reduce the risk of preterm birth. The trials reported very few perinatal deaths, and none reported substantive neonatal morbidity.

Another hypothesis argues that the events leading to preterm birth begin in very early stages of pregnancy, including conception and implantation of the embryo. To test this hypothesis, 241 women with a history of spontaneous preterm birth or pPROM between 16 and 34 weeks’ gestation were randomized to receive an oral course of azithromycin and metronidazole or placebo every 4 months until conception.²³ The 124 women who conceived and were available for follow-up showed no difference in the rate of preterm birth between the treatment and placebo groups. In fact, women who received an antibiotic tended to have a shorter pregnancy and a lower-birth-weight baby than those given placebo.