Based on available data, treatment with a short course of antibiotics such as erythromycin or ampicillin, or both, is recommended only in cases of pPROM.
Antenatal steroids improve outcome
Antenatal steroids reduce neonatal mortality and morbidity, including IVH and PVL, in infants born between 24 and 34 weeks’ gestation. One concern raised about antenatal steroid use is whether it increases the risk of neonatal infection and morbidity when intrauterine infection and inflammation are present. A retrospective analysis of infants who weighed 1,750 g or more at birth concluded that antenatal steroids significantly decreased neonatal mortality and morbidity—including IVH, PVL, and major brain lesions—without increasing neonatal sepsis in babies delivered following preterm labor or pPROM.24
In another retrospective analysis of 457 consecutive 23- to 32-week live-born singletons, antenatal steroids weren’t associated with significant worsening of any neonatal outcome. Steroids were associated with significant reductions in respiratory distress syndrome and neonatal systemic inflammatory response syndrome in infants with positive placental cultures and elevated cord blood IL-6 levels.25
These data suggest that antenatal steroids may not be contraindicated in the face of inflammation and infection; they may, in fact, be beneficial. In women with pPROM, weekly administration of ante-natal steroids doesn’t seem to improve neonatal outcomes more than single-course therapy and may increase the risk of chorioamnionitis.26
Some tocolytics may help
Tocolytic agents are often given to women with preterm contractions to delay delivery long enough to administer a course of antenatal corticosteroids.
Magnesium sulfate is commonly used in the United States. A 2007 Cochrane meta-analysis of four trials (3,701 babies) found that antenatal magnesium sulfate had no statistically significant effect on any major pediatric outcome, including death and neurologic problems such as CP in the first few years of life.27 Nor did antenatal magnesium therapy significantly affect combined rates of mortality and neurologic outcomes. Two trials involving 2,848 infants found a significant reduction in substantial gross motor dysfunction (RR=0.56; 95% CI, 0.33 to 0.97).
Betamimetics are also widely used for tocolysis, especially in resource-poor countries. Eleven randomized controlled trials, involving 1,332 women, compared betamimetics with placebo.28 Although betamimetics decreased the number of women in preterm labor who gave birth within 48 hours, they didn’t reduce perinatal or neonatal death. Data on CP were too sparse to allow comment. Because these drugs cause many maternal side effects, they aren’t considered first-line tocolytics.
Calcium-channel blockers are attracting growing interest as potentially effective and well-tolerated tocolytic agents. A meta-analysis of 12 randomized controlled trials involving 1,029 women suggests that calcium-channel blockers reduce the number of women giving birth within 7 days of receiving treatment, compared with other tocolytic agents (mainly betamimetics).29 They also decrease the frequency of neonatal morbidity, including IVH (RR, 0.59; 95% CI, 0.36 to 0.98).
Cyclooxygenase (COX) inhibitors are easy to administer and cause fewer maternal side effects than conventional tocolytics. A 2005 Cochrane meta-analysis includes outcome data from 13 trials with a total of 713 women.30 Indomethacin, a non-selective COX inhibitor, was used in 10 trials. COX inhibition reduced birth before 37 weeks’ gestation more effectively than other tocolytic agents, but data were insufficient to comment on neonatal outcomes.
In women with pPROM, starting tocolysis before onset of contractions prolongs latency. However, the utility of tocolytic therapy after pPROM remains controversial pending more powerful randomized trials.
Early delivery is an option
It has been suggested that exposure to infection, especially proinflammatory cytokines, reduces the threshold at which hypoxia becomes neurotoxic, making the brain much more vulnerable to even mild hypoxic insults. A recent study found that infants with encephalopathy were more than 90 times more likely to have experienced both neonatal intrapartum acidosis and maternal intrapartum fever than infants with no encephalopathy; maternal fever or neonatal acidosis increased the risk six- and 12-fold, respectively.31 Lack of interaction between maternal fever and acidosis suggests that these are separate causal pathways to adverse neonatal outcomes. Although intrapartum fever doesn’t always correlate with intrauterine inflammation, the findings of this study suggest that fetal acidosis should be avoided when intrauterine infection and inflammation are suspected.
Conservative management of pPROM remote from term has been shown to prolong pregnancy significantly and reduce complications in the infant when prophylactic antibiotics and ante-natal steroids are given concurrently. The benefit of this strategy is less clear after 32 weeks of gestation because:
- The efficacy of antenatal steroids after 32 weeks is unclear
- Beyond 32 weeks, the risk of severe complications of prematurity, including CP, is low if fetal lung maturity has been established by amniotic fluid samples collected vaginally or by amniocentesis.