Clinical Inquiries

What treatment approach to intrapartum maternal fever has the best fetal outcomes?

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A combination of beta-lactam and aminoglycoside antibiotics are the recommended empiric agents for the treatment of acute chorioamnionitis, given that no head-to-head trials exist (strength of recommendation [SOR]: C, based on expert opinion). Intrapartum antibiotic treatment is not superior to postpartum antibiotics for reducing neonatal sepsis and pneumonia (SOR: C, based on patient-oriented, underpowered randomized trials).

Clinical commentary

Carefully follow laboring patients with fever for other signs of chorioamnionitis
Jon O. Neher, MD
Valley Family Medicine, Renton, Wash

The data on the best antibiotic treatment of clinical chorioamnionitis remains as slim as ever, it appears. But since experts continue to recommend potentially toxic gentamicin as part of therapy, you should carefully monitor laboring patients at term who develop a fever for the development of other diagnostic signs of chorioamnionitis. While maternal and fetal tachycardia are frequently caused by conditions other than infection, their appearance in a febrile gravida should prompt full chorioamnionitis therapy (even in patients already on empiric antibiotics for group B streptococci). With epidural anesthesia, uterine tenderness is an unreliable sign of infection. Purulent amniotic fluid is a late sign and rarely contributes clinically.

Evidence summary

Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;1 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.1,2

Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.

Intrapartum antibiotics probably reduce sepsis

Although few well-designed trials stand out, a Cochrane review4 summarizing 2 relevant studies is available. Gibbs et al3 performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.3 Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.

Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.4

The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).1 There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).4


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