Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infection

Background In high-income countries, it is standard practice to give antibiotics to women with pre-term, pre-labour rupture of membranes (pPROM) to delay birth and reduce the risk of infection. In low and middle-income settings, where some 2 million neonatal deaths occur annually due to complications of pre-term birth or infection, many women do not receive antibiotic therapy for pPROM. Objectives To review the evidence for and estimate the effect on neonatal mortality due to pre-term birth complications or infection, of administration of antibiotics to women with pPROM, in low and middle-income countries. Methods We performed a systematic review to update a Cochrane review. Standardized abstraction forms were used. The quality of the evidence provided by individual studies and overall was assessed using an adapted GRADE approach. Results Eighteen RCTs met our inclusion criteria. Most were from high-income countries and provide strong evidence that antibiotics for pPROM reduce the risk of respiratory distress syndrome [risk ratio (RR) = 0.88; confidence interval (CI) 0.80, 0.97], and early onset postnatal infection (RR=0.61; CI 0.48, 0.77). The data are consistent with a reduction in neonatal mortality (RR=0.90; CI 0.72, 1.12). Conclusion Antibiotics for pPROM reduce complications due to pre-term delivery and post-natal infection in high-income settings. There is moderate quality evidence that, in low-income settings, where access to other interventions (antenatal steroids, surfactant therapy, ventilation, antibiotic therapy) may be low, antibiotics for pPROM could prevent 4% of neonatal deaths due to complications of prematurity and 8% of those due to infection.