Cousens S, Blencowe H, Gravett M, Lawn JE. Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infections. Int J Epidemiol. 2010 Apr; 39 (Suppl 1): i4134-i143.
- Complications of pre-term birth and infections account for about 2 million neonatal deaths annually. Pre-term (<37 weeks gestation), pre-labour (prior to onset of labour) rupture of membranes (pPROM) is associated with one-third of pre-term deliveries in high-income countries, and is associated with increased rates of neonatal and maternal infection. (1)
- Antibiotic therapy following pPROM has been demonstrated in high-income countries to increase the time period between pPROM and delivery and reduce the risks of maternal and neonatal infections. (1) While standard practice in high-income countries, in low and middle-income settings many women do not receive antibiotic therapy for pPROM.
- This paper presents an update of a Cochrane systematic review of randomized trials of antibiotics for pPROM which included 22 trials and concluded that antibiotic administration following pPROM delays delivery and reduces major markers of neonatal morbidity. (2)
Antibiotic Therapy for pPROM on Neonatal Morbidities (18 RCTs in mostly HIC)
- 12% reduced risk of respiratory distress syndrome (RDS) (RR: 0.88, 95% CI 0.80-0.97) – 13 studies (moderate quality of evidence)
- 39% reduced risk of early onset postnatal infection (sepsis) (RR: 0.61, 95% CI 0.48-0.77) – 13 studies (moderate quality of evidence)
- 24% reduced risk of necrotizing enterocolitis (RR: 0.76, 95% CI 0.56-1.05) – 13 studies (low quality of evidence)
- 33% reduced risk of intra-ventricular haemorrhage (RR: 0.67, 95% CI 0.49-0.92) – 12 studies (moderate quality of evidence)
- No strong evidence that effects differed between trials using IV antibiotics and trials using oral antibiotics only
Antibiotic Therapy for pPROM on Neonatal Mortality (low quality of evidence, 15 RCTs in mostly HIC)
- 10% reduction in neonatal mortality (RR: 0.90, 95% CI 0.72-1.12)
- Given that RDS is the most common complication and has the smallest effect estimate, we propose that antibiotics for pPROM can reduce deaths due to complications of prematurity by 12% among newborns born following pPROM. Assuming one-third (1) of preterm deliveries are associated with pPROM, we estimate that antibiotics for pPROM could prevent 4% of neonatal deaths due to complications of prematurity.
- If 60% of neonatal sepsis deaths occur in pre-term babies (3), one-third of which occur after pPROM, then 20% of sepsis deaths occur in pPROM babies. Antibiotics for pPROM could prevent 8% of neonatal sepsis deaths.
Intervention Recommendation: MODERATE
- Antibiotics for pPROM reduce complications due to pre-term delivery and post-natal infection in high-income settings. There is moderate quality evidence, in low-income settings, where access to other interventions (antenatal steroids, surfactant therapy, ventilation, antibiotic therapy) may be low.
References from Cousens Paper Cited Here:
Mercer B, Arhear K. Antimicrobial therapy in expectant management of preterm premature rupture of the membranes. Lancet 1995; 346: 1271-79.
Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochr Dbase Syst Rev 2003.
Bang AT, Reedy HM, Bang RA et al. Why do neonates die in rural Gadchiroli, India? (Part II): estimating population attributable risks and contribution of multiple morbidities for identifying a strategy to prevent death. J Perinatol 2005; 25(Suppl 1): S35-43.