Application of 4% chlorhexidine to the umbilical cord stump of newborn infants in lower income countries: a systematic review and meta-analysis

ABSTRACT: There are conflicting results from large randomized controlled trials in different populations regarding the effectiveness of topical application of 4% chlorhexidine to the umbilical stump of newborn infants at reducing neonatal mortality. Meta-analysis and systematic review of trials performed in South Asia and Europe support 4% chlorhexidine application to reduce neonatal mortality, whereas trials performed in Sub-Saharan Africa do not. The aim of this review is to determine the effectiveness of 4% chlorhexidine application to the umbilical stump of newborn infants born in lower income countries in order to reduce neonatal mortality when compared with usual cord care. Our search strategy included randomized trials published between January1(st) 2000 and September 4th, 2018, that compared 4% chlorhexidine with usual cord care (“dry cord care”). The outcome variable of interest was neonatal mortality. Pooled relative risks (RR) with 95% confidence intervals (CIs) using a random-effects model were calculated. Nine trials were included, from six countries: Zambia, Tanzania, Bangladesh, Nepal, India and Pakistan, with a total of 257,153 participants. Five studies (N = 119,833) reported neonatal mortality. There was a 21% reduction in neonatal mortality among with 4% chlorhexidine application: pooled RR (95% CI) 0.79 (0.69–0.90), P = 0.0005. The incidence of omphalitis was decreased by 35% with 4% chlorhexidine (6 studies, N = 108,263): pooled RR (95% CI) 0.65 (0.56–0.75), P = 0.00001. Chlorhexidine application delayed the umbilical cord separation time (4 studies, N = 28,917): mean difference (95% CI) 2.71 (2.63–2.78) days. In conclusion, this systematic review found that topical application of 4% chlorhexidine to the umbilical cord stump of newborn infants in lower income countries significantly reduces the incidence of neonatal mortality. Chlorhexidine also reduces the incidence of omphalitis, but prolongs umbilical cord separation time. TRIAL REGISTRATION: Systematic Review Registration: CRD42018109280.