Efficacy and Safety of Multiple Whole-Body Cleansing With Aqueous 0.5% Chlorhexidine in Stable NICU Preterm Infants—Randomized Controlled Trial

Abstract

Background: Single application of chlorhexidine soon after birth reduces skin colonization. The benefit is not sustained after 72 h and multiple repeated cleansing is suggested. Such interventions especially in preterm infants need evaluation. Objective: To evaluate efficacy and safety of multiple whole-body cleansing with aqueous 0.5% chlorhexidine during first week in preterm infants. Study Design: Randomized controlled trial with superiority design and triple blinding. Setting: Level-III neonatal intensive care unit of teaching hospital in India. Participants: A total of 120 hemodynamically stable preterm (28-34 weeks) infants without encephalopathy weighing ≥ 1,000 g admitted within 6 h of life. Intervention: Following stratified randomization (28-31 weeks n = 31; 32-34 weeks n = 89), 59 and 61 infants were cleansed with identically looking aqueous 0.5% chlorhexidine wipes and placebo (sterile-water wipes) respectively at 0, 48, and 96 h after recruitment and followed up until neonatal period. Outcomes: Primary outcome was skin colonization rate on day 7. Secondary outcomes include neonatal mortality, incidence of sepsis, adverse skin reactions, and hypothermic episodes and colony counts during first week. Results: We used intention to treat analysis. After multiple cleansings, skin colonization on day 7 with chlorhexidine was 50.9% (28/55) and sterile water was 92.8% (52/56). Risk reduction with chlorhexidine cleansing was 45% compared with sterile water (relative risk = 0.55; 95% confidence interval [CI]: 0.42,0.72). Absolute risk reduction = 41.95% (95% CI: 27.1, 56.78) and number needed to treat = 2.4 persons (95% CI: 1.8, 3.7). Neonatal mortality (10.1% vs 16.3%, P = .539), sepsis (10.1% vs 19.6%, P = .229) was not significant. None had adverse skin reactions. Temperature loss after wet cleansing was not different between chlorhexidine and water. Conclusion: Multiple whole-body cleansing with aqueous 0.5% chlorhexidine at 48 h interval during first week of life reduces skin colonization in preterm infants.