Elsevier

The Lancet

Volume 367, Issue 9514, 18–24 March 2006, Pages 910-918
The Lancet

Articles
Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial

https://doi.org/10.1016/S0140-6736(06)68381-5Get rights and content

Summary

Background

Omphalitis contributes to neonatal morbidity and mortality in developing countries. Umbilical cord cleansing with antiseptics might reduce infection and mortality risk, but has not been rigorously investigated.

Methods

In our community-based, cluster-randomised trial, 413 communities in Sarlahi, Nepal, were randomly assigned to one of three cord-care regimens. 4934 infants were assigned to 4·0% chlorhexidine, 5107 to cleansing with soap and water, and 5082 to dry cord care. In intervention clusters, the newborn cord was cleansed in the home on days 1–4, 6, 8, and 10. In all clusters, the cord was examined for signs of infection (pus, redness, or swelling) on these visits and in follow-up visits on days 12, 14, 21, and 28. Incidence of omphalitis was defined under three sign-based algorithms, with increasing severity. Infant vital status was recorded for 28 completed days. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. Analysis was by intention-to-treat. This trial is registered with Clinicaltrials.gov, number NCT00109616.

Findings

Frequency of omphalitis by all three definitions was reduced significantly in the chlorhexidine group. Severe omphalitis in chlorhexidine clusters was reduced by 75% (incidence rate ratio 0·25, 95% CI 0·12–0·53; 13 infections/4839 neonatal periods) compared with dry cord-care clusters (52/4930). Neonatal mortality was 24% lower in the chlorhexidine group (relative risk 0·76 [95% CI 0·55–1·04]) than in the dry cord care group. In infants enrolled within the first 24 h, mortality was significantly reduced by 34% in the chlorhexidine group (0·66 [0·46–0·95]). Soap and water did not reduce infection or mortality risk.

Interpretation

Recommendations for dry cord care should be reconsidered on the basis of these findings that early antisepsis with chlorhexidine of the umbilical cord reduces local cord infections and overall neonatal mortality.

Introduction

Most of the 4 million neonatal deaths every year are in low-income and middle-income countries.1 Infections account for an estimated 1·44 million (36%) deaths, and about half of deaths in regions with high neonatal mortality rates.2 Contamination of the umbilical cord can lead to omphalitis, characterised by pus, abdominal erythema, or swelling. Pathogens can enter the bloodstream through the patent vessels of the newly cut cord and lead to rapid demise, even in the absence of overt signs of cord infection.3 Hygienic delivery and postnatal-care practices are widely promoted as important interventions to reduce risk of omphalitis and death.4 There are few specific data, however, on omphalitis incidence and little evidence for optimum cord-care practices to prevent cord infections and mortality in the community, so better studies are urgently needed.

Investigators in hospital-based studies in developing countries have described the characteristics of omphalitis,5, 6, 7, 8, 9 and reported a range of incidence estimates (2–77 per 1000 hospital-born infants).7, 8 In the community, where infectious challenge is higher and many cases go unrecognised, risk could be higher. A review of omphalitis in Oman9 noted that the incidence rate in home-delivered neonates was 5·9 times higher than in hospital births.

Community-based case-control studies have focused on risk factors for neonatal tetanus,10, 11, 12, 13, 14, 15, 16, 17 and provide some evidence that topical antiseptics on the cord are protective.11, 17, 18 In settings where neonatal tetanus has been eliminated but unhygienic cord practices continue to place newborn babies at risk, topical antiseptics might protect against infection.19

In developed countries, many studies20, 21, 22, 23, 24, 25, 26, 27 have shown that single or repeated antiseptic applications to the cord can substantially reduce bacterial colonisation. The link between cord colonisation and infection, however, has not been firmly established,28, 29 prompting a trend towards dry cord care. WHO promotes dry cord care for developing countries, although notes that antiseptics might benefit infants in settings where harmful substances are traditionally applied.3 The current WHO recommendations for dry cord care, however, are based on inadequate data and could be inappropriate in areas with high omphalitis risk.

Of the numerous potential topical antimicrobials for cord care (eg, ethanol, silver sulfadiazine, triple dye, gentian violet, chlorhexidine, povidone iodine), chlorhexidine seems to be a favourable choice. It has broad-spectrum activity against gram-positive and gram-negative organisms, an extensive safety record, strong binding potential that results in residual effectiveness, and low cost.30 Chlorhexidine use substantially reduces bacterial colonisation of the cord stump28 and may be associated with reduced superficial skin infections.21, 22, 31 Chlorhexidine is currently included in the WHO Essential Drug List and can be maintained in non-alcohol aqueous solutions. Furthermore, WHO recommends that chlorhexidine is the preferred agent if an antiseptic is to be used on the cord, for example in settings in which it might be strategic to use antiseptic applications to the cord to discourage the use of dung or other unclean substances.3 We therefore aimed to investigate whether chlorhexidine applied to the cord prevents omphalitis and reduces mortality.

Section snippets

Settings and population

This double-masked, placebo-controlled, cluster-randomised, community-based trial was done by the Nepal Nutrition Intervention Project, Sarlahi (NNIPS), between November, 2002, and March, 2005. The NNIPS surveillance area consisted of 30 village development committees, each encompassing nine government-defined geopolitical units (wards), which we further divided into sectors on the basis of population. In every sector, a local female worker provided interventions to 50–100 households. All

Results

Between Nov 18, 2002, and March 8, 2005, 15 804 infants were born in the study area and were eligible for enrolment in the cord cleansing trial (figure 2). Of these, 208 (1·3%) infants died before implementation of the intervention, 37 (0·2%) mothers declined to participate, and 436 (2·8%) eligible infants were not met during the first 10 days of life. A total of 15 123 newborn babies were enrolled in the chlorhexidine (N=4934), soap and water (N=5107), and dry cord care (N=5082) clusters.

Discussion

These data provide evidence that umbilical cord cleansing with chlorhexidine can markedly reduce the risk of omphalitis. The risk of cord infection was reduced by 32–75% with greater effect on more severe grades of infection, and an 87% reduction in risk of the most severe grade of omphalitis was seen in those whose treatment was initiated within the first 24 h after birth. The time to first cleansing was an important modifying factor, with stronger evidence of protection against infection in

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