Of the annual 3.7 million global neonatal deaths, almost all (99%) occur in developing countries, and one-third to one half are attributed to infections[1
] such as sepsis, meningitis, pneumonia, omphalitis, tetanus, and diarrhea. In settings where home delivery is common and attendance by skilled personnel is low, many babies are born in unhygienic conditions and infections of the umbilical cord stump are common [2
]. Exposure of the freshly cut umbilical cord stump to pathogens on the cutting instrument, on the hands of caretakers, or elsewhere in the environment leads to local cord infections (omphalitis) that may progress to systemic infection and death [2
]. Alternatively, during the period immediately following birth, while the vessels of the umbilical cord remain patent, direct exposure to the bloodstream via the cord may lead to systemic infection without any visible signs of local cord infection [5
The World Health Organization (WHO) currently recommends keeping the cord clean and dry. The guidelines do not include a universal recommendation for application of any topical antiseptic, although their potential role is acknowledged for settings where harmful practices are common [2
]. Practical and effective implementation of this guidance, however, is challenging in both hospital and community-based low resource settings and is often less than optimal. Recently, there has been increased interest in both the overall role of exposure of the cord stump to invasive pathogens and the potential benefit of topical cord cleansing with chlorhexidine[6
], a safe and effective broad-spectrum antiseptic[7
A large community-based trial[8
] in rural southern Nepal conducted between 2002 and 2006 randomized babies within clusters to receive one of three cord care regimens: (1) 4.0% chlorhexidine cleansing for 7 of the first 10 days after birth or (2) soap and water cleansing for 7 of the first 10 days after birth, or (3) dry cord care. Mothers of all infants received educational messages about hygienic cord care (e.g., hand-washing, clean cutting, and avoidance of harmful topical applications). Depending on the severity of infection, omphalitis incidence was reduced by 32-75% among infants receiving chlorhexidine compared to those in the dry cord care group. Overall, mortality among enrolled infants was 24% lower in the chlorhexidine group compared to dry cord care. About two-thirds of the infants were reached within 24 hours of birth and evidence of a protective benefit of chlorhexidine cleansing among this subset was increased. Chlorhexidine cleansing reduced severe infection by 87% and mortality by 34% among those enrolled within 24 hours, while no difference between the groups was observed when cord cleansing was initiated after 24 hours[8
An expert consultative meeting convened in Washington, DC shortly after completion of the Nepal trial concluded that, prior to any changes in policy, at least one replication trial in South Asia would be necessary to expand the evidence base for chlorhexidine cleansing of the cord[9
]. Two specific questions were noted. First, would a similar beneficial effect of multiple cleansings of the cord through the first week of life be observed in a separate but similar population? Second, can a simpler regimen of cord cleansing only once and as soon as possible after birth, provide a similar protective benefit against omphalitis and mortality? Answering this second question is necessary as the intensive intervention (cleansing on 7 of first 10 days of life) followed in the Nepal efficacy trial might not be easily implemented in most programmatic settings, given associated logistical and financial barriers for outreach health workers. Furthermore, even if the intervention was delivered by caretakers themselves, compliance with the promoted instructions might be increased if the more simple recommendation of one-time cleansing as soon as possible after birth could be given. Moreover, a single application of antiseptic to the cord could more readily be incorporated into clean birth kits.
Thus, in addition to replicating the question of efficacy of multiple (i.e. daily for 7 days) cord cleansing with chlorhexidine (4%, as used in Nepal), it was deemed essential to also investigate the potential efficacy of a single application as soon as possible after birth. The second major research activity for the Projahnmo study site in rural Sylhet District of north eastern Bangladesh was designed to answer these questions and provide evidence to inform global guidelines for optimal umbilical cord care of newborns. In this manuscript, we discuss in detail the design and implementation of this community-based cluster randomized trial, including study site, randomization and intervention delivery procedures, follow-up data collection, and analysis plans.