Acceptability and Effectiveness of Umbilical Cord Cleansing with 4% Chlorhexidine for the Prevention of Newborn Infections in Uganda

Ninety-eight percent of the approximately 2.5 million annual deaths in the first 28 days of life occur in low and middle income countries (LMICs), a third are associated with serious infections and this proportion is higher in areas where many of the births occur at home, like in Uganda. Infections of the umbilical cord stump (omphalitis) seem to be a major contributor to these infections. Several interventions have been recommended to combat newborn infections, including full body skin cleansing with antiseptics like chlorhexidine (CHX), hand washing with soap and water and use of clean birth kits. The effects of such measures on the risk of serious infection and death in newborns are, however, unclear. Of the interventions, CHX cleansing of the umbilical cord stump is believed to be most promising. Studies indicate that daily applications of CHX on the umbilical cord of newborn babies over the first 7-10 days after birth can protect them from omphalitis but the studies have not convincingly shown that this translates to reduced risk of severe infection and death. To date, there has only been one study that has examined protection from a single CHX application. This study, conducted in Asia, showed that the babies were less likely to die in comparison to those that did not get a CHX application. Two very large trials in Sub-Saharan Africa (Zanzibar and Zambia) recently showed that daily CHX cleansing for 7-10 days substantially reduced the risk of omphalitis but it did regrettably not translate to increased survival. It is important, in a sub-Saharan African setting, to explore the effect of a single application, which is also programmatically much simpler to implement. Our study examines the effect of such an approach on the risk of omphalitis and, with additional funding and other support from the Center for Intervention Science in maternal and Child Health (www.cismac.org) at the University of Bergen, also on the risk of serious infections in newborns. The CISMAC support enable the study to expand from 1,600 to 4,761 enrolled newborns, thereby aiming to estimate an effect not only on omphalitis but on the rarer but much more dangerous serious newborn infections. The trial, conducted in partnership between Makerere University, College of Health Sciences, was included one month after the Ugandan authorities imposed lock downs and its data will be analyzed during 2021. A film describing the study is available at https://vimeo.com/218020917

WHO advocates dry umbilical cord care for newborns born in health facilities and at home where neonatal mortality (NMR) is < 30/1,000. In high NMR settings, CHX should be applied the cord stump after home birth. Daily 1-week CHX applications protects newborns from omphalitis but the effect on NMR varies. One study showed that a single CHX application (programmatically simpler) reduced NMR. Our study is the first in sub-Saharan Africa to explore the effect of such an approach on the risk of omphalitis and of serious infection in babies born in health facilities. If it shows that the risk of omphalitis is reduced with no effect on the risk of serious infections, it will support WHO guidelines but challenge the more proactive approach of the influential Healthy Newborn Network (www.tinyurl.com/NewBHealthNW; http://www.tinyurl.com/CWGGuidels). If it shows that a single CHX cleansing prevents serious newborn infections, it signals the need for revising the WHO guidelines of newborn care.

Nearly 3 million children die each year within 28 days of birth. Ninety-eight percent of these largely preventable deaths occur among poor people in low and middle income countries. Approximately a third of these deaths are attributable to infections. Infection of the umbilical cord stump (omphalitis) is a major contributor of serious infections in newborns. Topical application of 4% chlorhexidine, an antiseptic, on the umbilical stump of newborns in LMIC communities could, on its own, reduce the occurrence of these umbilical cord infections and, it has been estimated, could save 422,000 neonatal lives, significantly impacting SDG3. The UN commission's report has listed 4% chlorhexidine as one of the overlooked life-saving commodities. Yet, the report emphasizes the low awareness and use of this commodity. Our project also recognises that the three main trials on which the current 4% chlorhexidine evidence rests have all been performed in Asia, largely among home births and there were until recently no published studies from hospital settings in Africa or Asia. However, two very large randomized controlled trials in Africa, one in Zanzibar, the other in Kenya,casts doubt as to whether daily chlorhexidine application to the umbilical cord stump can, this actually, substantially reduce the risk of newborn death. Both trials used daily application for several days and one study in Asia indicates that a single application on the day the baby is born may be more effective. Our project will assess, for the first time in Africa, in realistic program-like conditions, the efficacy and acceptability of a single topical application of 4% chlorhexidine on the umbilical stump on the day the baby is born, using a facility-based randomized trial. Data will be collected on socio-cultural and contextual factors. This project is linked to the Center for Intervention Science on Maternal & Child Health (CISMAC), which has provided additional funding to expand the sample size from 1,600 to 4,760, thereby enabling us to assess the efficacy, not only on the risk of omphalitis but also on Severe illness, which is a clinical entity signalizing Possible serious bacterial infection. For further details, please see https://www.uib.no/en/cismac/117128/chlorhexidine and https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-017-2050-0. The project is also linked to an ongoing NORHED funded project: SURVIVAL PLUSS: Increasing capacity for mama-baby survival in post-conflict Uganda and South Sudan (reference number: 1300786-3QZA-0484). It will generate information that can influence health policy on scaling up and initiate an awareness-and-use campaign in the country. Finally, it will strengthen research capacity in Uganda as well as in Norway.