Chlorhexidine and newborn omphalitis and mortality
Authors: Stephen Hodgins
Journal: The Lancet Global Health (2017)

David Osrin and Tim Colbourn (November, 2016)1Osrin D Colbourn T No reason to change WHO guidelines on cleansing the umbilical cord.Lancet Glob Health. 2016; 4: e766Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar uphold a recommendation to restrict use of chlorhexidine to "infants born at home in environments with high neonatal mortality rates" and assert that "Cochrane reviews, a meta-analysis, and these two new trials have not supported an effect after hospital births". We do not think it is clear how one could come to such a conclusion from the evidence in the cited papers. The 2013 Cochrane review cited2Imdad A Bautista RM Senen KA Uy ME Mantaring 3rd, JB Bhutta ZA Umbilical cord antiseptics for preventing sepsis and death among newborns.Cochrane Database Syst Rev. 2013; 5 (CD008635.)Google Scholar included the three large community-based trials of chlorhexidine 4% solution in which application to the cord was done at home, although in the two largest of the studies, participants included both home and facility births. The review concluded that chlorhexidine reduces risk of both omphalitis (ranging from 27% to 65% depending on severity of infection) and death (risk ratio [RR] 0·77, 95% CI 0·63–0 ·94). A German trial3Kapellen TM Gebauer CM Brosteanu O Labitzke B Vogtmann C Kiess W Higher rate of cord-related adverse events in neonates with dry umbilical cord care compared to chlorhexidine powder: rresults of a randomized controlled study to compare efficacy and safety of chlorhexidine powder versus dry care in umbilical cord care of the newborn.Neonatology. 2009; 96: 13-18Crossref PubMed Scopus (31) Google Scholar of 669 healthy newborn babies was also included, with those in the intervention arm receiving chlorhexidine 1% powder applied to the cord after every diaper change, initiated in hospital and continued at home until 3 days after cord separation (and could therefore be seen as a hybrid hospital-based and community-based study). "Cord-related adverse events" (the main endpoint other than cord separation time)—including "erosion, irritation, lesion, omphalitis, erythema, umbilical granuloma, purulence, bleeding, discharge or weeping"—were seen in 29% of those receiving dry cord care and 16% receiving chlorhexidine (p=0·001). Omphalitis, as defined in the study, was seen in seven of 332 receiving dry cord care and two of 337 receiving chlorhexidine (p=0·1). This trial did not use mortality as an endpoint. The review came to no conclusions about differences in effectiveness by place of birth. A 2015 Cochrane review4Sinha A Sazawal S Pradhan A Ramji S Opiyo N Chlorhexidine skin or cord care for prevention of mortality and infections in neonates.Cochrane Database Syst Rev. 2015; 3 (CD007835.)PubMed Google Scholar retained the three community-based studies mentioned above and concluded that there was high-quality evidence of reduced risk of infection or omphalitis and death. The review also included two studies in which chlorhexidine was applied in a hospital setting: the above-described German study3Kapellen TM Gebauer CM Brosteanu O Labitzke B Vogtmann C Kiess W Higher rate of cord-related adverse events in neonates with dry umbilical cord care compared to chlorhexidine powder: rresults of a randomized controlled study to compare efficacy and safety of chlorhexidine powder versus dry care in umbilical cord care of the newborn.Neonatology. 2009; 96: 13-18Crossref PubMed Scopus (31) Google Scholar and a newer neonatal intensive care unit (NICU)-based study5Gathwala G Sharma D Bhakhri BK Effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial.J Trop Pediatr. 2013; 59: 209-213Crossref PubMed Scopus (25) Google Scholar conducted in India. On the basis of the results from these studies, the review concluded that there was moderate-quality evidence that chlorhexidine reduces risk of omphalitis or infections in hospital settings (RR 0·48, 95% CI 0·28–0·84). The Indian trial5Gathwala G Sharma D Bhakhri BK Effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial.J Trop Pediatr. 2013; 59: 209-213Crossref PubMed Scopus (25) Google Scholar enrolled only 140 participants, patients admitted to NICU of gestational age 32 weeks or older, who on admission were expected to require NICU care for at least 5 days. They received chlorhexidine 2·5% solution three times daily during their NICU stay. In addition to cord separation time, endpoints included umbilical colonisation, neonatal sepsis, culture-proven sepsis, meningitis, and death up to the time of discharge from NICU. The risk of culture-proven sepsis among these hospital births was higher in the dry cord care group than the chlorhexidine group (0·13, 0·01–0·40), although "incidence of probable sepsis and meningitis was … similar [across] groups". There were also more deaths in the dry cord care group (four of 70 patients) than in the chlorhexidine group (no deaths in 70 patients, p=0·042). The cited meta-analytic review6Imdad A Mullany LC Baqui AH et al.The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis.BMC Public Health. 2013; 13: 15Crossref PubMed Scopus (64) Google Scholar included only trials conducted in community settings in developing countries (ie, the three large trials discussed above) and concluded that chlorhexidine reduced risk of omphalitis and newborn death. It did not include any trials in which application was done solely in a hospital setting. However, as mentioned, two of these three trials did include births at home and in facilities; the authors provided a sub-analysis focusing on about 3000 facility births and reported that mortality risk was about half among those facility births receiving chlorhexidine (RR 0·50, 95% CI 0·27–0·92). Similar to the Nepal and Bangladesh trials, study participants in the two studies in The Lancet Global Health7Sazawal S Dhingra U Ali SM et al.Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: a community-based randomised controlled trial.Lancet Glob Health. 2016; 4: e837-e844Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 8Semrau KEA Herlihy J Grogan C et al.Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.Lancet Glob Health. 2016; 4: e827-e836Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar included both home and facility births, and chlorhexidine application was done only in the home. Both studies documented that chlorhexidine reduced risk of omphalitis. In the Pemba trial,7Sazawal S Dhingra U Ali SM et al.Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: a community-based randomised controlled trial.Lancet Glob Health. 2016; 4: e837-e844Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar relative risk for omphalitis varied from 0·61 to 0·76, depending on level of severity, with p-values for all levels <0·0001. The Zambia trial8Semrau KEA Herlihy J Grogan C et al.Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.Lancet Glob Health. 2016; 4: e827-e836Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar found a similar effect size (RR 0·73), but with an overall rate of omphalitis of only 0·6% in the control arm there was a relatively wide confidence interval, which included 1·0 (95% CI 0·47–1·13). It is true, as Osrin and Colbourn1Osrin D Colbourn T No reason to change WHO guidelines on cleansing the umbilical cord.Lancet Glob Health. 2016; 4: e766Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar stated, that these two trials did not show an effect of chlorhexidine in reduced risk of death among those born in hospital, just as no such effect was found for home births. Indeed, no difference was seen in effect sizes when comparing home versus facility births. For risk of infection to the cord, we see the same picture across all sources of evidence cited by Osrin and Colbourn; whether community-based6Imdad A Mullany LC Baqui AH et al.The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis.BMC Public Health. 2013; 13: 15Crossref PubMed Scopus (64) Google Scholar or hospital-based,3Kapellen TM Gebauer CM Brosteanu O Labitzke B Vogtmann C Kiess W Higher rate of cord-related adverse events in neonates with dry umbilical cord care compared to chlorhexidine powder: rresults of a randomized controlled study to compare efficacy and safety of chlorhexidine powder versus dry care in umbilical cord care of the newborn.Neonatology. 2009; 96: 13-18Crossref PubMed Scopus (31) Google Scholar, 4Sinha A Sazawal S Pradhan A Ramji S Opiyo N Chlorhexidine skin or cord care for prevention of mortality and infections in neonates.Cochrane Database Syst Rev. 2015; 3 (CD007835.)PubMed Google Scholar, 5Gathwala G Sharma D Bhakhri BK Effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial.J Trop Pediatr. 2013; 59: 209-213Crossref PubMed Scopus (25) Google Scholar home births,2Imdad A Bautista RM Senen KA Uy ME Mantaring 3rd, JB Bhutta ZA Umbilical cord antiseptics for preventing sepsis and death among newborns.Cochrane Database Syst Rev. 2013; 5 (CD008635.)Google Scholar, 3Kapellen TM Gebauer CM Brosteanu O Labitzke B Vogtmann C Kiess W Higher rate of cord-related adverse events in neonates with dry umbilical cord care compared to chlorhexidine powder: rresults of a randomized controlled study to compare efficacy and safety of chlorhexidine powder versus dry care in umbilical cord care of the newborn.Neonatology. 2009; 96: 13-18Crossref PubMed Scopus (31) Google Scholar, 4Sinha A Sazawal S Pradhan A Ramji S Opiyo N Chlorhexidine skin or cord care for prevention of mortality and infections in neonates.Cochrane Database Syst Rev. 2015; 3 (CD007835.)PubMed Google Scholar, 5Gathwala G Sharma D Bhakhri BK Effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial.J Trop Pediatr. 2013; 59: 209-213Crossref PubMed Scopus (25) Google Scholar, 6Imdad A Mullany LC Baqui AH et al.The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis.BMC Public Health. 2013; 13: 15Crossref PubMed Scopus (64) Google Scholar, 7Sazawal S Dhingra U Ali SM et al.Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: a community-based randomised controlled trial.Lancet Glob Health. 2016; 4: e837-e844Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 8Semrau KEA Herlihy J Grogan C et al.Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.Lancet Glob Health. 2016; 4: e827-e836Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar or facility births,3Kapellen TM Gebauer CM Brosteanu O Labitzke B Vogtmann C Kiess W Higher rate of cord-related adverse events in neonates with dry umbilical cord care compared to chlorhexidine powder: rresults of a randomized controlled study to compare efficacy and safety of chlorhexidine powder versus dry care in umbilical cord care of the newborn.Neonatology. 2009; 96: 13-18Crossref PubMed Scopus (31) Google Scholar, 4Sinha A Sazawal S Pradhan A Ramji S Opiyo N Chlorhexidine skin or cord care for prevention of mortality and infections in neonates.Cochrane Database Syst Rev. 2015; 3 (CD007835.)PubMed Google Scholar, 5Gathwala G Sharma D Bhakhri BK Effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial.J Trop Pediatr. 2013; 59: 209-213Crossref PubMed Scopus (25) Google Scholar, 6Imdad A Mullany LC Baqui AH et al.The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis.BMC Public Health. 2013; 13: 15Crossref PubMed Scopus (64) Google Scholar, 7Sazawal S Dhingra U Ali SM et al.Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: a community-based randomised controlled trial.Lancet Glob Health. 2016; 4: e837-e844Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 8Semrau KEA Herlihy J Grogan C et al.Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.Lancet Glob Health. 2016; 4: e827-e836Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar low-income settings2Imdad A Bautista RM Senen KA Uy ME Mantaring 3rd, JB Bhutta ZA Umbilical cord antiseptics for preventing sepsis and death among newborns.Cochrane Database Syst Rev. 2013; 5 (CD008635.)Google Scholar, 4Sinha A Sazawal S Pradhan A Ramji S Opiyo N Chlorhexidine skin or cord care for prevention of mortality and infections in neonates.Cochrane Database Syst Rev. 2015; 3 (CD007835.)PubMed Google Scholar, 5Gathwala G Sharma D Bhakhri BK Effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial.J Trop Pediatr. 2013; 59: 209-213Crossref PubMed Scopus (25) Google Scholar, 6Imdad A Mullany LC Baqui AH et al.The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis.BMC Public Health. 2013; 13: 15Crossref PubMed Scopus (64) Google Scholar, 7Sazawal S Dhingra U Ali SM et al.Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: a community-based randomised controlled trial.Lancet Glob Health. 2016; 4: e837-e844Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 8Semrau KEA Herlihy J Grogan C et al.Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.Lancet Glob Health. 2016; 4: e827-e836Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar or high-income settings,3Kapellen TM Gebauer CM Brosteanu O Labitzke B Vogtmann C Kiess W Higher rate of cord-related adverse events in neonates with dry umbilical cord care compared to chlorhexidine powder: rresults of a randomized controlled study to compare efficacy and safety of chlorhexidine powder versus dry care in umbilical cord care of the newborn.Neonatology. 2009; 96: 13-18Crossref PubMed Scopus (31) Google Scholar chlorhexidine reduces risk of such infection. As Sazawal and colleagues7Sazawal S Dhingra U Ali SM et al.Efficacy of chlorhexidine application to umbilical cord on neonatal mortality in Pemba, Tanzania: a community-based randomised controlled trial.Lancet Glob Health. 2016; 4: e837-e844Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar conclude, the results of the Pemba study suggest that use of chlorhexidine is justified for its effect in reducing risk of cord infection. Further, in settings where the underlying mortality risk in the population is high, chlorhexidine cleansing reduced mortality regardless of whether babies were born in facilities or at home. I declare no competing interests. No reason to change WHO guidelines on cleansing the umbilical cord20 years ago, neonatal survival was not on the global health agenda. In many low-income settings, infants died without recognition, causing untold grief. However, the past two decades have seen steady improvements in neonatal survival on a background of sustained advocacy, a culture of community-based trials, and improvements in quantity and quality of health care, health behaviour, and demand for services. Nevertheless, an annual 2·7 million newborn babies still do not survive their first month of life. Full-Text PDF Open AccessChlorhexidine and newborn omphalitis and mortality – Authors' replyStephen Hodgins says that cord application of chlorhexidine protects infants against omphalitis equally after birth at home or in hospital, and that we were incorrect to say that it was not effective for infants born in hospital. Full-Text PDF Open Access