Chlorhexidine and newborn omphalitis and mortality – Authors' reply
Authors: David Osrin, Tim Colbourn
Journal: The Lancet Global Health (2017)

Stephen 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. The first point is well taken. The 2015 Cochrane review1Sinha 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; (CD007835.)Crossref Scopus (46) Google Scholar suggests that risk ratios (RR) for omphalitis were similar in hospital (RR 0·48, 95% CI 0·28–0·84) and community trials (0·48, 0·40–0·57). The 2013 Cochrane review2Imdad A Bautista RMM Senen KAA Uy MEV Mantaring III, JB Bhutta ZA Umbilical cord antiseptics for preventing sepsis and death among newborns.Cochrane Database Syst Rev. 2013; (CD008635.)Crossref PubMed Scopus (87) Google Scholar included nine relevant hospital studies of chlorhexidine application. For omphalitis, one 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: results 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 suggested a benefit versus dry cord care (0·28, 0·06–1·35); another study4Oishi T Iwata S Nonoyama M Tsuji A Sunakawa K Double-blind comparative study on the care of the neonatal umbilical cord using 80% ethanol with or without chlorhexidine.J Hosp Infect. 2004; 58: 34-37Summary Full Text Full Text PDF PubMed Scopus (21) Google Scholar found no benefit versus alcohol (2·77, 0·12–66·49), and another5Meberg A Schoyen R Hydrophobic material in routine umbilical cord care and prevention of infections in newborn infants.Scand J Infect Dis. 1990; 22: 729-733Crossref PubMed Scopus (20) Google Scholar found no benefit over hydrophobic gauze (1·36, 0·55–3·36). Imdad and colleagues2Imdad A Bautista RMM Senen KAA Uy MEV Mantaring III, JB Bhutta ZA Umbilical cord antiseptics for preventing sepsis and death among newborns.Cochrane Database Syst Rev. 2013; (CD008635.)Crossref PubMed Scopus (87) Google Scholar suggested that, “…compared with dry cord care, no antiseptic was convincingly advantageous to reduce the incidence of omphalitis.” The 2015 Cochrane review addressed cord cleansing, more extensive skin cleansing, and maternal vaginal washing.1Sinha 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; (CD007835.)Crossref Scopus (46) Google Scholar One trial6Gathwala G Sharma D Bhakhri B 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 in India suggested that, compared with dry cord care, chlorhexidine cord cleansing was associated with a non-significant reduction in mortality (RR 0·11, 95% CI 0·01–2·04). This and a trial in Germany3Kapellen 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: results 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 suggested that chlorhexidine cord cleansing was associated with lower risk of omphalitis. The review1Sinha 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; (CD007835.)Crossref Scopus (46) Google Scholar made no recommendation for hospital births, saying that the “…quality of evidence for the effects on infection are moderate for cord application”. The trial in Germany3Kapellen 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: results 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 compared healthy term infants (>2500 g) in two neonatal nurseries treated with chlorhexidine 1% powder (337 infants) or dry cord care (332 infants). Sample size was based on the primary outcome of cord separation time but recruitment shortfalls necessitated respecification of the detectable difference. Hodgins summarises adverse events. Omphalitis was identified in two infants in the chlorhexidine group and seven in the dry cord care group. All cases but one were described as mild. The 2015 Cochrane review1Sinha 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; (CD007835.)Crossref Scopus (46) Google Scholar downgraded its classification because of “…serious risk of selection bias, performance bias and detection bias”. The trial in India6Gathwala G Sharma D Bhakhri B 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 compared application of chlorhexidine 2·5% solution to the cords of 70 infants with dry cord care for 70 infants, all of them older than 32 weeks and weighing more than 1499 g and judged on enrolment as likely to spend at least 5 days in a neonatal intensive care unit. The sample size was again based on the primary outcome of cord separation time. Culture-confirmed sepsis was lower in the chlorhexidine group (RR 0·13, 95% CI 0·02–0·40). The 2015 Cochrane review1Sinha 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; (CD007835.)Crossref Scopus (46) Google Scholar downgraded its classification of bias risk because of imprecision. Together, these trials included 809 infants. Hodgins' second point interprets a statement we made, quoting the WHO recommendation,7WHOWHO recommendations on postnatal care of the mother and newborn: 2013. World Health Organization, Geneva2014Google Scholar and saying that the Cochrane reviews,1Sinha 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; (CD007835.)Crossref Scopus (46) Google Scholar, 2Imdad A Bautista RMM Senen KAA Uy MEV Mantaring III, JB Bhutta ZA Umbilical cord antiseptics for preventing sepsis and death among newborns.Cochrane Database Syst Rev. 2013; (CD008635.)Crossref PubMed Scopus (87) Google Scholar a meta-analysis,8Imdad 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 and the two trials in The Lancet Global Health9Semrau KE 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, 10Sazawal 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 had not supported an effect after hospital births. Our Comment11Osrin 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 begins with, and is permeated by, an emphasis on newborn mortality. As Hodgins says, community-based trials8Imdad 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, 9Semrau KE 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, 10Sazawal 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 suggest that the effect on neonatal mortality was similar—even when non-significant—when infants were born in hospital. We do not take issue with this. Indeed, we acknowledge the complete statement by Sazawal and colleagues:10Sazawal 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 “The findings in our study suggest that use of chlorhexidine for the reduction of omphalitis is justified, but in an African setting there is insufficient evidence to promote this intervention to reduce neonatal mortality.” The emphasis of our Comment was on whether cord application of chlorhexidine might achieve appreciable reductions in newborn mortality in low-income and middle-income countries. We said that two recent trials9Semrau KE 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, 10Sazawal 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 did not provide evidence to alter current WHO guidelines,7WHOWHO recommendations on postnatal care of the mother and newborn: 2013. World Health Organization, Geneva2014Google Scholar which recommend it for infants born at home in environments with neonatal mortality rates of more than 30 per 1000 livebirths. We stand by this. DO does not work with but has been a co-author of six publications in the past 5 years with Robert Black, a named author of the paper from Tanzania. The publications were produced by large working groups and DO and TC both either contributed data from their research programmes or were members of a distributed expert group. 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 mortalityDavid Osrin and Tim Colbourn (November, 2016)1 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. Full-Text PDF Open Access