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4% chlorhexidine to umbilical stump - summary of study characteristics
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Study
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RegionHow was the intervention delivered?Birth settingWhat was provided to the control group?Risk of bias due to blindingIntervention coverageRisk of bias due to attritionTrial pre-registered?Baseline balance between groups?
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South Asia trials
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Arifeen et al. 2012 (2)Sylhet, BangladeshAt home via village health workers (VHWs): "Mothers and newborn babies in all three groups received postnatal home visits from VHWs for 7 days after enrolment." (Pg. 1024)UnclearDry cord care advice: "In the dry cord care group, the VHWs promoted cord care messages during home visits that are recommended by WHO, and did not apply chlorhexidine
to the cord." (Pg. 1024)		No: "Because of the nature of the interventions, we could not mask intervention workers and study participants to the study interventions." (Pg. 1024)<1% received no intervention (Table 1)Low (see figure 3) Yes: "This trial is registered with ClinicalTrials.gov, number NCT00434408" Pg. 1022Yes (Table 1)
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Mullany et al. 2006 (2)Southern NepalA local female worker: "[W]omen were approached for enrolment by the local female worker...After delivery, the local worker implemented the assigned skin cleansing treatment." (Pg. 3)Facility (8%) and home/outdoor (92%) (Table 1)Dry cord care advice: "In the control clusters (dry cord care), educational messages regarding clean cord care were provided, but the unbilical cord stump was not cleansed." (Page 3-4)Yes: "Study investigators, analysts, project field workers, and participants were masked to the chlorhexidine and to the soap and water treatments" (Pg. 3)On average women received 84% of 10 treatments. (Table 2). Low (see figure 3) Yes: "This trial is registered with Clinicaltrials.gov, number NCT00109616." (Pg. 1)Yes, in general, but slight (2%) difference in maternal literacy and region/ethnicity (plains vs. hills) (Table 1)
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Soofi et al., 2012Dadu, Rural district of PakistanTrained birth attendants delivered the intervention to babies at home: "The study interventions were delivered at the household level by TBAs working under the supervision of locally
recruited community health workers (CHWs)." (Pg. 1030) 		Facility (23%) and home (77%) (Table 1)Dry cord care advice and standard birth kits: "Families in group D (control cluster) received standard birth kits (without any CHX solution or soap). They were advised to practise dry cord care." (Pg. 1030)Only of research team: "Implementation and data collection
teams were masked to allocation" (Pg. 1030)		97% received at least one CHX application (Pg. 1033)Low (see figure 3) Yes: "The trial is registered with ClinicalTrials.gov, number NCT00682006" Pg. 1029In general, but slightly more skilled birth attendant in CHX group, some differences in regions across groups, other small differences (p-vals not reported) (Table 1)
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Sub-Saharan Africa trials
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Sazawal et al. 2016Pemba Island, ZanzibarVia maternal and child health workers: "All newborn babies...born in hospital or the community (home based) ..were eligible for inclusion in the study...For babies allocated to the chlorhexidine group and the placebo group (in phase 1), the MCH worker showed the mother or caretaker how to apply the solution to the baby, gave 3 days supply of the solution, and instructed the mother or caretaker to apply the solution to the cord every day including 3 days after the cord had dropped off. The mother or caretaker was informed that the MCH worker would visit again on day 4 and day 10 to apply the solution." (Pg. e838 and e839)Facility (53%) and home (47%) (Table 1)Dry cord care advice and neonatal care messages: "For babies assigned to the dry cord care group, in addition to the initial examination, data collection, and neonatal care messages, TBAs and hospital staff instructed the mothers and caretakers not to cleanse the umbilical cord stump and to keep it dry." (Pg. e839)No: "Masking of allocation of intervention to workers and participants during phase 2 was not possible because of the nature of the interventions." (Pg. e839)100% in treatment group received at least one CHX application (Table 2)Low (see table 2) Yes: "The trial is registered with ClinicalTrials.gov, number NCT01528852." Pg. e837Yes (Table 1)
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Semrau et al. 2016Southern Province, ZambiaVia home visits by field monitors: "In the chlorhexidine group, field monitors provided pregnant women with chlorhexidine and cotton swabs at the antenatal home visit, and instructed them on how to apply chlorhexidine to the umbilical stump. Liquid 4% chlorhexidine formulation was supplied in single-application 10 mL eyedropper bottles (Galentic Inc, Mumbai, India). Each mother in the chlorhexidine group received instructions and sufficient quantities for once a day application until 3 days after the umbilical stump had separated fully. The birth attendant, mother, or a relative applied the first dose; the mother or her family completed subsequent applications." (Pg. e829)Facility (64%) and home (35%) (Table 2)Dry cord care advice: "Participants in the dry cord care group were instructed by field monitors to keep the cord clean, dry, and free of topical substances, in accordance with the Zambian Ministry of Health policy." (Pg. e829)Not described, but likely not blind since control group is dry cord care only. 92% applied CHX until cord dropped off (Table 3) Low (see table 2) Yes: "This study is registered at ClinicalTrials.gov (NCT01241318)." (Pg. e827)Yes (Tables 1 and 2)
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(1) Risk of bias assessed using Cochrane Risk of Bias tool for RCTs, including random sequence generation, intention to treat, blinding, attrition bias, selective reporting
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(2) Nepal and Bangladesh trials conducted by the same study team. In 2017, authors pooled results for facility-based births only and found a strong effect on maternal mortality (Mullany et al. 2017; 10.5 vs. 19.4 deaths per 1k)
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