Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV)
This review found no evidence to support the hypothesis that vaginal washes with chlorhexidine prevent maternal and neonatal infections (excluding Group B streptococcus and HIV), although data suggest a small reduction in the incidence of endometritis. Future trials should be done with standardized volumes, concentrations and methods of chlorhexidine vaginal disinfection.
RHL Commentary by Cutland CL
1. EVIDENCE SUMMARY
Three high-quality, randomized, placebo-controlled trials (two blinded, one unblinded) of vaginal disinfection (irrigation with chlorhexidine solution or sterile water) were included in this Cochrane review (1). The maternal outcome under review was reduction of the incidence of peripartum infection, including chorioamnionitis and endometritis. The neonatal outcome under review was reduction in neonatal sepsis, (excluding Group B streptococcal sepsis and HIV) including blood-borne infections, pneumonia and meningitis, antibiotic use and perinatal death.
There was no statistically significant difference between the intervention and control groups in terms of the incidence of chorioamnionitis or postpartum endometritis. However, the data suggest a small reduction in the incidence of endometritis.
Reduction in neonatal sepsis was assessed in all three trials, and no significant difference was found between the intervention and control groups. Also, no significant difference was found when assessing the incidence of neonatal pneumonia (one trial), neonatal meningitis (one trial), blood culture-confirmed sepsis or perinatal mortality (two trials). There was a suggestion, however, that infants of mothers who received chlorhexidine washes had a higher tendency for receiving antibiotics.
This review included only randomized or quasi-randomized trials that compared chlorhexidine vaginal douching during labour with a placebo (or other vaginal disinfectant) with the aim of reducing neonatal and maternal infections (excluding Group B streptococcal sepsis and HIV). None of the trials identified included infant cleansing as part of the intervention. Other randomized trials in which chlorhexidine was used as a vaginal disinfectant, either as a washing medium (douching/syringing) or as mechanical wipes, with or without the addition of infant cleansing, were excluded either because they focused on HIV or Group B streptococcal sepsis or colonization (2, 3, 4, 5) or because they lacked randomization (6, 7).
The search methods used in the review were thorough. The selection of trials, however, was narrow, as trials that had used chlorhexidine application methods other than douching were excluded. Douching has been shown to be associated with increased incidence of bacterial vaginosis in women with imbalanced vaginal flora (8), so the use of a placebo douche may possibly have increased the incidence of sepsis in the placebo groups.
The study populations, including the location at which the included studies were performed, are not clearly described in this review. Factors that may confound the impact of chlorhexidine disinfection – including use of intrapartum antibiotics, frequency of interventional douches and frequency of caesarean sections – are not detailed. The primary and secondary endpoints and the power of the trials for the endpoints of the three trials reviewed should have been reported to assist readers in interpreting null results.
The included chlorhexidine vaginal disinfection trials used a variety of methods of application and different volumes and concentrations of chlorhexidine in their intervention arms. A general review of the trials would probably be more meaningful than the meta-analysis approach used in this review.
Pathogenesis of maternal and neonatal sepsis is often not culture-confirmed. The separation of Group B streptococcus sepsis and sepsis from other pathogens into two Cochrane reviews on chlorhexidine vaginal disinfection is problematic. The rationale for this decision and a description of the criteria used to exclude Group B streptococcal sepsis trials (e.g. colonization at delivery, invasive disease) would assist the reader in identifying differences between study populations and the population defined for the review.
2. RELEVANCE TO UNDER-RESOURCED SETTINGS
2.1. Magnitude of the problem
Maternal and neonatal infections are a significant cause of morbidity and mortality, especially in under-resourced settings. Bacteria colonizing the genital tract are the main cause of these infections. Vaginal and cervical disinfection prior to delivery with a widely-used medical disinfectant, chlorhexidine, could reduce the incidence of maternal peripartum and neonatal infections.
An estimated four million newborn babies die annually, almost 99% of them in middle- and low-income countries, which have an overall neonatal mortality rate of 33/1000 live births. Between 43% and 47% of deaths among children under the age of five years occur in the neonatal period. Severe infections, excluding tetanus, account for 26% of these deaths, and three quarters of neonatal deaths occur in the first week of life (9, 10). The Millennium Development Goal (MDG) four calls on countries to reduce, by 2015, mortality in children under five years of age by two thirds from the rate in 1990. In 2000, 38% of child deaths occurred in the neonatal period. Hence, reducing neonatal mortality is imperative for achieving this MDG.
In 2004, 559 significant pathogens were isolated from blood and cerebrospinal fluid samples taken from infants under three months of age (358 in infants <1 month of age) admitted to Chris Hani Baragwanath Hospital (CHBH, Soweto, South Africa. There were approximately 30 000 births in 2004 in the area serviced by the Hospital, giving an approximate incidence of culture-confirmed sepsis in young infants of 18/1000 (<1 months of age; incidence ~12/1000). Staphylococcus aureus (13.6%) was the most common pathogen in infants under three months of age, followed by Streptococcus agalactiae (12.3%), Eschericia coli (11.3%) Viridans streptococcus (9.1%) and Klebsiella pneumoniae (8.9%). Streptococcus agalactiae was the most commonly isolated pathogen from infants ≤3 days old (11).
2.2. Applicability of the results
All trials reviewed were conducted in a single developed country (USA), where the neonatal mortality rate is <5/1000 live births (12). Maternal mortality and morbidity are also markedly lower in these settings compared with developing countries. In addition to geographical variations in the incidence and severity of neonatal sepsis, the pathogen species causing neonatal sepsis have also been documented to vary geographically as well as between developed and developing countries. Sepsis pathogens are also likely to vary depending on whether a birth takes place at home or at a birthing facility, although this difference has not been well characterized.
Other factors that might change the risk of maternal and neonatal infection and response to the treatment include mode of delivery (the intervention is expected to be most effective for vaginal deliveries), maternal HIV infection status, whether or not HIV-infected mothers are receiving antiretroviral therapy, the birth setting (home or facility), whether or not the delivery is preterm, and nutrition status of the mother.
The results of the review need to be assessed in conjunction with trials that include an assessment of reduction of Group B streptococcal sepsis, as Group B streptococcal sepsis accounts for approximately 30% of neonatal infections and is associated with a high mortality rate (13). Also, several recent trials have assessed the combination of maternal vaginal disinfection and neonatal skin disinfection in a single arm (6, 7). The impact of combined interventions on neonatal outcomes is promising, although determining the relative contribution of each component of the intervention in completed trials is impossible. Neonatal skin/umbilical cord cleansing with chlorhexidine solution in community-based trials has also produced promising results, with reductions in infant mortality and omphalitis(14, 15).
2.3. Implementation of the intervention
Chlorhexidine vaginal disinfection, whether by washing or wiping, is an inexpensive procedure. Chlorhexidine solution is widely available globally and can be diluted to a suitable concentration with boiled drinking-quality water or sterile water. There are no known trials comparing chlorhexidine vaginal washes and mechanical wipes. Implementation of vaginal mechanical wipes is probably more cost–effective and more feasible than vaginal washes, as the materials used for wipes (cotton swabs) are more likely to be available in under-resourced settings rather than catheters, syringes or douching bulbs that are needed for performing washes.
It is feasible to implement chlorhexidine vaginal disinfection techniques in all health-care settings, including home-based deliveries. Minimal organizational changes would be required to implement this procedure in delivery settings (e.g. hospitals or clinics), as the required materials would be easily available. Implementation of the procedure in a community setting would require provision of an aqueous-based, alcohol-free, chlorhexidine solution with a concentration between 0.25% and 1% to trained birth attendants. Adequate training and information (including product details, target applications and methods) should be made available to all birth attendants. Potential cultural barriers to implementation of the intervention need to be identified, and plans made to manage any potential side-effects prior to implementation of chlorhexidine vaginal/neonatal disinfection (16). Also, prior to implementation, the stability of chlorhexidine solution in varying light and temperature conditions should be assessed. Care should also be taken to prevent fall in neonatal body temperature while performing infant washes (17).
As mentioned, the results reviewed need to be assessed in conjunction with trials focused on reduction of all forms of maternal and neonatal sepsis, including GBS. Two recent review articles of chlorhexidine antisepsis interventions to reduce maternal and neonatal mortality and morbidity 15, 17 have concluded that the interventions show potential in low-resource areas. More research is, however, required to ensure global acceptance and implementation of this intervention. Randomized trial evidence of intervention efficacy in limited-resource settings, cost effective analysis of intervention and comparison of intervention techniques (including chlorhexidine concentration) need to be included in the aims of future research.
Three randomized trials are being conducted in limited resource settings (Pakistan, Zimbabwe and South Africa), and may provide information required to make a global decision on implementation of this intervention.
Sources of support: Departments of Obstetrics, Neonatology, Paediatrics and Microbiology, Chris Hani Baragwanath Hospital, Soweto, South Africa; Health Information Division, Department of Health, Gauteng, South Africa; US Centres for Diseases Control and Prevention (Grant numbers U50/CCU021960 & 1U01 CI000318), Bill & Melinda Gates Foundation (Grant number 39415)
Acknowledgements: Prof. S.A. Madhi (Respiratory and Meningeal Pathogens Reference Unit, National Institute of Communicable Diseases, South Africa); Dr S. Schrag (Centres for Diseases Control and Prevention, USA)
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This document should be cited as: Cutland CL. Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV): RHL commentary (last revised: 29 August 2007). The WHO Reproductive Health Library; Geneva: World Health Organization.