Tetanus toxoid immunization to reduce mortality from neonatal tetanus

BACKGROUND: Neonatal tetanus remains an important and preventable cause of neonatal mortality globally. Large reductions in neonatal tetanus deaths have been reported following major increases in the coverage of tetanus toxoid immunization, yet the level of evidence for the mortality effect of tetanus toxoid immunization is surprisingly weak with only two trials considered in a Cochrane review. OBJECTIVE: To review the evidence for and estimate the effect on neonatal tetanus mortality of immunization with tetanus toxoid of pregnant women, or women of childbearing age. METHODS: We conducted a systematic review of multiple databases. Standardized abstraction forms were used. Individual study quality and the overall quality of evidence were assessed using an adaptation of the GRADE approach. Meta-analyses were performed. RESULTS: Only one randomised controlled trial (RCT) and one well-controlled cohort study were identified, which met inclusion criteria for meta-analysis. Immunization of pregnant women or women of childbearing age with at least two doses of tetanus toxoid is estimated to reduce mortality from neonatal tetanus by 94% [95% confidence interval (CI) 80-98%]. Additionally, another RCT with a case definition based on day of death, 3 case-control studies and 1 before-and-after study gave consistent results. Based on the consistency of the mortality data, the very large effect size and that the data are all from low/middle-income countries, the overall quality of the evidence was judged to be moderate. CONCLUSION: This review uses a standard approach to provide a transparent estimate of the high impact of tetanus toxoid immunization on neonatal tetanus.