Abstract: Two effectiveness trials (9823 infants) and one safety trial (48 mothers) were included. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. For our primary outcomes, there was no high-quality evidence according to GRADE assessments. One study (1182 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. A single dose did not provide significant protection against neonatal tetanus deaths, (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.26 to 1.24; 494 infants; GRADE: low-quality evidence). However, a two- or three-dose course did provide protection against neonatal deaths, (RR 0.02, 95% CI 0.00 to 0.30; 688 infants; GRADE: moderate-quality evidence). Administration of a two- or three-dose course resulted in significant protection when all causes of death are considered as an outcome (RR 0.31, 95% CI 0.17 to 0.55; 688 infants; GRADE: moderate-quality evidence). No effect was detected on causes of death other than tetanus. Cases of neonatal tetanus after at least one dose of tetanus toxoid were reduced in the tetanus toxoid group, (RR 0.20, 95% CI 0.10 to 0.40; 1182 infants; GRADE: moderate-quality evidence). Another study, involving 8641 children, assessed the effectiveness of tetanus-diphtheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. Neonatal mortality was reduced in the tetanus-diphtheria toxoid group (RR 0.68, 95% CI 0.56 to 0.82). In preventing deaths at four to 14 days, neonatal mortality was reduced again in the tetanus-diphtheria toxoid group (RR 0.38, 95% CI 0.27 to 0.55). The quality of evidence as assessed using GRADE was found to be low. The third small trial assessed that pain at injection site was reported more frequently among pregnant women who received tetanus diphtheria acellular pertussis than placebo (RR 5.68, 95% CI 1.54 to 20.94; GRADE: moderate-quality evidence). Available evidence supports the implementation of immunisation practices on women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites.

Plain-language summary: The evidence is current to January 2015, the review includes three trials. Two assessed the effectiveness of vaccinating women of reproductive age (9823 infants): one (1182 newborns) assessed the effects of tetanus toxoid against polyvalent influenza in preventing tetanus and deaths within the 30th day of life; the other (8641 newborns) assessed the effects of tetanus-diphtheria toxoid against cholera toxoid administered in women of reproductive age in preventing newborn deaths. The third trial (48 women and their newborns) assessed the safety of tetanus toxoid diphtheria acellular pertussis vaccine (Tdap) administration during pregnancy in comparison with placebo. A protective effect against deaths caused by tetanus was observed among the newborns from mothers who received at least two doses of the tetanus toxoid vaccine when compared with newborns from mothers who were immunised with influenza vaccine. A similar protective effect was seen with at least two doses of the tetanus vaccine against newborn deaths. Cases of tetanus were less frequent among newborns from women who received at least one dose of tetanus toxoid. This evidence was of moderate quality. In the second trial immunisation of women of reproductive age with tetanus diphtheria toxoid had a greater protective effect against newborn deaths than did cholera vaccine. The quality of the evidence was low for this outcome. In the third study no serious adverse events (during pregnancy or in babies) were related to the receiving of Tdap vaccine. The women experienced more pain with the vaccine injection than with the placebo. The available evidence supports the implementation of immunisation programs for women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of tetanus in newborn babies as at the two study sites.