Pregnancy outcomes after a mass vaccination campaign with an oral cholera vaccine: a systematic review and meta-analysis

BACKGROUND: Cholera has harmful effects on the fetus but safety data on the oral cholera vaccine in pregnant women are controversial. OBJECTIVES: We conducted the first meta-analysis of studies in pregnant women comparing the effect of oral cholera vaccination on pregnancy outcomes with unvaccinated women. Outcomes of interest were adverse pregnancy outcome, miscarriage, stillbirth, preterm delivery, low birthweight, abortion and malformation. SEARCH STRATEGY: The search was run in MEDLINE/PubMed, SCOPUS and Embase databases from inception up to December 2019. SELECTION CRITERIA: Inclusion criteria were: (1) studies that investigated the association between oral cholera vaccines and adverse pregnancy outcomes; (2) studies that reported outcomes with appropriate estimates; and (3) studies that contained an unvaccinated control group. DATA COLLECTION AND ANALYSIS: A random-effects model (DerSimonian and Laird) was run to evaluate the overall treatment effect (relative risk, RR). The PRISMA statement was followed in reporting this meta-analysis. MAIN RESULTS: Five studies included in meta-analysis with 5584 women (2920 exposed and 2664 not exposed). No significant increase in adverse pregnancy outcome (RR 1.03, 95% CI 0.79-1.34), miscarriage (RR 1.15, 95% CI 0.84-1.57) or stillbirth (RR 1.11, 95% CI 0.69-1.80) following cholera vaccine administration was found compared with control group. There was also no association with an increased risk of preterm delivery (RR 0.61, 95% CI 0.35-1.06) low birthweight (RR 0.84, 95% CI 0.56- 1.26), accidental abortion (RR 1.02, 95% CI 0.77-1.35) or malformation (RR 0.70, 95% CI 0.22-2.25). CONCLUSIONS: This study shows no evidence of an association between oral cholera vaccination and adverse pregnancy outcomes. The findings do not rigorously exclude the possibility that the vaccine protocol may result in some degree of harm. TWEETABLE ABSTRACT: There is no evidence of an association between oral cholera vaccination and adverse pregnancy outcomes. The findings do not rigorously exclude the possibility that the vaccine protocol may result in some degree of harm.