Safety of a bivalent, killed, whole-cell oral cholera vaccine in pregnant women in Bangladesh: evidence from a randomized placebo-controlled trial

Ashraful Islam Khan, Mohammad Ali, Julia Lynch, Alamgir Kabir, Jean-Louis Excler, Md Arifuzzaman Khan, Md Taufiqul Islam, Afroza Akter, Fahima Chowdhury, Amit Saha, Iqbal Ansary Khan, Sachin N Desai, Deok Ryun Kim, Nirod Chandra Saha, Ajit P Singh, John D Clemens, Firdausi Qadri, Ashraful Islam Khan, Mohammad Ali, Julia Lynch, Alamgir Kabir, Jean-Louis Excler, Md Arifuzzaman Khan, Md Taufiqul Islam, Afroza Akter, Fahima Chowdhury, Amit Saha, Iqbal Ansary Khan, Sachin N Desai, Deok Ryun Kim, Nirod Chandra Saha, Ajit P Singh, John D Clemens, Firdausi Qadri

Abstract

Background: Cholera increases the risk of harmful effects on foetuses. We prospectively followed pregnant women unaware of their pregnancy status who received a study agent in a clinical trial evaluating the association between exposure to an oral cholera vaccine (OCV) and foetal survival.

Methods: Study participants were selected from a randomized placebo-controlled trial conducted in Dhaka, Bangladesh. The vaccination campaign was conducted between January 10 and February 4, 2014. We enrolled women who were exposed to an OCV or placebo during pregnancy (Cohort 1) and women who were pregnant after the vaccination was completed (Cohort 2). Our primary endpoint was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were preterm delivery and low birth weight. We employed a log-binomial regression to calculate the relative risk of having adverse outcomes among OCV recipients compared to that among placebo recipients.

Result: There were 231 OCV and 234 placebo recipients in Cohort 1 and 277 OCV and 299 placebo recipients in Cohort 2. In Cohort 1, the incidence of pregnancy loss was 113/1000 and 115/1000 among OCV and placebo recipients, respectively. The adjusted relative risk for pregnancy loss was 0.97 (95% CI: 0.58-1.61; p = 0.91) in Cohort 1. We did not observe any variation in the risk of pregnancy loss between the two cohorts. The risks for preterm delivery and low birth weight were not significantly different between the groups in both cohorts.

Conclusions: Our study provides additional evidence that exposure to an OCV during pregnancy does not increase the risk of pregnancy loss, preterm delivery, or low birth weight, suggesting that pregnant women in cholera-affected regions should not be excluded in a mass vaccination campaign.

Trial registration: The study is registered at ( https://ichgcp.net/clinical-trials-registry/NCT02027207" title="See in ClinicalTrials.gov">NCT02027207 .

Keywords: Bangladesh; Cholera; OCV; Pregnant women; Safety.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Research Review Committee and the Ethical Review Committee of the icddr,b, Dhaka, Bangladesh, and the Institutional Review Board of the International Vaccine Institute. A data safety monitoring board also approved the study and monitored the progress of work. Written informed consent was obtained from all participants. In the case of minor participants, consent was obtained from the parents or guardians on the same consent form. The study is registered at (Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Assembling the study population for analysis

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