Date Published: December 29, 2015
Publisher: Public Library of Science
Author(s): Lise Grout, Isabel Martinez-Pino, Iza Ciglenecki, Sakoba Keita, Alpha Amadou Diallo, Balla Traore, Daloka Delamou, Oumar Toure, Sarala Nicholas, Barbara Rusch, Nelly Staderini, Micaela Serafini, Rebecca F. Grais, Francisco J. Luquero, Gary L. Simon. http://doi.org/10.1371/journal.pntd.0004274
Abstract: IntroductionSince 2010, WHO has recommended oral cholera vaccines as an additional strategy for cholera control. During a cholera episode, pregnant women are at high risk of complications, and the risk of fetal death has been reported to be 2–36%. Due to a lack of safety data, pregnant women have been excluded from most cholera vaccination campaigns. In 2012, reactive campaigns using the bivalent killed whole-cell oral cholera vaccine (BivWC), included all people living in the targeted areas aged ≥1 year regardless of pregnancy status, were implemented in Guinea. We aimed to determine whether there was a difference in pregnancy outcomes between vaccinated and non-vaccinated pregnant women.Methods and FindingsFrom 11 November to 4 December 2013, we conducted a retrospective cohort study in Boffa prefecture among women who were pregnant in 2012 during or after the vaccination campaign. The primary outcome was pregnancy loss, as reported by the mother, and fetal malformations, after clinical examination. Primary exposure was the intake of the BivWC vaccine (Shanchol) during pregnancy, as determined by a vaccination card or oral history. We compared the risk of pregnancy loss between vaccinated and non-vaccinated women through binomial regression analysis. A total of 2,494 pregnancies were included in the analysis. The crude incidence of pregnancy loss was 3.7% (95%CI 2.7–4.8) for fetuses exposed to BivWC vaccine and 2.6% (0.7–4.5) for non-exposed fetuses. The incidence of malformation was 0.6% (0.1–1.0) and 1.2% (0.0–2.5) in BivWC-exposed and non-exposed fetuses, respectively. In both crude and adjusted analyses, fetal exposure to BivWC was not significantly associated with pregnancy loss (adjusted risk ratio (aRR = 1.09 [95%CI: 0.5–2.25], p = 0.818) or malformations (aRR = 0.50 [95%CI: 0.13–1.91], p = 0.314).ConclusionsIn this large retrospective cohort study, we found no association between fetal exposure to BivWC and risk of pregnancy loss or malformation. Despite the weaknesses of a retrospective design, we can conclude that if a risk exists, it is very low. Additional prospective studies are warranted to add to the evidence base on OCV use during pregnancy. Pregnant women are particularly vulnerable during cholera episodes and should be included in vaccination campaigns when the risk of cholera is high, such as during outbreaks.
Partial Text: Cholera represents a risk of complications for pregnant women and their fetus. Published literature reports fetal loss rates during cholera episodes of between 2% and 36% [1–7]. However, comparison of pregnancy outcomes among different reports is difficult, due to differences in inclusion criteria, treatment provided, and access to care. Although the exact cause of fetal death during a cholera episode has not yet been identified, several studies suggest an association between fetal loss and the degree of dehydration and hypovolemia [2,4–7].
The study took place in Boffa Prefecture of Guinea where six sub-prefectures bordering the ocean were targeted for cholera vaccination campaigns. All residents one year of age and above were offered a first dose from 18 to 23 April and a second dose from 9 to 14 May 2012 (Fig 1). The retrospective cohort study was conducted in two of these sub-prefectures (Koba and Boffa), since the association between vaccine exposure and pregnancy outcomes was assumed independent of the sub-prefecture.
From 11 November to 4 December 2013, 10,211 households were visited; 315 were absent (3.1%) and 13 refused to participate (0.1%). A total of 15,732 women 16 to 50 years old were asked about their pregnancy status and 3,177 (20.2%) reported a pregnancy in 2012 (Fig 2). After applying the exclusion criteria, 2,724 women pregnant in 2012 were enrolled; however, 231 were excluded at the time of the analysis (Fig 2). One woman was pregnant twice in 2012. A total of 2,494 pregnancies were therefore included in the analyses; 1,543 in the primary analysis and 951 in the bias-indicator analysis.
These are the first estimates of the risk of pregnancy loss following vaccination of pregnant women with the bivalent, whole-cell only oral cholera vaccine. Exposure of the fetus to this vaccine was not significantly associated with the risk of pregnancy loss and malformation in this study. Vaccine coverage among pregnant women was high (83%) and similar to the overall vaccination coverage of the campaign . This suggests that pregnant women who were offered OCV during the campaign chose to participate rather than forego vaccination. Vaccination coverage was higher among women who were pregnant during the campaign than among those who become pregnant after the campaign. Pregnant women may have been better informed about the vaccination campaign, less occupied by outside activities on the day of vaccination, and more willing to follow the advice of the Ministry of Health to get the vaccination than non-pregnant women. Overall, vaccinated and non-vaccinated women had similar baseline characteristics, both in the primary and in the bias-indicator analyses. Vaccinated pregnant women included in the primary analysis were more likely to attend antenatal care services and delivered more frequently in health facilities than those not vaccinated, which could be the result of a greater interest and awareness of preventive activities during pregnancy.