The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis

Abstract

Study Question What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines? Summary Answer There is no evidence that COVID-19 vaccines are associated with an increased risk of miscarriage. What is Known Already In response to the COVID-19 pandemic, the mass roll-out of vaccines helped to boost herd immunity and reduced hospital admissions, morbidity and mortality. Still, many were concerned about the safety of vaccinesfor pregnancy, which may have limited their uptake among pregnant women and those planning a pregnancy. Study Design, Size, Duration For this systematic review and meta-analysis, we searched MEDLINE, EMBASE and Cochrane CENTRAL from inception until June 2022 using a combination of keywords and MeSH terms. Participants/Materials, Setting, Methods We included observational and interventional studies that enrolled pregnant women and evaluated any of the available COVID-19 vaccines compared to placebo or no vaccination. We primarily reported on miscarriage in addition to ongoing pregnancy and/or live birth. Main Results and The Role of Chance We included data from 21 studies (5 randomised trials and 16 observational studies) reporting on 149,685 women. The pooled rate of miscarriage among women who received a COVID-19 vaccine was 9% (n = 147,49/123,185, 95%CI 0.05-0.14). Compared to those who received a placebo or no vaccination, women who received a COVID-19 vaccine did not have a higher risk of miscarriage (RR 1.07, 95%CI 0.89-1.28, I2 35.8%) and had comparable rates for ongoing pregnancy or live birth (RR 1.00, 95%CI 0.97-1.03, I2 10.72%). Limitations, Reasons for Caution Our analysis was limited to observational evidence with varied reporting, high heterogeneity and risk of bias across included studies, which may limit the generalisability and confidence in our findings. Wider Implications of the Findings COVID-19 vaccines are not associated with an increase in the risk of miscarriage or reduced rates of ongoing pregnancy or live birth among women of reproductive age. The current evidence remains limited and larger population studies are needed to further evaluate the effectiveness and safety of COVID-19 in pregnancy. Study Funding/Competing Interest No direct funding was provided to support this work. MPR is funded by the Medical Research Council Centre for Reproductive Heath Grant No: MR/N022556/1. BHA hold a personal development award from the National Institute of Health Research in the UK. All authors declare no conflict of interest. REGISTRATION NUMBER CRD42021289098.

The remarkable ups and downs of birth rate in Switzerland 2020 to 2023 in a historical context

“…At present, the evidence is rapidly growing that the coronavirus vaccination itself cannot be directly and biologically linked to the decline in births and fertility (Wang et al, 2023; Zaçe et al, 2022). This unanimous opinion is supported by a growing number of studies with different designs and on male and female fertility (Aharon et al, 2022; Ba et al, 2023; Barda et al, 2022; Gonzalez et al, 2021; Morris, 2021; Reschini et al, 2022; Yang et al, 2023; Yildiz et al, 2023) and miscarriage (Yland et al, 2023; Zauche et al, 2021), including already some review articles (Rimmer et al, 2023; Wesselink et al, 2022; Zhang et al, 2023; Zhu et al, 2023). Several studies report changes in the duration of menstrual cycle length following COVID-19 vaccination (Alvergne et al, 2023), but these changes are small (+/-1 day) and resume in the next cycle, thus not threatening fertility (Alvergne, 2023).…”

Miscarriage after SARS‐CoV‐2 vaccination: A population‐based cohort study

“…A recent meta-analysis comprising 149 685 women, showed a relative risk for miscarriage of 0.71 (95% CI 0.89-1.28) in women vaccinated compared with controls. 25 A case-control study from the US Vaccine Safety Datalink included 13 160 cases with miscarriage and 92 286 controls with ongoing pregnancy and observed an odds ratio of 1.02 (95% CI 0.96-1.08) for miscarriage associated with SARS-CoV-2 vaccination in the preceding 28 days. 2 These estimates are also in keeping with other population-based registry studies from the Norway and Scotland.…”

“…These findings on SARS‐CoV‐2 vaccination and miscarriage are consistent with prior studies. A recent meta‐analysis comprising 149 685 women, showed a relative risk for miscarriage of 0.71 (95% CI 0.89–1.28) in women vaccinated compared with controls 25 . A case–control study from the US Vaccine Safety Datalink included 13 160 cases with miscarriage and 92 286 controls with ongoing pregnancy and observed an odds ratio of 1.02 (95% CI 0.96–1.08) for miscarriage associated with SARS‐CoV‐2 vaccination in the preceding 28 days 2 .…”

Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis

“…Early observational studies on vaccine effectiveness focused on reporting the effects of any COVID-19 vaccine in pregnancy on maternal SARS-CoV-2 infection 6–8. Subsequent reviews reporting pregnancy outcomes varied in their inclusion of studies, overlapped their search periods by only a few months and were rapidly outdated, limiting their relevance 9–12. Some reviews only included studies from specific regions or countries and did not provide a global outlook 13.…”