The last two years saw the commencement of mass vaccination campaigns for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to contain the coronavirus disease 2019 (COVID-19) pandemic. However, the rapid development and emergency use approval (EUA) of the COVID-19 vaccine raised concerns about its efficacy, safety, and long-term consequences. In particular, pregnant women or those planning a pregnancy were hesitant to be vaccinated.
Study: The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis. Image Credit: Blue Planet Studio / Shutterstock
Background
Initially, pregnant women were excluded from clinical studies designed to evaluate the efficacy of COVID-19 vaccines. As a result, limited evidence was available regarding the safety of vaccines in pregnancy. Currently, the majority of health officials have reported that COVID-19 vaccination is safe for pregnant women. This observation is based on the reduced risk of poor pregnancy outcomes in COVID-19-vaccinated women compared to unvaccinated pregnant women.
Some studies have indicated the potential risks of cross-reactivity of SARS-CoV-2 spike (S) protein antibodies after mRNA vaccination and human syncytin-1 protein in trophoblastic tissue, which could cause placental damage. In addition, autoreactive antibodies against syncytin-1 could lead to early pregnancy loss. Nevertheless, detailed characterization of S protein structure and amino acid sequencing revealed insignificant homology between the S protein antibodies generated post-vaccination and syncytin-1, which indicated COVID-19 vaccine safety.
About the Study
Scientists have recently reviewed existing literature to evaluate the rates of miscarriage and live birth among COVID-19-vaccinated pregnant women. This review is available in the Human Reproduction journal.
This study obtained all relevant data until June 2022 from MEDLINE, Cochrane CENTRAL, and EMBASE. The authors considered all studies related to miscarriages, live births, and ongoing pregnancies in women who received COVID-19 vaccines. Animal studies and those that reported non-clinical outcomes in human participants were excluded.
A total of 505 relevant citations were considered, including randomized control trials (RCTs) and observational studies. However, 21 studies were selected that satisfied all criteria.
Combining all studies, pregnancy outcomes in 149,685 women were studied. The participants received any one of the six COVID-19 vaccines manufactured by Pfizer-BioNTech (BNT162b2 mRNA), Moderna (mRNA-1273), Janssen (Ad26.COV2.S), AstraZeneca (ChAdOx1 nCoV184 19), Sinopharm (BBIBP-CorV), and Sinovac (CoronaVac). Overall, the studies considered in the present review exhibited a low to moderate risk of bias.
Study Findings
The average miscarriage rate among pregnant women receiving any COVID-19 vaccines was 9%. The risk of miscarriage among the COVID-19 vaccinated group, compared with the unvaccinated group, showed no significant difference in miscarriage rate between the two groups. In addition, both groups exhibited similar rates of ongoing pregnancies or live birth.
Limitations
The heterogeneity in the study designs and patient characteristics, along with the risk of bias, limited the generalizability of the current meta-analysis. It also highlights the need for better-quality research involving pregnant women in the future. Most studies performed suboptimal protocols, resulting in varied study outcomes. This restricted analysis of high-quality evidence. The low-quality data also decreased the certainty of pooled estimates, particularly for pregnancy outcomes. The incidence of stillbirth and ectopic pregnancy was not reported in any studies considered.
Several factors can contribute to the overall miscarriage rates during the pandemic, such as mode of conception, ethnicity, and access to maternity services during the lockdown period. The majority of studies were related to short-term assessment of COVID-19 vaccine safety. These studies do not offer insights into the long-term outcomes of the pregnancy.
Conclusions and Future Outlook
No apparent elevated risk of miscarriage was observed among pregnant women who received the COVID-19 vaccine. This rate was consistent with the miscarriage rate in the general population before the COVID-19 pandemic. However, the certainty of this observation is low due to the presence of inconsistencies in the data.
In the future, there is a need to evaluate the short and long-term safety and efficacy of all COVID-19 vaccines on pregnant women and their offspring. In addition, extensive prospective cohort studies matched controls, along with epidemiological and translational studies, must be conducted to analyze the effectiveness and safety of the different COVID-19 vaccination programs, which will help reduce adverse maternal and neonatal outcomes.
The authors recommended that future studies follow a standardized reporting system for core outcomes, i.e., miscarriage, fertility, and pregnancy. This will significantly reduce research wastage.
Inequities in COVID-19 vaccination coverage for older adults highlighted in global study