Female Preconception Vaccination Against COVID-19 And Spontaneous Abortion in A Prospective Preconception Cohort Study

Background: There are concerns about the potential effects of COVID-19 vaccination on pregnancy outcomes, particularly spontaneous abortion (SAB; pregnancy loss before 20 weeks’ completed gestation). Several studies have been conducted to evaluate COVID-19 vaccination and SAB. However, these studies have major limitations, including under-ascertainment of SAB, potential selection bias, and lack of a comparison group. Thus, it remains crucial to evaluate the safety of COVID-19 vaccines using a prospective design with regular follow-up.

Objectives: To estimate the effect of preconception vaccination against COVID-19, compared with no vaccination, on risk of SAB.

Methods: This prospective cohort study was conducted among 1,168 pregnant women residing in the United States who enrolled in Pregnancy Online Study (PRESTO) during January 2021-February 2022. PRESTO is a preconception cohort of North American couples aged 21-45 years. On baseline and follow-up questionnaires, individuals report whether they have ever received a COVID-19 vaccine, and if yes, the brand and date they received each dose. On follow-up questionnaires, participants report data on their menstrual periods, whether they are pregnant, and whether/when they had a pregnancy loss since their last questionnaire.

We estimated the incidence rate ratio (IRR) comparing individuals who received at least one dose of any COVID-19 vaccine (mRNA or viral vector) before conception, at any time since the development of COVID-19 vaccines, with those who had never received a COVID-19 vaccine before conception.

We used propensity score fine stratification to adjust for age; body mass index; race/ethnicity; geographical region; smoking status; education; type of health insurance; healthcare utilization (number of primary care visits in the past year); household income; employment status; job hours per week; diabetes; hypertension; asthma; use of multivitamins and folate supplements; perceived stress scale score; major depression inventory score; nightly sleep duration; number of pregnancy attempt cycles; parity; history of SAB; use of fertility treatment; history of subfertility or infertility; and calendar time.

Results: Among 1,168 PRESTO participants who became pregnant in 2021-2022, 869 (74%) had received at least one dose of the COVID-19 vaccine before conception. The adjusted IRR comparing vaccinated to unvaccinated individuals was 0.90 (95% confidence interval: 0.68, 1.17).

Conclusions: Our findings are consistent with no effect of COVID-19 vaccination on SAB. Recently published research in this cohort identified no adverse effect of COVID-19 vaccination on fecundability. Together, these results can be used to guide decision making around COVID-19 vaccination for couples planning pregnancy.