Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2023 May 1;6(5):e2314350.
doi: 10.1001/jamanetworkopen.2023.14350.

COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion

Elyse O Kharbanda  1 , Jacob Haapala  1 , Heather S Lipkind  2 , Malini B DeSilva  1 , Jingyi Zhu  1 , Kimberly K Vesco  3 , Matthew F Daley  4 , James G Donahue  5 , Darios Getahun  6 , Simon J Hambidge  7 , Stephanie A Irving  3 , Nicola P Klein  8 , Jennifer C Nelson  9 , Eric S Weintraub  10 , Joshua T B Williams  7 , Gabriela Vazquez-Benitez  1
Affiliations
Observational Study

COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion

Elyse O Kharbanda et al. JAMA Netw Open. .

Abstract

Importance: Adherence to COVID-19 booster vaccine recommendations has lagged in pregnant and nonpregnant adult populations. One barrier to booster vaccination is uncertainty regarding the safety of booster doses among pregnant people.

Objective: To evaluate whether there is an association between COVID-19 booster vaccination during pregnancy and spontaneous abortion.

Design, setting, and participants: This observational, case-control, surveillance study evaluated people aged 16 to 49 years with pregnancies at 6 to 19 weeks' gestation at 8 health systems in the Vaccine Safety Datalink from November 1, 2021, to June 12, 2022. Spontaneous abortion cases and ongoing pregnancy controls were evaluated during consecutive surveillance periods, defined by calendar time.

Exposure: Primary exposure was receipt of a third messenger RNA (mRNA) COVID-19 vaccine dose within 28 days before spontaneous abortion or index date (midpoint of surveillance period in ongoing pregnancy controls). Secondary exposures were third mRNA vaccine doses in a 42-day window or any COVID-19 booster in 28- and 42-day windows.

Main outcomes and measures: Spontaneous abortion cases and ongoing pregnancy controls were identified from electronic health data using a validated algorithm. Cases were assigned to a single surveillance period based on pregnancy outcome date. Eligible ongoing pregnancy time was assigned to 1 or more surveillance periods as an ongoing pregnancy-period control. Generalized estimating equations were used to estimate adjusted odds ratios (AOR) with gestational age, maternal age, antenatal visits, race and ethnicity, site, and surveillance period as covariates and robust variance estimates to account for inclusion of multiple pregnancy periods per unique pregnancy.

Results: Among 112 718 unique pregnancies included in the study, the mean (SD) maternal age was 30.6 (5.5) years. Pregnant individuals were Asian, non-Hispanic (15.1%); Black, non-Hispanic (7.5%); Hispanic (35.6%); White, non-Hispanic (31.2%); and of other or unknown (10.6%); and 100% were female. Across eight 28-day surveillance periods, among 270 853 ongoing pregnancy-period controls, 11 095 (4.1%) had received a third mRNA COVID-19 vaccine in a 28-day window; among 14 226 cases, 553 (3.9%) had received a third mRNA COVID-19 vaccine within 28 days of the spontaneous abortion. Receipt of a third mRNA COVID-19 vaccine was not associated with spontaneous abortion in a 28-day window (AOR, 0.94; 95% CI, 0.86-1.03). Results were consistent when using a 42-day window (AOR, 0.97; 95% CI, 0.90-1.05) and for any COVID-19 booster in a 28-day (AOR, 0.94; 95% CI, 0.86-1.02) or 42-day (AOR, 0.96; 95% CI, 0.89-1.04) exposure window.

Conclusions and relevance: In this case-control surveillance study, COVID-19 booster vaccination in pregnancy was not associated with spontaneous abortion. These findings support the safety of recommendations for COVID-19 booster vaccination, including in pregnant populations.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Lipkind reported receiving personal fees from Pfizer outside the submitted work. Dr Vesco reported receiving grants from Pfizer outside the submitted work. Dr Klein reported receiving grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur outside the submitted work. Dr Nelson reported receiving personal fees from Elsevier outside the submitted work. Dr Vazquez-Benitez reported receiving grants from AbbVie and Sanofi Pasteur outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Spontaneous Abortion (SAB) and Ongoing Pregnancy-Period Surveillance and COVID-19 Vaccine Boosters in 28-Day (or 42-Day) Exposure Window
Data are stratified by gestational age groups (6-8, 9-13, and 14-19 weeks), maternal age group, number of antenatal visits, race and ethnicity, and Vaccine Safety Datalink site. The dashed beige lines indicate time during pregnancy but outside the surveillance period; the amount of time represented varies by pregnancy and is not to scale with the figure. The solid blue lines represent pregnancy time during the surveillance period. LMP indicates last menstrual period.
Figure 2.
Figure 2.. Adjusted Odds Ratios (AORs) for Primary and Secondary Analyses, COVID-19 Booster Vaccination, and Spontaneous Abortion (SAB) at 8 Vaccine Safety Datalink Sites, November 1, 2021, to June 12, 2022
Generalized estimating equation models included gestational age group, surveillance period, maternal age group, number of antenatal visits, site, and race and ethnicity factors and accounted for unique pregnancies that included multiple pregnancy periods. mRNA indicates messenger RNA.
See this image and copyright information in PMC

References

    1. Worldometer COVID-19 coronavirus pandemic . Accessed March 18, 2022. https://worldometers.info/coronavirus/
    1. Regan AK, Arah OA, Fell DB, Sullivan SG. SARS-CoV-2 infection during pregnancy and associated perinatal health outcomes: a national US cohort study. J Infect Dis. 2022;225(5):759-767. doi:10.1093/infdis/jiab626 - DOI - PMC - PubMed
    1. Strid P, Zapata LB, Tong VT, et al. . Coronavirus disease 2019 (COVID-19) severity among women of reproductive age with symptomatic laboratory—confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by pregnancy status-United States, 1 January 2020–25 December 2021. Clin Infect Dis. 2022;75(suppl 2):S317-S325. doi:10.1093/cid/ciac479 - DOI - PMC - PubMed
    1. Dagan N, Barda N, Biron-Shental T, et al. . Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy. Nat Med. 2021;27(10):1693-1695. doi:10.1038/s41591-021-01490-8 - DOI - PubMed
    1. Goldshtein I, Nevo D, Steinberg DM, et al. . Association between BNT162b2 vaccination and incidence of SARS-CoV-2 infection in pregnant women. JAMA. 2021;326(8):728-735. doi:10.1001/jama.2021.11035 - DOI - PMC - PubMed

Publication types