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
. 2024 Aug 1;178(8):823-829.
doi: 10.1001/jamapediatrics.2024.1917.

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births

Elyse O Kharbanda  1 , Malini B DeSilva  1 , Heather S Lipkind  2 , Paul A Romitti  3 , Jingyi Zhu  1 , Kimberly K Vesco  4 , Thomas G Boyce  5 , Matthew F Daley  6 , Candace C Fuller  7 , Darios Getahun  8 , Lisa A Jackson  9 , Joshua T B Williams  10 , Ousseny Zerbo  11 , Eric S Weintraub  12 , Gabriela Vazquez-Benitez  1
Affiliations

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births

Elyse O Kharbanda et al. JAMA Pediatr. .

Abstract

Importance: COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited.

Objective: To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine.

Design, setting, and participants: This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink.

Exposures: Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series.

Main outcomes and measures: Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review.

Results: Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified.

Conclusions and relevance: In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Lipkind reported receiving data safety monitoring board fees from Pfizer outside the submitted work. Dr Vesco reported receiving grants from Pfizer outside the submitted work. Dr Fuller reported receiving funding for research from Pfizer and Johnson and Johnson outside the submitted work. Dr Jackson reported receiving grants from Pfizer during the conduct of the study. Dr Vazquez-Benitez reported receiving grants from Sanofi and AbbVie outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Adjusted Prevalence Ratios (aPR) and 95% CIs for Any Major Structural Defect and by Defect Type
See this image and copyright information in PMC

References

    1. Ko JY, DeSisto CL, Simeone RM, et al. Adverse pregnancy outcomes, maternal complications, and severe illness among US delivery hospitalizations with and without a Coronavirus Disease 2019 (COVID-19) diagnosis. Clin Infect Dis. 2021;73(Suppl 1):S24-S31. doi: 10.1093/cid/ciab344 - DOI - PMC - PubMed
    1. Ferrara A, Hedderson MM, Zhu Y, et al. Perinatal complications in individuals in California with or without SARS-CoV-2 infection during pregnancy. JAMA Intern Med. 2022;182(5):503-512. doi: 10.1001/jamainternmed.2022.0330 - DOI - PMC - PubMed
    1. McClymont E, Albert AY, Alton GD, et al. ; CANCOVID-Preg Team . Association of SARS-CoV-2 Infection during pregnancy with maternal and perinatal outcomes. JAMA. 2022;327(20):1983-1991. doi: 10.1001/jama.2022.5906 - DOI - PMC - PubMed
    1. Villar J, Soto Conti CP, Gunier RB, et al. ; INTERCOVID-2022 International Consortium . Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study. Lancet. 2023;401(10375):447-457. doi: 10.1016/S0140-6736(22)02467-9 - DOI - PMC - PubMed
    1. Schrag SJ, Verani JR, Dixon BE, et al. Estimation of COVID-19 mRNA vaccine effectiveness against medically attended COVID-19 in Pregnancy during periods of delta and omicron variant predominance in the US. JAMA Netw Open. 2022;5(9):e2233273. doi: 10.1001/jamanetworkopen.2022.33273 - DOI - PMC - PubMed

Substances