Association between maternal mRNA covid-19 vaccination in early pregnancy and major congenital anomalies in offspring: population based cohort study with sibling matched analysis

Sarah C J Jorgensen^{1

2}, Samantha S M Drover², Deshayne B Fell^{3

4}, Peter C Austin^{2

5}, Rohan D'Souza^{6

7}, Astrid Guttmann^{2

5

8

9

10}, Sarah A Buchan^{2

5

10

11}, Sarah E Wilson^{2

10

11

12}, Sharifa Nasreen^{2

10}, Kevin A Brown^{2

10

11}, Kevin L Schwartz^{2

10

11}, Mina Tadrous^{2

13

14}, Kumanan Wilson^{15

16

17}, Jeffrey C Kwong^{1

2

10

11

12

18

19}; Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN) Investigators

Affiliations

¹ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
² ICES, Toronto, Ontario, Canada.
³ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
⁴ Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
⁵ Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.
⁶ Departments of Obstetrics and Gynaecology and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
⁷ School of Graduate Studies, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Edwin SH Leong Centre for Healthy Children, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹¹ Public Health Ontario, Toronto, Ontario, Canada.
¹² Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, Ontario, Canada.
¹³ Women's College Hospital, Toronto, Ontario, Canada.
¹⁴ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
¹⁶ Bruyère Research Institute, Ottawa, Ontario, Canada.
¹⁷ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹⁸ Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁹ University Health Network, Toronto, Ontario, Canada.

PMID: 39574424
PMCID: PMC11579536
DOI: 10.1136/bmjmed-2023-000743

Association between maternal mRNA covid-19 vaccination in early pregnancy and major congenital anomalies in offspring: population based cohort study with sibling matched analysis

Sarah C J Jorgensen et al. BMJ Med. 2024.

. 2024 Sep 16;3(1):e000743.

doi: 10.1136/bmjmed-2023-000743. eCollection 2024.

Authors

Affiliations

¹ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
² ICES, Toronto, Ontario, Canada.
³ School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
⁴ Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
⁵ Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.
⁶ Departments of Obstetrics and Gynaecology and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
⁷ School of Graduate Studies, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
⁹ Edwin SH Leong Centre for Healthy Children, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹¹ Public Health Ontario, Toronto, Ontario, Canada.
¹² Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, Ontario, Canada.
¹³ Women's College Hospital, Toronto, Ontario, Canada.
¹⁴ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
¹⁶ Bruyère Research Institute, Ottawa, Ontario, Canada.
¹⁷ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹⁸ Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁹ University Health Network, Toronto, Ontario, Canada.

PMID: 39574424
PMCID: PMC11579536
DOI: 10.1136/bmjmed-2023-000743

Abstract

Objective: To examine the association between maternal mRNA covid-19 vaccination during the first trimester of pregnancy and the prevalence of major congenital anomalies in offspring.

Design: Population based cohort study with sibling matched analysis.

Setting: Multiple health administrative databases, linked and analysed at ICES, an independent, non-profit research institute that collects and analyses healthcare and demographic data, Ontario, Canada, from 16 October 2021 to 1 May 2023.

Population: 174 296 singleton live births >20 weeks' gestation with an expected birth date between 16 October 2021 and 1 May 2023: 34 181 (20%) born to mothers who received one or two doses of an mRNA covid-19 vaccine in the first trimester and 34 951 (20%) born to mothers who did not receive a vaccine before or during pregnancy. The sibling matched analysis included 13 312 infants exposed to a covid-19 vaccine in the first trimester and 15 089 matched older siblings with the same mother, with an expected birth date after 16 October 2016 and no reported in utero exposure to a covid-19 vaccine.

Main outcome measures: Major congenital anomalies, overall and grouped by specific organ systems, diagnosed within 28 days of birth.

Results: Major congenital anomalies were present in 832 (24.3 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester compared with 927 (26.5 per 1000 live births) infants not exposed to a vaccine, resulting in an adjusted prevalence ratio of 0.89 (95% confidence interval (CI) 0.79 to 1.01). Major congenital anomalies were present in 283 (21.3 per 1000 live births) and 343 (22.7 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester and their older siblings not exposed to a vaccine, respectively (adjusted prevalence ratio 0.91, 95% CI 0.77 to 1.07). First trimester vaccination was not associated with an increase in major congenital anomalies grouped by specific organ system in the primary or sibling matched analyses. Results were similar across a range of subgroup and sensitivity analyses.

Conclusions: In this large population based cohort study and sibling matched analysis, mRNA covid-19 vaccination during the first trimester of pregnancy was not associated with an increase in major congenital anomalies in offspring, overall or grouped by organ system.

Keywords: COVID-19; Infectious disease medicine; Neonatology; Obstetrics; Pediatrics.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from ICES, Canadian Immunization Research Network (CIRN), Public Health Agency of Canada, Canadian Institutes of Health Research, Public Health Agency of Canada, Vaccine Surveillance Working Party, Covid-19 Immunity Task Force, Ontario Health Data Platform, University of Toronto Department of Family and Community Medicine, and Canada Research Chairs for the submitted work; KW is a co-founder and the Chief Scientific Officer of CANImmunize, a digital immunisation solutions company; KW has also served on the safety advisory boards of Medicago and Moderna; SSMD serves as an independent consultant for CERobs Consulting; during the conduct of this work, DBF was employed by the University of Ottawa and had academic appointments at the Children’s Hospital of Eastern Ontario Research Institute and ICES; DBF is currently employed by Pfizer; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work; RD has received speaking honoraria and consultation fees from Pfizer, Sanofi, and Ferring, as well as grant funding from Ferring for unrelated projects.

Figures

Figure 1. Maternal covid-19 vaccination during the first trimester of pregnancy compared with no maternal covid-19 vaccination before conception or during pregnancy. Bottom panel=birth month and year by maternal vaccination status. Top panel=conception month and year by maternal vaccination status

See this image and copyright information in PMC

References

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Association between maternal mRNA covid-19 vaccination in early pregnancy and major congenital anomalies in offspring: population based cohort study with sibling matched analysis

Affiliations

Association between maternal mRNA covid-19 vaccination in early pregnancy and major congenital anomalies in offspring: population based cohort study with sibling matched analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources