A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection

Clara Calvert, Jade Carruthers, Cheryl Denny, Jack Donaghy, Lisa EM Hopcroft, Leanne Hopkins, Anna Goulding, Laura Lindsay, Terry McLaughlin, Emily Moore, Bob Taylor, Maria Loane, Helen Dolk, Joan Morris, Bonnie Auyeung, Krishnan Bhaskaran, Cheryl L Gibbons, Srinivasa Vittal Katikireddi, Maureen O'Leary, David McAllisterTing Shi, Colin R Simpson, Chris Robertson, Aziz Sheikh, Sarah J Stock, Rachael Wood

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Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6,731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR]=1.01, 95% Confidence Interval [CI]=0.83-1.24) or non-genetic anomalies (aOR=1.00, 95% CI=0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR=1.02, 95% CI=0.66-1.60) or non-genetic anomalies (aOR=0.94, 95% CI=0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.
Original languageEnglish
Article number107
Pages (from-to)1-11
Number of pages11
JournalNature Communications
Issue number1
Early online date6 Jan 2023
Publication statusPublished online - 6 Jan 2023

Bibliographical note

Funding Information:
We acknowledge the contribution of Sam Hillman to data analysis. Our thanks to the EAVE II Patient Advisory Group and Sands charity for their support. COPS is a sub-study of EAVE II, which is funded by the Medical Research Council (MC_PC_19075) (A.S.) with the support of BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004] (A.S.), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and Scottish Government DG Health and Social Care and the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation. COPS has received additional funding from Tommy’s charity (S.J.S.). S.J.S. is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). S.V.K. acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). K.B. is funded by a Wellcome Senior Research Fellowship (220283/Z/20/Z).

Publisher Copyright:
© 2023, The Author(s).


  • Epidemiology
  • Respiratory tract diseases
  • SARS-CoV-2
  • Vaccines
  • COVID-19
  • Pregnancy
  • BNT162 Vaccine
  • COVID-19 Vaccines
  • Humans
  • Vaccination
  • Female
  • Cohort Studies
  • SARS-CoV-2/genetics
  • Vaccination/adverse effects
  • COVID-19/epidemiology
  • COVID-19 Vaccines/adverse effects


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