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 McAllister; Ting Shi; Colin R Simpson; Chris Robertson; Aziz Sheikh; Sarah J Stock; Rachael Wood

doi:10.1038/s41467-022-35771-8

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 McAllister

Ting Shi, Colin R Simpson, Chris Robertson, Aziz Sheikh, Sarah J Stock, Rachael Wood

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

45 Downloads (Pure)

Abstract

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 language	English
Article number	107
Pages (from-to)	1-11
Number of pages	11
Journal	Nature Communications
Volume	14
Issue number	1
Early online date	6 Jan 2023
DOIs	https://doi.org/10.1038/s41467-022-35771-8
Publication status	Published 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).

Funding

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).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1038/s41467-022-35771-8

s41467-022-35771-8Final published version, 0.99 MBLicence: CC BY

Cite this

Calvert, C., Carruthers, J., Denny, C., Donaghy, J., Hopcroft, L. EM., Hopkins, L., Goulding, A., Lindsay, L., McLaughlin, T., Moore, E., Taylor, B., Loane, M., Dolk, H., Morris, J., Auyeung, B., Bhaskaran, K., Gibbons, C. L., Katikireddi, S. V., O'Leary, M., ... Wood, R. (2023). A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection. Nature Communications, 14(1), 1-11. Article 107. Advance online publication. https://doi.org/10.1038/s41467-022-35771-8

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

abstract = "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. ",

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

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{\textquoteright}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: {\textcopyright} 2023, The Author(s).",

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doi = "10.1038/s41467-022-35771-8",

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Calvert, C, Carruthers, J, Denny, C, Donaghy, J, Hopcroft, LEM, Hopkins, L, Goulding, A, Lindsay, L, McLaughlin, T, Moore, E, Taylor, B, Loane, M , Dolk, H, Morris, J, Auyeung, B, Bhaskaran, K, Gibbons, CL, Katikireddi, SV, O'Leary, M, McAllister, D, Shi, T, Simpson, CR, Robertson, C, Sheikh, A, Stock, SJ & Wood, R 2023, 'A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection', Nature Communications, vol. 14, no. 1, 107, pp. 1-11. https://doi.org/10.1038/s41467-022-35771-8

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T1 - A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection

AU - Calvert, Clara

AU - Carruthers, Jade

AU - Denny, Cheryl

AU - Donaghy, Jack

AU - Hopcroft, Lisa EM

AU - Hopkins, Leanne

AU - Goulding, Anna

AU - Lindsay, Laura

AU - McLaughlin, Terry

AU - Moore, Emily

AU - Taylor, Bob

AU - Loane, Maria

AU - Dolk, Helen

AU - Morris, Joan

AU - Auyeung, Bonnie

AU - Bhaskaran, Krishnan

AU - Gibbons, Cheryl L

AU - Katikireddi, Srinivasa Vittal

AU - O'Leary, Maureen

AU - McAllister, David

AU - Shi, Ting

AU - Simpson, Colin R

AU - Robertson, Chris

AU - Sheikh, Aziz

AU - Stock, Sarah J

AU - Wood, Rachael

N1 - 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).

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N2 - 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.

AB - 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.

KW - Epidemiology

KW - Respiratory tract diseases

KW - SARS-CoV-2

KW - Vaccines

KW - COVID-19

KW - Pregnancy

KW - BNT162 Vaccine

KW - COVID-19 Vaccines

KW - Humans

KW - Vaccination

KW - Female

KW - Cohort Studies

KW - SARS-CoV-2/genetics

KW - Vaccination/adverse effects

KW - COVID-19/epidemiology

KW - COVID-19 Vaccines/adverse effects

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DO - 10.1038/s41467-022-35771-8

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SN - 2041-1723

VL - 14

SP - 1

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JO - Nature Communications

JF - Nature Communications

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ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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