Meta-Analysis

. 2022 May 10;13(1):2414.

doi: 10.1038/s41467-022-30052-w.

Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy

Smriti Prasad^#¹, Erkan Kalafat^#^{2

3}, Helena Blakeway¹, Rosemary Townsend^{4

5}, Pat O'Brien^{6

7}, Edward Morris^{6

8}, Tim Draycott^{6

9}, Shakila Thangaratinam¹⁰, Kirsty Le Doare¹¹, Shamez Ladhani^{12

13}, Peter von Dadelszen¹⁴, Laura A Magee¹⁴, Paul Heath¹¹, Asma Khalil^{15

16}

Affiliations

¹ Fetal Medicine Unit, St George's Hospital, St George's University of London, London, UK.
² Department of Statistics, Faculty of Arts and Sciences, Middle East Technical University, Ankara, Turkey.
³ Department of Obstetrics and Gynaecology, School of Medicine, Koc University, Istanbul, Turkey.
⁴ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
⁵ Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
⁶ The Royal College of Obstetricians and Gynaecologists, London, UK.
⁷ University College London Hospitals NHS Foundation Trust, London, UK.
⁸ Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, Norfolk, UK.
⁹ North Bristol NHS Trust Department of Women's Health, Westbury-on-Trym, Bristol, UK.
¹⁰ Institute of Metabolism and Systems Research, WHO Collaborating Centre for Women's Health, University of Birmingham, Birmingham, UK.
¹¹ Paediatric Infectious Diseases Research Group and Vaccine Institute, Institute of Infection and Immunity, St George's University of London, London, UK.
¹² Immunisation and Countermeasures Division, Public Health England, England, UK.
¹³ British Paediatric Surveillance Unit, Royal College of Paediatrics and Child Health, England, UK.
¹⁴ Institute of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
¹⁵ Fetal Medicine Unit, St George's Hospital, St George's University of London, London, UK. akhalil@sgul.ac.uk.
¹⁶ Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK. akhalil@sgul.ac.uk.

^# Contributed equally.

PMID: 35538060
PMCID: PMC9090726
DOI: 10.1038/s41467-022-30052-w

Meta-Analysis

Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy

Smriti Prasad et al. Nat Commun. 2022.

. 2022 May 10;13(1):2414.

doi: 10.1038/s41467-022-30052-w.

Authors

Affiliations

¹ Fetal Medicine Unit, St George's Hospital, St George's University of London, London, UK.
² Department of Statistics, Faculty of Arts and Sciences, Middle East Technical University, Ankara, Turkey.
³ Department of Obstetrics and Gynaecology, School of Medicine, Koc University, Istanbul, Turkey.
⁴ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
⁵ Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
⁶ The Royal College of Obstetricians and Gynaecologists, London, UK.
⁷ University College London Hospitals NHS Foundation Trust, London, UK.
⁸ Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, Norfolk, UK.
⁹ North Bristol NHS Trust Department of Women's Health, Westbury-on-Trym, Bristol, UK.
¹⁰ Institute of Metabolism and Systems Research, WHO Collaborating Centre for Women's Health, University of Birmingham, Birmingham, UK.
¹¹ Paediatric Infectious Diseases Research Group and Vaccine Institute, Institute of Infection and Immunity, St George's University of London, London, UK.
¹² Immunisation and Countermeasures Division, Public Health England, England, UK.
¹³ British Paediatric Surveillance Unit, Royal College of Paediatrics and Child Health, England, UK.
¹⁴ Institute of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
¹⁵ Fetal Medicine Unit, St George's Hospital, St George's University of London, London, UK. akhalil@sgul.ac.uk.
¹⁶ Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK. akhalil@sgul.ac.uk.

^# Contributed equally.

PMID: 35538060
PMCID: PMC9090726
DOI: 10.1038/s41467-022-30052-w

Abstract

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I² = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I² = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.

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Conflict of interest statement

P.O.B. is co-chair of the Royal College of Obstetricians and Gynaecologists (RCOG) Vaccine Committee. P.O.B. and T.D. are RCOG Vice-Presidents. E.M. is RCOG President. P.H. is a member of the RCOG Vaccine Committee. P.H. is CI of the Preg-Cov trial (UK multicentre COVID vaccination in pregnancy). A.K. is obstetric PI of the Preg-Cov trial (UK multicentre COVID vaccination in pregnancy). A.K. is a member of the COVAX Working Group on COVID vaccination in pregnancy. A.K. is PI of the Pfizer COVID vaccination in pregnancy trial. The remaining authors declare no competing interests.

Figures

**Fig. 1. PRISMA flow diagram.**
Flow diagram summarises the number of studies excluded at each stage.

**Fig. 2. Forest plot of studies reporting vaccine effectiveness.**
Vertical ticks within the red boxes and horizontal lines show the mean effect and 95% confidences interval for each study. Black diamond at the bottom shows the cumulative effect with 95% confidence intervals.

**Fig. 3. Forest plot of studies reporting stillbirth rate.**
Vertical ticks within the blue boxes and horizontal lines show the mean effect and 95% confidences interval for each study. Black diamond at the bottom shows the cumulative effect with 95% confidence intervals.

**Fig. 4. Forest plot of studies reporting hypoxic brain injury.**
Vertical ticks within the blue boxes and horizontal lines show the mean effect and 95% confidences interval for each study. Black diamond at the bottom shows the cumulative effect with 95% confidence intervals.

**Fig. 5. Forest plot of studies reporting on preterm birth rate prior to 37 weeks' (a), 34 weeks' (b) and 32 weeks' (c) gestation.**
Vertical ticks within the blue boxes and horizontal lines show the mean effect and 95% confidences interval for each study. Black diamond at the bottom shows the cumulative effect with 95% confidence intervals.

**Fig. 6. Forest plot of studies reporting miscarriage rate and accounting for time-varying confounding.**
Vertical ticks within the red boxes and horizontal lines show the mean effect and 95% confidences interval for each study. Black diamond at the bottom shows the cumulative effect with 95% confidence intervals.

See this image and copyright information in PMC

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Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy

Affiliations

Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy

Authors

Affiliations

Abstract

Conflict of interest statement

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