COVID-19 diagnosis, vaccination during pregnancy, and adverse pregnancy outcomes of 865,654 women in England and Wales: a population-based cohort study

Elena Raffetti; Thomas Bolton; John Nolan; Luisa Zuccolo; Rachel Denholm; Gordon Smith; Ashley Akbari; Katie Harron; Gwenetta Curry; Elias Allara; Deborah A Lawlor; Massimo Caputo; Hoda Abbasizanjani; Tim Chico; Angela M Wood; CVD-COVID-UK/COVID-IMPACT Consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study

doi:10.1016/j.lanepe.2024.101037

COVID-19 diagnosis, vaccination during pregnancy, and adverse pregnancy outcomes of 865,654 women in England and Wales: a population-based cohort study

Lancet Reg Health Eur. 2024 Aug 22:45:101037. doi: 10.1016/j.lanepe.2024.101037. eCollection 2024 Oct.

Authors

Elena Raffetti^{1

2

3

4}, Thomas Bolton⁵, John Nolan⁵, Luisa Zuccolo^{6

7

8}, Rachel Denholm^{8

9

10}, Gordon Smith¹¹, Ashley Akbari¹², Katie Harron¹³, Gwenetta Curry¹⁴, Elias Allara^{1

2}, Deborah A Lawlor^{7

8}, Massimo Caputo¹⁵, Hoda Abbasizanjani¹², Tim Chico¹⁶, Angela M Wood^{1

2

5

17

18

19}; CVD-COVID-UK/COVID-IMPACT Consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study

Affiliations

¹ British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
² Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
³ Deparment of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Earth Sciences, Uppsala University, Uppsala, Sweden.
⁵ British Heart Foundation Data Science Centre, Health Data Research UK, London, UK.
⁶ Health Data Science Centre, Human Technopole, Milan, Italy.
⁷ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁸ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁹ NIHR Bristol Biomedical Research Centre, Bristol, UK.
¹⁰ Health Data Research UK South-West, Bristol, UK.
¹¹ Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK.
¹² Population Data Science, Swansea University Medical School, Faculty of Medicine, Health & Life Science, Swansea University, Swansea, UK.
¹³ Population, Policy & Practice Dept UCL GOS Institute of Child Health, London, UK.
¹⁴ Edinburgh Migration and Ethnicity Health Research Group, College of Medicine and Veterinary Medicine, Usher Institute, University of Edinburgh, UK.
¹⁵ Translational Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
¹⁶ Division of Clinical Medicine, School of Medicine and Population Health, The Medical School, University of Sheffield, Beech Hill Road, Sheffield, UK.
¹⁷ National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
¹⁸ Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
¹⁹ Cambridge Centre of Artificial Intelligence in Medicine, UK.

Abstract

Background: The extent to which COVID-19 diagnosis and vaccination during pregnancy are associated with risks of common and rare adverse pregnancy outcomes remains uncertain. We compared the incidence of adverse pregnancy outcomes in women with and without COVID-19 diagnosis and vaccination during pregnancy.

Methods: We studied population-scale linked electronic health records for women with singleton pregnancies in England and Wales from 1 August 2019 to 31 December 2021. This time period was divided at 8th December 2020 into pre-vaccination and vaccination roll-out eras. We calculated adjusted hazard ratios (HRs) for common and rare pregnancy outcomes according to the time since COVID-19 diagnosis and vaccination and by pregnancy trimester and COVID-19 variant.

Findings: Amongst 865,654 pregnant women, we recorded 60,134 (7%) COVID-19 diagnoses and 182,120 (21%) adverse pregnancy outcomes. COVID-19 diagnosis was associated with a higher risk of gestational diabetes (adjusted HR 1.22, 95% CI 1.18-1.26), gestational hypertension (1.16, 1.10-1.22), pre-eclampsia (1.20, 1.12-1.28), preterm birth (1.63, 1.57-1.69, and 1.68, 1.61-1.75 for spontaneous preterm), very preterm birth (2.04, 1.86-2.23), small for gestational age (1.12, 1.07-1.18), thrombotic venous events (1.85, 1.56-2.20) and stillbirth (only within 14-days since COVID-19 diagnosis, 3.39, 2.23-5.15). HRs were more pronounced in the pre-vaccination era, within 14-days since COVID-19 diagnosis, when COVID-19 diagnosis occurred in the 3rd trimester, and in the original variant era. There was no evidence to suggest COVID-19 vaccination during pregnancy was associated with a higher risk of adverse pregnancy outcomes. Instead, dose 1 of COVID-19 vaccine was associated with lower risks of preterm birth (0.90, 0.86-0.95), very preterm birth (0.84, 0.76-0.94), small for gestational age (0.93, 0.88-0.99), and stillbirth (0.67, 0.49-0.92).

Interpretation: Pregnant women with a COVID-19 diagnosis have higher risks of adverse pregnancy outcomes. These findings support recommendations towards high-priority vaccination against COVID-19 in pregnant women.

Funding: BHF, ESRC, Forte, HDR-UK, MRC, NIHR and VR.

Keywords: Adverse pregnancy outcomes; COVID-19; COVID-19 variants; Trimester; Vaccination.