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Severity of maternal infection and perinatal outcomes during periods of SARS-CoV-2 wildtype, alpha, and delta variant dominance in the UK: prospective cohort study
  1. Nicola Vousden1,
  2. Rema Ramakrishnan1,
  3. Kathryn Bunch1,
  4. Eddie Morris2,
  5. Nigel A B Simpson3,
  6. Christopher Gale4,
  7. Patrick O'Brien2,5,
  8. Maria Quigley1,
  9. Peter Brocklehurst6,
  10. Jennifer J Kurinczuk1 and
  11. Marian Knight1
  1. 1National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  2. 2Royal College of Obstetricians and Gynaecologists, London, UK
  3. 3Department of Women’s & Children’s Health, University of Leeds, Leeds, UK
  4. 4School of Public Health, Faculty of Medicine, Imperial College London, London, UK
  5. 5Institute for Women's Health, University College London, London, UK
  6. 6Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, West Midlands, UK
  1. Correspondence to Professor Marian Knight, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, Oxfordshire, UK; marian.knight{at}


Objective To compare the severity of maternal infection and perinatal outcomes during periods in which wildtype, alpha variant, and delta variant of SARS-CoV-2 were dominant in the UK.

Design Prospective cohort study.

Setting 194 obstetric units across the UK, during the following periods: between 1 March and 30 November 2020 (wildtype dominance), between 1 December 2020 and 15 May 2021 (alpha variant dominance), and between 16 May and 31 October 2021 (delta variant dominance).

Participants 4436 pregnant women admitted to hospital with covid-19 related symptoms.

Main outcome measures Moderate to severe maternal SARS-CoV-2 infection (indicated by any of the following: oxygen saturation <95% on admission, need for oxygen treatment, evidence of pneumonia on imaging, admission to intensive care, or maternal death), and pregnancy and perinatal outcomes (including mode and gestation of birth, stillbirth, live birth, admission to neonatal intensive care, and neonatal death).

Results 1387, 1613, and 1436 pregnant women were admitted to hospital with covid-19 related symptoms during the wildtype, alpha, and delta dominance periods, respectively; of these women, 340, 585, and 614 had moderate to severe infection, respectively. The proportion of pregnant women admitted with moderate to severe infection increased during the subsequent alpha and delta dominance periods, compared with the wildtype dominance period (wildtype 24.5% v alpha 36.2% (adjusted odds ratio 1.98, 95% confidence interval 1.66% to 2.37%); wildtype 24.5% v delta 42.8% (2.66, 2.21 to 3.20)). Compared with the wildtype dominance period, women admitted during the alpha dominance period were significantly more likely to have pneumonia, require respiratory support, and be admitted to intensive care; these three risks were even greater during the delta dominance period (wildtype v delta: pneumonia, adjusted odds ratio 2.52, 95% confidence interval 2.06 to 3.09; respiratory support, 1.90, 1.52 to 2.37; and intensive care, 2.71, 2.06 to 3.56). Of 1761 women whose vaccination status was known, 38 (2.2%) had one dose and 16 (1%) had two doses before their diagnosis (of whom 14 (88%) had mild infection). The proportion of women receiving drug treatment for SARS-CoV-2 management was low, but did increase between the wildtype dominance period and the alpha and delta dominance periods (10.4% wildtype v 14.9% alpha (2.74, 2.08 to 3.60); 10.4% wildtype v 13.6% delta (2.54, 1.90 to 3.38)).

Conclusions While limited by the absence of variant sequencing data, these findings suggest that during the periods when the alpha and delta variants of SARS-CoV-2 were dominant, covid-19 was associated with more severe maternal infection and worse pregnancy outcomes than during the wildtype dominance period. Most women admitted with SARS-CoV-2 related symptoms were unvaccinated. Urgent action to prioritise vaccine uptake in pregnancy is essential.

Study registration ISRCTN40092247.

  • COVID-19
  • pregnancy complications
  • neonatology

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  • Contributors All authors contributed to conceptualisation, writing, and editing of this study; had final approval of the version to be published; and agree to be accountable for all aspects of the work. KB, EM, NABS, CG, PO'B, MQ, PB, JJK, and MK contributed to funding acquisition, supervision, and methodology. NV, RR, KB, and MK contributed to data curation and formal analysis, and all had access to verify the underlying data. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. MK is study guarantor. Transparency: The lead author (the guarantor) also affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Funding The study was funded by the NIHR Health Services and Delivery Research Programme (project number 11/46/12). MK is an NIHR senior investigator. The funder played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; nor the decision to submit the paper for publication.

  • Competing interests Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: MK, MQ, PB, PO’B, and JJK received grants from the NIHR in relation to the submitted work; KB, NV, and NABS declare no conflicts of interest; EM is trustee of the Royal College of Obstetricians and Gynaecologists and British Menopause Society, and new chair of the board of trustees for Group B Strep Support; CG was financially supported by UK Medical Research Council (MRC)through a clinician scientist fellowship; PB was past chair of the MRC/NIHR Methodology Research Programme panel with previous grant funding from MRC, NIHR, and the Welcome Trust, and provides consultancy services for personal fees to AG Biotest.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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