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 Vousden
  2. Rema Ramakrishnan
  3. Kathryn Bunch
  4. Eddie Morris
  5. Nigel A B Simpson
  6. Christopher Gale
  7. Patrick O'Brien
  8. Maria Quigley
  9. Peter Brocklehurst
  10. Jennifer J Kurinczuk
  11. Marian Knight

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Abstract

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 .

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  3. Version published to 10.1136/bmjmed-2021-000053
  4. ScreenIT

    SciScore for 10.1101/2021.07.22.21261000: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableNominated reporting clinicians, facilitated by research midwives and nurses from the UK’s National Institute of Health Research Clinical Research Network, notified all pregnant women admitted to their hospital with confirmed SARS-CoV-2 infection.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisIn this national observational study, the study sample size was governed by the disease incidence, thus no formal power calculation was carried out.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical methods and analysis: Statistical analyses were performed using STATA version 15 (Statacorp, TX, USA).
    STATA
    suggested: (Stata, RRID:SCR_012763)
    Statacorp
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Whilst it is a limitation that women with mild infection diagnosed and treated in the community will not be included in this study, it is highly likely that all women with severe infection would have been captured. A further limitation of our study is that variant sequencing data were not available for individual women, therefore proxy time periods were utilised instead. However, the Delta VOC is now known to have contributed more than 90% of all sequenced cases since 7th June 2021 so major contamination is unlikely.17 Other time-dependent changes will exist which we cannot account for, for example varying thresholds for admission to hospital or ICU depending on clinician familiarity with managing COVID-19. In the general population, national guidance was updated in January 2021 to inform community management of those with oxygen saturations >92%.18 However, it is unclear that this admission threshold was used extensively in pregnancy and given that the RCOG has never released national admission guidance for pregnant patients, this is unlikely to account for differences observed. Differing thresholds based on bed capacity may have been a contributory factor during the peak of the Alpha VOC when hospital pressures may have restricted admission to the most severe cases. However, this is not supported by our finding of an increased proportion of admissions primarily for COVID-19 in this time compared to the Wildtype period. In addition, current hospital pressures from COVID-19 (...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  5. Version published to 10.1101/2021.07.22.21261000v1 on medRxiv