SARS‐CoV‐2 infection in pregnancy in Denmark—characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population‐based cohort study

  1. Anna J. M. Aabakke
  2. Lone Krebs
  3. Tanja G. Petersen
  4. Frank S. Kjeldsen
  5. Giulia Corn
  6. Karen Wøjdemann
  7. Mette H. Ibsen
  8. F. Jonsdottir
  9. Elisabeth Rønneberg
  10. Charlotte S. Andersen
  11. Iben Sundtoft
  12. Tine Clausen
  13. Julie Milbak
  14. Lars Burmester
  15. Birgitte Lindved
  16. Annette Thorsen‐Meyer
  17. Mohammed R. Khalil
  18. Birgitte Henriksen
  19. Lisbeth Jønsson
  20. Lise L. T. Andersen
  21. Kamilla K. Karlsen
  22. Monica L. Pedersen
  23. Åse Klemmensen
  24. Marianne Vestgaard
  25. Dorthe Thisted
  26. Manrinder K. Tatla
  27. Line S. Andersen
  28. Anne‐Line Brülle
  29. Arense Gulbech
  30. Charlotte B. Andersson
  31. Richard Farlie
  32. Lea Hansen
  33. Lone Hvidman
  34. Anne N. Sørensen
  35. Sidsel L. Rathcke
  36. Katrine H. Rubin
  37. Lone K. Petersen
  38. Jan S. Jørgensen
  39. Lonny Stokholm
  40. Mette Bliddal

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Abstract

Introduction

Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during pregnancy is essential to guide clinical care. Previous studies on SARS‐CoV‐2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS‐CoV‐2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS‐CoV‐2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission.

Material and methods

This was a prospective population‐based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS‐CoV‐2 test during pregnancy to non‐infected pregnant women. Cases of SARS‐CoV‐2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID‐19) symptoms.

Results

Among 82 682 pregnancies, 418 women had SARS‐CoV‐2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID‐19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41–3.41) and being foreign born (OR 2.12, 95% CI 1.70–2.64). Risk factors for hospital admission due to COVID‐19 included obesity (OR 2.74, 95% CI 1.00–7.51), smoking (OR 4.69, 95% CI 1.58–13.90), infection after gestational age (GA) 22 weeks (GA 22–27 weeks: OR 3.77, 95% CI 1.16–12.29; GA 28–36 weeks: OR 4.76, 95% CI 1.60–14.12), and having asthma (OR 4.53, 95% CI 1.39–14.79). We found no difference in any obstetrical or neonatal outcomes.

Conclusions

Only 1 in 20 women with SARS‐CoV‐2 infection during pregnancy required admission to hospital due to COVID‐19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS‐CoV‐2 infection in pregnancy were rare.

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  1. Version published to 10.1111/aogs.14252
  2. ScreenIT

    SciScore for 10.1101/2021.06.08.21258480: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableThe study used prospectively registered data from medical records registered in the Danish COVID-19 in pregnancy database (DCOD) and register data obtained from the following national registers: the Danish National Patient Register (DNPR),12 Danish Microbiology Database (MiBa),13 and the Civil Registration System.14 The overall study population was identified in DNPR and comprised all women registered with a pregnancy or birth-related ICD10 diagnosis or procedure between March 1 and October 31, 2020 as specified in Table S1.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: Non-reported cases identified by validation who were pregnant at the time of a positive SARS-CoV-2 PCR test were entered into the DCOD retrospectively.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data were analysed using Stata/MP16 (64-bit) and IBM SPSS statistics 27 (SPSS Inc).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    The study also has limitations. First, the register dataset was pseudoanonymised, making individual-level linkage to DCOD impossible. Additionally, data on SARS-CoV-2 cases in the DCOD were based on medical records and data in the national registers were based on mandatory nationally registered data, and these data might not be directly comparable. Nevertheless, the number of SARS-CoV-19 cases was similar in the two cohorts, and data did not differ significantly between the cohorts, indicating agreement between cases and data sources. Some descriptive variables including BMI and smoking status are not reported in the registers before delivery and are not reported for early pregnancy losses. The DCOD thus provided complete data, and made national surveillance of the infection possible to support national guidelines until register data were available.23–25 Secondly, the lack of association in some outcomes for severe cases might be due to low numbers. Thirdly, universal testing of pregnant women was not implemented in Denmark before May 2020, and we might therefore have missed SARS-CoV-2-positive cases early in the inclusion period. Furthermore, MiBa only included information on PCR tests, thus missing pregnant women diagnosed through antigen or antibody tests, which were possibly milder cases. Inclusion of these plausibly positive but non-identified cases in the comparison population of pregnancies might have affected our estimates.

    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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  3. Version published to 10.1101/2021.06.08.21258480v1 on medRxiv