SARS-CoV-2 in first trimester pregnancy: a cohort study

  1. N la Cour Freiesleben
  2. P Egerup
  3. K V R Hviid
  4. E R Severinsen
  5. A M Kolte
  6. D Westergaard
  7. L Fich Olsen
  8. L Prætorius
  9. A Zedeler
  10. A -M H Christiansen
  11. J R Nielsen
  12. D Bang
  13. S Berntsen
  14. J Ollé-López
  15. A Ingham
  16. J Bello-Rodríguez
  17. D M Storm
  18. J Ethelberg-Findsen
  19. E R Hoffmann
  20. C Wilken-Jensen
  21. F S Jørgensen
  22. H Westh
  23. H L Jørgensen
  24. H S Nielsen

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Abstract

STUDY QUESTION

Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss?

SUMMARY ANSWER

Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester.

WHAT IS KNOWN ALREADY

Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies.

STUDY DESIGN, SIZE, DURATION

Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent.

MAIN RESULTS AND THE ROLE OF CHANCE

Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08–24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies.

LIMITATIONS, REASONS FOR CAUTION

These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection.

WIDER IMPLICATION OF THE FINDINGS

Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection.

STUDY FUNDING/COMPETING INTEREST(S)

Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet’s research fund. H.S.N. has received speaker’s fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker’s fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest.

TRIAL REGISTRATION NUMBER

N/A

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  1. Version published to 10.1093/humrep/deaa311
  2. ScreenIT

    SciScore for 10.1101/2020.06.08.20125195: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: If they agreed to participate an informed consent form was signed and the women were included in the study (Cohort 1).
    IRB: Ethics: The study was approved by Knowledge Centre on Data Protection Compliance, The Capital Region of Denmark (P-2020-255) and by the Scientific Ethics Committee of the Capital Region of Denmark (journal number H-20022647).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAll pregnant women in Denmark are offered a combined first trimester risk assessment (performed at gestational age 11-14) as part of the public antenatal and obstetric health care service, free of charge.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody analysis: The stored excess serum from the double tests and the blood samples from women with pregnancy loss, 30 µl serum from each sample, were analyzed for antibodies (IgM and IgG) against SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    In accordance with the recommendations of the manufacturer, IgM and IgG antibody values ≤8 AU/mL were defined as negative results and values ≥12 AU/mL were defined as positive results.
    IgG
    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:
    Another potential limitation of the study is that not all invited women participated in the study. By the end of May 28, 2020, a total of 337 women had not responded to our study invitation. It could potentially introduce selection bias if the none-respondents were different in terms of rates of positive SARS-CoV-2 antibodies and pregnancy loss. To mitigate the risk of such bias, we included Cohort 2. The antibody analyses from these women’s blood samples, which were drawn at the day of pregnancy loss, did not show a high frequency of SARS-CoV-2 antibodies. This provides some certainty that we did not overlook a potential effect of SARS-CoV-2 at the earlier stage of pregnancy before the double test is taken.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.08.20125195v1 on medRxiv