The association between COVID-19 and preterm delivery: A cohort study with a multivariate analysis

  1. Spanish Obstetric Emergency Group
  2. Oscar Martínez Pérez

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Abstract

Objective

To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity.

Design and setting

Throughout Spain, 45 hospitals took part in universal screening of pregnant women going into labour using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020.

Methods

The cohort of exposed and unexposed pregnancies was followed up until 6-weeks post-partum. Multivariate logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of COVID-19 exposure, compared to non-exposure, with infection-related obstetric outcomes.

Main outcome measures

Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions.

Results

In the cohort of 1,009 screened pregnancies, 246 were COVID-19 positive. Compared to non-exposure, COVID-19 exposure increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32–3.36, p = 0.002), premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11–2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43 – 8.94, p< 0.001).

Conclusion

This first prospective cohort study demonstrated that pregnant women infected with SARS- CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.05.20188458: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics Committee Approval: All procedures were approved by Puerta de Hierro University Hospital (Madrid, Spain) ethics committees (reference number, 55/20).
    Consent: Written informed consent was obtained, sometimes in a delayed fashion, from the study patients at each centre when possible.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe healthy cohort (comparison group not exposed to COVID-19) included pregnant women who were negative for the PCR test, who were selected in each center based on the delivery date of the cases, selecting deliveries before and/or after that of the case,with maximum 3 healthy deliveries per each infected pregnant woman (Figure 1).

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical tests were two-sided and were performed with SPSS V.20 (IBM Inc., Chicago, Il, USA); statistically significant associations were considered to exist when the p value was less than 0.05.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and weaknesses: Ours is a cohort study carried out during a difficult pandemic situation whose continuing objective is to investigate the influence of COVID-19 on delivery and the puerperium. We wish to obtain the best epidemiological information in the shortest possible time with a follow-up 6 weeks after delivery. Patient recruitment continues in our registry and this is an initial analysis. Our work is one of the first prospective cohort studies to analyse the relationship between COVID-19 and prematurity. The relationship that we establish with premature rupture of membranes raises future lines of research. The most important limitation of our work is the inability to compare infected patients with healthy patients from the beginning due to the lack of diagnostic tests and the health sector crisis that occurred. When a screening system was established, there were not as many patients with severe symptoms and the number of events reduced the ability to analyse some effects of symptomatic COVID-19. Many cases of obstetric severe preeclampsia, haemorrhage, pulmonary thromboembolism and abruptio occurred mainly in the months of March and April before many centres started screening programmes and the cohort study began, so no distinction has been made between the different clinical presentations of the disease. We could not do a multivariate analysis of such conditions. No serological test was performed on patients who had a negative PCR test, either because the test...

    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.

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  2. Version published to 10.1101/2020.09.05.20188458v1 on medRxiv