Neonatal outcomes and indirect consequences following maternal SARS-CoV-2 infection in pregnancy: A systematic review

  1. Sarah Sturrock
  2. Shohaib Ali
  3. Chris Gale
  4. Cheryl Battersby
  5. Kirsty Le Doare

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Abstract

Objectives

Identify the association between maternal SARS-CoV-2 infection in pregnancy and individual neonatal morbidities and outcomes, particularly longer-term outcomes such as neurodevelopment.

Setting

Case-control and cohort studies from any location published after 1st January 2020, including pre-print articles.

Participants

Neonates born to pregnant women diagnosed with a SARS-CoV-2 infection at any stage during pregnancy, including asymptomatic women.

Primary and secondary outcome measures

Neonatal mortality and morbidity, including preterm birth, Caesarean delivery, small for gestational age, admission to neonatal intensive care unit, level of respiratory support required, diagnosis of culture-positive sepsis, evidence of brain injury, necrotising enterocolitis, visual or hearing impairment, neurodevelopmental outcomes, and feeding method. These outcomes were selected according to a Core Outcome Set developed between health professionals, researchers and parents.

Results

The search returned 3234 papers, from which 204 were included with a total of 45,646 infants born to mothers with SARS-CoV-2 infection during pregnancy across 36 countries. We found limited evidence of an increased risk of some neonatal morbidities, including respiratory disease. There was minimal evidence from low-income settings (1 study) and for neonatal outcomes following first trimester infection (17 studies). Neonatal mortality was very rare. Preterm birth, neonatal unit admission and small for gestational age status were more common in infants born following maternal SARS-CoV-2 infection in pregnancy in most larger studies.

Conclusions

There is limited data on neonatal morbidity and mortality following maternal SARS-CoV-2 infection in pregnancy, particularly from low-income countries and following early pregnancy infections. Large, representative studies addressing these outcomes are needed to better understand the consequences for babies born to women with SARS-CoV-2 in pregnancy.

Trial registration

PROSPERO ID: CRD42021249818

Strengths and limitations

  • Inclusion of studies of both asymptomatic and symptomatic SARS-CoV-2 infections at any point in pregnancy to maximise generalisability of findings

  • Focus on neonatal outcomes, as opposed to purely obstetric outcomes, to accurately quantify neonatal morbidity

  • Study is limited by available data; important data gap in low-income settings

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2022.05.20.22275313: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableWe included studies of the babies of pregnant women with a diagnosis of SARS-CoV-2 during pregnancy.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data were extracted into Microsoft Excel (Version 2201) by SS or SA using a proforma with the outcomes described above, study type and dates, location, participant definition and numbers, and method of SARS-CoV-2 diagnosis.
    Microsoft Excel
    suggested: (Microsoft Excel, RRID:SCR_016137)
    Statistical analysis was completed using Microsoft Excel, SPSS (IBM SPSS Statistics for Macintosh, Version 25, 2017[16]) and R (R Studio Version 2021.09.01[
    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:
    Our study has several limitations. Although we identified many studies reporting perinatal outcomes, there was little information reporting neonatal morbidity in depth. Granular detail describing the indirect neonatal consequences of maternal SARS-CoV-2 infection during pregnancy remain unclear. This limitation is particularly pronounced for neurodevelopmental outcomes. With the SARS-CoV-2 declared pandemic two years ago, we hope that more information regarding these crucial outcomes will emerge soon; one trial is currently recruiting (the ASPIRE trial) which will follow up infant outcomes for 1.5 years[40], and another (the SINEPOST study) will examine development from 18 months onwards[41]. Furthermore, we found that studies varied widely on their reporting of severity of maternal disease and maternal symptoms; therefore, we were unable to study the effect of maternal symptomology on neonatal outcomes. Finally, we found limited evidence from middle-, and particularly, low-income countries, and little data regarding infections in early pregnancy. These are key research priorities to allow clinicians to adequately inform expectant families.

    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

    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.

  2. Version published to 10.1101/2022.05.20.22275313v1 on medRxiv