Birth during the COVID-19 pandemic, but not maternal SARS-CoV-2 infection during pregnancy, is associated with lower neurodevelopmental scores at 6-months

  1. Lauren C. Shuffrey
  2. Morgan R. Firestein
  3. Margaret Kyle
  4. Andrea Fields
  5. Carmela Alcántara
  6. Dima Amso
  7. Judy Austin
  8. Jennifer M. Bain
  9. Jennifer Barbosa
  10. Mary Bence
  11. Catherine Bianco
  12. Cristina Fernández
  13. Sylvie Goldman
  14. Cynthia Gyamfi-Bannerman
  15. Violet Hott
  16. Yunzhe Hu
  17. Maha Hussain
  18. Pam Factor-Litvak
  19. Maristella Lucchini
  20. Arthur Mandel
  21. Rachel Marsh
  22. Danielle McBrian
  23. Mirella Mourad
  24. Rebecca Muhle
  25. Kimberly Noble
  26. Anna Penn
  27. Cynthia Rodriguez
  28. Ayesha Sania
  29. Wendy G. Silver
  30. Kally C. O’Reilly
  31. Melissa Stockwell
  32. Nim Tottenham
  33. Martha G. Welch
  34. Noelia Zork
  35. William P. Fifer
  36. Catherine Monk
  37. Dani Dumitriu

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Abstract

The intrauterine environment strongly influences development. Neurodevelopmental effects of in utero exposure to maternal SARS-CoV-2 infection are widely speculated but currently unknown. The COVID-19 Mother Baby Outcomes (COMBO) initiative was established at Columbia University Irving Medical Center (CUIMC) in New York City to prospectively study the health and wellbeing of infants with and without in utero exposure to maternal SARS-CoV-2 infection. We report findings on 6-month neurodevelopmental outcomes using the parental-report Ages & Stages Questionnaire, 3 rd Edition (ASQ-3), from 107 in utero exposed and 131 unexposed full-term infants born between March and December, 2020. We compare these infants to a historical cohort comprised of 62 infants born at CUIMC at least two months prior to the onset of the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with differences on any ASQ-3 subdomain regardless of infection timing or severity, however, infants born during the pandemic had significantly lower scores on gross motor, fine motor, and personal-social subdomains when compared to the historical cohort. Infants born to women who were in the first trimester of pregnancy during the peak of the pandemic in NYC had the lowest personal-social scores. Birth during the pandemic, but not maternal SARS-CoV-2 infection, was associated with differences in neurodevelopmental outcomes at 6-months. These early findings suggest significantly higher public health impact for the generation born during the COVID-19 pandemic than previously anticipated.

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    SciScore for 10.1101/2021.07.12.21260365: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study procedures were approved by the CUIMC Institutional Review Board (IRB) for the COMBO cohort and by the New York State Psychiatric Institute IRB for the historical cohort and informed consent was obtained from all participants.
    Consent: Study procedures were approved by the CUIMC Institutional Review Board (IRB) for the COMBO cohort and by the New York State Psychiatric Institute IRB for the historical cohort and informed consent was obtained from all participants.
    Sex as a biological variableExact exposure timing was determined for 79 of 107 mothers (74%) included in this analysis.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisPower analyses were based on the primary outcome investigating mean differences in ASQ-3 subdomain scores between infants with and without in utero exposure to maternal SARS-CoV-2 infection using analyses of covariance (ANCOVAs), for which we had 90% power to detect a 0.5 SD difference in each subdomain using a two-sided test with alpha±0.05 (see Supplementary Materials).
    Cell Line AuthenticationAuthentication: The ASQ-3 is a validated, widely used, standardized, level 1 screening tool based on parental-report that reliably assesses five key developmental domains: communication, fine and gross motor, problem solving, and personal-social skills.

    Table 2: Resources

    No key resources detected.

    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:
    Although consistent with prior studies of children born during natural disasters, interpretation of our results should take into account several limitations. The data included in this analysis represent a single center, which may impact generalizability. Critically, it is also possible that developmental outcomes beyond 6-months of age will show different patterns as this is a relatively early timepoint. The ASQ-3 has modest agreement with objective measures of development60,61 and is often used by general pediatricians62. However, as a parent-report measure, our results may reflect parental-perception of – rather than objective differences in – infant neurodevelopment. Nonetheless, parental perception of development also has implications for long-term child outcomes63. Notable strengths of our study include detailed medical records on maternal SARS-CoV-2 status, timing, and severity, and availability of a historical comparison group from the same hospital center using the same neurodevelopmental assessment. This first analysis of the neurodevelopment of infants born during the COVID-19 pandemic supports the critical need for long-term monitoring of these children to mitigate the substantial sequelae observed in generations born during previous pandemics.

    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.

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  2. Version published to 10.1101/2021.07.12.21260365v1 on medRxiv