Skip to main content
SpringerLink
Log in

Congenital anomalies during Covid-19: artifact of surveillance or a real TORCH?

  • COVID-19
  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

Infections in the first trimester of pregnancy can be teratogenic, but the possibility that Covid-19 could lead to birth defects is unclear. We examined whether SARS-CoV-2 infection during pregnancy or exposure to pandemic conditions were associated with the risk of congenital anomalies. We carried out a retrospective study of 420,222 neonates born in Quebec, Canada in two time periods: prepandemic (January 1, 2017 to March 12, 2020) vs. pandemic (March 13, 2020 to March 31, 2022). We classified pandemic births as early (first trimester completed before the pandemic) or late (first trimester during the pandemic), and identified patients with SARS-CoV-2 infections during pregnancy. We applied (1) adjusted log-binomial regression models to assess the association between SARS-CoV-2 infection and congenital anomalies, and (2) autoregressive interrupted time series regression to analyze temporal trends in the monthly number of defects in all patients regardless of infection. In total, 29,263 newborns (7.0%) had a congenital anomaly. First trimester SARS-CoV-2 infections were not associated with a greater risk of birth defects compared with no infection (RR 1.07, 95% CI 0.59–1.95). However, births during the late pandemic period were more likely to be diagnosed with congenital microcephaly compared with prepandemic births (RR 1.44, 95% CI 1.21–1.71). Interrupted time series analysis confirmed that the frequency of microcephaly increased during the late pandemic period, whereas other anomalies did not. We conclude that Covid-19 is likely not teratogenic, but enhanced surveillance of anomalies among late pandemic births may have heightened the detection of infants with microcephaly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Zhang L, Wang X, Liu M, Feng G, Zeng Y, Wang R, et al. The epidemiology and disease burden of congenital TORCH infections among hospitalized children in China: a national cross-sectional study. PLoS Negl Trop Dis. 2022;16:e0010861.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Neu N, Duchon J, Zachariah P. TORCH infections. Clin Perinatol. 2015;42:77–103. viii.

    Article  PubMed  Google Scholar 

  3. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects–reviewing the evidence for causality. N Engl J Med. 2016;374:1981–7.

    Article  CAS  PubMed  Google Scholar 

  4. Morris SK, Farrar DS, Miller SP, Ofner M, Bitnun A, Nelson CRM, et al. Population-based surveillance of severe microcephaly and congenital Zika syndrome in Canada. Arch Dis Child. 2021;106:855–61.

    Article  PubMed  Google Scholar 

  5. Nunez C, Morris A, Jones CA, Badawi N, Baynam G, Hansen M, et al. Microcephaly in Australian children, 2016–2018: national surveillance study. Arch Dis Child. 2021;106:849–54.

    Article  PubMed  Google Scholar 

  6. Knowles RL, Solebo AL, Sampaio MA, Brown CR, Sargent J, Oluonye N, et al. Incidence, aetiology and neurodisability associated with severe microcephaly: a national surveillance study. Arch Dis Child. 2023;108:211–7.

    Article  PubMed  Google Scholar 

  7. Khan MSI, Nabeka H, Akbar SMF, Al Mahtab M, Shimokawa T, Islam F, et al. Risk of congenital birth defects during COVID-19 pandemic: draw attention to the physicians and policymakers. J Glob Health. 2020;10:020378.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Heidarzadeh M, Taheri M, Mazaheripour Z, Abbasi-Khameneh F. The incidence of congenital anomalies in newborns before and during the Covid-19 pandemic. Ital J Pediatr. 2022;48:1–5.

    Article  Google Scholar 

  9. Hernández-Díaz S, Smith LH, Wyszynski DF, Rasmussen SA. First trimester COVID-19 and the risk of major congenital malformations-international registry of coronavirus exposure in pregnancy. Birth Defects Res. 2022;114:906–14.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Calvert C, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, et al. A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection. Nat Commun. 2023;14:107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ministry of Health and Social Services. Med-Echo System Normative Framework - Maintenance and Use of Data for the Study of Hospital Clientele [Internet]. Quebec: Government of Quebec. 2021. https://publications.msss.gouv.qc.ca/msss/fichiers/2000/00-601.pdf.

  12. Auger N, Marcoux S, Bégin P, Lewin A, Lee GE, Healy-Profitós J, et al. Matched cohort study of hospitalization in children who have siblings with cancer. Cancer. 2022;128:1684–91.

    Article  PubMed  Google Scholar 

  13. Institut national de santé publique du Québec. Timeline of COVID-19 in Quebec [Internet]. [cited 2023 Feb 24]. https://www.inspq.qc.ca/covid-19/donnees/ligne-du-temps.

  14. Wei SQ, Bilodeau-Bertrand M, Liu S, Auger N. The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. CMAJ. 2021;193:E540–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. DeSilva M, Munoz FM, Mcmillan M, Kawai AT, Marshall H, Macartney KK, et al. Congenital anomalies: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2016;34:6015–26.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Margulis AV, Setoguchi S, Mittleman MA, Glynn RJ, Dormuth CR, Hernández-Díaz S. Algorithms to estimate the beginning of pregnancy in administrative databases. Pharmacoepidemiol Drug Saf. 2013;22:16–24.

    Article  PubMed  Google Scholar 

  17. Canadian Institute for Health Information. International statistical classification of diseases and related health problems, tenth revision, Canada (ICD-10-CA): alphabetical index and tabular list. Ottawa, ON: CIHI; 2022.

    Google Scholar 

  18. Auger N, Wei SQ, Dayan N, Ukah UV, Quach C, Lewin A, et al. Impact of Covid-19 on rates of gestational diabetes in a North American pandemic epicenter. Acta Diabetol. 2023;60:257–64.

    Article  PubMed  Google Scholar 

  19. Sattolo M-L, Arbour L, Bilodeau-Bertrand M, Lee GE, Nelson C, Auger N. Association of birth defects with child mortality before age 14 years. JAMA Netw Open. 2022;5:e226739.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pampalon R, Hamel D, Gamache P, Simpson A, Philibert MD. Validation of a deprivation index for public health: a complex exercise illustrated by the Quebec index. Chronic Dis Inj Can. 2014;34:12–22.

    Article  CAS  PubMed  Google Scholar 

  21. Penfold RB, Zhang F. Use of interrupted time series analysis in evaluating health care quality improvements. Acad Pediatr. 2013;13:S38–44.

    Article  PubMed  Google Scholar 

  22. Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika virus. N Engl J Med. 2016;374:1552–63.

    Article  CAS  PubMed  Google Scholar 

  23. Harris SR. Measuring head circumference: update on infant microcephaly. Can Fam Physician. 2015;61:680–4.

    PubMed  PubMed Central  Google Scholar 

  24. Harville EW, Buekens PM, Cafferata ML, Gilboa S, Tomasso G, Tong V. Measurement error, microcephaly prevalence and implications for Zika: an analysis of Uruguay perinatal data. Arch Dis Child. 2020;105:428–32.

    Article  PubMed  Google Scholar 

  25. Auger N, Quach C, Healy-Profitós J, Lowe A-M, Arbour L. Congenital microcephaly in Quebec: baseline prevalence, risk factors and outcomes in a large cohort of neonates. Arch Dis Child Fetal Neonatal Ed. 2018;103:F167–72.

    Article  PubMed  Google Scholar 

  26. Barton M, Forrester AM, McDonald J. Update on congenital cytomegalovirus infection: prenatal prevention, newborn diagnosis, and management [Internet]. Canadian Paediatric Society Infectious Diseases and Immunization Committee; 2020 [cited 2023 Aug 28]. https://cps.ca/en/documents/position/update-on-congenital-cytomegalovirus-infection-prenatal-prevention-newborn-diagnosis-and-management.

  27. Sun S, Savitz DA, Wellenius GA. Changes in adverse pregnancy outcomes associated with the COVID-19 pandemic in the United States. JAMA Netw Open. 2021;4:e2129560.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Molina RL, Tsai TC, Dai D, Soto M, Rosenthal N, Orav EJ, et al. Comparison of pregnancy and birth outcomes before vs during the COVID-19 pandemic. JAMA Netw Open. 2022;5:e2226531.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mendoza M, Garcia-Ruiz I, Maiz N, Rodo C, Garcia‐Manau P, Serrano B, et al. Pre‐eclampsia‐like syndrome induced by severe COVID‐19: a prospective observational study. BJOG. 2020;127:1374–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shook LL, Sullivan EL, Lo JO, Perlis RH, Edlow AG. COVID-19 in pregnancy: implications for fetal brain development. Trends Mol Med. 2022;28:319–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Edlow AG, Castro VM, Shook LL, Kaimal AJ, Perlis RH. Neurodevelopmental outcomes at 1 year in infants of mothers who tested positive for SARS-CoV-2 during pregnancy. JAMA Netw Open. 2022;5:e2215787.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Canadian Institutes of Health Research (PUU-177957) and the Fonds de recherche du Québec – Santé (296785).

Author information

Authors and Affiliations

  1. University of Montreal Hospital Research Centre, Montreal, QC, Canada

    Nathalie Auger, Émilie Brousseau & Jessica Healy-Profitós

  2. Institut national de santé publique du Québec, Montreal, QC, Canada

    Nathalie Auger, Émilie Brousseau & Jessica Healy-Profitós

  3. Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, QC, Canada

    Nathalie Auger

  4. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada

    Nathalie Auger

  5. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

    Laura Arbour

  6. Medical Affairs and Innovation, Hema-Quebec, Montreal, QC, Canada

    Antoine Lewin

  7. Department of Pediatrics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, QC, Canada

    Thuy Mai Luu

Authors
  1. Nathalie Auger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Arbour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antoine Lewin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Émilie Brousseau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jessica Healy-Profitós
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thuy Mai Luu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NA, ÉB, and JHP conceived and designed the study. ÉB performed the data analysis with input from NA and JHP. All authors helped interpret the results. NA and ÉB drafted the article, and LA, AL, JHP, and TML revised it critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Nathalie Auger.

Ethics declarations

Ethics approval

This is an observational study. The institutional review board of the University of Montreal Hospital Centre waived the requirement for an ethics review and informed consent for this study.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Auger, N., Arbour, L., Lewin, A. et al. Congenital anomalies during Covid-19: artifact of surveillance or a real TORCH?. Eur J Epidemiol (2024). https://doi.org/10.1007/s10654-024-01122-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10654-024-01122-8

Keywords

Search

Navigation