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COVID-19 Pandemic and Infant Neurodevelopmental ImpairmentA Systematic Review and Meta-analysis

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Are neurodevelopmental outcomes during infancy changed by the COVID-19 pandemic?

Findings  This meta-analysis of 8 studies including 21 419 infants found that 7% of infants who had neurodevelopmental screening during the COVID-19 pandemic were at risk of neurodevelopmental impairment, and 12% of those with gestational exposure to SARS-CoV-2 were at risk for neurodevelopmental impairment. Communication impairment was the sole neurodevelopmental domain of significantly increased risk of occurrence during the COVID-19 pandemic.

Meaning  These findings suggest that overall neurodevelopment was not changed by the COVID-19 pandemic, but birth or being raised during the SARS-CoV-2 pandemic, regardless of gestational exposure, was associated with a significant risk of communication impairment among the infants.


Importance  Primary studies proposed that aberrant maternal antiviral immunity and/or giving birth in quarantine, such as during the ongoing COVID-19 pandemic, may be associated with the risk of neurodevelopmental impairment (NDI) in offspring.

Objectives  To evaluate the associations of birth and being raised during the COVID-19 pandemic with risk of NDI among infants and to assess the association of gestational exposure to SARS-CoV-2 with risk of NDI.

Data Sources  PubMed, Web of Science, Scopus, Embase, and preprint servers were systematically searched from inception to March 25, 2022.

Study Selection  Studies evaluating the neurodevelopment of infants born during the SARS-CoV-2 pandemic were included in this systematic review and meta-analysis. Studies using Ages and Stages Questionnaires, Third Edition (ASQ-3), were used for quantitative meta-analysis.

Data Extraction and Synthesis  Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, a random-effects model meta-analysis was used to pool the proportion and odds ratios (ORs) of overall NDI, as well as each developmental domain on ASQ-3 with the corresponding 95% CI.

Main Outcomes and Measures  The primary outcome was the risk of overall NDI among infants screened during the pandemic vs prepandemic. The secondary outcome was the comparison of NDI by ASQ-3 domain among infants born to women with known gestational exposure to SARS-CoV-2 vs no exposure.

Results  A total of 8 studies were included, including 21 419 infants (11 438 screened in pandemic and 9981 in prepandemic period). NDI was present in 330 of 8992 infants (7%; 95% CI, 4%-10%) screened during the COVID-19 pandemic from January 2020 to January 2021. Among the pandemic cohort, the prevalence of NDI among infants with gestational exposure to SARS-CoV-2 was 77 of 691 (12%; 95% CI, 6%-18%). Compared with the prepandemic cohort (2015-2019), the pandemic cohort was more likely to have communication impairment (OR, 1.70; 95% CI, 1.37-2.11; P < .001), without significant differences in other ASQ-3 domains (eg, gross motor, fine motor, personal-social, and problem-solving). In contrast, maternal SARS-CoV-2 infection was not associated with significant differences in any neurodevelopment domain in offspring, except for increasing the odds of fine motor impairment (OR, 3.46; 95% CI, 1.43-8.38; P < .001).

Conclusions and Relevance  In this systematic review and meta-analysis examining the association between COVID-19 pandemic and the risk of NDI, findings suggest that overall neurodevelopment in the first year of life was not changed by either being born or raised during the SARS-CoV-2 pandemic or by gestational exposure to SARS-CoV-2. Interestingly, the first year of life during the COVID-19 pandemic, regardless of maternal infection, was significantly associated with the risk of communication delay among the offspring.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: August 19, 2022.

Published: October 28, 2022. doi:10.1001/jamanetworkopen.2022.38941

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Hessami K et al. JAMA Network Open.

Corresponding Author: Alireza A. Shamshirsaz, MD, Maternal Fetal Care Center, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 (alireza.shamshirsaz@childrens.harvard.edu).

Author Contributions: Dr Hessami had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hessami, Arian, Aagaard.

Acquisition, analysis, or interpretation of data: Hessami, Norooznezhad, Monteiro, Barrozo, Shirdel Abdolmaleki, Arian, Zargarzadeh, Shekerdemian, Shamshirsaz.

Drafting of the manuscript: Hessami, Norooznezhad, Monteiro, Shirdel Abdolmaleki, Zargarzadeh, Shekerdemian, Aagaard, Shamshirsaz.

Critical revision of the manuscript for important intellectual content: Hessami, Monteiro, Barrozo, Arian, Shekerdemian.

Statistical analysis: Hessami, Barrozo, Shirdel Abdolmaleki, Zargarzadeh.

Administrative, technical, or material support: Shirdel Abdolmaleki, Shamshirsaz.

Supervision: Hessami, Monteiro, Shekerdemian, Shamshirsaz.

Conflict of Interest Disclosures: None reported.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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