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Comment & Response
November 1, 2021

The Need to Study Developmental Outcomes of Children Born During the COVID-19 Pandemic

Author Affiliations
  • 1Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy
JAMA Pediatr. 2022;176(1):103. doi:10.1001/jamapediatrics.2021.4342

To the Editor McCarthy and colleagues1 highlighted the need for researching developmental outcomes of children born to mothers with prenatal COVID-19 infection. Large-scale and multi-site studies on the life-course health of these children are critical, as prenatal COVID-19 infection might be associated with maternal morbidity and neonatal complications. Nonetheless, additional sources of developmental risk during the pandemic should be acknowledged even in mothers who did not have positive test results for SARS-CoV-2 but who reported high levels of psychological stress during pregnancy owing to the pandemic.

The lack of perceived control over an unprecedented threat, the hospitalization or death of loved ones, feelings of uncertainty, social isolation, and job loss are only some of the pandemic-related stressors that may affect the psychological health of individuals. During pregnancy, these stressors might be embedded into the regulatory machinery of the maternal-fetal compartment through epigenetic mechanisms (eg, DNA methylation) that can lead to inflammatory processes and neuroendocrine dysregulation. Previous retrospective research documented that such biological adaptations to maternal prenatal stress might ultimately affect the long-term health of the children.2

It is of paramount importance to monitor the developmental outcomes in mother-child dyads who were not exposed to SARS-CoV-2 infection but did experience pandemic-related stress during pregnancy. In May 2020, a multicenter prospective research project (the Measuring the Outcomes of Maternal COVID-19–Related Prenatal Exposure [MOM-COPE] study) was launched in northern Italy.3 Mothers who did not have positive test results for SARS-CoV-2 and their newborns were enrolled in 10 neonatal units at delivery and returned for follow-up at 3, 6, and 12 months. DNA methylation of well-known stress-related target genes was estimated in buccal cells obtained at birth from mothers and newborns. In this cohort, mothers who reported higher levels of pandemic-related prenatal stress during pregnancy gave birth to infants with greater temperamental difficulties at age 3 months.4 Notably, the association between prenatal pandemic-related stress exposure and temperament profile was at least partially mediated by the methylation status of the serotonin transporter gene in the offspring.5

The COVID-19 health care emergency is an unprecedented opportunity to obtain prospective and longitudinal data on the short- and long-term outcomes of prenatal stress exposure on child development. Additionally, by studying these outcomes, we can further bridge the gap between research and clinical practice, providing data to health care regulators and policymakers that may be useful in the development and delivery of adequate and timely preventive support for mother-child health during and after the COVID-19 pandemic.

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Article Information

Corresponding Author: Livio Provenzi, PhD, Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, via Mondino 2, Pavia, PV 27100, Italy (livio.provenzi@mondino.it).

Published Online: November 1, 2021. doi:10.1001/jamapediatrics.2021.4342

Conflict of Interest Disclosures: None reported.

McCarthy  J, Liu  D, Kaskel  F.  The need for life-course study of children born to mothers with prior COVID-19 infection.   JAMA Pediatr. Published online July 19, 2021. doi:10.1001/jamapediatrics.2021.2423PubMedGoogle Scholar
Van den Bergh  BRH, van den Heuvel  MI, Lahti  M,  et al.  Prenatal developmental origins of behavior and mental health: the influence of maternal stress in pregnancy.   Neurosci Biobehav Rev. 2020;117:26-64. doi:10.1016/j.neubiorev.2017.07.003PubMedGoogle ScholarCrossref
Provenzi  L, Grumi  S, Giorda  R,  et al; MOM-COPE Study Group.  Measuring the outcomes of maternal COVID-19–related prenatal exposure (MOM-COPE): study protocol for a multicentric longitudinal project.   BMJ Open. 2020;10(12):e044585. doi:10.1136/bmjopen-2020-044585PubMedGoogle Scholar
Provenzi  L, Grumi  S, Altieri  L,  et al; MOM-COPE Study Group.  Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: a longitudinal study.   Dev Psychopathol. 2021;1-9. doi:10.1017/S0954579421000766PubMedGoogle Scholar
Provenzi  L, Mambretti  F, Villa  M,  et al.  Hidden pandemic: COVID-19–related stress, SLC6A4 methylation, and infants’ temperament at 3 months.   Sci Rep. 2021;11(1):15658. doi:10.1038/s41598-021-95053-zPubMedGoogle ScholarCrossref