July 18, 2024

Left amygdalar volumes were smaller in newborns whose mothers had high psychological distress during the COVID-19 pandemic, a small cross-sectional study suggested.

Infants of mothers with elevated maternal distress during the pandemic had median reductions in white matter, right hippocampal, and left amygdala volumes compared with neonates whose mothers had low distress levels, reported Nickie Andescavage, MD, of Children’s National Hospital in Washington, D.C., and co-authors.

After adjusting for multiple comparisons and the cohort effect of the pandemic, elevated trait anxiety in mothers remained associated with smaller left amygdalar volumes in offspring (−0.71 cm3, 95% CI −1.12 to −0.29; adjusted P<0.001), the researchers wrote in JAMA Network Open.

“The findings did generally corroborate our previous work regarding prenatal stress, anxiety, and depression, but also unveiled an increased susceptibility of the amygdala to these changes during the pandemic,” Andescavage wrote in an email to MedPage Today.

In early 2020, the researchers showed that maternal distress led to impaired fetal brain development. Further work during the pandemic indicated that maternal stress and depression were significantly higher compared with pre-pandemic controls, and fetal white matter, hippocampal, and cerebellar volumes were decreased. “However, the potential enduring effects of these prenatal alterations in fetal brain development in the offspring remain unclear,” Andescavage and co-authors noted.

The findings highlight the importance of assessing prenatal stress and mental health, and “also how important it is to connect pregnant patients to community resources and mental health professionals when necessary to mitigate exposure to the fetus,” noted Cynthia Rogers, MD, of the Washington University School of Medicine and St. Louis Children’s Hospital in Missouri, who wasn’t involved with the study.

The researchers recruited mother-infant pairs at Children’s National Hospital between June 2020 and July 2022, and compared them with a cohort recruited from March 2014 through December 2019. Mothers with multiple gestation pregnancy, congenital infection, chromosomal abnormalities, contraindication to MRI, medications or substance use other than vitamins, and prenatal COVID-19 exposure were excluded. Infants with structural brain abnormalities or genetic syndromes confirmed postnatally were excluded.

In onsite visits, pregnant women completed the Spielberger State Anxiety Inventory (scores range from 20-80), the Spielberger Trait Anxiety Inventory (scores range from 20-80), and the Perceived Stress Scale (scores range from 0-40). Mothers who scored above 40, 40, and 15, respectively, on one or more of the assessments were considered psychologically distressed. MRI scans were performed on neonates during sleep, after being fed.

A total of 103 pre-pandemic and 56 pandemic mother-infant dyads were included, and 52.2% of infants were female. Median maternal age was 34.5 years; 55.3% of mothers were white, and 17% were Black. More than half of mothers (54.7%) had a graduate degree. Scores on anxiety and stress tests were significantly higher in the pandemic cohort than in the prepandemic cohort.

Infants born during the pandemic had significantly reduced white matter volume compared with prepandemic infants, after adjusting for gestational age, sex, and maternal age. Hippocampal, amygdalar, and cerebellum volumes were not significantly different between prepandemic and pandemic cohorts. Regardless of cohort, infants of mothers with elevated maternal distress showed reductions in white matter, right hippocampal, and left amygdala volumes compared with infants whose mothers had low distress levels.

Because mothers with COVID-19 exposure were excluded, “those with higher levels of distress due to their risk of exposure from their jobs, etc., may not be included,” Rogers pointed, “though for good reason, as we didn’t know the effect prenatal exposure to COVID could have on the developing brain.” Rogers also noted that symptoms of prenatal depression were not collected. Distress assessments were only taken once during pregnancy.

The researchers acknowledged that COVID-19 may have led to lifestyle changes that influenced both maternal and infant health. The pandemic cohort had an older gestational age at postnatal MRI than the prepandemic cohort.

All mental health data were reported by mothers, they added. Participants were predominantly white with high levels of education and employment, and may not be representative of other communities or regions. The sample size of the pandemic cohort was small and the cohort recruitment spanned periods of change in health risks and SARS-CoV-2 variants.

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    Sophie Putka is an enterprise and investigative writer for MedPage Today. Her work has appeared in the Wall Street Journal, Discover, Business Insider, Inverse, Cannabis Wire, and more. She joined MedPage Today in August of 2021. Follow


Funding for the study came from the National Heart, Lung, and Blood Institute of the National Institutes of Health; the Intellectual and Developmental Disabilities Research Center; and the A. James and Alice B. Clark Foundation.

Andescavage reported no conflicts of interest. A co-author reported a financial relationship with RTI.

Rogers reported no conflicts of interest.

Primary Source

JAMA Network Open

Source Reference: Weiner S, et al “Prenatal maternal psychological distress during the COVID-19 pandemic and newborn brain development” JAMA Netw Open; DOI 10.1001/jamanetworkopen.2024.17924.


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