A new study of the impact of the COVID-19 pandemic upon pregnant women, focusing on developmental outcomes in their offspring 6 months after birth, has reached some surprising, if provisional, conclusions.

No significant developmental differences were seen at 6 months between two groups of children born to mothers during the pandemic—one group consisting of newborns whose mothers tested positive for the virus during pregnancy and a matched group whose mothers were COVID-free during pregnancy.

The researchers, led by Dani Dumitriu, M.D., Ph.D., a 2014 BBRF Young Investigator at Columbia University, expected children born of mothers who contracted COVID during pregnancy would show at least some developmental delays or deficiencies relative to children born to mothers without COVID during pregnancy.

While they did not find this, a second surprise was that the combined cohort of children born during the pandemic (those with and without in utero exposure to maternal COVID disease) did have significantly lower scores in three neurodevelopmental areas relative to a "historical" cohort of children born before the pandemic started.

A great deal of past research has clearly demonstrated that a variety of "perturbations," or irregularities, in the intrauterine environment are "implicated in altered brain development and long-term offspring vulnerability for neurodevelopmental and psychiatric" consequences in offspring, the researchers said in their JAMA Pediatrics paper reporting these results.

Among these potentially harmful factors is maternal exposure to viruses, whose presence in the body triggers an immune system response. This activation in pregnant women, especially when it occurs in the first trimester of pregnancy, is most strongly linked with neurodevelopmental and psychiatric risk in the child.

It has been important to study this phenomenon in women who became pregnant during the pandemic. Globally, over 200 million infants have been born since it began, the researchers note. At Columbia University Irving Medical Center, where Dr. Dumitriu and colleagues conducted their study, 14% of women in labor tested positive for COVID-19 at the height of the pandemic in New York City in the spring of 2020. Globally, they are among millions of women with COVID who have given birth during the pandemic.

Dr. Dumitriu 's team spearheaded the COVID-19 Mother Baby Outcomes (COMBO) Initiative at the pandemic's peak in New York City in spring 2020. They enrolled postpartum women at the Medical Center, 114 of whom would test positive for COVID prior to or during their admission for labor and delivery, and 141 who were COVID-free during pregnancy. The median age of the women was 32. Fifty-six percent of the newborns were male. Mothers completed a questionnaire called the ASQ-3 at 6 months post-delivery. This screening tool, widely used in research and pediatric practice. has been shown to reliably assess five key developmental domains in newborns: communication, fine and gross motor skills, problem-solving, and personal/social skills.

While no significant differences in these five domains could be discerned between children born to mothers with and without COVID during pregnancy, three of the domains did show significant differences when children in both pandemic-period cohorts were compared with children born before the beginning of the pandemic.

The areas of diminished performance in the COVID-"era" cohorts were: gross motor, fine motor and personal/social domains, as deduced from mothers' responses to the ASQ-3 questionnaires. The "historical cohort" was comprised of a similar socio-demographic distribution, with infants born in the same medical center and assessed using the same questionnaire at the same age.

The largest differences between children born during the pandemic and the historical cohort were seen in those who were earliest in the gestational period when the pandemic was at its peak in New York City.

Regarding the lower rating in three of the five measured neurodevelopmental domains that their study detected, Dr. Dumitriu added this perspective: "It's important to stress that we did not observe frank differences in the percentage of infants requiring referrals for further assessment between the two sets of babies" born during the pandemic and prior to the pandemic. “These were subtle downward shifts in average neurodevelopmental scores."

What might account for the observed differences in the infants whose mothers were pregnant during the pandemic? COVID-19-related stress should be considered a potential underlying mechanism, the researchers said. Stressors across the population included job loss, food insecurity, and loss of housing. Related to these factors but also independent of them in many individuals, the pandemic resulted in significant increases in symptoms of anxiety and depression.

Why is this potentially important? “Numerous studies have demonstrated that prenatal perceived stress, loneliness, and objective stress, especially early in pregnancy, are associated with an increased risk for adverse neurodevelopmental outcomes in children," the researchers said.

While noting the need for more and continuing studies of the pandemic's impact on pregnant women and their offspring, Dr. Dumitriu added: "Each study is a snapshot in time. It is possible that infants born during the pandemic will catch up developmentally by age 2 or 3." But, she added, "it's also possible that the gap will keep growing." Hence the need for close continuing surveillance by researchers and clinicians.

The team also included Catherine Monk, Ph.D., 2001 and 1999 BBRF Young Investigator; and Rachel Marsh, Ph.D., 2007 BBRF Young Investigator.