A preliminary study of thousands of children born during the pandemic has found that those whose mothers tested positive for COVID-19 during pregnancy had increased risk of a developmental disorder diagnosis during their first 12 months of life.

A team led by Roy H. Perlis, M.D. M.Sc., a 2006 and 2001 BBRF Young Investigator at Massachusetts General Hospital, used electronic medical records covering births at six Massachusetts hospitals between March 2020 (soon after the pandemic began) and September 2020. The records captured 7,772 live births to 7,466 women, 222 of whom received a positive PCR test for COVID-19 during their pregnancy.

The mothers were in the early 30s, on average, and included women who identified as Hispanic (15%), Asian (10%), Black (8.4%), and White (69%). In all, 6.3%, or 14 of the 222 offspring whose mothers tested positive for COVID during pregnancy received a neurodevelopmental disorder diagnosis by age 12 months. This compared with 3%, or 227 of 7550 children born to mothers who did not receive a positive COVID test during pregnancy.

A wealth of data from epidemiologic studies has demonstrated over the years that maternal infection during pregnancy, including viral infection due to the flu, is associated with adverse neurodevelopmental outcomes in offspring. Risks for a wide range of disorders (autism spectrum disorder, schizophrenia, cerebral palsy, cognitive dysfunction, bipolar disorder, anxiety, and depression) are thought to be elevated to varying degrees depending on a number of variables, including severity of the infection and possible comorbid health conditions in the mother.

While most of these disorders take years to become evident in a young person, some—including various kinds of cognitive dysfunction—can be detected in the first years of life. While the 12-month milestone is usually too early to detect, for example, autism spectrum disorders, precursor developmental signs are thought by some to indicate heightened risk in a child. The developmental diagnoses registered in the study by Dr. Perlis and colleagues were for the most part disorders of motor function and speech.

It is thought that the link between maternal infection during pregnancy and heightened neurodevelopmental risk in the child can be traced to inflammation caused by the mother’s infection. Development of the fetal brain may be impacted by the mother’s immune response to inflammation that can be communicated via the placenta.

Emerging evidence, Dr. Perlis’ team notes, already suggests that COVID-19 infection may be associated with preterm delivery and possibly other birth complications. All of the specifically COVID-related studies including their own must be considered preliminary, however, since children born to mothers who were infected at the beginning of the pandemic are still only in their 3rd year of life. Data on the children born in the study by Dr. Perlis and colleagues also cannot reveal anything about differing levels of risk potentially corresponding with maternal infection by one of the more recent COVID variant strains.

Among the findings in the current study, it was clear that COVID infection during pregnancy was most likely to heighten the child’s neurodevelopmental risk when the infection occurred in the 3rd trimester of gestation; and that mothers with COVID infection were significantly more likely to have given birth prematurely (14.4% vs. 8.7%).

Since all infants who are born prematurely, taken together, have higher neurodevelopmental risk than infants born at full term, it was important for the team to quantify heightened neurodevelopmental risk in children of infected mothers who were born on schedule. After accounting for preterm delivery, the odds of a neurodevelopmental diagnosis were still 86% greater in children of infected moms, suggesting that the relation between COVID infection during pregnancy and neurodevelopmental risk in the child is not merely a reflection of more preterm births.

Dr. Perlis’ team as well as a commentator in the journal in which the study appeared, JAMA Network Open, noted that the results of this study were not designed to demonstrate a causal connection between maternal COVID infection and neurodevelopmental risk in the child, only an association.

This is among the reasons for the team’s call to the research community to perform larger and longer-lasting follow-up studies investigating the impact of COVID infection during pregnancy on both mothers and their children.