Children whose mothers had COVID-19 during pregnancy appear to have an increased likelihood of being diagnosed with developmental conditions by age three, including speech delays and autism. This new research, published in Obstetrics & Gynecology, suggests that maternal COVID-19 infection may influence fetal brain development.

The study provides evidence that exposure to the SARS-CoV-2 virus in the womb may be associated with neurodevelopmental differences in early childhood. This association appears more pronounced in male children and when the infection occurred in the third trimester of pregnancy.

COVID-19 is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pandemic that began in early 2020 raised many questions about the virus’s impact on various aspects of health, including pregnancy and child development.

Previous research on other maternal infections during pregnancy has indicated a potential link to various neurodevelopmental conditions in children. For instance, studies have shown that immune system activation in a pregnant individual can disrupt the developing brain of the fetus and affect offspring behavior in animal models.

Researchers at Mass General Brigham conducted this study to examine whether SARS-CoV-2 infection during pregnancy could be associated with similar outcomes. They had previously observed an elevated risk of neurodevelopmental diagnoses at 12 and 18 months in children exposed to maternal SARS-CoV-2 infection during pregnancy. The current study aimed to determine if these potential effects persisted into early childhood, specifically looking at diagnoses by age three.

The researchers analyzed data from 18,124 live births that occurred within the Mass General Brigham health system between March 2020 and May 2021. This period was selected because it featured universal SARS-CoV-2 testing in labor and delivery units and widespread screening for COVID-19 symptoms during pregnancy, which helped ensure reliable identification of both positive and negative cases. The team linked data from mothers and their children, examining maternal medical history, vaccination status, and sociodemographic information.

The main factor of interest was a positive SARS-CoV-2 PCR test result during pregnancy. The primary outcome the researchers looked for was at least one neurodevelopmental diagnosis within the first three years after birth, identified through specific diagnostic codes from medical records. These codes covered a range of conditions, including disorders of speech and language, motor function, and autism spectrum disorder. They also considered potential influencing factors such as maternal age, race, ethnicity, insurance type, and whether the birth was preterm.

Among the 18,124 live births included in the study, 861 children were exposed to maternal SARS-CoV-2 infection during pregnancy. The researchers found that 140 of these 861 children (16.3%) received a neurodevelopmental diagnosis by age three.

In comparison, among the 17,263 children whose mothers did not have SARS-CoV-2 infection during pregnancy, 1,680 (9.7%) received such a diagnosis. After accounting for other factors that could influence neurodevelopment, maternal SARS-CoV-2 infection during pregnancy was associated with a 29% higher odds of a child receiving a neurodevelopmental diagnosis by age three.

“These findings highlight that COVID-19, like many other infections in pregnancy, may pose risks not only to the mother, but to fetal brain development,” said senior author Andrea Edlow, MD MSc, a Maternal-Fetal Medicine specialist in the Department of Obstetrics and Gynecology at Mass General Brigham.

The study also investigated specific patterns within these findings. The association between maternal SARS-CoV-2 infection and neurodevelopmental diagnoses was found to be more pronounced when the infection occurred during the third trimester of pregnancy. Children exposed during the third trimester had a significantly increased risk of a neurodevelopmental diagnosis compared to the unexposed group. However, exposure during the first or second trimesters did not show a statistically significant difference in risk from the unexposed group.

Additionally, the researchers observed a difference in risk between male and female offspring. Third-trimester maternal SARS-CoV-2 infection was significantly associated with an increased risk of neurodevelopmental diagnosis in male children.

The magnitude of risk in female offspring with third-trimester exposure was smaller and did not reach statistical significance in this study. The most frequently identified neurodevelopmental diagnoses included disorders of speech and language, developmental disorder of motor function, autistic disorder, and other specified or unspecified disorders of psychological development.

While reducing risk is important, co-senior author Roy Perlis of the Mass General Brigham Department of Psychiatry noted, that the “overall risk of adverse neurodevelopmental outcomes in exposed children likely remains low.”

While these findings suggest an association, there are some aspects to consider. The study relied on medical record diagnoses, which may not capture all neurodevelopmental conditions and could potentially lead to some misclassification. However, such misclassification would likely lead to results that underestimate the true effect. Children who received diagnoses outside the Mass General Brigham health system would not have been included in the dataset. Also, asymptomatic SARS-CoV-2 infections during pregnancy might not have been consistently detected, which could also lead to an underestimation of the effects.

Future research could involve continued follow-up of these children to assess the long-term persistence and clinical impact of these early neurodevelopmental observations. Further studies may also explore the underlying biological mechanisms in greater detail.

First author and Maternal-Fetal Medicine specialist Lydia Shook added: :Parental awareness of the potential for adverse child neurodevelopmental outcomes after COVID-19 in pregnancy is key. By understanding the risks, parents can appropriately advocate for their children to have proper evaluation and support.:

The study, “Neurodevelopmental Outcomes of 3-Year-Old Children Exposed to Maternal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Utero,” was authored by Lydia L. Shook, Victor Castro, Laura Ibanez-Pintor, Roy H. Perlis, and Andrea G. Edlow.