A large study from Massachusetts found that babies whose mothers had COVID-19 while pregnant were slightly more likely to have a range of neurodevelopmental diagnoses by age 3. Most of these children had speech or motor delays, and the link was strongest when the mother was infected late in pregnancy and in boys.
The increase in risk was small for any one child, but because millions of women were pregnant during the pandemic, even a small increase matters. The study doesn't prove that COVID-19 infection during pregnancy causes autism or other brain conditions in the fetus, but it suggests that infections and inflammation during pregnancy can affect how a baby's brain grows, something scientists have seen before with other illnesses. It's reason to help pregnant women avoid COVID-19 and to keep a close eye on children who were exposed in the womb.
What the study found
Researchers at Massachusetts General Hospital examined medical records from more than 18,000 mothers and their children born between March 2020 and May 2021, before vaccines were widely available. Because everyone giving birth during that period was tested for COVID, the team could clearly see which pregnancies were exposed.
About 5% of those mothers had COVID while pregnant. Their children were modestly more likely to be diagnosed with a neurodevelopmental condition by age 3 than those whose mothers weren't infected, even after accounting for differences in maternal age, race, insurance status, and preterm birth.
The link appeared strongest when infection occurred in the third trimester and among boys. Still, the vast majority of children in both groups showed typical development.
"This was a very clean group to follow," said Dr. Andrea Edlow, a maternal-fetal medicine specialist at Mass General and one of the study's authors. "Because of universal testing early in the pandemic, we knew who had COVID and who didn't."
Experts say COVID, which causes a powerful immune response in some people, fits the biological pattern seen with other infections in pregnancy. Dr. Alan Brown, a professor of psychiatry and epidemiology at Columbia University, who studies maternal infection and brain development, explained, "COVID would be a very strong candidate for it to happen because the amount of inflammation is very extreme."
How might infection affect brain development?
Scientists are still piecing together how various types of infections in pregnancy affect fetal development. Severe illness can cause inflammation that disrupts brain growth or trigger preterm birth, which carries its own risks.
"There's a long history of evidence showing that maternal infection can slightly raise the risk for many neurodevelopmental disorders," said Dr. Roy Perlis, the vice chair for research in psychiatry at Massachusetts General Hospital and co-author of the new study.
Edlow's lab is investigating how infection and inflammation may interfere with brain development. In a healthy brain, immune cells help shape developing neural circuits by trimming away extra or unnecessary connections, a process known as "synaptic pruning," which sculpts the brain's wiring. When a mother's immune system is activated by infection, inflammatory molecules can reach the fetal brain and alter the pruning process.
Animal studies support Edlow's hypothesis. When scientists trigger inflammation in pregnant mice, their offspring often show changes in how brain cells grow and connect, changes that can alter learning and behavior.
Why late pregnancy and why boys?
In Edlow and Perlis' study, the link between COVID and developmental delays was strongest when infection occurred late in pregnancy, during the third trimester. That's also when the fetal brain is growing most rapidly, forming and refining millions of neural connections.
"When we think of organ development, we think earlier in pregnancy, but the brain is an exception in this regard, where there's a massive amount of brain development in the third trimester. And that continues after birth," said Perlis. "It is entirely plausible that the third trimester is a period of vulnerability specifically for brain development."
But not everyone agrees the third trimester is uniquely vulnerable. Dr. Brian Lee, a professor of epidemiology at Drexel University, cautioned that because most mothers in the study were tested at delivery, there were simply more late-pregnancy infections to analyze. "That gives the study more power to find a difference in the third trimester," he said. "It doesn't prove earlier infections aren't important."
The study also found stronger effects in boys. That pattern is familiar: boys are generally more likely than girls to have speech or motor delays and to be diagnosed with autism. Researchers suspect that male fetuses may be more sensitive to stress and inflammation before birth, though the biology isn't fully understood.
What the study can and can't show
Edlow and Perlis are careful to say the study shows an association, not proof that COVID infection in pregnancy causes developmental problems. Many other factors could explain the link.
Mothers who get sick with COVID may also have other health issues, like obesity, diabetes or mental health conditions, that increase the risk of developmental delays in children. "Persons with mental disorders are much more likely to get COVID. Women with mental disorders are much more likely to have kids with neurodevelopmental problems," Lee said. "Mothers with worse physical health are also at higher risk of having children with neurodevelopmental problems."
Lee's research has shown that even infections before or after pregnancy can be linked to autism, suggesting that shared genetics or environment, rather than the infection itself, could be at play. That's why experts say much larger, longer studies are needed to understand the extent of any risk from the infection.
Edlow, Perlis and their team plan to follow the children in their study as they grow older to see whether early differences persist or fade. They're also studying how inflammation during pregnancy affects the placenta and fetal brain, and how to counteract those effects.
What about vaccination?
Because this study followed pregnancies from early in the pandemic, before vaccines were widely available, it doesn't answer whether vaccination changes the risk. But other research offers reassurance.
A large national study in Scotland found no difference in early developmental outcomes between children whose mothers were vaccinated and those who weren't. Another study in the U.S. found the same: no link between prenatal COVID vaccination and developmental delays through 18 months. Both align with decades of data showing that vaccination during pregnancy is safe for both the mother and the baby.
"Vaccination is a short spike… your immune system revs up, then it goes back to normal," said Edlow. "COVID [infection] is much more prolonged, unpredictable, and people can get… a dysregulated immune phenomenon that really doesn't exist in vaccine responses."
What this means for parents and clinicians
Since late 2020, there's been widespread confusion and misinformation about the safety of COVID vaccination during pregnancy. Some women have hesitated to get vaccinated out of fear it might harm their baby. But the evidence since then has been clear: the COVID vaccine is safe in pregnancy. The American College of Obstetricians and Gynecologists strongly recommends COVID vaccination to protect both mother and child.
Experts say the broader lesson is that pregnancy is a period of vulnerability, and prevention matters, not only for COVID, but other infections as well.
Dr. Janet Currie, a professor of economics at Yale University, said these risks remain "underappreciated," despite decades of evidence. "Even though the flu vaccine is recommended for pregnant women, very few pregnant women get it," she said. "Physicians seem to be reluctant to vaccinate pregnant women."
As Dr. Gil Mor, scientific director of the C.S. Mott Center for Human Growth and Development at Wayne State University, put it, "Protecting the mother is protecting the long-term health of the offspring. … The best intervention is vaccination."
A century-old echo
The idea that what happens in the womb can shape life after birth began with studies of famine, like the Dutch Hunger Winter in the final months of World War II. Between 1944 and 1945, as German forces blockaded the western Netherlands, rations fell to just a few hundred calories a day. Thousands died of starvation, and women who were pregnant during that period gave birth to babies who later faced higher risks of heart disease, diabetes and schizophrenia. The episode became a cornerstone of the "fetal origins" idea, that deprivation or stress in pregnancy can have lifelong effects.
The 1918 flu pandemic broadened that idea to infection. Babies exposed to influenza in utero later showed small but lasting differences in education and earnings, one of the first signs that illness during pregnancy could affect brain development. Research in Taiwan, Sweden, Switzerland, Brazil, and Japan found similar impacts. Some argued that those findings reflected the disruptions of World War I, not the flu itself. But later studies, including those from the United Kingdom and Finland, have strengthened the case for a biological effect, reinforcing that the infection itself, not wartime upheaval, was the key driver.
"It isn't simply influenza that can alter fetal neurodevelopment," Dr. Kristina Adams Waldorf, a professor of obstetrics and gynecology at UW Medicine, explained. "Many types of infections… in the mother can be transmitted as a signal to the fetus, which can alter its brain development."
A century later, the same question has returned with COVID: could infection during pregnancy subtly shape how children grow and learn? The new Massachusetts General Hospital study offers an early look at the answer.
Edited by Paula Cohen
