A large study conducted in Massachusetts found that children whose mothers had Covid-19 during pregnancy by 3 years of age, they were slightly more likely to have a number of diagnoses associated with neuropsychological development disorders. Most of these children had speech or motor delays, with the association being strongest in boys and when the mother was infected late in pregnancy.
The increase in risk was small for any child, but with millions of women pregnant during the pandemic, even small increases make a difference. The study does not prove that Covid infection during pregnancy causes autism or other brain diseases in the fetus, but it does suggest that infections and inflammation during pregnancy may affect the growth of the child's brain, something scientists have previously observed in other diseases. This is a reason to help pregnant women avoid infection with coronavirus and closely monitor children infected in the womb.
What the study found
Researchers at Massachusetts General Hospital examined the medical records of more than 18,000 mothers and their babies born between March 2020 and May 2021, before vaccines became widely available to pregnant women. Because everyone who gave birth during this period was tested for Covid, the team could clearly see which pregnant women were exposed to the virus that causes it.
About 5% of these mothers had Covid during pregnancy. Their children were slightly more likely to be diagnosed with a neurodevelopmental disorder by age three than those whose mothers were not infected, even after controlling for differences in maternal age, race, insurance status, and preterm birth.
The association was strongest among boys and when infection occurred during the third trimester of their mother's pregnancy. However, the majority of children in both groups showed typical development.
“This was a very pure group to follow,” said Andrea Edlow, a maternal-fetal medicine specialist at Mass General and one of the study's authors. “Thanks to universal testing at the beginning of the pandemic, we knew who had Covid and who didn’t.”
Independent experts say Covid, which triggers a powerful immune response in some people, matches the biological pattern seen in other infections during pregnancy. Alan Brown, a professor of psychiatry and epidemiology at Columbia University who studies maternal infections and brain development and was not involved in this study, explained: “Covid would be a very strong candidate for this to happen because the amount of inflammation is so high.”
How can infection affect brain development?
Scientists are still figuring out how various infections during pregnancy can affect fetal development. Severe illness can cause inflammation that disrupts brain growth or maybe cause premature birthwhich carries its own risks.
“There is a long history of evidence that maternal infection may slightly increase the risk of many neurodevelopmental disorders,” said Roy Perlis, vice chair of psychiatry research at Massachusetts General Hospital and co-author of the new study.
Edlow's lab studies how infection and inflammation can influence brain development. In a healthy brain, immune cells help shape developing neural circuits by pruning redundant or unnecessary connections—a process known as “synaptic pruning”—that shapes the brain's wiring. When the 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 induce inflammation in pregnant mice, their offspring often show changes in the way brain cells grow and connect, changes that can alter learning and behavior.
Why late pregnancy and why boys?
In the study by Edlow and Perlis, the association between coronavirus and failure to thrive was strongest when infection occurred late in pregnancy, in the third trimester. It is during this period that the fetal brain grows the fastest, forming and improving millions of neural connections.
“When we think about organ development, we think about earlier in pregnancy, but the brain is an exception in this regard because significant development occurs in the third trimester. And this continues after birth,” Perlis said. “It is likely that the third trimester is a vulnerable period specifically for brain development.”
But not all researchers agree that the third trimester is especially vulnerable. Brian Lee, a professor of epidemiology at Drexel University, cautioned that because most of the mothers in the study were tested at birth, there were simply more infections later in pregnancy to analyze. “This gives the study more power to detect differences in the third trimester,” he said. “This does not prove that early infection does not matter.”
The study also found a stronger effect in boys. The pattern is familiar: Boys tend to be more likely than girls to have speech or motor delays or be diagnosed with autism. Researchers suspect that male fetuses may be more susceptible to stress and inflammation, although the biology of this is not fully understood.
What Research Can and Can't Show
Edlow and Perlis are careful to say the study shows an association, but not proof, that Covid infection during pregnancy causes developmental problems. Many other factors could explain the correlation.
Mothers with Covid may have other health problems, such as obesity, diabetes or mental health problems, that increase the risk of developmental delays in children. “People with mental disorders they are much more likely to get Covid. Women with mental disorders are much more likely to children are more likely to have neurodevelopmental problems– Lee said. — Mothers with deterioration in physical health are also at higher risk of having children with neurodevelopmental problems.”
Lee's research showed that even infections before or after pregnancy may be associated with autismsuggesting that overall genetics or environment may be to blame rather than the infection itself. That's why experts say much larger and longer studies are needed to understand the extent of any risk associated with the infection.
Edlow, Perlis and their team plan to follow the children in their study as they get older to see whether early differences persist or disappear. They are also studying how inflammation during pregnancy affects the placenta and fetal brain and how to counteract these effects.
What about vaccination?
Because this study tracked pregnancies from the start of the pandemic, it does not answer the question of whether vaccination changes risk. But other studies offer reassurance.
Large national study in Scotland found no differences in early developmental outcomes between children whose mothers were vaccinated and children who were not vaccinated. Another US study found the same thing: There is no association between prenatal Covid vaccination and failure to thrive at 18 months. Both are consistent with decades of data showing that vaccinations during pregnancy are safe for both mother and baby.
“Vaccination is a short burst…your immune system kicks into high gear and then bounces back,” Edlow said. “COVID-19 [infection] is much more long-lasting, unpredictable, and people can get… an immune dysregulation phenomenon that doesn't really exist in vaccine responses.”
What does this mean for parents and doctors?
Since late 2020, there has been widespread confusion and misinformation about the safety of Covid vaccination during pregnancy. Some women are hesitant to get the vaccine because they fear it could harm their baby. But the evidence has since become clear: Covid vaccines are safe during pregnancy. American College of Obstetricians and Gynecologists strongly recommends vaccination against covid protect both mother and child.
Experts say the broader lesson is that pregnancy is a vulnerable time and prevention is not only important for covidbut also other infections.
Janet Curry, an economics professor at Yale University, said these risks remain “underestimated” despite decades of evidence. “Although the flu shot is recommended for pregnant women, very few pregnant women receive it,” she said. “Doctors seem reluctant to vaccinate pregnant women.”
As Gil Mohr, scientific director of the K.S. Center for Human Growth and Development, said. Mott at Wayne State University in Detroit: “Protecting the mother means protecting the long-term health of the offspring… The best intervention is vaccination.”
Echo of a century ago
The idea that what happens in the womb can shape life after birth has taken root in studies of famines such as the Dutch “Hunger Winter” in the final months of World War II. In 1944 and 1945, when German troops blockaded the western Netherlands, the ration dropped to a few hundred calories a day. Thousands of people died of starvation, and women pregnant during this period gave birth to children who later faced a higher risk of infection. heart disease, diabetesAnd schizophrenia. This episode became the cornerstone “origin of the fruit” the idea that deprivation or stress during pregnancy can have lifelong consequences.
1918 influenza pandemic extended this idea to infection. Infants who contracted influenza in utero later experienced small but long-lasting difference in education and earningsa sign that illness during pregnancy may affect brain development. Researchers in Taiwan, Sweden, Switzerland, BrazilAnd Japan found similar effects. Some have argued that these results reflect the effects of World War I rather than the flu itself. But later studiesincluding from United Kingdom And Finlandstrengthened the case for a biological effect, confirming that the key factor was the infection itself, rather than wartime shocks.
“It's not just the flu that can alter fetal neurodevelopment,” explained Christina Adams Waldorf, a professor of obstetrics and gynecology at the University of Washington. “Many types of infections … in the mother can be transmitted as a signal to the fetus, which can alter the development of its brain.”
A century later, the same question has returned with Covid: can infection during pregnancy affect how children grow and learn? A new study from Massachusetts General Hospital offers an early look at the answer.
