Is Covid during pregnancy linked to autism? What a new study shows, and what it doesn’t

A large study from Massachusetts found this Children whose mothers contracted COVID-19 during pregnancy They were slightly more likely to have a range of neurodevelopmental diagnoses at age three. Most of these children had delayed speech or movement, and the association was stronger in boys and when the mother became infected late in pregnancy.

The increase in risk was small for one child, but because millions of women were pregnant during the pandemic, even a small increase is important. The study does not prove that infection with the Coronavirus during pregnancy causes autism or other brain diseases in the fetus, but it does indicate that infection and inflammation during pregnancy can affect how the child’s brain develops, something that scientists have seen before with other diseases. It’s a reason to help pregnant women avoid contracting the coronavirus and closely monitor babies who have been exposed to it 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 from March 2020 to May 2021, before vaccines were widely available to pregnant women. Because everyone born during that period was tested for the coronavirus, the team was able to clearly see which pregnancies were exposed to the virus that causes it.

About 5% of these mothers developed the disease during pregnancy. Their children were more likely to have a neurodevelopmental condition at age 3 than those whose mothers did not, even after accounting for differences in maternal age, race, insurance status, and preterm birth.

The association appeared stronger among boys and when infection occurred in their mothers’ third trimester of pregnancy. However, most children in both groups showed typical development.

“This was a very clean group to follow,” said Andrea Edlow, a specialist in maternal-fetal medicine at Mass General Hospital and one of the study’s authors. “Because of mass testing early in the pandemic, we knew who had COVID and who didn’t.”

Independent authorities say that the Corona virus, which causes a strong immune response in some people, fits the biological pattern that appears with other infections during pregnancy. “Covid would be a very strong candidate because the amount of inflammation is so intense,” explained Alan Brown, a professor of psychiatry and epidemiology at Columbia University who studies maternal infection and brain development and was not involved in this research.

How can infection affect brain development?

Scientists are still piecing together how various infections during pregnancy can affect fetal development. Severe disease can cause inflammation Disrupts brain development Or maybe Provoking premature birthwhich carries its own risks.

“There is a long history of evidence showing that maternal infection can 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 is investigating how infection and inflammation interfere with brain development. In a healthy brain, immune cells help shape developing neural circuits by cutting off extra or unnecessary connections, a process known as “synaptic pruning,” which sculpts 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 for Edlow’s hypothesis. When scientists cause inflammation in pregnant mice, their offspring often show changes in how brain cells grow and connect, changes that can alter learning and behavior.

Why was pregnancy delayed and why had children?

In Edlow and Perlis’ study, the association between COVID and developmental delay was strongest when infection occurred late in pregnancy, during the third trimester. It is also during this period that the fetal brain grows more rapidly, forming and improving millions of neural connections.

“When we think of organ development, we think of early pregnancy, but the brain is an exception in this regard,” Perlis said. “There is a tremendous amount of brain growth in the third trimester of pregnancy. That continues after birth.” “It is entirely plausible that the third trimester of pregnancy is a particularly vulnerable period for brain development.”

But not all researchers agree that the third trimester of pregnancy is uniquely 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 are simply more cases of late-pregnancy infections to analyze. “This gives the study greater power to find a difference in the third trimester of pregnancy,” he said. “This does not prove that early infection is not important.”

The study also found stronger effects for boys. This pattern is familiar: boys are generally more likely than girls to have delays in speech or movement and to be diagnosed with autism. Researchers suspect that male fetuses may be more vulnerable to stress and inflammation, although the biological factors are not fully understood.

What the study can and cannot show

Edlow and Perlis are careful to say that the study shows an association, not evidence, that coronavirus infection during pregnancy causes developmental problems. Many other factors That could explain the correlation.

Mothers infected with coronavirus may have other health problems, such as obesity, diabetes or mental health conditions, which increases the risk of developmental delays in children. “People with Psychological disorders They are more susceptible to infection with the Corona virus. Women with many mental disorders They are more likely to have children with neurodevelopmental problems“Mothers are with,” he told me Worse physical health They are also more likely to have children with neurodevelopmental problems.”

My research has shown this Even infections before or after pregnancy can be linked to autismWhich suggests that genetics or shared environment, rather than the infection itself, could play a role. That’s why experts say much larger and longer studies are needed to understand the extent of any risk from 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 away. They are also studying how inflammation during pregnancy affects the placenta and fetal brain, and how to counter these effects.

What about vaccination?

Because this study followed pregnancies from early in the pandemic, it does not answer whether vaccination changes the risk. But other research provides reassurance.

A large national study in Scotland He found no difference in early developmental outcomes Between children whose mothers were vaccinated and those whose mothers were not vaccinated. Another study in the United States Found the same thingThere is no link between prenatal vaccination against coronavirus and developmental delay within 18 months. Both are consistent with decades of data showing that vaccination during pregnancy is safe for both mother and baby.

“Vaccination is a short spike…it activates your immune system, and then it goes back to normal,” Edlow said. “Covid (infection) is much longer, more unpredictable, and people can develop dysregulated immune phenomena that don’t really exist in vaccine responses.”

What this means for parents and doctors

Since late 2020, there has been widespread confusion and misinformation about the safety of coronavirus vaccination during pregnancy. Some women hesitated to get vaccinated for fear it would harm their baby. But the evidence since then has been clear: Covid vaccines are safe during pregnancy. American College of Obstetricians and Gynecologists Vaccination against coronavirus is highly recommended For protection Both mother and child.

The broader lesson, experts say, is that pregnancy is a vulnerable time, and that prevention is important, and not only that For CovidBut other infections as well.

These risks remain “underappreciated,” despite decades of evidence, said Janet Currie, an economics professor at Yale University. “Although the flu vaccine is recommended for pregnant women, very few pregnant women get it,” she said. “Doctors seem reluctant to vaccinate pregnant women.”

As Jill Moore, scientific director of the C.S. Mott Center for Human Growth and Development at Wayne State University in Detroit, puts it, “Protecting the mother means 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 took hold with studies of famine, such as the Dutch “hunger winter” study in the final months of World War II. In 1944 and 1945, when German forces surrounded the western Netherlands, food rations were reduced to only a few hundred calories per day. Thousands died of starvation, and women who became pregnant during that period gave birth to children who later faced a higher risk of starvation My heart disease, Diabetesand schizophrenia. The episode became the cornerstone of “Origins of the fetusThe idea that deprivation or stress during pregnancy can have lifelong effects.

the Influenza pandemic of 1918 This idea extended to contagion. Babies who were exposed to influenza in the womb later showed a small, but permanent, size Differences in education and earningsA sign that illness during pregnancy can affect brain development. Researchers in Taiwan, Sweden, Switzerland, Braziland Japan Similar consequences were found. Some have claimed that these findings reflect the disruptions caused by World War I, rather than influenza itself. but Later studiesincluding from UK and FinlandThe argument in favor of biological influence was strengthened, reinforcing that infection itself, rather than wartime unrest, was the main driver.

“It’s not just the flu that can alter the neurodevelopment of the fetus,” explained Christina Adams-Waldorf, a professor of obstetrics and gynecology at the University of Washington. “Many types of infections…can be transmitted in the mother as a signal to the fetus, which may alter its brain development.”

A century later, the same question returned with the coronavirus: Could infection during pregnancy subtly affect how children grow and learn? A new study from Massachusetts General Hospital offers an early look at the answer.