Damaging a fetal security system
The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.
That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.
But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.
Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.
Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.
Rewiring the immune system
In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.
In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.
The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.
Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.
“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”
Increasing the risk for boys
Boys could face higher risks from COVID, even before birth.
Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.
But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.
That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.
Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.
Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.
New research on COVID could help illuminate this vulnerability.
In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.
Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.
When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.
The sex of a fetus can influence its mother’s response to other illnesses, as well.
For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.
Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”