A very interesting article published in EurekAlert! discusses this highly relevant issue. “Preterm labor, a common pregnancy complication, has long been a mystery to scientists. But a new study from UC San Francisco shows it may sometimes happen when the fetal immune system “wakes up” too early and begins to reject the mother, causing the uterus to start contracting.

The fetal immune response may trigger preterm laborfetal inmunue system role in preterm labor

“The researchers think the fetal immune system becomes triggered in a case of mistaken identity. An initial infection in the mother can result in inflammation and arouse the fetal immune system. The fetal immune cells confuse the mother’s cells for an invader and mount an attack, in the form of inflammatory chemicals. These chemicals then trigger contractions, leading to preterm labor, the leading cause of infant mortality.

It may have a role in pregnancy complications

“The dogma has always been that the fetus has a very immature immune system, and as a result, people haven’t really considered its possible role in pregnancy complications,” said senior author Tippi MacKenzie, MD, associate professor in the UCSF Division of Pediatric Surgery and the Fetal Treatment Center. “We showed that in patients who have preterm labor as a result of some kind of infection or inflammation–the most common cause of preterm labor–the fetal immune system awakens prematurely and may trigger labor.”

The fetal immune response leading to preterm labor appears to be produced by activation in two types of immune cells in the cord blood of preterm infants

In the new study, published Wednesday, April 25, 2018, in Science Translational Medicine, the researchers tested umbilical cord blood, which contains fetal cells, along with blood taken from 89 women who had healthy pregnancies and 70 who went into early labor. But the scientists saw no signs of an immune response in the mother’s blood. Instead, they detected activation in two types of immune cells in the cord blood of preterm infants. The researchers also found greater numbers of the mother’s cells circulating in the cord blood of preterm infants.

During pregnancy, cells from the mother and the fetus travel back and forth across the placenta. Just as in an organ transplant, the immune systems of the mother and the fetus have to tolerate one another, so the fetus is not rejected. This tolerance is governed by immune cells known as regulatory T cells, which dampen the immune system by keeping the other types of T cells in check.

However, during preterm labor, the infant’s immune system was found to be activated specifically to attack the mother’s cells. The researchers detected higher levels of both dendritic cells and effector T cells in the cord blood of preterm infants; dendritic cells present foreign substances to the T cells to signify that they are a potential threat, and T cells–the primary fighter cells of the immune system–then mount an attack by releasing inflammatory chemicals.

T cells from preterm infants made significantly higher levels of these inflammatory chemicals, TNF alpha and interferon-gamma than those from full-term infants, and in a laboratory model of uterine contraction, the researchers discovered that these chemicals induced contraction of uterine cells. 

A lab is now pursuing biomarkers in the mother’s blood that can identify whether the fetal immune system is activated and increases the risk for preterm labor.” (EurekaAlert Science News, Apr 25, 2018). They concluded that the discovery upends conventional thinking about immune development. Our Observatory is following this line of research with great interest.

Related articles: Article of Roberto Romero, MD, DMedSci, NIH Chief, Perinatology Research Branch