Most potential explanations of premature birth revolve around the mother, and what might cause her body to reject her developing fetus.
But what if it’s the other way around?
A new study suggests some preterm births occur because the fetus rejects the mother, after its immune system is triggered too early and senses maternal cells as foreign invaders.
Researchers found that umbilical cord blood drawn from preemies contained elevated levels of immune cells generated by the fetus. Subsequent lab tests revealed that this immune response had been activated specifically to attack the mother’s cells.
The flood of inflammatory chemicals released during this fetal immune response can induce contractions in the uterus, causing preterm labor, the study concludes.
“We’re showing that in the context of maternal infection or inflammation — the most common cause of preterm labor — the naive fetal immune system wakes up, gets activated too early, and can actually identify and reject the mother’s cells,” said lead researcher Dr. Tippi MacKenzie.
More than one in 10 pregnancies are affected by preterm labor, in which a baby is born earlier than 37 weeks of gestation, said MacKenzie. She is an associate professor with the University of California, San Francisco pediatric surgery and fetal treatment center.
Preterm birth is the leading cause of infant mortality in the United States and the world. Children who survive may go on to face a lifetime of health problems.
Despite this, the causes of preterm labor remain “one of the big mysteries in science,” MacKenzie said.
Some recent studies have hinted that one cause might be the mother’s immune system rejecting the fetus. Much like an organ transplant, pregnancy requires the immune system of the mother to tolerate the fetus so it is not rejected.
Until now, no one has considered that the fetus might play a role, because the fetal immune system is still developing when preterm birth occurs, MacKenzie said.
In their study, the researchers tested umbilical cord blood and maternal blood taken from 89 women who had healthy pregnancies and 70 who went into early labor.
There were no signs of immune response in the mother’s blood. However, researchers found that the cord blood of preterm infants had higher levels of two types of immune cells: T cells, which attack foreign agents and promote immune response; and antigen-presenting cells, which guide the T cells to the foreign bodies under attack.
“Both of those cell types were quite immature in the blood of normal healthy term babies we looked at, but both of those cells were quite activated in the preterm labor blood we looked at,” MacKenzie said.
Further tests showed that the fetal immune cells were attacking cells from the mother, and releasing significantly higher levels of inflammatory chemicals as part of their attack.
In a laboratory model, the researchers showed these chemicals induced contractions in the uterus.
The scientists suspect the fetal immune system becomes triggered as a result of an infection in the mother, and mistakenly identifies the mother as a threat.
Dr. Scott Sullivan, head of maternal-fetal medicine at the Medical University of South Carolina in Charleston, welcomed the report.
“I really applaud their work, because one of the glaring holes we have with preterm labor and preterm birth is we don’t have a good understanding of the basic mechanisms and underpinning of the symptoms we see,” said Sullivan.
At the same time, Sullivan and MacKenzie agreed that this is probably just one of many different ways in which preterm labor occurs.
High blood pressure, diabetes, improper fetal development, early water breaking or a short cervix are other likely risk factors for premature birth, Sullivan said.
“As we understand the basic mechanisms, it helps us think of and develop treatments and preventative strategies,” Sullivan said. “Ultimately, there’s not likely to be one treatment that’s going to work for everybody. Ideally, we’re going to end up with different treatments for different mechanisms.”
That said, these results might eventually help doctors detect and head off preterm delivery caused specifically by a fetal immune response, MacKenzie noted.
“We can potentially develop some biomarkers that allow us to diagnose it earlier,” MacKenzie said. “And if we know exactly which cell types and which mechanisms are involved, we can potentially develop specific medicines to treat it.”
The study was published April 25 in the journal Science Translational Medicine.