Genetics 3 min read

Six Genes May Hold Clues to Preterm Birth

A new study identifies gene regions that influence the length of pregnancy and the timing of birth

By Audrey Carson featured image

Last month, a landmark study on preterm birth shed light on what scientists have suspected for decades: The risk of preterm birth may be linked to genetic factors. Based on data from more than 50,000 mothers, researchers identified six gene regions, or loci, that may affect whether a woman is likely to deliver a baby before it reaches full term. The findings could lead to new tests, medications, and supplements to help more women reach full-term pregnancies.

Preterm births and their resulting complications are the leading cause of death for children under 5 years old, according to the World Health Organization. Babies born before 37 weeks of pregnancy can face several health problems, including impairments in breathing and vision, developmental delays, and disorders such as cerebral palsy. In 2015, about 1 in every 10 infants in the U.S. was born prematurely. But the March of Dimes, a major funding source of the study, hopes to cut this number in half by 2030.

The March of Dimes is pioneering a novel team approach to examine the complex problem of preterm birth from every angle,” says Stacey Stewart, president of the March of Dimes. “At our network of five centers, scientists from many diverse disciplines work together to develop new strategies to understand and, ultimately, develop preventions for preterm labor.”

The large international team isolated DNA from women who delivered preterm or at term and compared the common gene variations between the two groups. First, they looked at samples of about 44,000 women who provided saliva to the genetic testing company 23andMe. Next, the researchers compared their findings to data from 8,643 women and 4,090 infants from three different genetic studies in Finland, Denmark, and Norway.

The scientists found gene variants at the WNT4, ADCY5, and RAP2C loci played a role in gestational duration while variants at the EBF1, EEFSEC, and AGTR2 loci were associated with both gestational duration and preterm birth. Their tests indicated that these genes most likely influenced pregnancies from the maternal side, rather than from the fetus.

Although the study won’t put an end to preterm births anytime soon, it gives preterm birth researchers new target areas to study moving forward. For example, the WNT4 locus was found to be a critical player in preparing the uterine lining for implantation and pregnancy. These endometrial cells could play an unexpected role in the length of pregnancy, providing researchers with a new focus for early labor prevention therapies.

Also of note was the EEFSEC locus, which plays a role in the uptake of the nutrient selenium into the body. Selenium is a mineral that serves in critical cell functions such as antioxidant defenses and controlling inflammatory responses, both of which have been linked to preterm birth. But since selenium is not naturally produced in the body, those low in the mineral must get it from outside sources such as nuts, seeds, and seafood.

We now have a much more solid foundation for pathways that contribute to variation in human birth timing and risk for preterm birth,” says Louis Muglia, senior study author and principal investigator of the March of Dimes Prematurity Research Center Ohio Collaborative. “We have identified micronutrient pathways that could be targets for supplementation if future studies support the importance of not just the genes associated with selenium biology, but selenium itself.”

The study findings, published in a September issue of the New England Journal of Medicine, will be included in a March of Dimes Prematurity Research Center database so researchers can put these newly identified gene regions in the context of other possible preterm birth factors under investigation, including the microbiome, nutrition, and fetal-maternal signaling.