Researchers Identify New Approach to Personalize Pre-term Birth Prevention

New research findings that physicians from the Intermountain Medical Center fetal medicine program helped play a key role in discovering may soon help doctors personalize pre-term birth prevention treatments by identifying which women at higher risk for preterm birth will be helped by progesterone injections.

Injections of one type of progesterone, a synthetic form of a hormone that is naturally produced during pregnancy, have been shown to reduce the risk of recurrent preterm birth by about a third.

Nearly half a million babies are born too soon each year in the United States. Pre-term birth (birth before 37 weeks of pregnancy) is the leading cause of newborn death, and babies who survive an early birth often face an increased risk of a lifetime of health challenges, such as breathing problems, cerebral palsy, intellectual disabilities and others. Even babies born just a few weeks early have higher rates of hospitalization and illness than full-term infants. It is a serious health problem that costs the United States more than $26 billion annually.

Tracy Manuck, MD, assistant professor of Maternal Fetal medicine and co-director of the University of Utah Prematurity Prevention Clinic at the University of Utah Health Care, is the chief investigator of the study, which received the prestigious March of Dimes award for best research in prematurity at this week’s annual meeting of the Society for Maternal-Fetal Medicine.

Manuck worked closely with a team of collaborative investigators from the University of Utah and Intermountain Healthcare’s Maternal Fetal medicine program at Intermountain Medical Center, including Marc Jackson, MD, Sean Esplin, MD, and Michael Varner, MD, to understand why progesterone treatments prevent preterm birth for some women, but not for others.

The team hopes to determine whether there is a way to personalize the treatment of women at risk for preterm birth based on their genetic makeup.

Their latest findings, titled “Genetic variation in key biologic processes may influence response to 17-alpha hydroxyprogesterone caproate (17P) for recurrent preterm birth” were presented at the Society for Maternal Fetal Medicine’s 34th annual meeting in New Orleans.

“This is the first step in using pharmacogenomics to prevent preterm birth,” said Edward R. B. McCabe, MD, March of Domes chief medical officer. “There is a group of women in whom progesterone will be effective and others for whom it will not be and who will need different treatments. Knowing which group a woman belongs to would fast track her to the proper treatment. The goal is to find personalized treatments that work for individuals to prevent preterm birth.”

Dr. McCabe presented the team with the prestigious March of Dimes award for Best Abstract in Prematurity. This is the second time in five years that this collaborative team has won this award. Dr. Manuck was the principal investigator on both studies. Dr. Manuck and her colleagues at Intermountain looked at 50 women followed in a prematurity prevention clinic headed by Dr. Esplin at Intermountain Medical Center in Murray, Utah.

All of the women received progesterone treatment, but some delivered prematurely despite treatment. The team then sequenced all of the areas of the women’s genomes that code for proteins and general biologic pathways that are involved in progesterone metabolism. They found that several genes and mutations were more likely to be expressed in women who did not respond to progesterone.

“There are a lot of reasons that women have pre-term babies, and there is not going to be a single "fix" that cures the problem for everyone,” says Dr. Jackson. “But this research is important because it can help identify women who would benefit from treatment with progesterone, lowering their risk for preterm birth. And it may be especially important in some families who have multiple women – sisters, aunts, and cousins - having premature babies, as they can share a genetic predisposition for preterm birth.”

Intermountain supports work such as this in several ways.

This research received financial support from the Intermountain Research and Medical Foundation. The study is also part of an ongoing clinical effort to reduce pre-term births in Utah, including the Prematurity Prevention Clinic in Maternal Fetal Medicine at Intermountain Medical Center that is staffed by Dr. Esplin.

This clinic, which focuses on the pregnancy care of women who have already had one pre-term baby, has shown that specialized care can lower the rates of recurrent preterm birth and NICU admission. The results from that clinic have already been published in the American Journal of Obstetrics and Gynecology, with Drs. Manuck, Esplin, and Jackson as authors with others.