Effectiveness Of Progesterone In Reducing Preterm Births May Be Altered By Genetic Predisposition

The drug, 17 alpha-hydroxyprogesterone caproate (or 17P), a synthetic form of the progesterone hormone naturally produced during pregnancy, has been demonstrated in clinical trials to prevent some recurrent preterm births – but not all.

"This study helps strengthen the theory that genetic variation in the human progesterone receptor plays an important role in the effectiveness of 17P," states Tracy Manuck, M.D., study author and SMFM member.

Women who have a spontaneous preterm delivery are at greatly increased risk of preterm delivery in subsequent pregnancies. Preterm birth is a leading cause of infant death in the United States and babies who survive face serious lifelong health problems. More than 543,000 babies are born too soon each year and recent federal statistics show that the nation's preterm birth rate has risen to 12.8 percent -- a 36 percent increase since the early 1980s.

"Dr. Manuck's research gives us a tantalizing clue as to why 17P works for some women, but not for others," said Alan R. Fleischman, M.D., senior vice president and medical director of the March of Dimes. "With further research along these lines, we hope to someday be able to prevent preterm birth from happening in the first place by screening women before they get pregnant, and identifying those whose babies could get a healthy start in life with the help of 17P."

The research, which was sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Network and the University of Utah, assessed whether women with genetic variations known as single nucleotide polymorphisms (SNPs) in the human progesterone receptor gene were more or less likely to respond to 17P for the prevention of recurrent spontaneous preterm birth.

All patients had at least one prior spontaneous preterm birth. The study extracted DNA from the saliva of 389 patients, and then genotyped 20 SNPs in the region of the progesterone receptor gene. Two hundred and fifty-eight (66 percent) of the study participants received 17P and 131 (34 percent) were controls and received a placebo.

Spontaneous preterm birth was less common among women who received 17P. However, after controlling for factors known to be associated with recurrent prematurity, including smoking, number of prior preterm deliveries, and pre-pregnancy body mass index, two SNPs were identified among African-American patients to be predictive of response to progesterone treatment. There was also an interaction between progesterone treatment and genotype of 3 additional polymorphisms for non-African-American women delivering very preterm (less than 32 weeks gestation).

Today's award-winning study, The Relationship Between Polymorphisms in the Human Progesterone Receptor and Clinical Response to 17 Alpha-Hydroxyprogesterone Caproate for the Prevention of Recurrent Spontaneous Preterm Birth, is the sixth study by SMFM members to be honored by the March of Dimes for innovative research focused on preventing premature births. The March of Dimes is conducting a multi-year, multi-million dollar campaign aimed at using research and awareness to reduce the growing rate of premature birth.