The pharmacogenomics of spontaneous preterm birth prevention

Preterm infants, born earlier than 37 weeks gestation, account for more than 70% of the neonatal deaths in the United States. Survivors are at an increased risk for serious complications, including cerebral palsy, respiratory illness, blindness and deafness. Despite the magnitude of this clinical problem, few therapeutic interventions for spontaneous preterm birth (SPTB) have proven effective.

One notable exception is 17 alpha-hydroxyprogesterone caproate (17P), which is derived from the hormone progesterone, and is proven to reduce the rate of SPTB in a subset of those who are at risk. Unfortunately, two-thirds of high-risk women do not respond to 17P. Understanding why some women respond to 17P, and others do not, is crucial to optimizing prediction and therapeutic strategies.

A research team led by Tracy Manuck, MD, has preliminary evidence that variable responsiveness to 17P results from genetic variation found in at-risk women. Her team is building upon this finding by sequencing women with the most severe SPTB phenotypes. The studies are made possible by a unique clinical and biospecimen databsase, a collaboration between the University of Utah and Intermountain Healthcare. Database samples come from women with early and/or recurrent SPTB, including a subset of which received 17P due to a prior SPTB. Of these, a portion did not receive significant benefit from 17P and had a recurrent SPTB (‘non-responders’). The remaining women delivered at term or delivered significantly later when taking 17P (‘responders’). The researchers are comparing responders and non-repsonders to identify genes that may influence responsiveness to 17P.

By identifying novel gene targets, this study will help elucidate who is likely to respond to 17P for the prevention of SPTB. Tailoring optimum preterm birth interventions for individuals who are most likely to benefit will significantly lower the overall rate of both primary and recurrent SPTB, and corresponding health complications and deaths in premature infants.

Spontaneous Preterm Birth (SPTB)

More than 12% of infants born in the United States are born preterm, at less than 37 weeks’ gestation. Survivors are at an increased risk for serious complications, including cerebral palsy, respiratory illness, blindness and deafness. A study led by Tracy Manuck, MD, seeks to identify genetic factors that enable women who are predisposed to spontaneous preterm birth (SPTB) to respond to known therapeutic treatment. The finding will lead to individualized treatments for SPTB.