Use of Progesterone to Reduce Preterm Birth

By Dina Deldon-Saltin, D.O.

The rate of preterm birth in the United States has been rising over the last 15 years. Nationally, preterm birth affects 12% of all babies delivered in the US or approximately 480,000 births. In the last decade, preterm birth has increased by 27% and accounts for 85% of all perinatal morbidity and mortality. In 2005, the annual societal economic cost (medial, educational, and lost productivity) associated with preterm birth in the US was at least $26.2 billion.

There is increasing evidence that progesterone supplementation can reduce the rate of preterm birth in high-risk women. Progestogens are steroid hormones that induce myometrial quiescence (make the uterus quiet) by suppressing the contractile genes and promoting relaxation and may suppress immunity to prevent rejection of fetal cells.

A large trial was conducted using 17 alpha –hydroxyprogesterone caproate (“17P”) therapy for the prevention of preterm birth in a select, high-risk group of women (documented history of a previous spontaneous singleton birth at less than 37 weeks of gestation) was conducted for the National Institute of Child Health and Human Development (NICHD). This study demonstrated significant reductions in preterm and early preterm birth, low birth-weight, as well as significant reductions in infant complications with progesterone therapy. Four-year follow up found no adverse health outcomes of surviving children. This study as well as follow up studies support the hypothesis that progesterone supplementation reduced preterm birth in women at risk for preterm birth, with a prior preterm birth.

The effectiveness of progesterone supplementation has been evaluated in several other high-risk groups for preterm delivery with conflicting results. Studies were performed in women who carried twin and triplet gestations, and no benefit was found to support using 17P in multiple gestations. Further investigation is needed to determine if there is a benefit of using 17P in women with a shortened cervix.

Despite the apparent benefits of progesterone in some situations, the ideal formation is unknown. 17 is specially formulation and is not currently commercially available, it must be purchased through specialty compounding pharmacies. Other formulations of progesterone were given in other trials with mixed results. These differences in efficacy may reflect differences in dosages, variation in absorption and/ or bioavailability with different preparations.

Progesterone supplementation for the prevention of recurrent preterm birth should be offered to women with a singleton pregnancy and a prior spontaneous preterm birth due to spontaneous preterm labor ore premature rupture of membranes. Current evidence does not support the routine use of progesterone in women with multiple gestations.

SOURCES

Use of Progesterone to Reduce Preterm Birth: ACOG Committee Opinion: Number 419. October 2008

Preventing Preterm Birth: The role of 17P: ACOG District II: compiled January 2009