The Rebirth of Progesterone in the Prevention of Preterm Labor

Preterm birth, defined as childbirthoccurring at <37 weeks ’ gestational age, is the chief cause of neonatal mor-bidity and mortality in the US.1 The rate of preterm delivery has increased by ap-proximately 20 % since 1997, representing 12.8 % of all live births in the US in 2007.1 In 2005, preterm birth was associated with a cost of approximately $26.2 billion.2 Al-though medical interventions have been successful at improving neo natal out-comes in premature infants, strategies to prevent preterm birth, by pre venting or halting preterm labor, have been largely unsuccessful.3 Additionally, risk factors for recurrent preterm birth, including pri-or preterm birth, gestational age at prior preterm birth, African American race, and short cervical length (<25 mm) shown on transvaginal ultrasound, are useful in identifying women at increased risk, but are not useful for determining cause.4,5 These infants are at increased risk for respiratory distress syndrome (RDS), necrotizing enterocolitis, and retinopathy, and many have long-term complications such as learning disabili-ties and cerebral palsy.3 Premature birth is classified as medically indicated, re-sulting from a complication in the mother or fetus, or spon-taneous, which results in preterm labor or preterm rupture of the membranes. Spontaneous preterm labor is attributed to pathologic changes in the normal parturition process. This process includes cervical ripening, membrane rup-ture, and coordination of myometrial contractions, and is primarily modulated through maturation of the fetal hy-pothalamus-pituitary axis.6 As pregnancy advances, rising levels of corticotrophin-releasing hormone stimulate in-creased fetal production of cortisol and dehydroepiandros