Progestins and Preterm Birth

Premature delivery (PTD), defined as birth prior to 37 weeks’ gestation, remains one of the major problems that lead to perinatal morbidity and mortality in the developed countries (Goldenberg et al., 2008). It affects approximately 12.7% of all deliveries in the United States and 4.4 – 8.2% in many other developed countries such as Australia, New Zealand, Sweden, Canada and Japan (Hamilton et al., 2006; Jenkins et al., 2006; Morken et al., 2005; Health Canada 2003). One third of these occur before 34 weeks’ gestation (Amon, 1999; Behrman & Butler et al., 2007). In the United States, the preterm birth (PTB) rate has increased more than 30% since 1984 and equates to nearly 500,000 PTBs each year (March of Dimes, 2007). This prematurity rate has been increasing probably as a result of delayed child bearing, increased frequency of multifetal pregnancies from assisted reproductive technology (Tough et al., 2002; Reynolds et al.,2003), general non-interventional approach at or beyond 34 weeks’ gestation and the increase in labor inductions and cesarean deliveries including those medically indicated (Damus et al., 2008). Prematurity causes an estimated 60-80% of all neonatal deaths of non-anomalous infants in developed countries (Guyer et al., 1997). Neonatal mortality is directly correlated with gestational age (GA) at delivery. For example, the mortality rate for infants born at less than 32 weeks’ gestation is almost 70 times the rate of a term infant, and for infants born less than 37 weeks’ gestation it is 15 times the term infant rate (2.6/1000 live births)(March of Dimes Birth Defects Foundation, 2005). Reported neonatal morbidity is also a major concern, especially for infants born at less than 32 weeks’ gestation. Neonatal complications include intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), jaundice and anemia (Behrman and Butler et al., 2007). Economically, care for these infants is responsible for an estimated $51,600 investment per child in neonatal care, contributing more than $26 billion to annual healthcare costs in the US (Behrman and Butler et al., 2007). Among the infants who survive, 10% -15% are burdened with significant handicaps, such as cerebral palsy, mental retardation, retinopathy, or hearing impairment (Gluckman & Hanson, 2004). More importantly, low birth weight (LBW) infants who are spared significant neonatal morbidity are at higher risk for cardiovascular disease (myocardial infarction, stroke, and hypertension) and diabetes as adults (Gluckman & Hanson, 2004). Therefore, greater attention should be focused on very PTBs < 32 weeks’ gestation, because, although this group represents only 1-2% of all deliveries, it accounts for about 60% of perinatal mortality