Grand Rounds: Can progesterone prevent preterm birth?

No one has to remind ob/gyns that preterm birth (PTB) takes a heavy toll both medically and financially on the American public. Unfortunately, in recent decades clinicians have had little success is reining in this problem, which is no doubt why so much attention has been given to recent research on the preventative effects of 17-alpha-hydroxyprogesterone caproate (17P). But in order to achieve the most benefit from this therapy, several educational and logistical barriers need to be addressed, and both physicians and patients need to understand more about the appropriate use of the medication and compliance support with the therapy. With appropriate planning, overcoming these obstacles is possible within an organized education and support network.

Appreciating the scope of the problem

Preterm birth, birth prior to 37 completed weeks of pregnancy, complicates 12.3% of all births in the United States annually.¹ In 2002, that translated into an estimated 480,000 preterm infants. Although advances in neonatal care have improved survival for these newborns, the rate of prematurity has steadily increased over the past three decades.^1,2 The incidence of delivery before 37 weeks' gestation increased from 9.4% of live births in 1981 to 11.0% in 1994 and 12.3% in 2004.^1,2 These increases are attributed to increases in the multiple birth rate, although PTB is also increasing among singleton deliveries.¹ The rate of PTB in black women is nearly double the rate in white women.¹

Of course, morbidity is also a major concern, especially for infants born at less than 32 weeks' gestation. Complications include respiratory distress syndrome, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and cerebral palsy. Preterm infants are also at risk for associated medical conditions extending into childhood and adulthood. One prospective study found that 25% of very premature infants have significant long-term neuro-developmental impairments not improved by educational intervention.⁵ The extent of cognitive impairment extending into childhood for infants born at less than 26 weeks' gestation has been underestimated. New estimates suggest that 41% of these extremely preterm infants have serious cognitive deficits at 6 years of age.^6,7

In addition to the devastating toll on infant mortality and morbidity, prematurity exacts a heavy financial cost on the US health-care system. In 2001 alone, charges for hospital stays for infants with any diagnosis of prematurity were approximately $13.6 billion or about 50% of all birth-related spending.⁸ Researchers have estimated that prematurity and low birthweight combined accounted for 35% of all direct infant care expenditures in the US. ⁹ Aetna, a national health benefits company serving 13.7 million Americans and covering over 140,000 deliveries a year, estimates that the cost of care through the first year of life for infants born at less than 37 weeks' gestation is $34,000 and for infants born at less than 32 weeks' gestation is $119,000.¹⁰ This excludes the associated maternal care costs. By comparison, the average cost of care through the first year of life for a term birth is $1,373. The financial cost of prematurity for the Medicaid population is no doubt greater because the proportion of births that are preterm is greater.

Understanding risk factors for spontaneous preterm birth

Preterm births are generally considered to be either "spontaneous" or "indicated." Spontaneous PTBs are initiated by spontaneous preterm labor with intact fetal membranes or preterm premature rupture of membranes (PPROM). Indicated PTBs result from either induction of labor or cesarean delivery without labor, most commonly in response to maternal complications of pregnancy such as hypertensive disorders or diabetes or fetal complications such as growth restriction or placental bleeding. Of all PTBs, about 20% are indicated while 80% are unanticipated or spontaneous.¹¹ As spontaneous and indicated PTB have different clinical presentations and probably different underlying causes as well, interventions to prevent one may not prevent the other.