Preterm birth continues to be a major problem for our patients and for our society. Although the preterm birth rate in the United States fell for a fourth consecutive year in 2010, it remains alarmingly high. The incidence of preterm birth was almost 12% in 2009, according to the Centers for Disease Control and Prevention. It has been estimated, moreover, that two-thirds of preterm births in the United States are spontaneous.
Tocolysis can delay preterm birth by up to 48 hours and improve neonatal outcomes by allowing time for administration of corticosteroids. In general, however, tertiary prevention has been ineffective in decreasing the number of preterm births, and our attention has shifted to primary and secondary prevention. Several risk factors – from body mass index to various infections – have been studied, but their sensitivity or positive predictive value has been disappointing. However, two of these factors – a history of prior preterm birth and short cervical length – have proved to be important independent predictors of preterm delivery.
Term labor is preceded by cervical ripening and effacement by several days. It would make logical sense that preterm cervical effacement would similarly predict preterm delivery. Since the 1990s, research from various countries has shown that cervical effacement, detected as a short cervix by transvaginal ultrasound in the midtrimester, is indeed a powerful predictor of spontaneous preterm birth. Detecting women at high risk for preterm birth without proven effective therapies or interventions, however, would only create anxiety for the mother and frustration for the physician. Routine screening, therefore, traditionally was not offered.
Today, however, we have ample evidence from the past decade of the safety and benefit of vaginal progesterone – and possibly other interventions – in women with singleton gestation and cervical shortening. Multiple studies have demonstrated that vaginal progesterone can significantly cut the rate of spontaneous preterm birth among the approximately 2% of women who have asymptomatic short cervix (most commonly defined as less than or equal to 2 cm) in the midtrimester.
Transvaginal ultrasound, in the meantime, has been widely recognized as a relatively safe, easy-to-perform, sensitive, and reproducible method for detecting shortened cervical length. It can easily be performed at 18-22 weeks’ gestation in conjunction with the fetal anatomic survey.
We currently have the knowledge and tools, therefore, to further reduce the incidence of preterm birth. By screening for short cervix, we can offer hope to more women that preterm birth can be averted. We also can improve the rates of neonatal and infant morbidity and mortality as well as longer-term prematurity-related medical problems and societal issues. It is time to recommend routine cervical length screening of women with singleton gestation at midtrimester, and to offer prophylactic treatment to those with short cervical length.
Efficacy of Progesterone
The first meaningful advance with respect to progesterone and prevention of preterm birth came in 2003 with the da Fonseca study using daily vaginal progesterone (Am. J. Obstet. Gynecol. 2003;188:419-24) and the Meis study using weekly injections of 17-alpha-hydroxyprogesterone (17P). Both double-blind, placebo-controlled studies looked at prevention of recurrent preterm delivery in women with a singleton pregnancy who had previously delivered prematurely, and both showed efficacy of progesterone. Dr. Meis and colleagues, for instance, reported that progesterone treatment reduced the risk of delivery at less than 37 weeks’ gestation by approximately one-third (N. Engl. J. Med. 2003;348:2379-85).
The value of careful history taking and prophylactic intervention for women with a prior preterm birth was recognized and approved by medical organizations and widely implemented in practice.
Subsequently, several other studies demonstrated a benefit of vaginal progesterone, which is less painful than 17P, in women with a short cervix. The Fetal Medicine Foundation Second Trimester Screening Group from London, for instance, reported a 44% lower rate of spontaneous delivery before 34 weeks’ gestation in women who were randomized to receive daily vaginal progesterone than in those randomized to receive a placebo (19.2% vs. 34.4%). The 250 asymptomatic women who participated had a cervical length of 15 mm or less at 20-25 weeks’ gestation; they represented 1.7% of 24,620 women who were screened during routine prenatal care, but accounted for approximately 26% of all spontaneous preterm births (N. Engl. J. Med. 2007;357:462-9).
An even larger National Institutes of Health–collaborated, randomized, double-blind trial conducted at 44 centers in 10 countries documented a 45% reduction in the rate of preterm birth before 33 weeks’ gestation in women who received daily progesterone gel compared with placebo. The study enrolled 458 asymptomatic women with cervical length of 10-20 mm at 19-23 weeks’ gestation.