Screening and prevention of preterm birth: what is a clinician to do?

The last few years have witnessed some guarded optimism regarding our ability to screen for preterm birth using transvaginal cervical length (CL), which was further encouraged by promising results of being able to prevent a significant number of preterm deliveries by the use of either vaginal progesterone or intramuscular 17-alpha hydroxyprogesterone caproate (17 OHPC). Recent studies are however sounding a note of caution that we should not run too fast. Although a short cervix has been associated with increased risk of preterm delivery, the concept of universal screening of low-risk population remains controversial, and has not been mandated by professional bodies such as the Society for Maternal Fetal Medicine (SMFM) (1). The findings of the nuMoM2b Network study, which evaluated 9401 nulliparous women with CL and fetal fibronectin (fFN) and found that a CL <25 mm had an AUC of 0.67 (95% CI, 0.64–0.70) for predicting preterm birth with no improvement when combined with fFN, further reduces enthusiasm for universal screening (ref) (2). When a short cervix is detected clinically, the interventional options are really limited vaginal progesterone or cerclage in appropriately selected patients. There is compelling evidence for the utility of vaginal progesterone for prevention of preterm birth in women with a short cervix, with preterm delivery reduction of approximately 45% (3,4). The OPPTIMUM study evaluated 1228 women randomly assigned to vaginal progesterone versus placebo group and concluded that progesterone had no significant effect in preventing preterm birth or neonatal morbidity (5). Despite the large sample size, the inclusion criteria to the OPPTIMUM trial was significantly different from the PREGNANT trial study reported by Hassan et al (4) and the type of vaginal progesterone. However, an individual patient level data meta-analysis including all trials using vaginal progesterone (OPPTIMUM study was included) still demonstrated a significant reduction of preterm birth <34 weeks (6). It is now generally well known that all progesterone are not the same. The indications for vaginal progesterone are different from those for 17 OHPC, the latter being mostly used for prevention of recurrent preterm birth. The study by Meis et al. in 2003 established the use of 17 OHPC for the prevention of preterm birth in the USA (7). That study compared 301 women on 17 OHPC with 153 on placebo and found a 34, 33 and 42% prevention of preterm birth <37, 35 and 32 weeks, respectively in the intervention group. Although there has been several criticism of the Meis study, there are also numerous reports of successful pregnancy outcomes with the use of 17 OHPC. It is on this background that a large prospective observational study was recently published. Nelson et al. conducted a prospective cohort study involving 430 consecutive women with prior births ≤35 weeks (8). They were treated with 17 OHPC. The primary outcome was the recurrence of birth ≤35 weeks for the entire study cohort compared to a historical referent rate of 16.8% of recurrent preterm birth rate for their population. 17 OHPC did not significantly reduce the rates of recurrence regardless of prior preterm birth. In addition, the plasma 17 OHPC levels were not significantly different at the two time periods tested between those who delivered prematurely and those who did not. In addition, the incidence of gestational diabetes was higher in the intervention group. Given these recently published conflicting reports on screening and preterm birth prevention, clinicians are wont to be confused regarding the best course of management for their patients. Prior to becoming too pessimistic about the current state of affairs, it is important to bear in mind important differences and limitations of the recent publications. Regarding cervical length screening, the report by Esplin et al. (2) merely reminds us that screening may be of limited value in low risk women, but does not detract from the association between a short cervix and preterm birth, especially in a high-risk