Journal Review

by Michael E. Speer, M.D.
Professor of Pediatrics–Neonatology

Elliott JP, Miller HS, Coleman S, et al. A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin. J Perinatol 2005;25:626–630.

Introduction: Bed rest or other activity restriction has not been demonstrated to prolong gestation and may lead to complications such as fetal growth restriction, maternal bone mineral loss, or maternal thromboembolic disease. Nonetheless, more than 700,000 women per year are prescribed bed rest. The presence of fetal fibronectin (fFN) is identified with an increased risk of preterm delivery; the converse is not necessarily true. This study examined the impact of activity restriction on the preterm birth rate among women experiencing preterm labor with a negative fFN.

Methods: Entry criteria were successful tocolysis with magnesium sulfate, a negative fFN, >14 years of age, intact membranes, documented uterine contractions >6 hours at admission, 23–33 6/7 weeks’ gestation, and <3 cm cervical dilation at the time of fFN testing. Exclusion criteria were conditions that required immediate delivery, prolonged hospitalization, or major fetal malformations. After randomization, all patients were treated with restricted activity. Following discharge, the treatment group (AR) continued restricted activity (bed rest with bathroom and showering privileges plus travel from home to physician’s office); the control group (NAR) was allowed to return to normal daily activities. All patients received information about the signs and symptoms of preterm labor.

Treatment failures were considered to be (1) recurrent preterm labor, defined as >6 contractions per hour and (2) cervical advancement of >1 cm or >25% effacement from the previous exam. Patients with treatment failures received identical treatment as at study entry. If stabilization occurred, subjects resumed their original group assignment. The study was discontinued when the pregnancy reached 37 weeks’ gestation or delivery occurred. The primary study endpoint was the prolongation of pregnancy.

Results: A total of 882 women were screened; 246 were eligible and 73 were enrolled (36 into the AR group and 37 into the NAR group). There were no differences in regard to either neonatal or maternal outcomes. Prolongation of pregnancy in both groups averaged 43.5 days. Preterm delivery occurred in 44.4% of the AR group and in 35.1% of the NAR group (P = 0.478). Overall, delivery occurred within 7 days in 3% and within 14 days in 9.6%.

Discussion: The sample size calculation for pregnancy prolongation had determined that 1625 patients should have been enrolled to find a difference of 7±20 days between the 2 groups. Thus, the finding of no pregnancy prolongation with AR, while consistent with other reported studies, is not helpful in clarifying either the positive or negative value of this treatment method. What is of interest was the finding that the previously reported negative predictive value of a negative fFN may not be valid, particularly in certain high-risk women. Previous reports suggested that women with a negative fFN were at minimal risk of delivery within 7 days (<1%), within 14 days (<3%) or before 37 weeks’ gestation (<10–12%), percentages that are are far less than those reported from this study. Further large-scale trials may be warranted to re-examine the value of a negative fFN in predicting the incidence of early and overall preterm delivery.