Randomized comparison of nifedipine and placebo in fibronectin-negative women with symptoms of preterm labor and a short cervix (APOSTEL-I Trial)

OBJECTIVE: To evaluate whether tocolysis with nifedipine can be omitted in women with symptoms of preterm labor, a shortened cervix, and negative fetal fibronectin test. STUDY DESIGN: A randomized noninferiority trial was performed in all Dutch perinatal centers. Women with symptoms of preterm labor between 24 and 34 weeks, intact membranes, cervical length between 10 and 30 mm, and negative fibronectin test were randomly allocated to nifedipine (80 mg/day) or placebo. The primary outcome was delivery within 7 days. Secondary outcomes were severe neonatal morbidity and mortality. We also followed all eligible nonrandomized women. RESULTS: We allocated 37 women to nifedipine and 36 women to placebo. In the nifedipine group, three women (8.1%) delivered within 7 days, compared with one woman (2.8%) in the placebo group (difference -5.3%; one-sided 95% confidence limit 4.5%). Median gestational age at delivery were respectively 37 + 0 (interquartile range [IQR] 34 + 6 to 38 + 5) and 38 + 2 (IQR 37 + 0 to 39 + 6) weeks (p = 0.008). In the nifedipine group, three pregnancies (8.1%) had a poor outcome; there were no poor outcomes in the placebo group. We observed similar trends in eligible nonrandomized women. CONCLUSION: In symptomatic women with preterm labor, a shortened cervix, and negative fibronectin test, placebo treatment is not inferior to tocolysis with nifedipine.Jolande Y. Vis, Gert-Jan van Baaren, Femke F. Wilms, Martijn A. Oudijk, Anneke Kwee, Martina M. Porath, Hubertina C. Scheepers, Marc E. Spaanderman, Kitty W. Bloemenkamp, Jan M. van Lith, Antoinette C. Bolte, Caroline J. Bax, Jérôme Cornette, Johannes J. Duvekot, Sebastiaan W. Nij Bijvank, Jim van Eyck, Maureen T. Franssen, Krystyna M. Sollie, Mallory Woiski, Frank P. Vandenbussche, Joris A. van der Post, Patrick M. Bossuyt, Brent C. Opmeer, Ben W. Mo

Risk stratification with cervical length and fetal fibronectin in women with threatened preterm labor before 34 weeks and not delivering within 7 days

OBJECTIVE: To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after 7 days. DESIGN: Prospective observational study. SETTING: Nationwide cohort of women with threatened preterm labor from the Netherlands. POPULATION: Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission. METHODS: Kaplan-Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery. MAIN OUTCOME MEASURES: Spontaneous delivery between 7 and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks. RESULTS: The risk of delivery between 7 and 14 days was significantly increased for women with a CL < 15 mm or a CL ≥15 to <30 mm and a positive fFN, compared with women with a CL ≥30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL ≥15 to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5-8.7)] or negative fFN [HR 3.0 (95% CI 1.2-7.1)] compared with women with a CL ≥ 30 mm. CONCLUSIONS: In women remaining pregnant 7 days after threatened preterm labor, CL and fFN results can be used in risk stratification for spontaneous delivery.Frederik J.R. Hermans, Merel M.C. Bruijn, Jolande Y. Vis, Femke F. Wilms, Martijn A. Oudijk, Martina M. Porath, Hubertina C.J. Scheepers, Kitty W.M. Bloemenkamp, Caroline J. Bax, Jérôme M.J. Cornette, Bas W.A. Nij Bijvanck, Maureen T.M. Franssen, Frank P.H.A. Vandenbussche, Marjolein Kok, William A. Grobman, Joris A.M. Van Der Post, Patrick M.M. Bossuyt, Brent C. Opmeer, Ben Willem J. Mol, Ewoud Schuit, and Gert-Jan Van Baare