title: Effect of maintenance tocolysis with nifedipine in threatened preterm labor on perinatal outcomes: a randomized controlled trial.
abstract: OBJECTIVE
  In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome.
  
  
  OBJECTIVE
  To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth.
  
  
  METHODS
  APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in The Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010).
  
  
  METHODS
  Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n = 201) or placebo (n = 205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses.
  
  
  METHODS
  Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis.
  
  
  RESULTS
  Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45).
  
  
  CONCLUSIONS
  In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time.
  
  
  BACKGROUND
  trialregister.nl Identifier: NTR1336.
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Local Postal Code 791, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. c.roos@obgyn.umcn.nl
authors.forename: Carolien
authors.initials: C
authors.lastname: Roos
authors.forename: Marc E A
authors.initials: ME
authors.lastname: Spaanderman
authors.forename: Ewoud
authors.initials: E
authors.lastname: Schuit
authors.forename: Kitty W M
authors.initials: KW
authors.lastname: Bloemenkamp
authors.forename: Antoinette C
authors.initials: AC
authors.lastname: Bolte
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cornette
authors.forename: Johannes J J
authors.initials: JJ
authors.lastname: Duvekot
authors.forename: Jim
authors.initials: J
authors.lastname: van Eyck
authors.forename: Maureen T M
authors.initials: MT
authors.lastname: Franssen
authors.forename: Christianne J
authors.initials: CJ
authors.lastname: de Groot
authors.forename: Joke H
authors.initials: JH
authors.lastname: Kok
authors.forename: Anneke
authors.initials: A
authors.lastname: Kwee
authors.forename: Ashley
authors.initials: A
authors.lastname: Merién
authors.forename: Bas
authors.initials: B
authors.lastname: Nij Bijvank
authors.forename: Brent C
authors.initials: BC
authors.lastname: Opmeer
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Oudijk
authors.forename: Mariëlle G
authors.initials: MG
authors.lastname: van Pampus
authors.forename: Dimitri N M
authors.initials: DN
authors.lastname: Papatsonis
authors.forename: Martina M
authors.initials: MM
authors.lastname: Porath
authors.forename: Hubertina C J
authors.initials: HC
authors.lastname: Scheepers
authors.forename: Sicco A
authors.initials: SA
authors.lastname: Scherjon
authors.forename: Krystyna M
authors.initials: KM
authors.lastname: Sollie
authors.forename: Sylvia M C
authors.initials: SM
authors.lastname: Vijgen
authors.forename: Christine
authors.initials: C
authors.lastname: Willekes
authors.forename: Ben Willem J
authors.initials: BW
authors.lastname: Mol
authors.forename: Joris A M
authors.initials: JA
authors.lastname: van der Post
authors.forename: Fred K
authors.initials: FK
authors.lastname: Lotgering
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control; D005260:Female; D005313:Fetal Death; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000517:prevention & control*; D020300:Intracranial Hemorrhages / Q000517:prevention & control; D007969:Leukomalacia, Periventricular / Q000517:prevention & control; D008171:Lung Diseases / Q000517:prevention & control; D009543:Nifedipine / Q000008:administration & dosage*; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D018805:Sepsis / Q000517:prevention & control; D015149:Tocolytic Agents / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D015149:Tocolytic Agents; D009543:Nifedipine