title: Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis.
abstract: BACKGROUND
  Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven.
  
  
  OBJECTIVE
  To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA).
  
  
  METHODS
  We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour.
  
  
  METHODS
  We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment.
  
  
  METHODS
  The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed.
  
  
  RESULTS
  Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01).
  
  
  CONCLUSIONS
  Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice.
  
  
  CONCLUSIONS
  Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.
authors.affiliation: Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Eog
authors.initials: E
authors.lastname: van Vliet
authors.affiliation: Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: G H
authors.initials: GH
authors.lastname: Dijkema
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.|Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands.|Department of Medicine, Stanford Prevention Research Centre, Stanford University, Stanford, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Schuit
authors.affiliation: Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: K Y
authors.initials: KY
authors.lastname: Heida
authors.affiliation: Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Roos
authors.affiliation: Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jam
authors.initials: J
authors.lastname: van der Post
authors.affiliation: Consultant Maternal Fetal Medicine Service, Auckland District Health Board, Auckland, New Zealand.
authors.forename: E C
authors.initials: EC
authors.lastname: Parry
authors.affiliation: Obstetrics and Gynaecology, University Medical Centre Auckland, Auckland, New Zealand.
authors.forename: L
authors.initials: L
authors.lastname: McCowan
authors.affiliation: Obstetrics and Gynaecology, Stanford University Medical School, Stanford, CA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lyell
authors.affiliation: Obstetrics and Gynaecology, Stanford University Medical School, Stanford, CA, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: El-Sayed
authors.affiliation: Obstetrics and Gynaecology, University of Washington, Washington, DC, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Carr
authors.affiliation: Obstetrics and Gynaecology, University of Washington, Washington, DC, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Clark
authors.affiliation: Obstetrics and Gynaecology, National University of Malaysia Medical Center, Cheras, Malaysia.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Mahdy
authors.affiliation: Obstetrics and Gynaecology, National University of Malaysia Medical Center, Cheras, Malaysia.
authors.forename: M
authors.initials: M
authors.lastname: Uma
authors.affiliation: Obstetrics and Gynaecology, Trakya University, Edime, Turkey.
authors.forename: N C
authors.initials: NC
authors.lastname: Sayin
authors.affiliation: Obstetrics and Gynaecology, Trakya University, Edime, Turkey.
authors.forename: G F
authors.initials: GF
authors.lastname: Varol
authors.affiliation: School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
authors.forename: B W
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Obstetrics and Gynaecology, University Medical Centre Utrecht, Utrecht, The Netherlands. m.a.oudijk@amc.nl.|Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands. m.a.oudijk@amc.nl.
authors.forename: M A
authors.initials: MA
authors.lastname: Oudijk
mesh_terms: D000328:Adult; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000401:mortality / Q000517:prevention & control; D009543:Nifedipine / Q000627:therapeutic use*; D066087:Perinatal Death / Q000517:prevention & control; D054238:Perinatal Mortality; D011247:Pregnancy; D047928:Premature Birth / Q000401:mortality / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D015145:Tocolysis / Q000379:methods*; D015149:Tocolytic Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015149:Tocolytic Agents; D009543:Nifedipine
keywords: Individual participant data meta-analysis; maintenance tocolysis; nifedipine; outcome; preterm birth