title: Enrollment of extremely low birth weight infants in a clinical research study may not be representative.
abstract: OBJECTIVE
  The Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT) antenatal consent study demonstrated that mothers of infants enrolled in the SUPPORT trial had significantly different demographics and exposure to antenatal steroids compared with mothers of eligible, but not enrolled infants. The objective of this analysis was to compare the outcomes of bronchopulmonary dysplasia, severe retinopathy of prematurity, severe intraventricular hemorrhage or periventricular leukomalacia (IVH/PVL), death, and death/severe IVH/PVL for infants enrolled in SUPPORT in comparison with eligible, but not enrolled infants.
  
  
  METHODS
  Perinatal characteristics and neonatal outcomes were compared for enrolled and eligible but not enrolled infants in bivariate analyses. Models were created to test the effect of enrollment in SUPPORT on outcomes, controlling for perinatal characteristics.
  
  
  RESULTS
  There were 1316 infants enrolled in SUPPORT; 3053 infants were eligible, but not enrolled. In unadjusted analyses, enrolled infants had significantly lower rates of death before discharge, severe IVH/PVL, death/severe IVH/PVL (all < 0.001), and bronchopulmonary dysplasia (P = .003) in comparison with eligible, but not enrolled infants. The rate of severe retinopathy of prematurity was not significantly different. After adjustment for perinatal factors, enrollment in the trial was not a significant predictor of any of the tested clinical outcomes.
  
  
  CONCLUSIONS
  The results of this analysis demonstrate significant outcome differences between enrolled and eligible but not enrolled infants in a trial using antenatal consent, which were likely due to enrollment bias resulting from the antenatal consent process. Additional research and regulatory review need to be conducted to ensure that large moderate-risk trials that require antenatal consent can be conducted in such a way as to ensure the generalizability of results.
authors.affiliation: University of California at San Diego, San Diego, California, USA. wrich@ucsd.edu
authors.forename: Wade
authors.initials: W
authors.lastname: Rich
authors.forename: Neil N
authors.initials: NN
authors.lastname: Finer
authors.forename: Marie G
authors.initials: MG
authors.lastname: Gantz
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Newman
authors.forename: Angelita M
authors.initials: AM
authors.lastname: Hensman
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Hale
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Auten
authors.forename: Kurt
authors.initials: K
authors.lastname: Schibler
authors.forename: Roger G
authors.initials: RG
authors.lastname: Faix
authors.forename: Abbot R
authors.initials: AR
authors.lastname: Laptook
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Yoder
authors.forename: Abhik
authors.initials: A
authors.lastname: Das
authors.forename: Seetha
authors.initials: S
authors.lastname: Shankaran
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000328:Adult; D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D004374:Ductus Arteriosus, Patent / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D004608:Eligibility Determination; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D007969:Leukomalacia, Periventricular / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D008297:Male; D015999:Multivariate Analysis; D018579:Patient Selection; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods; D012016:Reference Values; D012178:Retinopathy of Prematurity / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013256:Steroids / Q000008:administration & dosage / Q000009:adverse effects*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D013256:Steroids