Enrollment of Extremely Low Birth Weight Infants in a Clinical Research Study May Not Be Representative

• Published in: Pediatrics (Evanston) Vol. 129; no. 3; pp. 480 - 484
• Main Authors: RICH, Wade, FINER, Neil N, YODER, Bradley A, DAS, Abhik, SHANKARAN, Seetha, GANTZ, G, NEWMAN, Nancy S, HENSMAN, Angelita M, HALE, Ellen C, AUTEN, Kathy J, SCHIBLER, Kurt, FAIX, Roger G, LAPTOOK, Abbot R
• Format: Journal Article
• Language: English
• Published: Elk Grove Village, IL American Academy of Pediatrics 01-03-2012
• Subjects: Abnormalities, Drug-Induced - diagnosis; Abnormalities, Drug-Induced - mortality; Abnormalities, Drug-Induced - therapy; Adult; Babies; Biological and medical sciences; Birth weight; Birth weight, Low; Bronchopulmonary dysplasia; Bronchopulmonary Dysplasia - diagnosis; Bronchopulmonary Dysplasia - mortality; Bronchopulmonary Dysplasia - therapy; Care and treatment; Clinical trials; Demographics; Diagnosis; Disease; Diseases of mother, fetus and pregnancy; Ductus Arteriosus, Patent - diagnosis; Ductus Arteriosus, Patent - mortality; Ductus Arteriosus, Patent - therapy; Eligibility Determination; Evaluation Studies as Topic; Female; General aspects; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases - diagnosis; Infant, Premature, Diseases - mortality; Infant, Premature, Diseases - therapy; Infants; Intraventricular hemorrhage; Leukomalacia, Periventricular - diagnosis; Leukomalacia, Periventricular - mortality; Leukomalacia, Periventricular - therapy; Low birth weight; Male; Medical sciences; Multivariate Analysis; Patient Selection; Pediatrics; Pregnancy; Pregnancy. Fetus. Placenta; Prenatal Care - methods; Prevention; Reference Values; Retinopathy of Prematurity - diagnosis; Retinopathy of Prematurity - mortality; Retinopathy of Prematurity - therapy; Risk Assessment; Sensitivity and Specificity; Steroids - administration & dosage; Steroids - adverse effects; Survival Analysis; Treatment Outcome; Human; Premature; Corticosteroid; Pediatrics; Neonatal; Pregnancy disorders; Infant; Clinical research; clinical research/trials; Extremely low birthweight; Very low birthweight; Symptomatology; Newborn diseases; Newborn; Prematurity; antenatal steroids; Informed consent; Clinical trial
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2011-2121

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.
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.
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.
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.