primary outcome:
Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes
We chose primary outcomes to be most representative of the clinically important measures of effectiveness and safety, including serious outcomes, for the women and their fetuses/infants, the infant in early childhood (age two to less than five years), the infant in mid‐ to late childhood (age five to less than 18 years) and the infant as an adult. These outcomes were changed from the previous version of the review after first identifying outcomes considered of clinical importance by the review authors, refining their definitions by discussion among the review authors, and ranking their importance using the criteria described in the GRADE handbook in Types of outcome measures. The changes to outcome descriptions are summarised in the Differences between protocol and review section.Primary outcomes were predominantly focused on neonatal morbidity and mortality. Seven trials used a composite primary outcome incorporating both neonatal death, either RDS or severe RDS and other measures of neonatal morbidity (Aghajafari 2002; Garite 2009; Guinn 2001; Mazumder 2008; Murphy 2008; Peltoniemi 2007; Wapner 2006). Crowther 2006 reported primary outcomes of RDS, lung disease severity, measures of respiratory support and growth measurements. For TEAMS 1999, the primary outcomes were neonatal death and neurodevelopmental delay at age two years (corrected for gestational age at birth). Aghajafari 2002 reported primary outcomes focussed on the rate of recruitment over a 12‐month period, risk of complications requiring discontinuation of study treatment, and measures of maternal and fetal HPA function following birth. The primary outcomes for McEvoy 2002 and McEvoy 2010 were measures of lung function: functional residual capacity and respiratory compliance.All trials had a range of secondary outcomes of clinical relevance.At early childhood follow‐up, primary outcomes varied by trial. For Crowther 2006, the prespecified primary outcomes were survival at two years' corrected age free of major neurodisability (defined as survival free of moderate or severe disability); and body size (weight, height and head circumference). For Murphy 2008, the primary outcome was death or the presence of neurological impairment at 18 to 24 months' corrected age. Neurological impairment was defined as the presence of cerebral palsy or cognitive delay. For Peltoniemi 2007, the power analysis at follow‐up was based on survival without neurodevelopmental impairment. For Wapner 2006, the power analysis was based on the prespecified developmental outcome of the Bayley Mental Developmental Index score. Two studies performed follow‐up in mid‐childhood (Crowther 2006; Murphy 2008). For Crowther 2006, the primary outcome for mid‐childhood follow‐up was survival free of any neurosensory disability at six to eight years' corrected age. For Murphy 2008, the primary outcome for mid‐childhood follow‐up was a composite of death or survival with a neurodevelopmental disability at five years of age. Five trials reported data in full for early childhood follow‐up, and we included these in the meta‐analysis (Crowther 2006; Murphy 2008; Peltoniemi 2007; TEAMS 1999; Wapner 2006). The outcome total deaths after randomisation up to early childhood follow‐up used all fetuses randomised as the denominator. Denominators for all other analyses were defined as all babies randomised minus those children for whom there were no outcome data available. Two trials reported data for children in mid‐ to late childhood (Crowther 2006; Murphy 2008). The outcome total deaths after randomisation up to mid‐ to late childhood follow‐up used all fetuses randomised as the denominator. Denominators for all other analyses were defined as all babies randomised minus those children for whom there was no outcome data available. No trials reported data for follow‐up into adulthood.