Abstract
Objective To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal
mortality and morbidities by gestational age (GA) for use in preterm labor clinical
trials.
Study Design A descriptive, retrospective analysis of the Medical University of South Carolina
Perinatal Information System database was conducted. Neonatal morbidities were assessed
for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental
impairment, frequency, and association with GA in a mother–neonate linked cohort,
comprising women with uncomplicated singleton pregnancies delivered at ≥24 weeks'
GA.
Results Among 17,912 mother–neonate pairs, neonates were at a risk of numerous severe but
infrequent morbidities. Clinically important, predominantly rare events were combined
into a CE comprising neonatal mortality and morbidities, which decreased in frequency
with increasing GA. The highest CE frequency occurred at <31 weeks. High frequency
of respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis drove the
CE. Median length of hospital stay was longer at all GAs in those with the CE compared
with those without.
Conclusions Descriptive epidemiological assessment and clinical input were used to develop a
CE to measure neonatal benefit, comprising clinically meaningful outcomes. These empirical
data and CE allowed trials investigating tocolytics to be sized appropriately.
Keywords
neonatal benefit - composite endpoint - preterm birth - preterm labor - gestational
age - tocolytics
