Neonatal morbidity associated with late preterm and early term birth: the roles of gestational age and biological determinants of preterm birth

Background The aim of this study was to elucidate the role of gestational age in determining the risk of neonatal morbidity among infants born late preterm (34-36 weeks) and early term (37-38 weeks) compared with those born full term (39-41 weeks) by examining the contribution of gestational age within the context of biological determinants of preterm birth. Methods This was a retrospective cohort study. The sample included singleton live births with no major congenital anomalies, delivered at 34-41 weeks of gestation to London-Middlesex (Canada) mothers in 2002-11. Data from a city-wide perinatal database were linked with discharge abstract data. Multivariable models used modified Poisson regression to directly estimate adjusted relative risks (aRRs). The roles of gestational age and biological determinants of preterm birth were further examined using mediation and moderation analyses. Results Compared with infants born full term, infants born late preterm and early term were at increased risk for neonatal intensive care unit triage/admission [late preterm aRR = 6.14, 95% confidence interval (CI) 5.63, 6.71; early term aRR = 1.54, 95% CI 1.41, 1.68] and neonatal respiratory morbidity (late preterm aRR = 6.16, 95% CI 5.39, 7.03; early term aRR = 1.46, 95% CI 1.29, 1.65). The effect of gestational age was partially explained by biological determinants of preterm birth acting through gestational age. Moreover, placental ischaemia and other hypoxia exacerbated the effect of gestational age on poor outcomes. Conclusions Poor outcomes among infants born late preterm and early term are not only due to physiological immaturity but also to biological determinants of preterm birth acting through and with gestational age to produce poor outcomes.