We aimed to test the hypothesis that determinants of the perinatal clinical exposome related to the underlying etiology of
premature birth (PTB) impact differently on select neonatal outcomes. We conducted a prospective longitudinal study of 377 singleton preterm neonates [gestational age (GA) at birth: 23-34 weeks] separated into three distinct contemporaneous newborn cohorts: i) spontaneous PTB in the setting of intra-amniotic
infection/
inflammation (yes-IAI, n = 116); ii) spontaneous PTB in the absence of IAI (no-IAI, n = 130), and iii) iatrogenic PTB for
preeclampsia (iPTB-PE, n = 131). Newborns (n = 372) were followed until death or discharge. Amniotic fluid
defensins 1&2 and calgranulins A&C were used as
biomarkers of IAI. An algorithm considering cord blood
interleukin-6 (IL-6) and
haptoglobin (Hp switch-on) was used to assess fetal exposure to IAI. Intraventricular
hemorrhage (IVH),
periventricular leukomalacia (PVL),
necrotizing enterocolitis (NEC),
bronchopulmonary dysplasia (BPD),
retinopathy of prematurity (ROP), early-onset neonatal (EONS) and late-onset (LOS)
sepsis, death. Independent risk factors for adverse outcomes were: i) IVH (n = 53): histologic
chorioamnionitis, GA,
fetal growth restriction, male sex, Hp switch-on; ii) PVL (n = 11): cord blood IL-6; iii) NEC (n = 25), GA; iv) BPD (n = 53):
ventilator support, need for
surfactant, GA; v) ROP (n = 79):
ventilator support, Hp switch-on, GA; vi) fetal and
neonatal death (n = 31): GA, amniotic fluid IL-6; vii) suspect EONS (n = 92): GA, Hp switch-on; viii) LOS (n = 81): GA. Our findings are applicable to pregnancies delivered between 23 and 34 weeks' gestation in the setting of IAI and PE, and suggest that GA and inflammatory intrauterine environment play key roles in occurrence of IVH, PVL, ROP, death, EONS and LOS. Postnatal determinants seem to play major role in NEC and BPD.