Abstract
The aim of this review is to gather the most recent data on the association between intrauterine inflammation and neurodevelopmental disorders in preterm infants. Two major methodological challenges will be emphasized: first, the heterogeneity of definitions of intrauterine inflammation; and second, the heterogeneity of study populations, in which the causes of preterm birth (spontaneous labor, preterm premature rupture of membranes, maternal hypertensive disorders, etc.) are not always distinguished. These elements introduce a risk of confounding bias and partly explain the divergence between studies. In the short term, intrauterine inflammation is associated with an increased risk of early-onset sepsis and necrotizing enterocolitis. However, the effects on respiratory and neurological outcomes are less clear, and whether an association exists remains controversial. In the longer term, in populations homogeneous with respect to the cause of prematurity, clinical chorioamnionitis has been associated with an increased risk of cerebral palsy at 2 years, a risk further amplified when combined with histological chorioamnionitis. However, this risk of cerebral palsy does not appear to persist beyond 5 years, and no major association has been reported on cognitive, sensory, coordination, or behavioral functions. Regarding isolated histological chorioamnionitis, most studies conducted on homogeneous populations do not report an association with neurodevelopmental disorders. Nevertheless, some suggest that severe inflammation, particularly in the presence of a fetal inflammatory response, may increase the risk of neurodevelopmental impairment. In conclusion, while intrauterine inflammation is associated with increased neonatal morbidity, its long-term impact on neurodevelopment appears limited and dependent on the severity of the inflammation. These findings highlight the importance of conducting longitudinal studies on homogeneous populations to refine our understanding of developmental trajectories in preterm infants.