671 - Neonatal Brain Maturation Relates to Necrotizing Enterocolitis (NEC) and Predicts Childhood Neurodevelopmental Outcomes in Very Preterm Infants

Publication Number: 1648.671

Maysaa Banjari, University of Toronto Temerty Faculty of Medicine, Toronto, ON, Canada; Thiviya Selvanathan, University of British Columbia, Vancouver, BC, Canada; Vann Chau, The Hospital for Sick Children, Toronto, ON, Canada; Stephanie Au-Young, The Hospital for Sick Children, Toronto, ON, Canada; Steven Ufkes, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Cecil M. Y.. Chau, University of British Columbia, Vancouver, BC, Canada; Linh G. Ly, The Hospital for Sick Children, Toronto, ON, Canada; Helen Branson, The Hospital for Sick Children, Toronto, ON, Canada; Edmond N. Kelly, University of Toronto Temerty Faculty of Medicine, Toronto, ON, Canada; Ruth Grunau, Unversity of British Columbia, Vancouver, BC, Canada; Steven P,.. Miller, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Ting Guo, The Hospital for Sick Children, Toronto, ON, Canada

Background: Necrotizing enterocolitis (NEC) is a significant early-life complication, and related to brain injury and neurodevelopmental abnormality in very preterm infants. Associations between NEC and abnormal white matter (WM) maturation were found at term-equivalent age (TEA). However, if brain changes at an earlier age relate to NEC and how they are associated with childhood outcomes are unclear.

Objective: assess brain maturation across WM regions at early-life and TEA using quantitative fractional anisotropy (FA) between infants with and without proven NEC (Bell stage ≥ II), and (2) determine how neonatal brain maturation is associated with neurodevelopmental outcomes at 4.5 years in preterm infants considering other factors.

Design/Methods: A multi-site prospective cohort of very preterm infants (24-32 weeks' gestation) were included. FA values from seven WM regions were quantified on early-life and TEA brain MRI. Detailed clinical data were collected. Cognitive and motor outcomes at 4.5 years were assessed using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) and Movement ABC (MABC) respectively. FA values between infants with and without proven NEC were compared. Generalized linear models (GLM) were used to investigate how NEC relates to brain maturation at early-life and at TEA, adjusting for birth gestational age, post-menstrual age at MRI, brain injury, severity of illness, bronchopulmonary dysplasia, and multiple infection. The associations of neonatal FA with cognitive and motor performances at 4.5 years were assessed using GLM, controlling NEC and other key factors.

Results: 326 very preterm infants (56% male) were included. FA values in several WM regions were significantly different between infants with and without proven NEC at TEA (Table 1). Interestingly, differences in FA within genu (p=0.002) and splenium (p=0.01) of corpus callosum (CC) were detected even at early-life. Proven NEC was associated with lower FA values within genu (early-life: p=0.048, TEA: p=0.001) and splenium (early-life: p=0.049, TEA: p=0.001). At early-life, FA in genu predicted WPPSI full scale IQ (ß=62.50, p=0.001), FA in genu (ß=64.62, p< 0.001) and splenium (ß=50.94, p< 0.017) predicted MABC score at 4.5 years (Figure 1).

Conclusion(s): NEC contributes to abnormal brain maturation reflected by lower FA in CC measured even at early-life, which strongly predict childhood cognitive and motor outcomes. FA values in CC can serve as an early biomarker in preterm infants.

Table 1. Unadjusted Fractional Anisotropy (FA) in Major White Matter Regions in Infants With and Without Proven NEC


Figure 1. Fractional Anisotropy Values in Corpus Callosum at Early-Life Predict Neurodevelopmental Outcomes at 4.5 Years in Very Preterm Infants