68 - Impact of Severe Fetal Inflammatory Response on Neurodevelopmental Outcomes in Preterm Brain Injury

Publication Number: 1061.68

Lynn Bitar, University of Texas Southwestern Medical School, Dallas, TX, United States; Imran Mir, University of Texas Southwestern Medical School, Dallas, TX, United States; Michelle Machie, University of Texas Southwestern Medical School, Dallas, TX, United States; Pollieanna Sepúlveda, UT Southwestern Medical Center, Dallas, TX, United States; Jennifer Joukhdar, University of Texas Southwestern Medical School, Dallas, TX, United States; Lina Chalak, Childrens Health Dallas UT Southwestern, DALLAS, TX, United States

Background: Fetal inflammatory response (FIR), a histological indicator of intrauterine inflammation, is associated with adverse outcomes in extremely preterm infants. While FIR has been linked to early brain injury, its long-term impact on neurodevelopment remains underexplored.

Objective: To assess the relationship between FIR severity and neurodevelopmental outcomes at two years in infants born < 29 weeks’ gestation and to examine whether MRI brain abnormalities mediate this association.

Design/Methods: In this prospective cohort study, 93 preterm infants underwent standardized placental pathology classified according to the Amsterdam criteria, term-equivalent brain MRI scored via the Kidokoro system, and Bayley-III assessments at two years. The primary outcome was defined as cognitive score < 85. FIR was classified into three categories: no FIR, Stage 1 (mild), and ≥Stage 2 (severe). Multivariate regression assessed associations between FIR, MRI findings, and neurodevelopmental scores.

Results: FIR was present in 52% of the cohort. Infants with Stage 1 FIR had significantly higher cognitive (98.8 ± 5.2) and language (95.0 ± 16.9) scores than those with no FIR or ≥Stage 2 FIR (p < 0.01), suggesting a biphasic relationship. Severe FIR (≥Stage 2) was associated with elevated MRI global brain abnormality scores, particularly in white matter. Mediation analysis indicated that brain injury partially mediated the relationship between FIR and neurodevelopmental scores.

Conclusion(s): FIR severity in preterm infants demonstrates a complex relationship with neurodevelopment, where mild inflammation may be neuroprotective and severe inflammation detrimental. Early MRI may help identify at-risk infants, and findings underscore the need for stratified neuroprotective approaches. Future studies should explore underlying mechanisms and long-term outcomes.

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