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Published on: November 20, 2015
Association of fetal inflammatory response with brain MRI findings and neurodevelopmental outcomes in preterm infants
Lynn Bitar1, Imran N Mir2, Michelle Machie1
1Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Medical Center, Dallas, TX, USA.
Insights
Fetal inflammatory response (FIR) in preterm infants is linked to brain abnormalities and impacts neurodevelopment at two years. Severe FIR poses a greater risk, with MRI findings partially explaining the link between inflammation and later cognitive/language outcomes.
Area of Science:
- Neonatal research
- Neuroscience
- Developmental pediatrics
Background:
- Fetal inflammatory response (FIR), a marker of intrauterine inflammation, is linked to adverse outcomes in extremely preterm infants.
- The long-term neurodevelopmental impact of FIR remains underexplored.
- Understanding FIR's role is crucial for improving outcomes in high-risk neonates.
Purpose of the Study:
- To assess the relationship between FIR severity and neurodevelopmental outcomes at two years in infants born before 29 weeks' gestation.
- To examine if term-equivalent MRI brain abnormalities are associated with these outcomes.
- To investigate the mediating role of MRI findings in the FIR-neurodevelopmental outcome relationship.
Main Methods:
- Prospective cohort study of 93 preterm infants (<29 weeks' gestation).
- Standardized placental histopathology for FIR, term-equivalent brain MRI (Kidokoro system), and Bayley-III assessments at two years.
- Multivariable regression models adjusted for gestational age to analyze associations.
Main Results:
- FIR was present in 52% of infants.
- FIR was associated with higher global brain abnormality scores on MRI, primarily white matter injury.
- FIR correlated with differences in cognitive and language outcomes at two years; MRI findings partially mediated these associations.
Conclusions:
- Placental FIR is associated with early brain MRI abnormalities and neurodevelopmental outcomes in extremely preterm infants.
- Severe FIR may confer a disproportionate risk, indicating a biphasic relationship with neurodevelopment.
- Early brain injury, particularly white matter injury, partially mediates the link between intrauterine inflammation and later cognitive/language development.
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. To assess the relationship between FIR severity and neurodevelopmental outcomes at two years in infants born <29 weeks' gestation and to examine whether term-equivalent MRI brain abnormalities are associated with these outcomes.
Methods:
In this prospective cohort study, 93 preterm infants underwent standardized placental histopathologic assessment for FIR, term-equivalent brain MRI scored using the Kidokoro system, and Bayley-III assessments at two years. Primary analyses compared infants with no FIR versus any FIR. Stratified analyses by FIR severity (Stage 1 vs ≥Stage 2) were conducted as secondary, exploratory analyses. Multivariable linear regression models adjusted for gestational age were used to assess associations among FIR, MRI findings, and neurodevelopmental scores. Exploratory attenuation analyses were performed to assess whether MRI abnormalities influenced observed associations.
Results:
Among 93 infants included in the analysis, FIR was present in 52%. Compared with infants without FIR, those with FIR had higher global brain abnormality scores on term-equivalent MRI, driven primarily by white matter injury. In adjusted models, FIR was associated with differences in cognitive and language outcomes at two years. Exploratory stratified analyses suggested heterogeneity by FIR severity; MRI abnormalities attenuated associations between FIR and neurodevelopmental outcomes, suggesting that early brain injury may represent an important correlate along the pathway linking inflammation and later development.
Conclusions:
In extremely preterm infants, placental FIR is associated with early brain MRI abnormalities and neurodevelopmental outcomes at two years. These findings highlight the importance of intrauterine inflammation as an early biologic exposure while underscoring the contribution of cumulative prenatal and postnatal factors to brain injury and long-term development. Larger studies incorporating detailed postnatal inflammatory trajectories are needed to confirm these associations and clarify underlying mechanisms.
Impact:
Demonstrates that severity of placental fetal inflammatory response is associated with neurodevelopmental outcomes at two years of age in extremely preterm infants Identifies a biphasic relationship between FIR severity and neurodevelopment, underscoring that severe intrauterine inflammation may confer disproportionate risk compared with milder inflammatory exposure Provides evidence that term-equivalent brain MRI abnormalities, particularly white matter injury, partially mediate the association between intrauterine inflammation and later cognitive and language development.
