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Effect of histologic chorioamnionitis on white matter development in preterm infants: a tract-based spatial statistics study

Presented at the Neonatal Society 2016 Spring Meeting.

Anblagan D1, Pataky R1, Evans MJ2, Sparrow S1, Piyasena C1, Telford EJ1, Semple SI1, Wilkinson AG3, Bastin ME1, Boardman JP1

1 University of Edinburgh, UK
2 Royal Infirmary of Edinburgh, UK
3 Royal Hospital for Sick Children, Edinburgh, UK

Background: Preterm infants are susceptible to inflammation-induced white matter injury but the exposures that lead to this are uncertain. Histologic chorioamnionitis (HCA) reflects intrauterine inflammation, can trigger a fetal inflammatory response, and is closely associated with premature birth. We processed neonatal brain magnetic resonance imaging (MRI) data using Tract-based Spatial Statistics (TBSS) (1) which enables voxel-wise comparison of fractional anisotropy (a marker of white matter integrity), to test the hypothesis that HCA is an independent antenatal risk factor for preterm brain injury.

Methods: Participants: 26 preterm infants born with HCA (defined in Redline et al) (2) at mean postmenstrual age (PMA) of 27 ± 6 weeks and 64 preterm infants born without HCA at mean PMA of 29 ± 3 weeks were scanned on a 3 T clinical scanner at term equivalent age (PMA 40 ± 1 weeks). All infants were scanned axially using a whole brain dMRI protocol consisting of 11 T2- and 64 diffusion-weighted (b = 750 s/mm2) single-shot spin echo EPI volumes with 2 mm isotropic voxels. Analysis: dMRI data were pre-processed using FSL tools and analyses were run based on a TBSS pipeline optimised for neonates (1). Statistical comparison between the groups born with and without HCA was performed with FSL’s Randomise using a general linear univariate model, with PMA at birth, PMA at scan and bronchopulmonary dysplasia (BPD) listed as covariates. All images were subject to family-wise error correction for multiple comparisons following threshold-free cluster enhancement and are shown at p < 0.05.

Results: Preterm infants exposed to HCA demonstrated decreased FA in the genu of the corpus callosum, cingulum cingulate gyri, centrum semiovale, inferior longitudinal fasciculi, anterior and posterior limbs of the internal capsule, external capsule and cerebellum (p < 0.05 corrected, Fig. on right: Mean FA skeleton (yellow) overlaid on the mean FA map in axial, coronal and sagittal planes. These regions represent voxels where there were no significant difference between infants born with or without chorioamnionitis. Voxels demonstrating significantly lower FA in the chorioamnionitis group are overlaid in blue.). Skeleton wide FA was 5% lower in preterm infants with HCA compared to infants born without this complication.

Effect of histologic chorioamnionitis on white matter development in preterm infants: a tract-based spatial statistics study

Conclusion: Chorioamnionitis is associated with diffuse white matter injury in preterm infants, and this is independent of known predictors for abnormal brain development after preterm birth.

Corresponding author: devasuda.anblagan@ed.ac.uk

1. Ball G, et al. (2010) Neuroimage 53: 94-102
2. Redline RW, et al. (2003) Ped and Develop Path 6: 435-488.

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