Abstract
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. In a cohort of 90 preterm infants with detailed placental histology and neonatal brain magnetic resonance imaging (MRI) data at term equivalent age, we used Tract-based Spatial Statistics (TBSS) to perform voxel-wise statistical comparison of fractional anisotropy (FA) data and computational morphometry analysis to compute the volumes of whole brain, tissue compartments and cerebrospinal fluid, to test the hypothesis that HCA is an independent antenatal risk factor for preterm brain injury. Twenty-six (29%) infants had HCA and this was associated with decreased FA in the genu, cingulum cingulate gyri, centrum semiovale, inferior longitudinal fasciculi, limbs of the internal capsule, external capsule and cerebellum (p < 0.05, corrected), independent of degree of prematurity, bronchopulmonary dysplasia and postnatal sepsis. This suggests that diffuse white matter injury begins in utero for a significant proportion of preterm infants, which focuses attention on the development of methods for detecting fetuses and placentas at risk as a means of reducing preterm brain injury.
Highlights
Preterm infants are susceptible to inflammation-induced white matter injury but the exposures that lead to this are uncertain
Preterm infants with Histologic chorioamnionitis (HCA) had a lower GA at birth (p = 0.001), and the prevalence of prolonged rupture of membranes (>24 hours before delivery) was higher in this group (69% versus 8%)
By combining histological diagnosis of chorioamnionitis with quantitative brain magnetic resonance imaging (MRI), we have shown that inflammation in utero contributes to altered microstructure in major white matter tracts of preterm infants at term equivalent age
Summary
Preterm infants are susceptible to inflammation-induced white matter injury but the exposures that lead to this are uncertain. Infants had HCA and this was associated with decreased FA in the genu, cingulum cingulate gyri, centrum semiovale, inferior longitudinal fasciculi, limbs of the internal capsule, external capsule and cerebellum (p < 0.05, corrected), independent of degree of prematurity, bronchopulmonary dysplasia and postnatal sepsis This suggests that diffuse white matter injury begins in utero for a significant proportion of preterm infants, which focuses attention on the development of methods for detecting fetuses and placentas at risk as a means of reducing preterm brain injury. Adverse outcome is strongly associated with a phenotype that combines diffuse white matter injury and reduced connectivity of developing neural systems apparent on neonatal brain magnetic resonance imaging (MRI), with cognitive impairment and educational under-attainment in childhood[2,3,4,5] This phenotype is partly explained by co-morbidities such as bronchopulmonary dysplasia (BPD)[6] and postnatal sepsis[7], and is influenced by nutritional[8] and genetic factors[9]. Some of these uncertainties may be attributable to study designs that have used variable case definitions (clinical or histopathological diagnostic criteria), and many studies were conducted before the era of quantitative neonatal brain MRI for defining cerebral outcome
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