Association between preterm brain injury and exposure to chorioamnionitis during fetal life

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.

The Unifying Effects of Maternal-Placental-Fetal Axis Dysregulation on Neurodevelopment Following Infectious and Toxic In Utero Insults

“…In term infants with HI encephalopathy, the presence of CHORIO predicts limited responsiveness to hypothermia treatment (244,246). Indeed, recent neuroimaging studies of preterm infants with detailed placental histology and neonatal neuroimaging at term equivalent age show histological CHORIO is an independent antenatal risk factor for preterm brain injury (247). Additionally, placental abnormalities are an independent risk factor in the pathogenesis of perinatal stroke (223,224,(248)(249)(250) (221,(254)(255)(256)(257)(258)(259)(260)(261).…”

“…Indeed, numerous studies confirm decreased microstructure in the corpus callosum, cingulum, internal capsule, external capsule and cerebellum. Together with changes in the thalamus in preterm infants, these abnormalities correlate with poor outcome later in life, especially with respect to cognitive, behavioral, and motor performance (221,247,258,(291)(292)(293)(294)(295)(296). Like ZIKV, prenatal alcohol exposure, and neonatal abstinence syndrome, the brain injury associated with CHORIO and preterm birth is easily an expansive review topic in its own right, with numerous contributions from multidisciplinary investigative teams around the globe.…”

Placental Pathology and Stillbirth: A Review of the Literature and Guidelines for the Less Experienced

“…Confirmatory evidence of infection leading to stillbirth is not always possible as this requires seeing a fetal response within the lung parenchyma, for example. However, there is an association between the inflammatory response noted histologically and neurodevelopmental outcome in live born infants [30]. In such cases, clinical correlation becomes crucial and placental and fetal swabs should be sent fresh after delivery.…”

Human Umbilical Cord Blood Therapy Protects Cerebral White Matter from Systemic LPS Exposure in Preterm Fetal Sheep

“…Neuroinflammation can be characterised by inflammatory cell infiltration into the brain and activation of resident microglia and astrocytes, which can then lead to cell death and impaired white matter development [9,10]. Magnetic resonance imaging (MRI) studies indicate that cerebral microstructure is altered in preterm infants exposed to chorioamnionitis compared to age-matched controls, at term equivalent follow-up [11]. This includes disorganised white matter reflected in altered fibre density and complexity compared to those infants not exposed to chorioamnionitis [11].…”

“…Magnetic resonance imaging (MRI) studies indicate that cerebral microstructure is altered in preterm infants exposed to chorioamnionitis compared to age-matched controls, at term equivalent follow-up [11]. This includes disorganised white matter reflected in altered fibre density and complexity compared to those infants not exposed to chorioamnionitis [11]. These subtle changes to white matter microstructure contribute to life-long learning and behavioural deficits [12].…”