Hindbrain regional growth in preterm newborns and its impairment in relation to brain injury

Abstract

Premature birth globally affects about 11.1% of all newborns and is a risk factor for neurodevelopmental disability in surviving infants. Histology has suggested that hindbrain subdivisions grow differentially, especially in the third trimester. Prematurity-related brain injuries occurring in this period may selectively affect more rapidly developing areas of hindbrain, thus accompanying region-specific impairments in growth and ultimately neurodevelopmental deficits. The current study aimed to quantify regional growth of the cerebellum and the brainstem in preterm neonates (n=65 with individually multiple scans). We probed associations of the regional volumes with severity of brain injury. In neonates with no imaging evidence of injury, our analysis using a mixed-effect linear model showed faster growth in the pons and the lateral convexity of anterior/posterior cerebellar lobes. Different patterns of growth impairment were found in relation to early cerebral intraventricular hemorrhage and cerebellar hemorrhage (p<0.05), likely explaining different mechanisms through which neurogenesis is disrupted. The pattern of cerebellar growth identified in our study agreed excellently with details of cerebellar morphogenesis in perinatal development, which has only been observed in histological data. Our proposed analytic framework may provide predictive imaging biomarkers for neurodevelopmental outcome, enabling early identification and treatment of high-risk patients.

Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns

“…We have recently reported that cerebellar hemorrhage are associated with impaired cerebellar growth in preterm newborns. 22 Limperopoulos et al have shown that cerebellar injury in preterm newborns is associated with impaired growth of specific cerebral regions, 23 which in turn is associated with regional-specific functional deficits. 39 Taken together, these studies suggest that cerebellar hemorrhage may lead to neurodevelopmental disabilities through disruption of cerebellar-cortical connections secondary to impaired cerebellar growth.…”

“…A subset of this cohort was included in our prior study of the association between cerebellar hemorrhage and cerebellar volume (n=56). 22 Parental consent was obtained following a protocol approved by the UCSF Committee on Human Research.…”

“…13,15–17 MRI-detected cerebellar hemorrhage in premature newborns is associated with impaired cerebellar growth, 22 and thinning of the cerebral cortex, 23 as well as motor, cognitive and behavioral deficits in early childhood. 13,18,19 …”

NEOCIVET: Towards accurate morphometry of neonatal gyrification and clinical applications in preterm newborns

“…The effects upon brain growth may differ in the presence of different perinatal clinical conditions such as preterm birth (Padilla et al, 2015), low body weight at birth (Parikh et al, 2013), prematurity-related brain injuries (Kim et al, accepted for publication; Kim et al, 2016; Tam et al, 2011b), and the related treatments (Tam et al, 2011a). Cortical folding may also be impaired as a result of such clinical factors (Engelhardt et al, 2015).…”

The Vulnerable Newborn Brain: Imaging Patterns of Acquired Perinatal Injury

“…Using a variety of volumetric techniques, it has been shown that cerebellar growth is affected by supratentorial injury such as IVH, whereas WMI showed no association [27]. Evaluating the growth of the entire hindbrain, Kim et al [28] found that moderate-to-severe IVH did indeed slow growth and this was also seen with severe cerebellar hemorrhage.…”