Neurodevelopmental Consequences of Preterm Isolated Cerebellar Hemorrhage: A Systematic Review

Hortensius, Lisa M.; Dijkshoorn, Aicha B. C.; Ecury-Goossen, Ginette M.; Steggerda, Sylke J.; Hoebeek, Freek E.; Benders, Manon J. N. L.; Dudink, Jeroen

doi:10.1542/peds.2018-0609

Cited by 52 publications

(54 citation statements)

References 42 publications

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“…This is likely in part due to poor documentation of perinatal resuscitation events and limited accessibility to adequate neonatal resuscitation. We found that the prevalence of cerebellar haemorrhage (1.7%) and cPVL (2.4%) were comparable with expected rates from HICs; there are no comparable data currently available from LICs in Africa (32) .…”

Section: Risk Factorsmentioning

confidence: 41%

Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: The IVHU study

MacLeod

Paulson²,

Okalany

et al. 2020

Preprint

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Background Globally, 15 million neonates are born prematurely every year, over half in low income countries (LICs). Premature and low birth weight neonates have a higher risk of intraventricular haemorrhage (IVH). There are minimal data regarding IVH in sub-Saharan Africa. This study aimed to examine the incidence, severity and timing of and modifiable risk factors for IVH amongst low-birth-weight neonates in Uganda.Methods This is a prospective cohort study of neonates with birthweights of ≤2000g admitted to a neonatal unit (NNU) in a regional referral hospital in eastern Uganda. Maternal data were collected from interviews and medical records. Neonates had cranial ultrasound (cUS) scans on the day of recruitment and days 3, 7 and 28 after birth. Risk factors were tabulated and are presented alongside odds ratios (ORs) and adjusted odds ratios (aORs) for IVH incidence. Outcomes included incidence, timing and severity of IVH and 28-day survival. Results Overall, 120 neonates were recruited. IVH was reported in 34.2% of neonates; 19.2% had low grade (Papile grades 1-2) and 15% had high grade (Papile grades 3-4). Almost all IVH (90.2%) occurred by day 7, including 88.9% of high grade IVH. Of those with known outcomes, 70.4% (81/115) were alive on day 28 and survival was not associated with IVH. We found that vaginal delivery, gestational age (GA) <32 weeks, resuscitation in the NNU and being small for gestational age (SGA, <10th centile) increased the odds of IVH. Of the 6 neonates who received 2 doses of antenatal steroids, none had IVH. Conclusion In this resource limited NNU in eastern Uganda, more than a third of neonates born weighing ≤2000g had an IVH and the majority of these occurred by day 7. We found that vaginal birth, earlier gestation, being SGA and need for resuscitation after admission to the NNU increased the risk of IVH. This study had a high rate of SGA neonates and the risk factors and relationship of these factors with IVH in this setting needs further investigation. The role of antenatal steroids in the prevention of IVH in LICs also needs urgent exploration.

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Section: Risk Factorsmentioning

confidence: 41%

Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: The IVHU study

MacLeod

Paulson²,

Okalany

et al. 2020

Preprint

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“…We found the most significant case-cohort differences in the CbH infants with vermis involvement. Interestingly, a recent systematic review revealed that damage in the vermis is associated with severe neurodevelopmental disability in multiple outcome domains 16 . Vermal cerebellar cortex projects to the fastigial nucleus from which axons cross at the decussation and project to the contralateral intralaminar, ventromedial and mediolateral geniculate nuclei of the thalamus and subsequently diffusely project to layers of the contralateral cerebral cortex 51,52 .…”

Section: Discussionmentioning

confidence: 99%

“…risk factors, these results suggest that neonatal cerebellar damage make them especially vulnerable for the development of neurodevelopmental defects. This incidence was most seen in infants with vermis involvement (87-93%) and large bleed (46-82%) 16 . Indeed, studies show a strong link between neonatal CbH and autism 14,[17][18][19] .…”

mentioning

confidence: 96%

Preterm infants with isolated cerebellar hemorrhage show bilateral cortical alterations at term equivalent age

Dijkshoorn

Turk

Hortensius

et al. 2020

Sci Rep

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the cerebellum is connected to numerous regions of the contralateral side of the cerebrum. Motor and cognitive deficits following neonatal cerebellar hemorrhages (CbH) in extremely preterm neonates may be related to remote cortical alterations, following disrupted cerebello-cerebral connectivity as was previously shown within six CbH infants. In this retrospective case series study, we used MRI and advanced surface-based analyses to reconstruct gray matter (GM) changes in cortical thickness and cortical surface area in extremely preterm neonates (median age = 26; range: 24.9-26.7 gestational weeks) with large isolated unilateral CbH (N = 5 patients). Each CbH infant was matched with their own preterm infant cohort (range: 20-36 infants) based on sex and gestational age at birth. On a macro level, our data revealed that the contralateral cerebral hemisphere of CbH neonates did not show less cortical thickness or cortical surface area than their ipsilateral cerebral hemisphere at term. None of the cases differed from their matched cohort groups in average cortical thickness or average cortical surface area in the ipsilateral or contralateral cerebral hemisphere. On a micro (i.e. vertex) level, we established high variability in significant local cortical GM alteration patterns across case-cohort groups, in which the cases showed thicker or bigger volume in some regions, among which the caudal middle frontal gyrus, insula and parahippocampal gyrus, and thinner or less volume in other regions, among which the cuneus, precuneus and supratentorial gyrus. This study highlights that cerebellar injury during postnatal stages may have widespread bilateral influence on the early maturation of cerebral cortical regions, which implicate complex cerebello-cerebral interactions to be present at term birth. The cerebellum is fundamental for cognitive and coordinated motor function, varying from sensorimotor mapping to language regulation (as reviewed by Caligiore et al.) 1. Pioneering work in both animal and human studies has established that the cerebellum collaborates with the cerebral cortex and sends output to, and receives input from, contralateral cortical areas via enclosed-loops 2-5 , In human these projection areas include multiple higher-order cerebral regions, such as the dorsolateral prefrontal cortex, the parietal and superior temporal lobes 6-8. Cerebello-cerebral loops are thought to be anatomically separated and involved in distinct functional processes 1,9. Many of these efferent and afferent connections have been identified as early as term-equivalent age (TEA) in preterm infants 10-12. Cerebellar hemorrhage (CbH) is a common neonatal complication with an ultrasound-detected incidence of 7.6% in extremely preterm infants (gestational age at birth <28 weeks) 13. In general the most immature and the sickest children are at a higher risk for developing CbH 14,15 , The actual incidence, however, may be higher as it has likely been underdiagnosed clinically. A recent review demonstrates that between 43% and 75% of t...

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“…In infants born extremely preterm (i.e. below 28 weeks of gestation) a clear association was found between early cerebellar injury and long-term behavioural problems (10,13).…”

Section: Introductionmentioning

confidence: 99%

Uneven distribution of Purkinje cell injury in the cerebellar vermis of term neonates with hypoxic-ischemic encephalopathy

Annink

Leeuwen

et al. 2020

Preprint

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Introduction:In term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxicischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated. The aim of this study was to determine the distribution of PC injury in the cerebellar vermis of term born neonates with HIE. Methods:Term born neonates with HIE that underwent post-mortem autopsy of the cerebellar vermis were included.Haematoxylin & Eosin (H&E) stained sections of the vermis were used to determine total PC count and morphology (normal, abnormal or non-classified) at the bases and crown of the folia and of the lobules in both the anterior and posterior lobes. Differences in PC count and PC morphology between the anterior and posterior lobe and between the bases and crown were calculated using the paired samples T-test or Wilcoxon-signed rank test. Results:The total number of PCs were significantly higher at the crown compared to the bases (p<0.001) irrespective of the precise location. Besides, PCs at the bases more often had an abnormal morphology. No significant difference between the total number of PCs in the anterior and posterior lobe was observed. Conclusion:The abnormal PC count and morphology in term neonates with HIE resembles supratentorial ulegyria.

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Neurodevelopmental Consequences of Preterm Isolated Cerebellar Hemorrhage: A Systematic Review

Cited by 52 publications

References 42 publications

Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: The IVHU study

Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: The IVHU study

Preterm infants with isolated cerebellar hemorrhage show bilateral cortical alterations at term equivalent age

Uneven distribution of Purkinje cell injury in the cerebellar vermis of term neonates with hypoxic-ischemic encephalopathy

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