Severe retinopathy of prematurity is associated with reduced cerebellar and brainstem volumes at term and neurodevelopmental deficits at 2 years

Drost, Femke J; Keunen, Kristin; Moeskops, Pim; Claessens, Nathalie H.P.; Kalken, Femke van; Išgum, Ivana; Voskuil-Kerkhof, Elsbeth S M; Groenendaal, Floris; Vries, Linda S. de; Termote, J.

doi:10.1038/pr.2018.2

Cited by 24 publications

(30 citation statements)

References 38 publications

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“… Sveinsdóttir et al (2018) showed a relation between ROP and lower cerebellar volume and lower unmyelinated white matter volume at TEA. Moreover, Drost et al (2018) showed an association between severe ROP and reduced cerebellar and brainstem volumes measured by automatic segmentation method at TEA. Both of those studies concluded to neurodevelopmental deficits at 2 years ( Drost et al, 2018 ; Sveinsdóttir et al, 2018 ).…”

Section: Discussionmentioning

confidence: 86%

“…Moreover, Drost et al (2018) showed an association between severe ROP and reduced cerebellar and brainstem volumes measured by automatic segmentation method at TEA. Both of those studies concluded to neurodevelopmental deficits at 2 years ( Drost et al, 2018 ; Sveinsdóttir et al, 2018 ). For medical teams that do not have these measurement techniques available, VSA is an easy to measure indicator in routine MRI.…”

Section: Discussionmentioning

confidence: 86%

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Visual Maturation at Term Equivalent Age in Very Premature Infants According to Factors Influencing Its Development

et al. 2018

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Introduction: Visual impairment is a concern in premature infants as perinatal factors may alter maturation during visual development. This observational study aimed at evaluating visual maturation at term equivalent age and factors associated with impaired visual maturation.Methods: Infants born before 32 weeks’ gestation were evaluated with routine brain MRI, visual acuity, refraction, fundus, and clinical eye examination. Environmental factors were collected from infant’s files.Results: Fifty-four infants (29.5 ± 1.7 weeks’ gestation, birth weight 1194 ± 288 g) were studied at term equivalent age. Visual acuity was higher in premature infants at term equivalent age than in a reference publication with the same method in term newborns at birth (1.54 ± 0.67 vs. 0.99 ± 0.40 cycles/degree, p = 0.008). In multivariate analysis, abnormal brain MRI was the only factor associated with visual acuity (r2= 0.203; p = 0.026). Incomplete retinal vascularization was observed in 29/53 of infants at term equivalent age and associated with MRI abnormalities of the posterior fossa (p = 0.027) and larger refractive sphere difference between both eyes (1.2 ± 0.8 vs. 0.6 ± 0.4 diopters; p = 0.0005). Retinopathy of prematurity was associated with indices of smaller cerebral volume (p = 0.035).Conclusion: Higher visual acuity in premature infants at term equivalent age than in term newborns at birth may be related to longer visual experience from birth. Lower visual acuity was correlated with abnormal MRI in preterm infants at term equivalent age.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 86%

Visual Maturation at Term Equivalent Age in Very Premature Infants According to Factors Influencing Its Development

et al. 2018

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“…In this cohort, we observed an independent association of systemic infection and NEC with several metabolic alterations in the developing cerebellum in the early postnatal period. Decreased white matter and cerebellar volumes on quantitative MRI has been reported in infants with any stage of ROP 40,41 but MR spectroscopic alterations are unknown. In our study, infants with ROP (stage 2 or higher) had lower NAA and Cr concentrations compared to those without ROP although the relationship lost statistical significance after adjusting for co-variates.…”

Section: Discussionmentioning

confidence: 98%

Third Trimester Cerebellar Metabolite Concentrations are Decreased in Very Premature Infants with Structural Brain Injury

Basu

Pradhan

Kapse

et al. 2019

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Advanced neuroimaging techniques have improved our understanding of microstructural changes in the preterm supratentorial brain as well as the cerebellum and its association with impaired neurodevelopmental outcomes. However, the metabolic interrogation of the developing cerebellum during the early postnatal period after preterm birth remains largely unknown. Our study investigates the relationship between cerebellar neurometabolites measured by proton magnetic spectroscopy (1H-MRS) in preterm infants with advancing post-menstrual age (PMA) and brain injury during ex-utero third trimester prior to term equivalent age (TEA). We prospectively enrolled and acquired high quality 1H-MRS at median 33.0 (IQR 31.6–35.2) weeks PMA from a voxel placed in the cerebellum of 53 premature infants born at a median gestational age of 27.0 (IQR 25.0–29.0) weeks. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentrations of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr). We noted positive correlations of cerebellar concentrations of NAA, Cho and Cr (Spearman correlations of 0.59, 0.64 and 0.52, respectively, p value < 0.0001) and negative correlation of Cho/Cr ratio (R −0.5, p value 0.0002) with advancing PMA. Moderate-to-severe cerebellar injury was noted on conventional magnetic resonance imaging (MRI) in 14 (26.4%) of the infants and were noted to have lower cerebellar NAA, Cho and Cr concentrations compared with those without injury (p value < 0.001). Several clinical complications of prematurity including necrotizing enterocolitis, systemic infections and bronchopulmonary dysplasia were associated with altered metabolite concentrations in the developing cerebellum. We report for the first time that ex-utero third trimester cerebellar metabolite concentrations are decreased in very preterm infants with moderate-to-severe structural cerebellar injury. We report increasing temporal trends of metabolite concentrations in the cerebellum with advancing PMA, which was impaired in infants with brain injury on MRI and may have early diagnostic and prognostic value in predicting neurodevelopmental outcomes in very preterm infants.

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“…Fetal growth restriction (FGR) complicates 5–10% of pregnancies and is associated with increased risks of perinatal morbidity and mortality (Bernstein et al., 2000). FGR is linked to adverse perinatal outcomes, including stillbirth, prematurity, and need for neonatal intensive care; as well as long-term adverse outcomes including metabolic syndromes, hypertension, and neurological deficits (Baschat, 2011; Mayer and Joseph, 2013; Albu et al., 2014; Drost et al., 2018). FGR is principally caused by placental insufficiency, which results in reduced utero-placental transfer of oxygen and nutrients to the developing fetus (Figueras and Gardosi, 2011).…”

Section: Introductionmentioning

confidence: 99%

Fetal Growth Restriction Alters Cerebellar Development in Fetal and Neonatal Sheep

et al. 2019

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Fetal growth restriction (FGR) complicates 5–10% of pregnancies and is associated with increased risks of perinatal morbidity and mortality. The development of cerebellar neuropathology in utero , in response to chronic fetal hypoxia, and over the period of high risk for preterm birth, has not been previously studied. Therefore, the objective of this study was to examine the effects of FGR induced by placental insufficiency on cerebellar development at three timepoints in ovine fetal and neonatal development: (1) 115 days gestational age (d GA), (2) 124 d GA, and (3) 1-day-old postnatal age. We induced FGR via single umbilical artery ligation (SUAL) at ~105 d GA in fetal sheep, term is ~147 d GA. Animals were sacrificed at 115 d GA, 124 d GA, and 1-day-old postnatal age; fetuses and lambs were weighed and the cerebellum collected for histopathology. FGR lambs demonstrated neuropathology within the cerebellum after birth, with a significant, ~18% decrease in the number of granule cell bodies (NeuN+ immunoreactivity) within the internal granular layer (IGL) and an ~80% reduction in neuronal extension and branching (MAP+ immunoreactivity) within the molecular layer (ML). Oxidative stress (8-OHdG+ immunoreactivity) was significantly higher in FGR lambs within the ML and the white matter (WM) compared to control lambs. The structural integrity of neurons was already aberrant in the FGR cerebellum at 115 d GA, and by 124 d GA, inflammatory cells (Iba-1+ immunoreactivity) were significantly upregulated and the blood-brain barrier (BBB) was compromised (Pearls, albumin, and GFAP+ immunoreactivity). We confirm that cerebellar injuries develop antenatally in FGR, and therefore, interventions to prevent long-term motor and coordination deficits should be implemented either antenatally or perinatally, thereby targeting neuroinflammatory and oxidative stress pathways.

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Severe retinopathy of prematurity is associated with reduced cerebellar and brainstem volumes at term and neurodevelopmental deficits at 2 years

Cited by 24 publications

References 38 publications

Visual Maturation at Term Equivalent Age in Very Premature Infants According to Factors Influencing Its Development

Visual Maturation at Term Equivalent Age in Very Premature Infants According to Factors Influencing Its Development

Third Trimester Cerebellar Metabolite Concentrations are Decreased in Very Premature Infants with Structural Brain Injury

Fetal Growth Restriction Alters Cerebellar Development in Fetal and Neonatal Sheep

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