Neonatal Cranial Ultrasound Findings among Infants Born Extremely Preterm: Associations with Neurodevelopmental Outcomes at 10 Years of Age

Campbell, Heather; Check, Jennifer; Kuban, Karl; Leviton, Alan; Joseph, Robert M.; Frazier, Jean A.; Douglass, Laurie M.; Roell, Kyle; Allred, Elizabeth N.; Fordham, Lynn Ansley; Hooper, Stephen R.; Jara, Hernán; Paneth, Nigel; Mokrova, Irina L.; Ru, Hongyu; Santos, Hudson P.; Fry, Rebecca C.

doi:10.1016/j.jpeds.2021.05.059

Cited by 17 publications

(12 citation statements)

References 56 publications

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“…These include immune response, apoptosis, metabolism, and hormone-related signaling in relation to echolucency and ventriculomegaly. These results are clinically relevant as cerebral white matter injury occurs in 12% of ELGAN survivors and is associated strongly with ASD ( Dean et al, 2016 ), cerebral palsy ( Kuban et al, 2009 ) and cognitive impairment ( Campbell et al, 2021 ).…”

Section: Discussionmentioning

confidence: 86%

“…Fourth, neonatal cranial ultrasound identifies only macroscopic white matter damage and is less sensitive than magnetic resonance imaging for detection of white matter damage ( Ciambra et al, 2013 ). Nevertheless, in the ELGAN study, the presence of either echolucency or ventricular enlargement was strongly associated with subsequent development of cerebral palsy ( Kuban et al, 2009 ), epilepsy ( Campbell et al, 2021 ), and cognitive impairment ( Campbell et al, 2021 ) and were the ultrasound lesions most predictive of neurodevelopmental impairments. Furthermore, we understand that the scope of neurodevelopment among ELGANs and other infants who survive preterm birth cannot be accounted for solely by the presence of structural brain abnormalities.…”

Section: Discussionmentioning

confidence: 97%

“…Among individuals born preterm, white matter damage is strongly associated with neurodevelopmental impairment, but specific treatment methods are not available for this disease. Among individuals born extremely preterm, neonatal cerebral white matter damage has been associated with an increased risk of autism spectrum disorder ( Dean et al, 2016 ), cognitive impairment, epilepsy, and cerebral palsy ( Campbell et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Placental transcriptional signatures associated with cerebral white matter damage in the neonate

Marable

Roell²,

Kuban³

et al. 2022

Front. Neurosci.

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Cerebral white matter is the most common anatomic location of neonatal brain injury in preterm newborns. Factors that predispose preterm newborns to white matter damage are understudied. In relation to studies of the placenta-brain-axis, dysregulated placental gene expression may play a role in preterm brain damage given its implication in programming early life origins of disease, including neurological disorders. There is a critical need to investigate the relationships between the placental transcriptome and white matter damage in the neonate. In a cohort of extremely low gestational age newborns (ELGANs), we aimed to investigate the relationship between the placental transcriptome and white matter damage as assessed by neonatal cranial ultrasound studies (echolucency and/or ventriculomegaly). We hypothesized that genes involved in inflammatory processes would be more highly expressed in placentas of ELGANs who developed ultrasound-defined indicators of white matter damage. Relative to either form of white matter damage, 659 placental genes displayed altered transcriptional profiles. Of these white matter damage-associated genes, largely distinct patterns of gene expression were observed in the study (n = 415/659 genes). Specifically, 381 genes were unique to echolucency and 34 genes were unique to ventriculomegaly. Pathways involved in hormone disruption and metabolism were identified among the unique echolucency or ventriculomegaly genes. Interestingly, a common set of 244 genes or 37% of all genes was similarly dysregulated in the placenta relative to both echolucency and ventriculomegaly. For this common set of white matter damage-related genes, pathways involved in inflammation, immune response and apoptosis, were enriched. Among the white matter damage-associated genes are genes known to be involved in Autism Spectrum Disorder (ASD) and endocrine system disorders. These data highlight differential mRNA expression patterning in the placenta and provide insight into potential etiologic factors that may predispose preterm newborns to white matter damage. Future studies will build upon this work to include functional measures of neurodevelopment as well as measures of brain volume later in life.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Placental transcriptional signatures associated with cerebral white matter damage in the neonate

Marable

Roell²,

Kuban³

et al. 2022

Front. Neurosci.

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“…At present, the types of brain injury in premature infants diagnosed by brain ultrasound mainly include periventricular intraventricular hemorrhage and periventricular leukomalacia. The ultrasonographic manifestations of periventricular intraventricular hemorrhage in different periods are as follows ( 20 ): ① Acute hemorrhage showed a moderate strong echo, thin edge, and clear boundary; ② 2–3 days later, if there was no fresh bleeding, the local echo of the hemorrhage was uniformly enhanced; ③ 7–10 days later, blood clots into the absorption period. There was no echo in the center of the clot, and the bleeding lesions were completely absorbed or formed cysts.…”

Section: Comparison Of Different Imaging Methods In the Diagnosis Of ...mentioning

confidence: 99%

Review on the application of imaging examination for brain injury in premature infants

Zhang

Zhou²

2023

Front. Neurol.

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Brain injury is the main factor leading to the decline of the quality of life in premature infants. The clinical manifestations of such diseases are often diverse and complex, lacking obvious neurological symptoms and signs, and the disease progresses rapidly. Due to missed diagnosis, it is easy to miss the best treatment opportunity. Brain ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and other imaging methods can help clinicians diagnose and assess the type and extent of brain injury in premature infants to some extent, but the three methods have their own characteristics. This article briefly reviews the diagnostic value of these three methods for brain injury in premature infants.

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“…Brain imaging reveals that premature birth before the gestational age of 32 weeks is associated with specific white matter abnormalities which are visible in the neonatal period using ultrasound scans or at term-equivalent age through magnetic resonance imaging (MRI). Interestingly, this white matter damage (WMD) is associated with poorer motor and cognitive outcomes in very preterm infants ( Woodward et al, 2006 , 2012 ; Spittle et al, 2011 ; Campbell et al, 2021 ). Advances in brain imaging demonstrate that these white matter abnormalities are embedded in a more global brain damage defining the encephalopathy of prematurity (EoP) ( Volpe, 2009 ; Hinojosa-Rodríguez et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Alteration of the Oligodendrocyte Lineage Varies According to the Systemic Inflammatory Stimulus in Animal Models That Mimic the Encephalopathy of Prematurity

et al. 2022

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Preterm birth before the gestational age of 32 weeks is associated with the occurrence of specific white matter damage (WMD) that can compromise the neurological outcome. These white matter abnormalities are embedded in more global brain damage defining the encephalopathy of prematurity (EoP). A global reduction in white matter volume that corresponds to chronic diffuse WMD is the most frequent form in contemporary cohorts of very preterm infants. This WMD partly results from alterations of the oligodendrocyte (OL) lineage during the vulnerability window preceding the beginning of brain myelination. The occurrence of prenatal, perinatal and postnatal events in addition to preterm birth is related to the intensity of WMD. Systemic inflammation is widely recognised as a risk factor of WMD in humans and in animal models. This review reports the OL lineage alterations associated with the WMD observed in infants suffering from EoP and emphasizes the role of systemic inflammation in inducing these alterations. This issue is addressed through data on human tissue and imaging, and through neonatal animal models that use systemic inflammation to induce WMD. Interestingly, the OL lineage damage varies according to the inflammatory stimulus, i.e., the liposaccharide portion of the E.Coli membrane (LPS) or the proinflammatory cytokine Interleukin-1β (IL-1β). This discrepancy reveals multiple cellular pathways inducible by inflammation that result in EoP. Variable long-term consequences on the white matter morphology and functioning may be speculated upon according to the intensity of the inflammatory challenge. This hypothesis emerges from this review and requires further exploration.

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Neonatal Cranial Ultrasound Findings among Infants Born Extremely Preterm: Associations with Neurodevelopmental Outcomes at 10 Years of Age

Cited by 17 publications

References 56 publications

Placental transcriptional signatures associated with cerebral white matter damage in the neonate

Placental transcriptional signatures associated with cerebral white matter damage in the neonate

Review on the application of imaging examination for brain injury in premature infants

Alteration of the Oligodendrocyte Lineage Varies According to the Systemic Inflammatory Stimulus in Animal Models That Mimic the Encephalopathy of Prematurity

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