Apolipoprotein E gene polymorphisms and intraventricular haemorrhage in infants born preterm: a large prospective multicentre cohort study

Dzietko, Mark; Schulz, Soeren; Preuss, Michael; Haertel, Christoph; Stein, Anja; Felderhoff‐Mueser, Ursula; Goepel, Wolfgang

doi:10.1111/dmcn.13987

Cited by 7 publications

(10 citation statements)

References 27 publications

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“…Due to the advances in genomics, a growing body of evidence believed genetic variants to be involved in various mechanisms underlying IVH development. Polymorphisms in the gene encoding vitamin K metabolism (vitamin K epoxide reductase complex 1) [ 96 ] and transportation ( APOE2 and APOE4 ) [ 29 ] have been demonstrated to influence the risk of IVH in preterm infants. Szpecht et al [ 105 ] reported that endothelial nitric oxide synthase and fibronectin-1 polymorphism genes [ 103 ] are respectively associated with a 3.4- and 7-fold higher risk of IVH in preterm infants.…”

Section: Genetic Predisposing Factorsmentioning

confidence: 99%

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants

Tsao¹

2023

J Korean Neurosurg Soc

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Intraventricular haemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm 4 infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

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Section: Genetic Predisposing Factorsmentioning

confidence: 99%

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants

Tsao¹

2023

J Korean Neurosurg Soc

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“…As we have analyzed infants with successful genotyping, our follow-up cohort represents a part of infants of the primary cohort of Dzietko et al They have used data from VLBWI born and enrolled in the GNN between 2009 and December 2014. 7…”

Section: Study Design and Participantsmentioning

confidence: 99%

“…A characterization of this cohort at neonatal age is previously described and can be found elsewhere. 7 For follow-up at 5 to 6 years, 2467 children were invited between January 1, 2014 and December 31, 2019, and 2215 children participated finally (Figure 1). Reasons for missing participation at follow-up are given in Table I ICH (APOE-ε4 versus ε3; n=6/39; 15.4 [6.7-29.0] versus n=2/105; 1.9 [0.4%-6.0%], P=0.002; Figure 3).…”

Section: Cohort Characteristicsmentioning

confidence: 99%

Association of ApoE Genotypes and Recovery From Intracerebral Hemorrhage in Very Low Birth Weight Infants

Humberg

Dzietko

Schulz

et al. 2022

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Background and Purpose: Associations of APOE genotypes with intracerebral hemorrhage (ICH) in preterm infants were previously described. In adults, APOE-ε4 genotype has been proposed as susceptibility factor for impaired recovery after cerebral insult. We here aim to determine APOE genotype-specific neurological consequences of neonatal ICH at school age. Methods: In this multicenter observational cohort study, very low birth weight (<1500 g, <32 weeks gestational age) children were studied for cerebral palsy (CP) after ultrasound diagnosed ICH stratified by APOE genotype. Follow-up examination was done at the age of 5 to 6 years. Study personnel were blinded for perinatal information and complications. Participants were born between January 1, 2009 and December 31, 2013 and enrolled in the German Neonatal Network. Of 8022 infants primarily enrolled, 2467 children were invited for follow-up between January 1, 2014 and December 31, 2019. Univariate analyses and multivariate logistic regression models were used to assess the impact of APOE genotype (APOE-ε2, APOE-ε3, APOE-ε4) on CP after ICH. Results: Two thousand two hundred fifteen children participated at follow-up, including 363 children with ultrasound diagnosed neonatal ICH. In univariate analyses of children with a history of ICH, APOE-ε3 carriers had lower frequencies of CP (n=33/250; 13.2 [95% CI, 9.4%–17.8%]), as compared to APOE-ε2 (n=15/63; 23.8 [14.6%–35.3%], P =0.037) and –ε4 carriers (n=31/107; 29.0 [21.0%–38.0%], P <0.001), respectively. Regression models revealed an association of APOE-ε4 genotype and CP development (odds ratio, 2.77 [1.44–5.32], P =0.002) after ICH. Notably, at low-grade ICH (grade I) APOE-ε4 expression resulted in an increased rate of CP (n=6/39; 15.4 [6.7–29.0]) in comparison to APOE-ε3 (n=2/105; 1.9 [0.4%–6.0%], P =0.002). Conclusions: APOE-ε4 carriers have an increased risk for long-term motor deficits after ICH. We assume an effect even after low-grade neonatal ICH, but more data are needed to clarify this issue.

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“…„Less Invasive Surfactant Application“ [LISA]) oder Beatmung möglicherweise positiv beeinflussen [ 53 , 63 ]. Genetische Prädispositionen wie Apolipoprotein(Apo)-E-Polymorphismen wiederum sind Risikofaktoren für das Auftreten einer intraventrikulären Blutung und auch für die spätere Entwicklung einer CP, wie in einer gemeinsamen Studie mit den German Neonatal Network (GNN) gezeigt wurde [ 26 , 46 ]. Auch die Art der Ernährung, insbesondere mit Muttermilch, hat einen entscheidenden Einfluss auf die Entwicklung und sollte einbezogen werden [ 108 ].…”

Section: Klinische Daten Und Biomarkerunclassified

Biomarker und Neuromonitoring zur Entwicklungsprognose nach perinataler Hirnschädigung

Felderhoff-Müser

Hüning

2022

Monatsschr Kinderheilkd

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Das sich entwickelnde Gehirn ist in der Perinatalperiode besonders empfindlich für eine Vielzahl von Insulten, wie z. B. Extremfrühgeburtlichkeit und perinatale Asphyxie. Ihre Komplikationen können zu lebenslangen neurokognitiven, sensorischen und psychosozialen Einschränkungen führen; deren Vorhersage bleibt eine Herausforderung. Eine Schlüsselfunktion kommt der möglichst exakten Identifikation von Hirnläsionen und funktionellen Störungen zu. Die Prädiktion stützt sich auf frühe diagnostische Verfahren und die klinische Erfassung der Meilensteine der Entwicklung. Zur klinischen Diagnostik und zum Neuromonitoring in der Neonatal- und frühen Säuglingsperiode stehen bildgebende Verfahren zur Verfügung. Hierzu zählen zerebrale Sonographie, MRT am errechneten Termin, amplitudenintegriertes (a)EEG und/oder klassisches EEG, Nah-Infrarot-Spektroskopie, General Movements Assessment und die frühe klinische Nachuntersuchung z. B. mithilfe der Hammersmith Neonatal/Infant Neurological Examination. Innovative Biomarker und -muster (Omics) sowie (epi)genetische Prädispositionen sind Gegenstand wissenschaftlicher Untersuchungen. Neben der Erfassung klinischer Risiken kommt psychosozialen Faktoren im Umfeld des Kindes eine entscheidende Rolle zu. Eine möglichst akkurate Prognose ist mit hohem Aufwand verbunden, jedoch zur gezielten Beratung der Familien und der Einleitung von frühen Interventionen, insbesondere vor dem Hintergrund der hohen Plastizität des sich entwickelnden Gehirns, von großer Bedeutung. Diese Übersichtsarbeit fokussiert die Charakterisierung der oben genannten Verfahren und ihrer Kombinationsmöglichkeiten. Zudem wird ein Ausblick gegeben, wie innovative Techniken in Zukunft die Prädiktion der Entwicklung und Nachsorge dieser Kinder vereinfachen können.

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Apolipoprotein E gene polymorphisms and intraventricular haemorrhage in infants born preterm: a large prospective multicentre cohort study

Abstract: APOE2 and APOE4 genotypes are relevant risk factors for IVH in infants born preterm. Our findings improve our understanding of the genetic contributions to IVH.

Cited by 7 publications

References 27 publications

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants

Association of ApoE Genotypes and Recovery From Intracerebral Hemorrhage in Very Low Birth Weight Infants

Biomarker und Neuromonitoring zur Entwicklungsprognose nach perinataler Hirnschädigung

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