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Role of endothelial nitric oxide synthase and endothelin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants.

ABSTRACT: In the pathogenesis of neonatal intraventricular hemorrhage (IVH) in preterm infants, an important role is played by changes in venous and arterial cerebral flows. It has been shown that the ability of autoregulation of cerebral flows in response to variations in arterial blood pressure in preterm infants is impaired. This impaired autoregulation causes an increased risk of germinal matrix rupture and IVH occurrence. We examined three polymorphisms of genes, related to regulation of blood flow, for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32?+?0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. These polymorphisms include: eNOS (894G?>?T and -786T?>?C) and EDN1 (5665G?>?T?) gene. We found that infants with genotype GT eNOS 894G?>?T have 3.4-fold higher risk developing of IVH born before 28?+?6 weeks of gestation. Our investigation did not confirm any significant prevalence for IVH development according to eNOS -786T?>?C genes polymorphism. Our novel investigations in EDN1 5665G?>?T polymorphism did not show any link between alleles or genotypes and IVH. Future investigations of polymorphisms in blood-flow associated genes may provide valuable insight into the pathogenetic mechanisms underlying the development of IVH.

SUBMITTER: Szpecht D

PROVIDER: S-EPMC5304177 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Role of endothelial nitric oxide synthase and endothelin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants.

Szpecht Dawid D Gadzinowski Janusz J Seremak-Mrozikiewicz Agnieszka A Kurzawińska Grażyna G Szymankiewicz Marta M

Scientific reports 20170213

In the pathogenesis of neonatal intraventricular hemorrhage (IVH) in preterm infants, an important role is played by changes in venous and arterial cerebral flows. It has been shown that the ability of autoregulation of cerebral flows in response to variations in arterial blood pressure in preterm infants is impaired. This impaired autoregulation causes an increased risk of germinal matrix rupture and IVH occurrence. We examined three polymorphisms of genes, related to regulation of blood flow, ...[more]

PMID: 28211916

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Project description:ImportanceNo trials to date have demonstrated the benefits of tocolysis on death and/or neonatal morbidity in preterm infants; tocolytics may affect the fetal blood-brain barrier.ObjectivesTo assess the risks associated with tocolysis in women delivering prematurely as measured by death and/or intraventricular hemorrhage (IVH) in preterm infants and to compare the association of calcium channel blockers (CCBs) nifedipine and nicardipine hydrochloride vs atosiban used for tocolysis with death and/or IVH.Design, settings, and participantsThe French 2011 EPIPAGE-2 (Enquête Épidémiologique sur les Petits Âges Gestationnels) cohort was limited to mothers admitted for preterm labor without fever, who delivered from 24 to 31 weeks of gestation from April 1 through December 31, 2011. Groups of preterm infants with vs without tocolytic exposure and groups with atosiban vs CCB exposure were compared. Data analysis was performed from June 7, 2014, through September 3, 2017.ExposuresTocolytics.Main outcomes and measuresThe primary outcome was a composite of death and/or IVH in preterm infants. Secondary outcomes included death, IVH, and a composite of death and/or grades III to IV IVH.ResultsA total of 1127 mothers (mean [SD] age, 25.5 [6.0] years) experienced preterm labor and gave birth to 1343 preterm infants with a male to female ratio of 1.23 and mean (SD) gestational age of 27?(2.5) weeks. Of these, 789 mothers (70.0%) received tocolytics; 314 (39.8%) received only atosiban, and 118 (15.0%) received only a CCB. In the first analysis, the primary outcome (death and/or IVH) was not significantly different in preterm infants with vs without tocolytic exposure (183 of 363 [50.4%] vs 207 of 363 [57.0%]; relative risk [RR], 0.88; 95% CI, 0.77-1.01; P?=?.07). The secondary outcome (death and/or grades III-IV IVH) was significantly lower in preterm infants with vs without tocolytic exposure (92 of 363 [25.3%] vs 118 of 363 [32.5%]; RR, 0.78; 95% CI, 0.62-0.98; P?=?.03). Other outcomes did not differ significantly. In the secondary analysis, death and/or IVH was not significantly different in preterm infants with atosiban vs CCB exposure (96 of 214 [44.9%] vs 62 of 121 [51.2%]; RR, 0.88; 95% CI, 0.70-1.10; P?=?.26), nor was IVH (77 of 197 [39.1%] vs 48 of 106 [45.3%]; RR, 0.86; 95% CI, 0.66-1.13; P?=?.29).Conclusions and relevanceIn this population-based study, findings suggest that tocolytics were associated with a reduction of death and severe IVH. Other studies are necessary to compare perinatal outcomes after use of atosiban vs CCBs.

Dataset Information

Role of endothelial nitric oxide synthase and endothelin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants.

Publications

Role of endothelial nitric oxide synthase and endothelin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants.

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