Progress in understanding the genetics of bronchopulmonary dysplasia

Shaw, Gary M.; O’Brodovich, Hugh

doi:10.1053/j.semperi.2013.01.004

Cited by 54 publications

(38 citation statements)

References 42 publications

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“…A BPD genetikai rizikófaktorait tekintve jelentős elő-rehaladás következett be, számos jelölt gén van, amelyeknek szerepük lehet a jövő klinikai tanulmányaiban, majd pedig a betegség kezelésében [44,45]. A BPD komplexitására utal a genetika faktorok és a környezet tanulmányozását segítő biomarkercsalád összeállítása.…”

Section: A Bpd Egyéb Kockázati Faktoraiunclassified

Chronic morbidities of premature newborns

Balla

Szabó

2013

Orvosi Hetilap

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A retinopathia prematurorum, a bronchopulmonalis dysplasia, az intraventricularis haemorrhagia és a periventricularis leukomalacia a koraszülöttek legfontosabb krónikus utóbetegségei, amelyek alapvetően befolyásolják a gyermekek életminőségét. Mivel Magyarországon a koraszülés gyakorisága az elmúlt években nem csökkent, és a kialakult kórképek nehezen kezelhetők, a megelőzés jelentősége óriási. Kockázatifaktor-elemzések bebizonyították, hogy mindegyik kórkép multifaktoriális, a számos közös kóroki tényező közül a fejlődő szervek angiogenesise az egyik legfontosabb. A koraszülés következtében számos stresszhatás miatt károsodhat az érfejlődés. A megszületés után, a méhen belüli élethez viszonyítva, a relatív hyperoxia és a csökkenő vascularis növekedési faktorok szintje érsérü-lést, akár vascularis apoptózist okozhat. Mindezek következtében, a folyamat későbbi fázisában, a hypoxia által indukált gének aktiválódnak, óriási mértékű és kóros neovascularisatio, krónikus szervkárosodás alakul ki. A normális angiogenesis megtartása és a reaktív neovascularisatio gátlása a koraszülöttek jobb életminőségét eredményezheti. Orv. Hetil., 2013, 154, 1498-1511 Kulcsszavak: retinopathia prematurorum, bronchopulmonalis dysplasia, intraventricularis haemorrhagia, periventricularis leukomalacia Chronic morbidities of premature newbornsThe most important chronic morbidities of premature newborns, deeply infl uencing quality of life, are retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage and periventricular leukomalacia. Since the rate of premature birth has not decreased in recent years in Hungary, and treatments of these end stage disorders are extremely diffi cult, prevention gains tremendous signifi cance. Effective prevention is based on detailed knowledge of the pathophysiological mechanisms of these special diseases having multifactorial nature sharing several common risk factors, and one is the pathological angiogenesis. This sensitive system is affected by several stress situations which are the consequences of prematurity leading to abnormal vascular growth. After birth, relative hyperoxia, compared to intrauterine life, and decreasing concentrations of vascular growth factors result in vascular injury, moreover, may cause vessel apoptosis. The consequence of this phenomenon is the activation of hypoxia responsible genes resulting in robust pathological neovascularization and organ damage during the later phase. Saving normal angiogenesis and inhibiting reactive neovascularization may lead to better quality of life in these premature infants. Orv. Hetil., 2013, 154, 1498-1511 Keywords: retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia (Beérkezett: 2013. augusztus 6.; elfogadva: 2013. augusztus 22.) A szerkesztőség felkérésére készült közlemény. Rövidítések ANGPT-2 = angiopoetin-2; β-ARs = béta-adrenerg receptorok; BPD = bronchopulmonalis dysplasia; CP = cerebral palsy; ELBW = (extremely low birthweight) extrém kis születés...

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Section: A Bpd Egyéb Kockázati Faktoraiunclassified

Chronic morbidities of premature newborns

Balla

Szabó

2013

Orvosi Hetilap

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“…[9][10][11][12] Mechanical ventilation, oxygen therapy, patent ductus arteriosus, neonatal infection, male gender, and genetic factors are other risk factors. 10,13,14 Moreover, placentamediated pregnancy complications were recently suggested to be associated with BPD. These include maternal disorders resulting from placental dysfunction such as gestational hypertension and preeclampsia and fetal disorders such as fetal growth restriction (FGR), which can occur without maternal hypertension.…”

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confidence: 99%

Placental Complications and Bronchopulmonary Dysplasia: EPIPAGE-2 Cohort Study

et al. 2016

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OBJECTIVE: To investigate the relationship between placenta-mediated pregnancy complications and bronchopulmonary dysplasia (BPD) in very preterm infants.METHODS: National prospective population-based cohort study including 2697 singletons born before 32 weeks' gestation. The main outcome measure was moderate to severe BPD. Three groups of placenta-mediated pregnancy complications were compared with no placenta-mediated complications: maternal disorders only (gestational hypertension or preeclampsia), fetal disorders only (antenatal growth restriction), and both maternal and fetal disorders. RESULTS:Moderate to severe BPD rates were 8% in infants from pregnancies with maternal disorders, 15% from both maternal and fetal disorders, 23% from fetal disorders only, and 9% in the control group (P < .001). When we adjusted for gestational age, the risk of moderate to severe BPD was greater in the groups with fetal disorders only (odds ratio [OR] = 6.6; 95% confidence interval [CI], 4.1-10.7), with maternal and fetal disorders (OR = 3.7; 95% CI, 2.5-5.5), and with maternal disorders only (OR = 1.7; 95% CI, 1.0-2.7) than in the control group. When we also controlled for birth weight, the relationship remained in groups with fetal disorders only (OR = 4.2; 95% CI, 2.1-8.6) and with maternal and fetal disorders (OR = 2.1; 95% CI, 1.1-3.9).CONCLUSIONS: Placenta-mediated pregnancy complications with fetal consequences are associated with moderate to severe BPD in very preterm infants independently of gestational age and birth weight, but isolated maternal hypertensive disorders are not. Fetal growth restriction, more than birth weight, could predispose to impaired lung development.

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“…Twin studies have shown that even after controlling for covariates, genetic factors account for 53% of the variance in susceptibility to BPD (3). In the past, components of the innate immune system and antioxidant defenses, mechanisms of vascular and lung remodeling, and surfactant proteins have been the focus of genetic-association studies in BPD (4,5). Candidate genes for further research have been identified in these studies; however, any particular gene or gene pathway was not concluded to have a substantial contribution to the underlying etiology of BPD (5).…”

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confidence: 99%

Association of vitamin D receptor gene polymorphisms and bronchopulmonary dysplasia

et al. 2014

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Background: Vitamin D and its receptor (VDR) have important roles in perinatal lung development. The aim of this study was to investigate the relationship between VDR gene polymorphism and bronchopulmonary dysplasia (BPD) in preterm infants. Methods: VDR Fok I, Bsm I, Apa I, and Taq I polymorphisms were genotyped using restriction fragment length polymorphism in 109 preterm infants (47 with BPD, 62 without BPD). results: In univariate analysis, Ff (odds ratio (OR) = 3.937, P = 0.022, 95% confidence interval (CI) = 1.22-12.69) and ff (OR = 5.23, P = 0.004, 95% CI = 1.69-16.23) genotypes of Fok I were associated with the increased risk of BPD; whereas tt genotype of Taq 1 was associated with a protective effect against BPD (OR = 0.30, P = 0.04, 95% CI = 0.09-0.94). In multivariate logistic regression analysis, variant Fok 1 genotype increased risk of BPD (OR = 4.11, 95% CI = 1.08-15.68, P = 0.038) independent of patent ductus arteriosus, sepsis, mechanical ventilation, and surfactant treatment. Taq 1, Bsm 1, and Apa 1 polymorphisms did not have any effect. conclusion: After adjusting for multiple confounders, VDR Fok 1 polymorphism was associated with the increased frequency of BPD. Further studies are needed to assess the contribution of VDR signaling to the pathogenesis of BPD and to determine if VDR polymorphisms may be suitable for identifying infants at high risk for BPD.

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Progress in understanding the genetics of bronchopulmonary dysplasia

Cited by 54 publications

References 42 publications

Chronic morbidities of premature newborns

Chronic morbidities of premature newborns

Placental Complications and Bronchopulmonary Dysplasia: EPIPAGE-2 Cohort Study

Association of vitamin D receptor gene polymorphisms and bronchopulmonary dysplasia

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