Somaschini Marco, Castiglioni Emanuela, Volonteri Chiara, Cursi Marco, Ferrari Maurizio, Carrera Paola
Genomic Unit for Diagnosis of Human Pathologies, Center for Translational Genomics and Bioinformatics, Ospedale San Raffaele, Milan, Italy.
J Matern Fetal Neonatal Med. 2012 Oct;25 Suppl 4:127-30. doi: 10.3109/14767058.2012.714995.
Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in preterm newborn infants. It is a multifactorial disease caused by the interaction between environmental and genetic factors. The aim of this study is to identify genetic variants contributing to BPD development using next-generation sequencing (NGS) technology. We prospectively evaluated 378 premature newborn infants with a gestational age <32 weeks in a multicentre study from 12 Italian neonatal intensive care unit from 2009 to 2012. Infants were divided into two groups: normal controls (225) and BPD-affected infants (141) with mild (65, 46.1%), moderate (40, 28.4%) and severe (36, 25.5%) BPD. BPD was more frequent in infants with lower weight and gestational age. Antenatal steroid administration was more frequent in the control group. Postnatal infection, respiratory distress syndrome, patent ductus arterious, cerebral haemorrhage, surfactant administration, ventilatory support, diuretics and postnatal steroid administration correlated with severity of BPD. Among BPD, moderate and severe cases will be selected as BPD "extreme phenotypes", and in fact variations in 28-day oxygen need-based BPD were previously shown to be fully attributable to environmental effects whereas dependence on supplemental oxygen at 36 weeks seems to better reflect underlying genetic susceptibility. Exome analysis by NGS is in progress. Identifications of genetic markers predisposing to BPD may allow development of personalized and preventive treatments.
支气管肺发育不良(BPD)是早产新生儿中最常见的慢性肺部疾病。它是一种由环境因素和遗传因素相互作用引起的多因素疾病。本研究的目的是使用下一代测序(NGS)技术鉴定导致BPD发生的基因变异。在2009年至2012年期间,我们在一项来自12个意大利新生儿重症监护病房的多中心研究中,对378名孕周<32周的早产新生儿进行了前瞻性评估。婴儿被分为两组:正常对照组(225名)和患有BPD的婴儿(141名),其中轻度BPD(65名,46.1%)、中度BPD(40名,28.4%)和重度BPD(36名,25.5%)。体重和孕周较低的婴儿中BPD更为常见。对照组中产前使用类固醇更为频繁。产后感染、呼吸窘迫综合征、动脉导管未闭、脑出血、表面活性剂使用、通气支持、利尿剂和产后类固醇使用与BPD的严重程度相关。在BPD中,中度和重度病例将被选为BPD“极端表型”,事实上,先前已表明基于28天氧需求的BPD变化完全归因于环境影响,而36周时对补充氧气的依赖似乎更好地反映了潜在的遗传易感性。NGS外显子组分析正在进行中。鉴定易患BPD的遗传标记可能有助于开发个性化和预防性治疗方法。