Division of Pediatric Cardiology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California.
Stanford Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, California.
Birth Defects Res. 2019 Jul 1;111(11):640-648. doi: 10.1002/bdr2.1501. Epub 2019 Mar 28.
Congenital heart disease (CHD) is the most common birth defect group and a significant contributor to neonatal and infant death. CHD with single ventricle anatomy, including hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA), and various double-inlet ventricle (DIV) malformations, is the most complex with the highest mortality. Prenatal risk factors associated with HLHS have been studied, but such data for DIV are lacking.
We analyzed DIV cases and nonmalformed controls in the National Birth Defects Prevention Study, a case-control, multicenter population-based study of birth defects. Random forest analysis identified potential predictor variables for DIV, which were included in multivariable models to estimate effect magnitude and directionality.
Random forest analysis identified pre-pregnancy diabetes, history of maternal insulin use, maternal total lipid intake, paternal race, and intake of several foods and nutrients as potential predictors of DIV. Logistic regression confirmed pre-pregnancy diabetes, maternal insulin use, and paternal race as risk factors for having a child with DIV. Additionally, higher maternal total fat intake was associated with a reduced risk.
Maternal pre-pregnancy diabetes and history of insulin use were associated with an increased risk of having an infant with DIV, while maternal lipid intake had an inverse association. These novel data provide multiple metabolic pathways for investigation to identify better the developmental etiologies of DIV and suggest that public health interventions targeting diabetes prevention and management in women of childbearing age could reduce CHD risk.
先天性心脏病（CHD）是最常见的出生缺陷群体，也是新生儿和婴儿死亡的主要原因。具有单心室解剖结构的 CHD，包括左心发育不全综合征（HLHS）、三尖瓣闭锁（TA）和各种双入口心室（DIV）畸形，是最复杂的，死亡率最高。已经研究了与 HLHS 相关的产前危险因素，但缺乏 DIV 的此类数据。
我们分析了国家出生缺陷预防研究中的 DIV 病例和非畸形对照，这是一项针对出生缺陷的病例对照、多中心基于人群的研究。随机森林分析确定了 DIV 的潜在预测变量，这些变量被纳入多变量模型以估计效应的大小和方向性。
随机森林分析确定了孕前糖尿病、母亲胰岛素使用史、母亲总脂质摄入量、父亲种族以及几种食物和营养素的摄入是 DIV 的潜在预测因素。逻辑回归证实了孕前糖尿病、母亲胰岛素使用和父亲种族是孩子患有 DIV 的危险因素。此外，母亲总脂肪摄入量较高与风险降低相关。
母亲孕前糖尿病和胰岛素使用史与婴儿患有 DIV 的风险增加有关，而母亲脂质摄入量则呈负相关。这些新数据为调查提供了多种代谢途径，以更好地确定 DIV 的发育病因，并表明针对育龄妇女的糖尿病预防和管理的公共卫生干预措施可能会降低 CHD 风险。
