Khoury M J, Erickson J D
Division of Birth Defects and Developmental Disabilities, Centers for Disease Control, Atlanta, Georgia 30333.
Am J Med Genet. 1992 Aug 1;43(6):1016-22. doi: 10.1002/ajmg.1320430620.
Although the manifestations of Down syndrome (DS) are well known, certain major birth defects such as duodenal atresia and endocardial cushion defects are present in some infants but not others, suggesting the possible role of other genetic or environmental factors interacting with the trisomy genotype. To explore the possible role of maternal factors in the presence of major defects among DS infants, we examined data from an epidemiologic study of DS conducted in metropolitan Atlanta. Of 219 DS infants born between 1968 and 1980, 50 had recorded cardiac defects, 9 had selected gastrointestinal atresias and 4 had oral clefts. We evaluated the association of these defects with several maternal factors including age, race, first trimester cigarette smoking, alcohol use, and fever. We found that different maternal factors were associated with several defects: (1) mother's race with cardiac defects (40% in blacks vs. 17% in whites, P less than 0.01), (2) mother's age with oral clefts (6% for less than 25 years, 1% for 25-34, and 0% for greater than 34, P less than 0.05), and (3) maternal first trimester fever with gastrointestinal defects (15% in infants with history of fever and 3% in infants without a history of fever, P less than 0.01). We also observed an inverse relationship between maternal alcohol use and the presence of ventricular septal defect. These findings suggest that maternal risk factors may influence the clinical manifestations of DS. In addition to searching for a genetic basis for the DS phenotype, we suggest that the role of environmental factors and maternal exposures be specifically explored in clarifying the genesis of various birth defects in Down syndrome.
尽管唐氏综合征（DS）的表现广为人知，但某些主要出生缺陷，如十二指肠闭锁和心内膜垫缺损，在一些婴儿中存在而在另一些婴儿中不存在，这表明其他基因或环境因素可能与三体基因型相互作用。为了探究母亲因素在DS婴儿出现主要缺陷中的可能作用，我们研究了在大亚特兰大地区进行的一项DS流行病学研究的数据。在1968年至1980年间出生的219名DS婴儿中，50名有心脏缺陷记录，9名有特定的胃肠道闭锁，4名有腭裂。我们评估了这些缺陷与几个母亲因素的关联，包括年龄、种族、孕早期吸烟、饮酒和发热。我们发现不同的母亲因素与几种缺陷相关：（1）母亲的种族与心脏缺陷（黑人中为40%，白人中为17%，P<0.01），（2）母亲的年龄与腭裂（小于25岁的为6%，25 - 34岁的为1%，大于34岁的为0%，P<0.05），以及（3）母亲孕早期发热与胃肠道缺陷（有发热史的婴儿中为15%，无发热史的婴儿中为3%，P<0.01）。我们还观察到母亲饮酒与室间隔缺损的存在呈负相关。这些发现表明母亲风险因素可能影响DS的临床表现。除了寻找DS表型的遗传基础外，我们建议在阐明唐氏综合征各种出生缺陷的发生机制时，特别探索环境因素和母亲暴露的作用。
