Rothman K J, Moore L L, Singer M R, Nguyen U S, Mannino S, Milunsky A
Evans Department of Medicine, Boston University School of Medicine, MA 02118, USA.
N Engl J Med. 1995 Nov 23;333(21):1369-73. doi: 10.1056/NEJM199511233332101.
Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest.
Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest.
For defects associated with cranial-neural-crest tissue, the ratio of the prevalence among the babies born to women who consumed more than 15,000 IU of preformed vitamin A per day from food and supplements to the prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 10,000 IU per day to that among the babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation.
High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.
动物研究表明天然形式的维生素A具有致畸性。化学结构与维生素A相似的合成类视黄醇可导致人类出生缺陷；与动物情况一样，这些缺陷似乎会影响源自颅神经嵴的组织。
在1984年10月至1987年6月期间，我们通过检测孕妇血清甲胎蛋白或进行羊膜穿刺术对22748名孕妇进行了筛查。护士访谈员收集了这些妇女在妊娠头三个月的饮食、用药和疾病信息，以及她们的家族和病史以及接触环境因素的信息。我们从接生婴儿的产科医生或妇女本人那里获取了妊娠结局的信息。在这22748名妇女中，有339名婴儿患有出生缺陷；其中121名婴儿的缺陷发生在源自颅神经嵴的部位。
对于与颅神经嵴组织相关的缺陷，每天从食物和补充剂中摄入超过15000国际单位预形成维生素A的妇女所生婴儿的患病率与母亲每天摄入5000国际单位或更少的婴儿患病率之比为3.5（95%置信区间为1.7至7.3）。仅就补充剂中的维生素A而言，每天摄入超过10000国际单位的妇女所生婴儿的患病率与母亲每天摄入5000国际单位或更少的婴儿患病率之比为4.8（95%置信区间为2.2至10.5）。通过平滑回归曲线，我们发现每天补充维生素A接近10000国际单位时存在一个明显的阈值。缺陷发生率的增加集中在妊娠第7周前摄入高水平维生素A的妇女所生的婴儿中。
饮食中高摄入量的预形成维生素A似乎具有致畸性。在每天以补充剂形式摄入超过10000国际单位预形成维生素A的妇女所生的婴儿中，我们估计约每57名婴儿中有1名畸形可归因于补充剂。
