Shaw Gary M, Nelson Verne, Carmichael Suzan L, Lammer Edward J, Finnell Richard H, Rosenquist Thomas H
March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Oakland, California 94606, USA.
Epidemiology. 2002 Nov;13(6):625-30. doi: 10.1097/00001648-200211000-00005.
The mechanisms by which folic acid may contribute to reductions in risk of several congenital anomalies are unknown. The data gap includes a lack of information on possible effect modification between maternal folic acid use and other maternal exposures. We hypothesized that effects of congenital anomalies associated with maternal fever, cigarette smoking or alcohol use would be modified by intake of vitamins.
We explored case-control data that showed risk reductions among infants and fetuses whose mothers consumed vitamins. Data were from California deliveries of infants and fetuses in the period 1987-1989. Maternal telephone interviews were completed for 207 (87%) conotruncal cases, 489 (85%) orofacial cleft cases, 265 (84%) neural tube defect cases, 165 (82%) limb anomaly cases, and 734 controls (nonmalformed infants).
Considering women who reported vitamin use and no periconceptional fever as referents, for each anomaly group we observed elevated effects for the combinations of maternal vitamin use/fever, no use/no fever and no use/fever. Effects were most elevated for the combination of no vitamin use and fever. Adjusted for maternal body mass index, education and race/ethnicity, odds ratios were 2.4 (95% confidence inter-val = 1.0-5.9) for conotruncal defects, 2.9 (1.4-5.8) for cleft lip with or without cleft palate, 1.3 (0.4-3.9) for cleft palate, 3.1 (1.4-6.8) for neural tube defects, and 2.6 (1.0-6.4) for limb-deficiency defects. These interactions were further investigated relative to maternal use of fever-reducing medications. Effects tended to be highest among those women who did not use vitamins, had fevers, and did not use fever-reducing medications. Compared with women who used vitamins and did not smoke periconceptionally, anomaly risks tended to be highest among women who did not use vitamins and smoked. No specific pattern emerged involving alcohol intake.
These data further suggest that the underlying mechanisms of folic acid associated with congenital anomalies may be complex.
叶酸可能有助于降低多种先天性异常风险的机制尚不清楚。数据缺口包括缺乏关于孕妇叶酸使用与其他孕妇暴露因素之间可能存在的效应修正信息。我们假设与孕妇发热、吸烟或饮酒相关的先天性异常效应会因维生素摄入而发生改变。
我们探讨了病例对照数据，这些数据显示母亲服用维生素的婴儿和胎儿的风险降低。数据来自1987 - 1989年加利福尼亚州的婴儿和胎儿分娩情况。对207例（87%）圆锥动脉干病例、489例（85%）口面部裂病例、265例（84%）神经管缺陷病例、165例（82%）肢体异常病例以及734名对照（非畸形婴儿）的母亲进行了电话访谈。
将报告服用维生素且孕期无发热的女性作为参照，对于每个异常组，我们观察到孕妇维生素使用/发热、未使用/未发热和未使用/发热组合的效应升高。未使用维生素且发热的组合效应升高最为明显。在调整了孕妇体重指数、教育程度和种族/族裔因素后，圆锥动脉干缺陷的比值比为2.4（95%置信区间 = 1.0 - 5.9），唇裂伴或不伴腭裂的比值比为2.9（1.4 - 5.8），腭裂的比值比为1.3（0.4 - 3.9），神经管缺陷的比值比为3.1（1.4 - 6.8），肢体缺陷的比值比为2.6（1.0 - 6.4）。相对于孕妇使用退热药物，对这些相互作用进行了进一步研究。效应往往在未使用维生素、发热且未使用退热药物的女性中最高。与孕期服用维生素且不吸烟的女性相比，未使用维生素且吸烟的女性异常风险往往最高。未出现涉及酒精摄入的特定模式。
这些数据进一步表明，叶酸与先天性异常相关的潜在机制可能很复杂。
