Department of Community Mental Health, University of Haifa, Haifa, Israel.
Department of Mental Health, Meuhedet Health Services, Tel Aviv, Israel.
JAMA Psychiatry. 2018 Feb 1;75(2):176-184. doi: 10.1001/jamapsychiatry.2017.4050.
The association of maternal use of folic acid and multivitamin supplements before and during pregnancy with the risk of autism spectrum disorder (ASD) in offspring is unclear.
To examine the associations between the use of maternal folic acid and multivitamin supplements before and during pregnancy and the risk of ASD in offspring.
DESIGN, SETTING, AND PARTICIPANTS: A case-control cohort study of 45 300 Israeli children born between January 1, 2003, and December 31, 2007, were followed up from birth to January 26, 2015, for the risk of ASD. The cases were all children diagnosed with ASD and the controls were a random sample of 33% of all live-born children.
Maternal vitamin supplements were classified for folic acid (vitamin B9), multivitamin supplements (Anatomical Therapeutic Chemical A11 codes vitamins A, B, C, and D), and any combination thereof exposed in the intervals before and during pregnancy.
The association between maternal vitamin supplementation and the risk of ASD in offspring was quantified with relative risks (RRs) and their 95% CIs fitting Cox proportional hazards regression models adjusted for confounders. Sensitivity analyses were performed to test the robustness of the results.
Of the 45 300 children in the study (22 090 girls and 23 210 boys; mean [SD] age, 10.0 [1.4] years at the end of follow-up), 572 (1.3%) received a diagnosis of ASD. Maternal exposure to folic acid and/or multivitamin supplements before pregnancy was statistically significantly associated with a lower likelihood of ASD in the offspring compared with no exposure before pregnancy (RR, 0.39; 95% CI, 0.30-0.50; P < .001). Maternal exposure to folic acid and/or multivitamin supplements during pregnancy was statistically significantly associated with a lower likelihood of ASD in offspring compared with no exposure during pregnancy (RR, 0.27; 95% CI, 0.22-0.33; P < .001). Corresponding RRs were estimated for maternal exposure to folic acid before pregnancy (RR, 0.56; 95% CI, 0.42-0.74; P = .001), maternal exposure to folic acid during pregnancy (RR, 0.32; 95% CI, 0.26-0.41; P < .001), maternal exposure to multivitamin supplements before pregnancy (RR, 0.36; 95% CI, 0.24-0.52; P < .001), and maternal exposure to multivitamin supplements during pregnancy (RR, 0.35; 95% CI, 0.28-0.44; P < .001). The results generally remained statistically significant across sensitivity analyses.
Maternal exposure to folic acid and multivitamin supplements before and during pregnancy is associated with a reduced risk of ASD in the offspring compared with the offspring of mothers without such exposure.
母亲在怀孕前和怀孕期间使用叶酸和多种维生素补充剂与自闭症谱系障碍（ASD）风险之间的关联尚不清楚。
研究母亲在怀孕前和怀孕期间使用叶酸和多种维生素补充剂与后代 ASD 风险之间的关联。
设计、地点和参与者：这是一项在以色列进行的病例对照队列研究，纳入了 2003 年 1 月 1 日至 2007 年 12 月 31 日期间出生的 45300 名以色列儿童，从出生开始随访至 2015 年 1 月 26 日，以评估 ASD 的发病风险。病例均为确诊为 ASD 的儿童，对照组为所有活产儿的 33%的随机样本。
将维生素补充剂（维生素 B9 叶酸、多种维生素补充剂（解剖治疗化学分类法 A11 编码的维生素 A、B、C 和 D））分为怀孕前和怀孕期间的暴露情况。
采用 Cox 比例风险回归模型调整混杂因素后，定量评估母亲维生素补充与后代 ASD 风险之间的关联，计算相对风险（RR）及其 95%置信区间。进行敏感性分析以检验结果的稳健性。
在这项研究中的 45300 名儿童（22090 名女孩和 23210 名男孩；平均[SD]年龄为 10.0[1.4]岁，随访结束时）中，有 572 名（1.3%）被诊断为 ASD。与怀孕前无暴露相比，母亲在怀孕前接触叶酸和/或多种维生素补充剂与后代 ASD 的可能性降低显著相关（RR，0.39；95%CI，0.30-0.50；P<0.001）。与怀孕期间无暴露相比，母亲在怀孕期间接触叶酸和/或多种维生素补充剂与后代 ASD 的可能性降低显著相关（RR，0.27；95%CI，0.22-0.33；P<0.001）。估计了母亲在怀孕前接触叶酸（RR，0.56；95%CI，0.42-0.74；P=0.001）、母亲在怀孕期间接触叶酸（RR，0.32；95%CI，0.26-0.41；P<0.001）、母亲在怀孕前接触多种维生素补充剂（RR，0.36；95%CI，0.24-0.52；P<0.001）和母亲在怀孕期间接触多种维生素补充剂（RR，0.35；95%CI，0.28-0.44；P<0.001）的相应 RR。总体而言，这些结果在敏感性分析中仍具有统计学意义。
与未接触此类补充剂的母亲的后代相比，母亲在怀孕前和怀孕期间接触叶酸和多种维生素补充剂与后代 ASD 风险降低相关。
