BACKGROUND Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. OBJECTIVES We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. METHODS We used data from the Maternal-Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between log2-transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. RESULTS Third-trimester BLLs were associated with increased SRS-2 scores [βadj=3.3; 95% confidence interval (CI): 1.1, 5.5] among participants with low (<10th percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null (βadj=-0.3; 95% CI: -1.2, 0.5) among those in the middle category (≥10th and <80th percentiles) (p-interaction <0.001). FA supplementation also attenuated these associations. Both folate indicators modified first-trimester BLL-SRS-2 associations, but to a lesser extent. Third-trimester BLL-SRS-2 associations were slightly stronger among participants who were homozygous for the T (minor) allele of the MTHFR 677C>T SNP (βadj=0.9; 95% CI: -1.2, 3.1) than those without the T allele (βadj=-0.3; 95% CI: -1.3, 0.7), but the difference was not statistically significant (p-interaction=0.28). DISCUSSION Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479.

中文翻译：

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来自 MIREC 妊娠和出生队列的加拿大儿童在怀孕期间联合接触叶酸和铅以及自闭症样行为。


背景 补充叶酸 （FA） 可能会减弱妊娠期暴露于某些化学物质与自闭症或类似自闭症的行为之间的关联，但据我们所知，这尚未针对铅进行评估。目的 我们检查了妊娠期血浆总叶酸浓度、FA 补充剂和母体亚甲基四氢叶酸还原酶 （MTHFR） 677C>T 基因型是否改变了妊娠期血铅水平 （BLL） 与自闭症样行为之间的关系。方法 我们使用了来自加拿大妊娠和分娩队列研究 Maternal-Infant Research on Environmental Chemicals 研究 （2008-2011） 的数据。使用社会反应量表 2 （SRS-2） 记录了 601 名 3-4 岁儿童的童年自闭症样行为，其中分数越高表示越像自闭症的行为。我们测量了妊娠早期和晚期的 BLL 和血浆总叶酸浓度。我们还通过调查估计了妊娠期 FA 补充剂，并对母体 MTHFR 677C>T 单核苷酸多态性 （SNP） 进行了基因分型。我们使用线性回归通过叶酸暴露和母体 MTHFR 677C>T 基因型两个指标估计 log2 转换的 BLL 和 SRS-2 评分之间的混杂调整关联。结果 孕晚期 BLL 与 SRS-2 评分增加相关 [βadj=3.3;95% 置信区间 （CI）： 1.1， 5.5] 在孕晚期血浆总叶酸浓度较低的参与者中，但 BLL-SRS-2 关联为零 （βadj=-0.3;95% CI： -1.2， 0.5） 在中间类别 （≥第 10 和 <80 个百分位数） 中（p 交互作用 <0.001）。FA 补充剂也减弱了这些关联。 两种叶酸指标都改变了孕早期 BLL-SRS-2 的关联，但程度较小。与 T 等位基因纯合的参与者相比，孕晚期 BLL-SRS-2 关联略强 MTHFR 677C>T SNP 的 T （次要） 等位基因纯合子 （βadj=0.9;95% CI： -1.2， 3.1） 与没有 T 等位基因的参与者 （βadj=-0.3;95% CI： -1.3， 0.7），但差异无统计学意义 （p-相互作用=0.28）。讨论 叶酸可能会改变妊娠铅暴露与儿童自闭症样行为之间的关联，表明它可以减轻产前铅暴露的神经毒性作用。https://doi.org/10.1289/EHP14479。