Raghavan Ramkripa, Riley Anne W, Volk Heather, Caruso Deanna, Hironaka Lynn, Sices Laura, Hong Xiumei, Wang Guoying, Ji Yuelong, Brucato Martha, Wahl Anastacia, Stivers Tom, Pearson Colleen, Zuckerman Barry, Stuart Elizabeth A, Landa Rebecca, Fallin M Daniele, Wang Xiaobin
Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Wendy Klag Center for Autism and Developmental Disabilities & Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Paediatr Perinat Epidemiol. 2018 Jan;32(1):100-111. doi: 10.1111/ppe.12414. Epub 2017 Oct 6.
To examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B levels at birth and child's Autism Spectrum Disorder (ASD) risk.
This report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B were measured from samples taken 2-3 days after birth.
Moderate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5).
There was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B exposure in-utero on early brain development.
研究孕期补充多种维生素与出生时母体血浆叶酸和维生素B水平的生物标志物指标以及儿童自闭症谱系障碍(ASD)风险之间的前瞻性关联。
本报告纳入了1257对母婴,他们在出生时被招募,并在波士顿医学中心进行了从出生到儿童期的前瞻性随访。ASD由电子病历中的诊断代码定义。通过问卷调查评估母体多种维生素的补充情况;在出生后2 - 3天采集的样本中测量母体血浆叶酸和维生素B水平。
与先前的研究结果一致,孕期自我报告的中等程度(每周3 - 5次)补充多种维生素与ASD风险降低相关。以该组为参照,低(每周≤2次)和高(每周>5次)补充多种维生素与ASD风险增加相关。在调整包括亚甲基四氢叶酸还原酶(MTHFR)基因型等协变量后,出生时母体血浆叶酸水平极高(≥60.3 nmol/L)的儿童患ASD的风险增加了2.5倍[95%置信区间(CI)1.3, 4.6]。同样,维生素B水平极高(≥536.8 pmol/L)的儿童患ASD的风险增加了2.5倍(95% CI 1.4, 4.5)。
母体补充多种维生素的频率与ASD风险之间存在“U型”关系。出生时母体血浆叶酸和维生素B水平极高与ASD风险相关。这项产生假设的研究并非质疑孕期摄入足够叶酸和维生素B的重要性;相反,它提出了关于子宫内血浆叶酸和维生素B水平极高对早期大脑发育影响的新问题。