Yang Kefeng, Chen Cheng, Yan Qi, Shen Xiuhua, Jiang Linlei, Ma Rui, Lu Liping, Zhu Jie, Tian Ying, Cai Wei, D'Alton Mary E, Zhang Jun, Kahe Ka
Department of Nutrition, Xin Hua Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
Department of Obstetrics and Gynecology, Vagelos College of Physicians and Surgeons, Columbia University, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
Environ Res. 2022 May 1;207:112186. doi: 10.1016/j.envres.2021.112186. Epub 2021 Oct 7.
Previous studies on long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) and infant neurodevelopment did not consider effect modifications of mercury (Hg) and selenium (Se).
To examine the joint association of prenatal LCn3PUFAs, Hg and Se with infant cognitive performance, and to explore whether DNA methylation may explain this potential association.
A total of 484 newborns were enrolled from the Shanghai Birth Cohort with available data on cord blood LCn3PUFA, nail Hg and Se during 2015-2016. Cord blood LCn3PUFA concentrations were assessed by gas chromatography, and nail Hg and Se concentrations were measured using clippings collected within 6 months of birth by inductively coupled plasma mass spectrometry. Five aspects of infant neurodevelopment (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Age and Stage Questionnaire (ASQ) at ages 6 and 12 months. Multivariable-adjusted generalized estimating equations models were performed to examine the associations between cord blood LCn3PUFA concentrations and ASQ test scores, and these associations were stratified by nail Hg and Se levels. Epigenome-wide DNA methylation in cord blood was compared in a random subgroup consisting of 19 infants from the highest and 21 from the lowest decile of LCn3PUFA concentrations.
LCn3PUFAs were not significantly associated with any ASQ test scores. However, in the subgroup with lower Hg (<median 0.13 ppm) and higher Se (≥median 0.87 ppm) levels, infants with higher LCn3PUFA concentrations had higher ASQ scores indicating better performance in gross motor skills [quartile 4 vs. 1: mean difference = 7.78; 95% confidence interval=(3.47, 12.09); P<0.01; P = 0.03]. Additionally, twenty CpG sites were differentially methylated when comparing high to low LCn3PUFA groups.
The association of prenatal LCn3PUFA concentrations with infant neurodevelopment, particularly gross motor skills, may be observed among infants with high Se and low Hg levels.
先前关于长链n-3多不饱和脂肪酸（LCn3PUFAs）与婴儿神经发育的研究未考虑汞（Hg）和硒（Se）的效应修饰作用。
研究产前LCn3PUFAs、Hg和Se与婴儿认知能力的联合关联，并探讨DNA甲基化是否可以解释这种潜在关联。
从上海出生队列中招募了484名新生儿，他们在2015 - 2016年期间有脐带血LCn3PUFA、指甲Hg和Se的可用数据。通过气相色谱法评估脐带血LCn3PUFA浓度，使用出生后6个月内采集的指甲剪，通过电感耦合等离子体质谱法测量指甲Hg和Se浓度。在6个月和12个月时，使用年龄与发育进程问卷（ASQ）评估婴儿神经发育的五个方面（沟通、大运动、精细运动、解决问题和个人社交技能）。采用多变量调整的广义估计方程模型来研究脐带血LCn3PUFA浓度与ASQ测试分数之间的关联，并按指甲Hg和Se水平进行分层。在由LCn3PUFA浓度最高十分位数的19名婴儿和最低十分位数的21名婴儿组成的随机亚组中，比较了脐带血中全基因组DNA甲基化情况。
LCn3PUFAs与任何ASQ测试分数均无显著关联。然而，在Hg水平较低（<中位数0.13 ppm）且Se水平较高（≥中位数0.87 ppm）的亚组中，LCn3PUFA浓度较高的婴儿ASQ分数较高，表明其在大运动技能方面表现更好[四分位数4与1：平均差异 = 7.78；95%置信区间=(3.47, 12.09)；P<0.01；P = 0.03]。此外，在比较高LCn3PUFA组与低LCn3PUFA组时，有20个CpG位点存在差异甲基化。
在高Se和低Hg水平的婴儿中，可能观察到产前LCn3PUFA浓度与婴儿神经发育，尤其是大运动技能之间的关联。
