Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Department of Complex Genetics and Epidemiology, CAPHRI School for Public Health and Primary Care, University of Maastricht, Maastricht, the Netherlands.
JAMA Netw Open. 2020 Mar 2;3(3):e201007. doi: 10.1001/jamanetworkopen.2020.1007.
The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown.
To assess the associations of fish intake and mercury exposure during pregnancy with metabolic syndrome in children and alterations in biomarkers of inflammation in children.
DESIGN, SETTING, AND PARTICIPANTS: This population-based prospective birth cohort study used data from studies performed in 5 European countries (France, Greece, Norway, Spain, and the UK) between April 1, 2003, and February 26, 2016, as part of the Human Early Life Exposome (HELIX) project. Mothers and their singleton offspring were followed up until the children were aged 6 to 12 years. Data were analyzed between March 1 and August 2, 2019.
Maternal fish intake during pregnancy (measured in times per week) was assessed using validated food frequency questionnaires, and maternal mercury concentration (measured in micrograms per liter) was assessed using maternal whole blood and cord blood samples.
An aggregate metabolic syndrome score for children was calculated using the z scores of waist circumference, systolic and diastolic blood pressures, and levels of triglyceride, high-density lipoprotein cholesterol, and insulin. A higher metabolic syndrome score (score range, -4.9 to 7.5) indicated a poorer metabolic profile. Three protein panels were used to measure several cytokines and adipokines in the plasma of children.
The study included 805 mothers and their singleton children. Among mothers, the mean (SD) age at cohort inclusion or delivery of their infant was 31.3 (4.6) years. A total of 400 women (49.7%) had a high educational level, and 432 women (53.7%) were multiparous. Among children, the mean (SD) age was 8.4 (1.5) years (age range, 6-12 years). A total of 453 children (56.3%) were boys, and 734 children (91.2%) were of white race/ethnicity. Fish intake consistent with health recommendations (1 to 3 times per week) during pregnancy was associated with a 1-U decrease in metabolic syndrome score in children (β = -0.96; 95% CI, -1.49 to -0.42) compared with low fish consumption (<1 time per week) after adjusting for maternal mercury levels and other covariates. No further benefit was observed with fish intake of more than 3 times per week. A higher maternal mercury concentration was independently associated with an increase in the metabolic syndrome score of their offspring (β per 2-fold increase in mercury concentration = 0.18; 95% CI, 0.01-0.34). Compared with low fish intake, moderate and high fish intake during pregnancy were associated with reduced levels of proinflammatory cytokines and adipokines in children. An integrated analysis identified a cluster of children with increased susceptibility to metabolic disease, which was characterized by low fish consumption during pregnancy, high maternal mercury levels, decreased levels of adiponectin in children, and increased levels of leptin, tumor necrosis factor α, and the cytokines interleukin 6 and interleukin 1β in children.
Results of this study suggest that moderate fish intake consistent with current health recommendations during pregnancy was associated with improvements in the metabolic health of children, while high maternal mercury exposure was associated with an unfavorable metabolic profile in children.
目前，尚不清楚怀孕期间摄入鱼类的汞风险与营养益处之间的平衡，以及这对后代代谢健康的影响。
评估怀孕期间鱼类摄入量和汞暴露与儿童代谢综合征以及儿童炎症生物标志物变化的相关性。
设计、地点和参与者：本基于人群的前瞻性出生队列研究使用了 2003 年 4 月 1 日至 2016 年 2 月 26 日期间在 5 个欧洲国家（法国、希腊、挪威、西班牙和英国）进行的研究中的数据，作为人类早期生活外显子组（HELIX）项目的一部分。对母亲及其单胎后代进行随访，直至儿童 6 至 12 岁。数据分析于 2019 年 3 月 1 日至 8 月 2 日进行。
使用经过验证的食物频率问卷评估孕妇怀孕期间的鱼类摄入量（每周几次），并使用母亲全血和脐血样本评估母亲的汞浓度（每升微克）。
使用腰围、收缩压和舒张压以及甘油三酯、高密度脂蛋白胆固醇和胰岛素水平的 z 分数计算儿童的综合代谢综合征评分。代谢综合征评分较高（评分范围-4.9 至 7.5）表示代谢状况较差。使用三种蛋白质面板测量儿童血浆中的几种细胞因子和脂肪因子。
该研究纳入了 805 名母亲及其单胎子女。在母亲中，纳入队列或婴儿出生时的平均（SD）年龄为 31.3（4.6）岁。共有 400 名女性（49.7%）具有较高的教育水平，432 名女性（53.7%）为多产。在儿童中，平均（SD）年龄为 8.4（1.5）岁（年龄范围 6-12 岁）。共有 453 名儿童（56.3%）为男孩，734 名儿童（91.2%）为白人。与低鱼类摄入量（每周<1 次）相比，怀孕期间摄入符合健康建议（每周 1 至 3 次）的鱼类与儿童代谢综合征评分降低 1 个单位（β=-0.96；95%CI，-1.49 至-0.42）相关，调整了母亲的汞水平和其他协变量后。每周摄入鱼类超过 3 次没有进一步的益处。较高的母体汞浓度与后代代谢综合征评分的增加独立相关（β每增加 2 倍汞浓度=0.18；95%CI，0.01-0.34）。与低鱼类摄入量相比，怀孕期间适量和高量的鱼类摄入与儿童体内促炎细胞因子和脂肪因子水平降低有关。综合分析确定了一群儿童对代谢疾病的易感性增加，其特征是怀孕期间鱼类摄入量低、母亲汞水平高、儿童脂联素水平降低以及瘦素、肿瘤坏死因子-α和白细胞介素 6 和白细胞介素 1β水平升高。
这项研究的结果表明，怀孕期间摄入适量的鱼类，符合当前的健康建议，与儿童的代谢健康改善有关，而母体高汞暴露与儿童不良的代谢状况有关。
