BACKGROUND Low-dose mercury (Hg) exposure has been associated with cardiovascular diseases, diabetes, and obesity in adults, but it is unknown the metabolic consequence of in utero Hg exposure. This study aimed to investigate the association between in utero Hg exposure and child overweight or obesity (OWO) and to explore if adequate maternal folate can mitigate Hg toxicity. METHODS This prospective study included 1442 mother-child pairs recruited at birth and followed up to age 15 years. Maternal Hg in red blood cells and plasma folate levels were measured in samples collected 1-3 days after delivery (a proxy for third trimester exposure). Adequate folate was defined as plasma folate ≥ 20.4 nmol/L. Childhood OWO was defined as body mass index ≥ 85% percentile for age and sex. RESULTS The median (interquartile range) of maternal Hg levels were 2.11 (1.04-3.70) μg/L. Geometric mean (95% CI) of maternal folate levels were 31.1 (30.1-32.1) nmol/L. Maternal Hg levels were positively associated with child OWO from age 2-15 years, independent of maternal pre-pregnancy OWO, diabetes, and other covariates. The relative risk (RR = 1.24, 95% CI 1.05-1.47) of child OWO associated with the highest quartile of Hg exposure was 24% higher than those with the lowest quartile. Maternal pre-pregnancy OWO and/or diabetes additively enhanced Hg toxicity. The highest risk of child OWO was found among children of OWO and diabetic mothers in the top Hg quartile (RR = 2.06; 95% CI 1.56-2.71) compared to their counterparts. Furthermore, adequate maternal folate status mitigated Hg toxicity. Given top quartile Hg exposure, adequate maternal folate was associated with a 34% reduction in child OWO risk (RR = 0.66, 95% CI 0.51-0.85) as compared with insufficient maternal folate. There was a suggestive interaction between maternal Hg and folate levels on child OWO risk (p for interaction = 0.086). CONCLUSIONS In this US urban, multi-ethnic population, elevated in utero Hg exposure was associated with a higher risk of OWO in childhood, and such risk was enhanced by maternal OWO and/or diabetes and reduced by adequate maternal folate. These findings underscore the need to screen for Hg and to optimize maternal folate status, especially among mothers with OWO and/or diabetes.

中文翻译：

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子宫内接触汞和儿童超重或肥胖：母体叶酸状态的抵消作用。

背景 低剂量汞 (Hg) 暴露与成人心血管疾病、糖尿病和肥胖有关，但子宫内汞暴露的代谢后果尚不清楚。本研究旨在调查子宫内汞暴露与儿童超重或肥胖 (OWO) 之间的关系，并探讨是否有足够的母体叶酸可以减轻汞毒性。方法 这项前瞻性研究包括 1442 对出生时招募的母子对，并随访至 15 岁。在分娩后 1-3 天收集的样本中测量母体红细胞中的 Hg 和血浆叶酸水平（代表妊娠晚期暴露）。叶酸充足定义为血浆叶酸≥20.4 nmol/L。儿童 OWO 定义为年龄和性别的体重指数≥ 85%。结果 母体 Hg 水平的中位数（四分位距）为 2。11（1.04-3.70）微克/升。母体叶酸水平的几何平均值 (95% CI) 为 31.1 (30.1-32.1) nmol/L。母亲 Hg 水平与 2-15 岁的儿童 OWO 呈正相关，与母亲孕前 OWO、糖尿病和其他协变量无关。与最高四分位数的汞暴露相关的儿童 OWO 的相对风险（RR = 1.24, 95% CI 1.05-1.47）比最低四分位数的儿童高 24%。产妇孕前 OWO 和/或糖尿病额外增强了 Hg 毒性。与同龄人相比，在 OWO 的孩子和最高四分位数的糖尿病母亲中发现儿童 OWO 的风险最高（RR = 2.06；95% CI 1.56-2.71）。此外，足够的母体叶酸状态可减轻汞毒性。鉴于最高四分位数的汞暴露，足够的母体叶酸与儿童 OWO 风险降低 34% 相关（RR = 0.66，95% CI 0.51-0.85) 与母体叶酸不足相比。母体 Hg 和叶酸水平对儿童 OWO 风险存在暗示性交互作用（交互作用的 p = 0.086）。结论 在这个美国城市多种族人口中，子宫内汞暴露升高与儿童期 OWO 风险升高相关，而母体 OWO 和/或糖尿病会增加这种风险，而母体叶酸充足会降低这种风险。这些发现强调了筛查 Hg 和优化母亲叶酸状态的必要性，尤其是在患有 OWO 和/或糖尿病的母亲中。子宫内汞暴露升高与儿童期 OWO 风险升高相关，而母体 OWO 和/或糖尿病会增加这种风险，而母体叶酸充足则可降低这种风险。这些发现强调了筛查 Hg 和优化母亲叶酸状态的必要性，尤其是在患有 OWO 和/或糖尿病的母亲中。子宫内汞暴露升高与儿童期 OWO 风险升高相关，而母体 OWO 和/或糖尿病会增加这种风险，而母体叶酸充足则可降低这种风险。这些发现强调了筛查 Hg 和优化母亲叶酸状态的必要性，尤其是在患有 OWO 和/或糖尿病的母亲中。