Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: Results from the Mediterranean PHIME cohort
Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: Results from the Mediterranean PHIME cohort
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DOI：
10.1016/j.ijheh.2018.07.011
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发表时间：
2019-01-01
影响因子：
6
通讯作者：
Horvat, Milena
中科院分区：
文献类型：
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作者：
Barbone, Fabio;Rosolen, Valentina;Horvat, Milena
简介：产前急性接触高剂量汞 (Hg) 导致的神经毒性已有充分记录。然而，产前接触低汞水平对儿童神经发育的影响以及怀孕期间吃鱼的“安全”问题仍然存在争议。对母婴生物样本中的汞浓度和出生队列研究中嵌入的神经发育评分进行国际比较，可能会为探索这一问题提供有用的证据。 材料和方法：地中海（意大利、斯洛文尼亚、克罗地亚和希腊）队列研究包括 1308 对母子，这些母子参与了易受影响人群长期、低水平、混合元素暴露对公共健康影响的欧盟第六框架计划 (PHIME)。收集母亲的头发和静脉血、脐带血和母乳样本，并测量总汞（THg）水平。在随访的不同阶段通过问卷收集人口统计和社会经济信息、生活方式和营养习惯。使用贝利婴幼儿发育量表第三版 (BSID-III) 对 18 个月大的儿童进行神经发育测试。对每个国家进行多元线性和逻辑回归，以评估 THg 和 BSID-III 评分之间的关联，获得调整后的 beta 系数和比值比 (OR)。这些值用于进行荟萃分析，探索各国之间可能存在的异质性，并获得 THg 暴露与 BSID-III 评分之间关联的综合估计。结果：THg 中位数 (ng/g) 为：母体头发中 704、母血中 2.4、脐带血中 3.6、母乳中 0.6。 THg 浓度在希腊最高，在斯洛文尼亚最低。克罗地亚和斯洛文尼亚的 BSID-III 神经发育评分较高。多元线性模型的荟萃分析发现，语言综合得分、接受性交流评分与母体头发 THg 增加之间总体呈正相关（分别为 n = 1086；beta = 0.55；95%CI：0.05-1.05 和 n = 1075；beta = 0.12；95%CI：0.02-0.22）。逻辑回归模型的荟萃分析显示，脐带血中的 THg 与次优粗大运动评分之间的总体调整 OR 具有临界显着性（n = 882；OR = 1.03；95%CI：1.00-1.07）。在母体血液中的语言综合评分以及脐带血和母乳中的精细运动评分方面，四个子队列中发现了异质性。在克罗地亚，语言综合评分与母亲静脉血中的 THg 浓度呈正相关（n = 58；β = 4.29；CI95% (-0.02, 8.60)），母亲静脉血中 THg 增加 1 ng/g 与儿童语言评分最低五分位的风险降低 31% 相关（n = 58；OR = 0.69；CI 95%： 0.37、1.01）。通过多元线性回归模型获得的 13 个系数的比较显示，克罗地亚（n = 54；β = -0.53；CI 95%：-1.10，0.04）和斯洛文尼亚（n = 225；β = -0.25；CI 95%：-0.49，-0.01）的精细运动评分与脐带血中 THg 浓度呈负相关。在斯洛文尼亚，母乳中的 THg 水平与次优的精细运动表现相关（n = 195；OR = 5.25；CI 95%：1.36，21.10）。结论：这项研究显示 THg 水平与 18 个月时的发育运动评分之间呈负相关，尽管证据薄弱且部分内部和外部不一致。在这些浓度和年龄下，没有发现 THg 对认知和语言结果产生不利影响的证据。
Introduction: Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about "safety" of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue.Materials and methods: The Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores, obtaining adjusted beta coefficients and odds ratios (ORs). These values were used to conduct a meta-analysis, to explore possible heterogeneity among countries and to obtain combined estimates of the association between THg exposure and BSID-III scores.Results: Median THg (ng/g) was: 704 in maternal hair, 2.4 in maternal blood, 3.6 in cord blood, and 0.6 in breast milk. THg concentrations were highest in Greece and lowest in Slovenia. BSID-III neurodevelopmental scores were higher in Croatia and Slovenia. The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair (n = 1086; beta = 0.55; 95%CI: 0.05-1.05 and n = 1075; beta = 0.12; 95%CI: 0.02-0.22, respectively). The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant (n = 882; OR = 1.03; 95%CI: 1.00-1.07). Heterogeneity was found across the four sub-cohorts for language composite score in maternal blood, and for fine motor scaled score in cord blood and breast milk. Language composite score and THg concentrations in maternal venous blood were positively related (n = 58; beta = 4.29; CI95% (-0.02, 8.60)) in Croatia and an increase of 1 ng/g of THg in maternal venous blood was associated with a reduced risk for children to fall in the lowest quintile of language score by 31% (n = 58; OR = 0.69; CI 95%: 0.37, 1.01). The comparison of 13 coefficients obtained by multiple linear regression model showed an inverse association between fine motor score and THg concentrations in cord blood for Croatia (n = 54; beta = -0.53; CI 95%: -1.10, 0.04) and Slovenia (n = 225; beta = -0.25; CI 95%: -0.49,-0.01). In Slovenia THg level in breast milk was associated with suboptimal fine motor performance (n = 195; OR = 5.25; CI 95%: 1.36, 21.10).Conclusions: This study showed an inverse relation between THg levels and developmental motor scores at 18 months, although the evidence was weak and partially internally and externally inconsistent. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age.