母亲孕早期金属暴露与子代1岁及3岁体格发育关联的前瞻性队列研究

张晓; 蒋杨倩; 庞丽雅; 杜江波; 林苑; 马红霞

doi:10.16835/j.cnki.1000-9817.2025142

母亲孕早期金属暴露与子代1岁及3岁体格发育关联的前瞻性队列研究

doi: 10.16835/j.cnki.1000-9817.2025142

张晓^{1, 2},
蒋杨倩^{1, 3},
庞丽雅^{1, 3},
杜江波^{1, 2},
林苑^{1, 3},
马红霞^{1, 2}

1.
南京医科大学生殖医学与子代健康全国重点实验室，江苏 211166
2.
南京医科大学公共卫生学院流行病学系
3.
南京医科大学公共卫生学院儿少卫生与妇幼保健学系

基金项目:

国家重点研发计划项目 2024YFC2706904

详细信息

作者简介:
张晓(2000-)，女，四川德阳人，在读硕士，主要研究方向为孕期环境暴露与儿童生长发育

利益冲突声明 所有作者声明无利益冲突。
中图分类号: R179 R194.3 R715.3
计量
- 文章访问数: 12
- HTML全文浏览量: 7
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2025-01-07
- 修回日期: 2025-03-24
- 网络出版日期: 2025-08-30
- 刊出日期: 2025-08-25

A prospective cohort study of association between maternal metal exposure during early pregnancy and physical development in offspring at ages 1 and 3

ZHANG Xiao^{1, 2},
JIANG Yangqian^{1, 3},
PANG Liya^{1, 3},
DU Jiangbo^{1, 2},
LIN Yuan^{1, 3},
MA Hongxia^{1, 2}

1.
State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China

摘要

摘要: 目的分析母亲孕早期金属暴露对子代1岁及3岁时体格发育的影响，为减少重金属对婴幼儿健康的影响提供科学依据。方法选取2014—2018年江苏出生队列(JBC)的1 588对母子为研究对象，采用多元线性回归模型、广义估计方程(GEE)和加权分位数和(WQS)回归模型评估母亲孕早期尿液中经尿比重(SG)校正的24种金属质量体积浓度与子代1和3岁时年龄别身长/身高Z评分(HAZ)、年龄别体重Z评分(WAZ)、身长/身高别体重Z评分(WHZ)、年龄别头围Z评分(HCAZ)的关联。结果 GEE分析发现，在调整混杂因素后，母亲孕早期尿液中钒、锡、铈、铅和铀浓度每增加1个自然对数单位，子代1和3岁时HCAZ平均降低14.29%，4.82%，2.62%，5.04%，8.33%(校正P值均 < 0.05)。多元线性回归分析发现，尿液中钒质量体积浓度增加与子代1岁时HAZ降低相关，尿液中钒、铬、锡、锑和铀质量体积浓度增加与子代1岁时HCAZ降低相关(校正P值均 < 0.05)。在WQS回归模型中，WQS指数每增加1个单位，子代1岁时HCAZ降低22.64%，其中锡在关联中具有最大贡献权重(22.2%)，其次是铀(16.2%)、铅(11.5%)、钒(10.0%)、砷(6.5%)和铬(5.0%)。结论孕早期特定金属及其混合物暴露对子代1岁及3岁时体格发育，尤其是头围可能产生重要影响。应加强孕早期金属暴露的监测，以减少环境金属污染对婴幼儿健康的潜在威胁。
- 母亲 /
- 受孕期 /
- 金属 /
- 体格检查 /
- 队列研究
Abstract: Objective To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health. Methods From 2024 to 2018, a total of 1 588 mother-child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height-for-age Z-score(HAZ), weight-for-age Z-score(WAZ), weight-for-length/height Z-score(WHZ), and head circumference-for-age Z-score(HCAZ) at 1 and 3 years of age. Results After adjusting for confounders, GEE analysis revealed that each natural log-unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62%, 5.04%, and 8.33%, respectively, at 1 and 3 years of age (FDR-P < 0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR-P < 0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%). Conclusions Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.
- Mothers /
- Fertile period /
- Mental health /
- Physical examination /
- Cohort studies
注释:

1) 利益冲突声明 所有作者声明无利益冲突。

HTML全文

图 1 基于WQS模型的金属混合物暴露与子代1岁时HCAZ的关联及各金属权重

Figure 1. Associations between mixed metal mixtures and HCAZ at 1 year based on WQS model, and corresponding metal weights

下载: 全尺寸图片幻灯片

表 1 母亲尿液中金属检出率及经尿比重校正后的质量体积浓度分布[M(P₂₅, P₇₅)]

Table 1. The detection rates and mass concentration distributions of maternal SG-corrected urinary metal concentrations [M(P₂₅, P₇₅)]

金属	检测限/ (μg·L^-1)	检出率/%	尿比重校正质量体积浓度/(μg·L^-1)
砷	0.017 3	100.0	26.90(18.72, 41.56)
钡	0.006 7	99.7	20.74(5.07, 57.91)
镉	0.000 2	100.0	0.57(0.37, 0.96)
铈	0.000 3	99.7	0.19(0.02, 0.64)
钴	0.001 0	99.8	0.43(0.27, 0.72)
铬	0.003 0	99.9	0.69(0.39, 1.14)
铯	0.772 8	99.9	12.15(9.81, 15.33)
铜	0.035 0	99.9	17.6(13.51, 22.59)
镧	0.000 7	96.4	0.02(0.01, 0.06)
锰	0.083 4	95.7	0.62(0.33, 1.17)
钼	0.010 5	100.0	58.72(45.62, 75.37)
镍	0.009 7	99.9	3.45(2.29, 5.35)
铅	0.003 0	100.0	1.83(1.03, 3.16)
铷	0.274 4	100.0	2 289.60(1 782.34, 2 862.61)
铼	0.000 1	100.0	0.05(0.03, 0.07)
锑	0.001 3	99.8	0.13(0.09, 0.19)
硒	0.016 2	100.0	11.03(8.42, 14.25)
锡	0.032 7	99.6	1.16(0.57, 3.13)
锶	0.036 5	100.0	147.20(94.01, 212.82)
铊	0.000 7	100.0	0.41(0.31, 0.54)
铀	0.000 6	97.4	0.01(0.01, 0.02)
钒	0.000 1	100.0	0.21(0.16, 0.30)
钛	0.024 8	100.0	147.01(95.59, 211.71)
锌	0.553 9	100.0	443.25(288.30, 672.27)

下载: 导出CSV

参考文献(32)

[1]	TAYLOR C M, GOLDING J, EMOND A M. Lead, cadmium and mercury levels in pregnancy: the need for international consensus on levels of concern[J]. J Dev Orig Health Dis, 2014, 5(1): 16-30. doi: 10.1017/S2040174413000500
[2]	ISSAH I, DUAH M S, ARKO-MENSAH J, et al. Exposure to metal mixtures and adverse pregnancy and birth outcomes: a systematic review[J]. Sci Total Environ, 2024, 908: 168380. doi: 10.1016/j.scitotenv.2023.168380
[3]	王子函, 陶兴永. 孕期环境重金属暴露与儿童体格发育水平及生长轨迹关联的研究进展[J]. 环境与职业医学, 2024, 41(5): 586-591. WANG Z H, TAO X Y. Research progress on environmental heavy metal exposure during pregnancy and children's physical development level and growth trajectory[J]. J Environ Occup Med, 2024, 41(5): 586-591. (in Chinese)
[4]	AHMADI S, BOTTON J, ZOUMENOU R, et al. Lead exposure in infancy and subsequent growth in Beninese children[J]. Toxics, 2022, 10(10): 595. doi: 10.3390/toxics10100595
[5]	LI C, WU C, ZHANG J, et al. Associations of prenatal exposure to vanadium with early-childhood growth: a prospective prenatal cohort study[J]. J Hazard Mater, 2021, 411: 125102. doi: 10.1016/j.jhazmat.2021.125102
[6]	LIU L, YAO L, DONG M, et al. Maternal urinary cadmium concentrations in early pregnancy in relation to prenatal and postpartum size of offspring[J]. J Trace Elem Med Biol, 2021, 68: 126823. doi: 10.1016/j.jtemb.2021.126823
[7]	CLAUS HENN B, COULL B A, WRIGHT R O. Chemical mixtures and children's health[J]. Curr Opin Pediatr, 2014, 26(2): 223-229. doi: 10.1097/MOP.0000000000000067
[8]	ZHANG X, WEI H, GUAN Q, et al. Maternal exposure to trace elements, toxic metals, and longitudinal changes in infancy anthropometry and growth trajectories: a prospective cohort study[J]. Environ Sci Technol, 2023, 57(32): 11779-11791. doi: 10.1021/acs.est.3c02535
[9]	ZHOU Y, ZHOU J, HE Y, et al. Associations between prenatal metal exposure and growth rate in children: based on Hangzhou Birth Cohort Study[J]. Sci Total Environ, 2024, 916: 170164. doi: 10.1016/j.scitotenv.2024.170164
[10]	HUANG W, IGUSA T, WANG G, et al. In-utero co-exposure to toxic metals and micronutrients on childhood risk of overweight or obesity: new insight on micronutrients counteracting toxic metals[J]. Int J Obes, 2005, 2022, 46(8): 1435-1445.
[11]	WOO J G. Infant growth and long-term cardiometabolic health: a review of recent findings[J]. Curr Nutr Rep, 2019, 8(1): 29-41. doi: 10.1007/s13668-019-0259-0
[12]	DU J, LIN Y, XIA Y, et al. Cohort profile: the Jiangsu Birth Cohort[J]. Int J Epidemiol, 2023, 52(6): e354-e363. doi: 10.1093/ije/dyad139
[13]	WHO Multicentre Growth Reference Study Group. WHO child growth standards based on length/height, weight and age[J]. Acta Paediatr Suppl, 2006, 450: 76-85.
[14]	WAI K M, SER P H, AHMAD S A, et al. In-utero arsenic exposure and growth of infants from birth to 6 months of age: a prospective cohort study in rural Bangladesh[J]. Int J Environ Health Res, 2020, 30(4): 421-434. doi: 10.1080/09603123.2019.1597835
[15]	KIM S S, MEEKER J D, AUNG M T, et al. Urinary trace metals in association with fetal ultrasound measures during pregnancy[J]. Environ Epidemiol, 2020, 4(2): e075. doi: 10.1097/EE9.0000000000000075
[16]	KIM S S, XU X, ZHANG Y, et al. Birth outcomes associated with maternal exposure to metals from informal electronic waste recycling in Guiyu, China[J]. Environ Int, 2020, 137: 105580. doi: 10.1016/j.envint.2020.105580
[17]	ZHANG W, LIU W, BAO S, et al. Association of adverse birth outcomes with prenatal uranium exposure: a population-based cohort study[J]. Environ Int, 2020, 135: 105391. doi: 10.1016/j.envint.2019.105391
[18]	HOOVER J H, COKER E S, ERDEI E, et al. Preterm birth and metal mixture exposure among pregnant women from the Navajo Birth Cohort Study[J]. Environ Health Perspect, 2023, 131(12): 127014. doi: 10.1289/EHP10361
[19]	XIE S, SHI J, WANG J, et al. Head circumference growth reference charts of children younger than 7 years in Chinese rural areas[J]. Pediatr Neurol, 2014, 51(6): 814-819. doi: 10.1016/j.pediatrneurol.2014.08.014
[20]	GILMORE J H, LANGWORTHY B, GIRAULT J B, et al. Individual variation of human cortical structure is established in the first year of life[J]. Biol Psychiatry Cogn Neurosci Neuroimag, 2020, 5(10): 971-980.
[21]	李辉, 朱宗涵, 张德英. 2005年中国九市七岁以下儿童体格发育调查[J]. 中华儿科杂志, 2007, 45(8): 609-614. LI H, ZHU Z H, ZHANG D Y. Physical development survey of children under seven years old in nine cities of China in 2005[J]. Chin J Pediatr, 2007, 45(8): 609-614. (in Chinese)
[22]	WRIGHT C M, EMOND A. Head growth and neurocognitive outcomes[J]. Pediatrics, 2015, 135(6): e1393-e1398. doi: 10.1542/peds.2014-3172
[23]	FERRER M, GARCÍA-ESTEBAN R, IÑIGUEZ C, et al. Head circumference and child ADHD symptoms and cognitive functioning: results from a large population-based cohort study[J]. Eur Child Adolesc Psychiatry, 2019, 28(3): 377-388. doi: 10.1007/s00787-018-1202-4
[24]	ZHU Z, SHEN J, ZHU Y, et al. Head circumference trajectories during the first two years of life and cognitive development, emotional, and behavior problems in adolescence: a cohort study[J]. Eur J Pediatr, 2022, 181(9): 3401-3411. doi: 10.1007/s00431-022-04554-0
[25]	ZHOU Y, ZHU Q, MA W, et al. Prenatal vanadium exposure, cytokine expression, and fetal growth: a gender-specific analysis in Shanghai MCPC Study[J]. Sci Total Environ, 2019, 685: 1152-1159. doi: 10.1016/j.scitotenv.2019.06.191
[26]	YAO L, LIU L, DONG M, et al. Trimester-specific prenatal heavy metal exposures and sex-specific postpartum size and growth[J]. J Exp Sci Environ Epidemiol, 2023, 33(6): 895-902. doi: 10.1038/s41370-022-00443-8
[27]	KIM S S, MEEKER J D, KEIL A P, et al. Exposure to 17 trace metals in pregnancy and associations with urinary oxidative stress biomarkers[J]. Environ Res, 2019, 179(Pt B): 108854.
[28]	PAITHANKAR J G, SAINI S, DWIVEDI S, et al. Heavy metal associated health hazards: an interplay of oxidative stress and signal transduction[J]. Chemosphere, 2021, 262: 128350. doi: 10.1016/j.chemosphere.2020.128350
[29]	USENDE I L, OLOPADE J O, EMIKPE B O, et al. Oxidative stress changes observed in selected organs of African giant rats (Cricetomys gambianus) exposed to sodium metavanadate[J]. Int J Vet Sci Med, 2018, 6(1): 80-89. doi: 10.1016/j.ijvsm.2018.03.004
[30]	TIAN Y, MA X, YANG C, et al. The impact of oxidative stress on the bone system in response to the space special environment[J]. Int J Mol Sci, 2017, 18(10): 2132. doi: 10.3390/ijms18102132
[31]	YANG Y, DAI C, CHEN X, et al. Role of uranium toxicity and uranium-induced oxidative stress in advancing kidney injury and endothelial inflammation in rats[J]. BMC Pharmacol Toxicol, 2024, 25(1): 14. doi: 10.1186/s40360-024-00734-w
[32]	XU C, GONG H, NIU L, et al. Maternal exposure to dietary uranium causes oxidative stress and thyroid disruption in zebrafish offspring[J]. Ecotoxicol Environ Saf, 2023, 265: 115501. doi: 10.1016/j.ecoenv.2023.115501