多种微量元素联合暴露与早产的关系

王颖; 邬惟为; 张萍; 郭慧; 刘思嘉; 陈曦; 冯永亮; 杨海澜; 王素萍; 张亚玮

doi:10.16462/j.cnki.zhjbkz.2025.06.006

多种微量元素联合暴露与早产的关系

doi: 10.16462/j.cnki.zhjbkz.2025.06.006

王颖^{1, 2},
邬惟为^{1, 2},
张萍¹,
郭慧¹,
刘思嘉¹,
陈曦³,
冯永亮^{1, 2},
杨海澜⁴,
王素萍^{1, 2, ,},
张亚玮^5, ,

1.
山西医科大学公共卫生学院流行病学教研室，太原 030001
2.
山西医科大学临床流行病学与循证医学中心，太原 030001
3.
中国疾病预防控制中心环境与健康相关产品安全所，北京 100000
4.
山西医科大学第一医院妇产科，太原 030001
5.
国家癌症中心，国家肿瘤临床医学研究中心，中国医学科学院北京协和医学院肿瘤医院，北京 100000

基金项目:

国家自然科学基金 82204145

国家自然科学基金 82373677

山西省基础研究计划 20210302124583

中央引导地方科技发展资金 YDZX20201400001058

山西医科大学博士启动基金 XD2023

山西省高等教育“百亿工程”科技引导专项 2024

详细信息

通讯作者:
王素萍，E-mail: supingwang@sxmu.edu.cn

张亚玮，E-mail: zhangya69@foxmail.com

中图分类号: R181;R17
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出版历程
- 收稿日期: 2024-12-19
- 修回日期: 2025-03-11
- 刊出日期: 2025-06-10

Multiple trace elements co-exposure and risk of preterm birth

WANG Ying^{1, 2},
WU Weiwei^{1, 2},
ZHANG Ping¹,
GUO Hui¹,
LIU Sijia¹,
CHEN Xi³,
FENG Yongliang^{1, 2},
YANG Hailan⁴,
WANG Suping^{1, 2
, ,},
ZHANG Yawei^{5
, ,}

1.
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
2.
Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
3.
National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100000, China
4.
Obstetrics and Gynecology, First Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, China
5.
Department of Cancer Prevention and Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100000, China

Funds:

National Natural Science Foundation of China 82204145

National Natural Science Foundation of China 82373677

Natural Science Basic Research Program of Shanxi Province 20210302124583

Central Government Guides Local Science and Technology Development Fund Project YDZX20201400001058

Doctoral Initiation Fund of Shanxi Medical University XD2023

Shanxi Province Higher Education " Billion Prigect" Science and Techonology Guidance Project 2024

More Information

Corresponding author: WANG Suping, E-mail: supingwang@sxmu.edu.cn; ZHANG Yawei, E-mail: zhangya69@foxmail.com

摘要

摘要: 目的了解孕妇微量元素内暴露水平，探讨多种微量元素联合暴露与早产的关系。方法选取2012年3月―2016年2月于山西医科大学第一医院产科住院分娩的1 922对母婴作为研究对象，采用感耦合等离子体质谱法测定母血及脐带血中钒(Vanadium, V)、铬(Chromium, Cr)、锰(Manganese, Mn)、钴(Cobalt, Co)、镍(Nickel, Ni)、铜(Copper, Cu)、锌(Zinc, Zn)、硒(Selenium, Se)、钼(Molybdenum, Mo)的浓度，利用分位数g-计算(quartile g-computation, QGCOMP)分析多种微量元素联合暴露与早产的关系。结果与Cu低水平相比，母血Cu中水平是早产的危险因素(OR=1.58, 95% CI：1.01~2.49)；与Se低水平相比，母血Se高水平是早产的保护因素(OR=0.50, 95% CI：0.26~0.96)；与Mn低水平相比，脐带血Mn高水平是早产的危险因素(OR=1.70, 95% CI：1.04~2.78)；与Zn低水平相比，脐带血Zn中水平(OR=0.41, 95% CI：0.26~0.66)和高水平(OR=0.54, 95% CI：0.33~0.88)均是早产的保护因素。QGCOMP分析结果显示，母血、脐带血中微量元素联合暴露对早产影响的总效应值分别为-0.53(95% CI：-0.86~-0.19)、-0.47(95% CI：-0.84~-0.09)。母血中微量元素联合暴露对降低孕妇早产发生贡献程度最大的是Cr，脐带血微量元素联合暴露中Zn的负向权重最大。结论微量元素联合暴露与早产的发生有关，Zn、Se和Cr高水平能够降低早产的发生风险。
- 微量元素 /
- 联合暴露 /
- 早产
Abstract: Objective To examine the association between trace elements co-exposure and risk of preterm birth. Methods A total of 1 922 mother infant pairs who joined a birth cohort in taiyuan from 2012 to 2016 were selected as the study population. The concentrations of Vanadium (V), Chromium (Cr), Manganese (Mn), Cobalt (Co), Nickel (Ni), Copper (Cu), Zinc (Zn), Selenium (Se), and Molybdenum (Mo) in maternal and umbilical cord blood were determined using inductively coupled plasma mass spectrometry (ICP-MS). We employed quartile g-computation (QGCOMP) to examine trace elements co-exposure in relation to preterm birth. Results An increased risk of preterm birth was associated with maternal Cu (OR=1.58, 95% CI: 1.01-2.49). High maternal exposure level of Se was associated with preterm birth (OR=0.50, 95% CI: 0.26-0.96). An increased risk of preterm birth was associated with cord blood Mn (OR=1.70, 95% CI: 1.04-2.78). Both medium (OR=0.41, 95% CI: 0.26-0.66) and high (OR=0.54, 95% CI: 0.33-0.88) cord blood level of Zn was associated with preterm birth. The QGCOMP showed that preterm birth was associated with maternal metal co-exposure (-0.53, 95% CI: -0.86--0.19) and cord metal co-exposure (-0.47, 95% CI: -0.84--0.09). Cr contributed the most to the reduction in preterm birth in maternal trace elements co-exposure and Zn contributed the most in cord trace elements co-exposure. Conclusions Our study suggested that trace elements are associated with preterm birth, and the decreasing risk is driven by Zn, Se and Cr.
- Trace elements /
- Co-exposure /
- Preterm birth

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图 1 母血微量元素水平与早产的关系

V：钒；Cr：铬；Mn：锰；Co：钴；Ni：镍；Cu：铜；Zn：锌；Se：硒；Mo：钼；调整孕妇年龄、孕妇文化程度、孕期体育活动、孕前BMI、孕期增重、妊娠期高血压疾病、孕期主被动吸烟。

Figure 1. Relationship between maternal blood trace element levels and premature delivery

V: Vanadium; Cr: Chromium; Mn: Manganese; Co: Cobalt; Ni: Nickel; Cu: Copper; Zn: Zinc; Se: Selenium; Mo: Molybdenum; The adjustment factors were maternal age, maternal education level, pre-pregnancy BMI, pregnancy weight gain, gestational hypertension, and active and passive smoking during pregnanay.

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图 2 脐带血微量元素水平与早产的关系

Figure 2. Relationship between umbilical cord blood trace element levels and premature delivery

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图 3 母血和脐带血微量元素联合暴露与早产的关系

Cr：铬；Mo：钼；Zn：锌；Mn：锰；Cu：铜；Se：硒；Ni：镍；调整因素为孕妇年龄、孕妇文化程度、孕前BMI、孕期增重、妊娠期高血压、孕期主被动吸烟。

Figure 3. Relationship between combined exposure of trace elements in maternal blood and umbilical cord blood and premature birth

Cr: Chromium; Mo: Molybdenum; Zn: Zinc; Mn: Manganese; Cu: Copper; Se: Selenium; Ni: Nickel; The adjustment factors were maternal age, maternal education level, pre-pregnancy BMI, pregnancy weight gain, gestational hypertension, and active and passive smoking during pregnanay.

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表 1 孕妇早产一般情况及影响因素分析

Table 1. Analysis of general situation and influencing factors of premature birth in pregnant woman

变量Variable	早产Premature delivery^①(n=152)	足月产Term birth^①(n=1 770)	P值vaule
孕妇年龄/岁Maternal age/years			0.971^②
< 25	15(9.87)	120(6.78)
25~＜30	52(34.21)	690(38.98)
30~45	85(55.92)	960(54.24)
孕妇文化程度Educational level of pregnant women			0.001^②
初中及以下Junior high school and below	47(30.92)	306(17.29)
高中/中专/大专High school / technical secondary school/college	47(30.92)	587(33.16)
大学及以上University and above	58(38.16)	877(49.55)
孕前BMI Pre pregnancy BMI			0.697^②
较低Lower	25(16.45)	235(13.28)
正常Normal	85(55.92)	1 129(63.78)
超重/肥胖Overweight/obese	42(27.63)	406(22.94)
孕期增重Weight gain during pregnancy			0.031^②
不足Deficiency	44(28.95)	309(17.46)
适宜Suitable	43(28.29)	626(35.37)
增多Increase	65(42.76)	835(47.17)
孕期主被动吸烟Active and passive smoking during pregnancy			0.663^③
是Yes	130(85.53)	1 536(86.78)
否No	22(14.47)	234(13.22)
孕期体育活动/(h·周^-1) Physical activity during pregnancy/(h·week^-1)			0.003^②
< 7	61(40.13)	528(29.83)
7~＜10	53(34.87)	624(35.25)
≥10	38(25.00)	618(34.92)
产次Parity			0.413^③
初产Primipara	106(69.74)	1 289(72.82)
多产Prolific	46(30.26)	481(27.18)
妊娠期高血压疾病Hypertensive disorder complicating pregnancy			0.001^③
是Yes	57(37.5)	121(6.84)
否No	95(62.5)	1 649(93.16)
妊娠期糖尿病Gestational diabetes mellitus			0.741^③
是Yes	64(42.11)	721(40.73)
否No	88(57.89)	1 049(59.27)
注：①以人数(占比/%)表示；②采用秩和检验；③采用χ²检验。 Note: ① Number of people (proportion/%); ② Rank sum test was used; ③ Test with χ².

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表 2 早产和足月产孕妇微量元素水平

Table 2. Micronutrient levels in preterm and term pregnant women

微量元素Trace element	总人群Total population (n=1 922)		早产Premature delivery (n=152)		足月产Term birth (n=1 770)		r
微量元素Trace element	检出人数Number of people detected/%	P₅₀(P₂₅, P₇₅)	检出人数Number of people detected/%	P₅₀(P₂₅, P₇₅)	检出人数Number of people detected/%	P₅₀(P₂₅, P₇₅)	r
母血Maternal blood
V/(μg·L^-1)	1 554(80.85)	17.60(10.39, 22.68)	129(84.87)	17.64(11.96, 22.45)	1 425(80.51)	17.60(10.38, 22.70)	0.68
Cr/(μg·L^-1)	1 443(75.08)	3(0.22, 29.59)	107(70.39)	4.72(0.10, 16.47)	1 336(75.48)	7.28(0.33, 30.90)	0.46
Mn/(μg·L^-1)	1 768(91.99)	28.97(19.15, 39.81)	133(87.50)	24.94(17.53, 37.71)	1 635(92.37)	29.20(19.26, 40.10)	0.11
Co/(μg·L^-1)	1 014(52.76)	0.33(0.05, 1.93)	82(53.95)	0.27(0.05, 1.42)	932(52.66)	0.34(0.05, 1.94)	0.45
Ni/(μg·L^-1)	1 150(59.83)	6.48(1.50, 13.22)	85(55.92)	5.58(1.50, 12.66)	1 065(60.17)	6.62(1.50, 13.34)	0.39
Cu/(mg·L^-1)	1 922(100.00)	1.35(1.09, 1.59)	152(100.00)	1.32(1.13, 1.52)	1 770(100.00)	1.35(1.09, 1.59)	0.33
Zn/(mg·L^-1)	1 922(100.00)	6.47(5.35, 7.66)	152(100.00)	6.31(5.00, 7.82)	1 770(100.00)	6.48(5.39, 7.65)	0.28
Se/(μg·L^-1)	1 922(100.00)	249.79(191.91, 376.59)	152(100.00)	233.29(181.28, 371.90)	1 770(100.00)	250.58(193.48, 378.01)	0.52
Mo/(μg·L^-1)	1 600(83.25)	4.10(0.97, 11.19)	130(85.53)	4.04(0.93, 11.25)	1 470(83.05)	4.11(0.97, 11.18)	0.52
脐带血Umbilical cord blood
V/(μg·L^-1)	1 406(73.15)	15.41(2.00, 21.74)	117(76.97)	16.26(4.88, 21.27)	1 289(72.82)	15.37(2.00, 21.74)
Cr/(μg·L^-1)	1 656(86.16)	8.71(3.30, 42.93)	135(88.82)	8.67(3.23, 46.10)	1 521(85.93)	8.74(3.31, 41.63)
Mn/(μg·L^-1)	1 922(100.00)	54.63(42.16, 72.00)	152(100.00)	57.42(42.28, 79.14)	1 770(100.00)	54.41(42.13, 71.47)
Co/(μg·L^-1)	1 056(54.94)	0.26(0.05, 0.74)	87(57.24)	0.26(0.05, 1.17)	969(54.75)	0.26(0.05, 0.73)
Ni/(μg·L^-1)	973(50.62)	3.15(1.50, 12.51)	85(55.92)	6.17(1.50, 13.48)	888(50.17)	3.03(1.50, 12.47)
Cu/(mg·L^-1)	1 922(100.00)	0.52(0.44, 0.62)	152(100.00)	0.52(0.44, 0.60)	1 770(100.00)	0.52(0.44, 0.62)
Zn/(mg·L^-1)	1 922(100.00)	2.54(2.15, 2.99)	152(100.00)	2.30(1.93, 2.88)	1 770(100.00)	2.56(2.17, 3.01)
Se/(μg·L^-1)	1 922(100.00)	240.24(200.44, 295.76)	152(100.00)	229.20(194.02, 279.15)	1 770(100.00)	241.09(201.44, 297.99)
Mo/(μg·L-1)	1 603(83.40)	2.10(0.79, 7.55)	128(84.21)	1.72(0.76, 7.68)	1 475(83.33)	2.17(0.79, 7.54)
注：V，钒；Cr，铬；Mn，锰；Co，钴；Ni，镍；Cu，铜；Zn，锌；Se，硒；Mo，钼。 Note: V, Vanadium; Cr, Chromium; Mn, Manganese; Co, Cobalt; Ni, Nickel; Cu, Copper; Zn, Zinc; Se, Selenium; Mo, Molybdenum.

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参考文献(15)

[1]	Qiao J, Wang YY, Li XH, et al. A Lancet Commission on 70 years of women′s reproductive, maternal, newborn, child, and adolescent health in China [J]. Lancet, 2021, 397(10293): 2497-2536. doi: 10.1016/S0140-6736(20)32708-2.
[2]	Zhang WX, Chen H, Xia W, et al. Associations of plasma manganese with adverse pregnancy outcomes: nested case-control studies in a Chinese birth cohort [J]. Chemosphere, 2023, 345: 140550. doi: 10.1016/j.chemosphere.2023.140550.
[3]	Hao YX, Yan LL, Pang YM, et al. Maternal serum level of manganese, single nucleotide polymorphisms, and risk of spontaneous preterm birth: a nested case－control study in China[J]. Environ Pollut, 2020,262:114187. DOI: 10.1016/j.envpol.2020.114187.
[4]	Issah I, Duah MS, 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.
[5]	Gohari H, Khajavian N, Mahmoudian A, et al. Copper and zinc deficiency to the risk of preterm labor in pregnant women: a case-control study [J]. BMC Pregnancy Childbirth, 2023, 23(1): 366. doi: 10.1186/s12884-023-05625-2.
[6]	Ashrap P, Watkins DJ, Mukherjee B, et al. Performance of urine, blood, and integrated metal biomarkers in relation to birth outcomes in a mixture setting [J]. Environ Res, 2021, 200: 111435. doi: 10.1016/j.envres.2021.111435.
[7]	Kumari D, Garg S, Bhawrani P. Zinc homeostasis in immunity and its association with preterm births [J]. Scand J Immunol, 2022, 95(4): e13142. doi: 10.1111/sji.13142.
[8]	Barman M, Brantsæter AL, Nilsson S, et al. Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery [J]. Br J Nutr, 2020, 123(2): 209-219. doi: 10.1017/S0007114519002113.
[9]	McDougall AR, Dore G, Aboud L, et al. The effect of selenium supplementation in pregnant women on maternal, fetal, and newborn outcomes: a systematic review and Meta-analysis [J]. Am J Obstet Gynecol MFM, 2023, 5(11): 101160. doi: 10.1016/j.ajogmf.2023.101160.
[10]	Liu J, Ruan FY, Cao ST, et al. Associations between prenatal multiple metal exposure and preterm birth: comparison of four statistical models [J]. Chemosphere, 2022, 289: 133015. doi: 10.1016/j.chemosphere.2021.133015.
[11]	Freire C, Amaya E, Gil F, et al. Placental metal concentrations and birth outcomes: the environment and childhood (INMA) project [J]. Int J Hyg Environ Health, 2019, 222(3): 468-478. doi: 10.1016/j.ijheh.2018.12.014.
[12]	Eaves LA, Keil AP, Jukic AM, et al. Toxic metal mixtures in private well water and increased risk for preterm birth in North Carolina [J]. Environ Health, 2023, 22(1): 69. doi: 10.1186/s12940-023-01021-7.
[13]	Zhao L, Wang SL, Liu M, et al. Maternal urinary metal(loid)s and risk of preterm birth: a cohort study in the Tibetan Plateau [J]. Environ Pollut, 2023, 333: 122085. doi: 10.1016/j.envpol.2023.122085.
[14]	Huang H, Wei LM, Chen X, et al. Cord serum elementomics profiling of 56 elements depicts risk of preterm birth: evidence from a prospective birth cohort in rural Bangladesh [J]. Environ Int, 2021, 156: 106731. doi: 10.1016/j.envint.2021.106731.
[15]	Wang ZK, Huang SD, Zhang WL, et al. Chemical element concentrations in cord whole blood and the risk of preterm birth for pregnant women in Guangdong, China [J]. Ecotoxicol Environ Saf, 2022, 247: 114228. doi: 10.1016/j.ecoenv.2022.114228.