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浙江大学学报（医学版）
浙江大学学报（医学版）  2022, Vol. 51 Issue (3): 326-333    DOI: 10.3724/zdxbyxb-2022-0073
原著     
母亲孕期空气污染物混合暴露对子代先天性心脏病的联合作用
曲艳吉1,周芯俪1,刘小清1,王晰朦1,杨博逸2,陈功博2,3,郭玉明3,聂志强1,欧艳秋1,高向民1,吴勇1,董光辉2,庄建1,陈寄梅1,*()
1.广东省心血管病研究所 广东省人民医院 广东省医学科学院，广东 广州 510080
2.中山大学公共卫生学院劳动与环境卫生学系，广东 广州 510080
3.澳大利亚莫纳什大学流行病学与预防医学系，澳大利亚 墨尔本 3004
Risk of maternal exposure to mixed air pollutants during pregnancy for congenital heart diseases in offspring
QU Yanji1,ZHOU Xinli1,LIU Xiaoqing1,WANG Ximeng1,YANG Boyi2,CHEN Gongbo2,3,GUO Yuming3,NIE Zhiqiang1,OU Yanqiu1,GAO Xiangmin1,WU Yong1,DONG Guanghui2,ZHUANG Jian1,CHEN Jimei1,*()
1. Guangdong Provincial Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China;
2. Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China;
3. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia
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摘要：

目的：探索母亲孕期空气污染物中可入肺颗粒物（PM1）、细颗粒物（PM2.5）、可吸入颗粒物（PM10）和二氧化氮（NO2）混合暴露对子代先天性心脏病发生风险的影响，并估计上述几种污染物的作用权重。方法：纳入广东省先天性心脏病防治登记网（GRCHD）2007—2016年登记的来自21个地市、40家医疗机构的6038例先天性心脏病患儿（病例组）及5227名健康对照儿童（对照组）。采用logistic回归模型评估母亲暴露于单个空气污染物对子代先天性心脏病发生的影响，采用spearman相关系数分析各种污染物之间的相关性。并采用Quantile g-computation评估空气污染物混合暴露对先天性心脏病发生的联合效应及各种污染物的权重。结果：病例组PM1、PM2.5、PM10和NO2的暴露浓度显著高于对照组（均P<0.01）。PM1、PM2.5、PM10、NO2之间的相关系数均大于0.80。母亲孕期PM1、PM2.5、PM10和NO2暴露均与子代先天性心脏病发生风险显著升高有关。当这些紧密相关的污染物混合暴露时，先天性心脏病的发生风险较其独立暴露时更高。混合暴露物与先天性心脏病风险之间呈单调递增关系，混合暴露每升高一个分位数，先天性心脏病的发生风险增加47%（OR=1.47，95%CI：1.34~1.61）。母亲孕早期空气污染物混合暴露对先天性心脏病发生的影响最大，但孕早、中、晚期任一时间段的暴露效应均不及整个孕期的混合暴露效应强。混合暴露中PM10的作用权重最大（81.3%）。结论：母亲孕期空气污染物混合暴露会增加子代先天性心脏病的发生风险，且较各污染物独立暴露时效应更强。PM10在混合暴露中的作用权重最大。
关键词： 先天性心脏病;  空气污染;  可入肺颗粒物;  细颗粒物;  可吸入颗粒物;  二氧化氮;  混合暴露;  联合效应    
Abstract:

Objective: To explore the risk of maternal exposure to mixed air pollutants of particulate matter 1 (PM1), particulate matter 2.5 (PM2.5), particulate matter 10 (PM10) and NO2 for congenital heart disease (CHD) in offspring, and to estimate the ranked weights of the above pollutants. Methods: 6038 CHD patients and 5227 healthy controls from 40 medical institutions in 21 cities in Guangdong Registry of Congenital Heart Disease (GRCHD) from 2007 to 2016 were included. Logistic regression model was used to estimate the effect of maternal exposure to a single air pollutant on the occurrence of CHD in offspring. Spearman correlation coefficient was used to analyze the correlation between various pollutants, and Quantile g-computation was used to evaluate the joint effects of mixed exposure of air pollutants on CHD and the weights of various pollutants. Results: The exposure levels of PM1, PM2.5, PM10 and NO2 in the CHD group were significantly higher than those in the control group (all P<0.01). The correlation coefficients among PM1, PM2.5, PM10 and NO2 were greater than 0.80. PM1, PM2.5, PM10 and NO2 exposure were associated with a significantly increased risk of CHD in offspring. Mixed exposure of these closely correlated pollutants presented much stronger effect on CHD than exposure of any single pollutants. There was a monotonic increasing relationship between mixed exposure and CHD risk. For each quantile increase in mixed exposure, the risk of CHD increased by 47% (OR=1.47, 95%CI: 1.34–1.61). Mixed exposure had greater effect on CHD in the early pregnancy compared with middle and late pregnancy, but the greatest effect was the exposure in the whole pregnancy. The weight of PM10 is the highest in the mixed exposure (81.3%). Conclusions: Maternal exposure to the mixture of air pollutants during pregnancy increases the risk of CHD in offspring, and the effect is much stronger than that of single exposure of various pollutants. PM10 has the largest weights and the strongest effect in the mixed exposure.
Key words: Congenital heart disease    Air pollution    Particulate matter 1    Particulate matter 2.5    Particulate matter 10    Nitrogen dioxide    Mixed exposure    Joint effects
收稿日期: 2022-02-28 出版日期: 2022-09-21
CLC:  R12  
基金资助: 广东省基础与应用基础研究基金（2021A1515110332）；国家重点研发计划（2018YFC1002600）
通讯作者: 陈寄梅     E-mail: chenjimei@gdph.org.cn
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曲艳吉
周芯俪
刘小清
王晰朦
杨博逸
陈功博
郭玉明
聂志强
欧艳秋
高向民
吴勇
董光辉
庄建
陈寄梅

引用本文:

曲艳吉,周芯俪,刘小清,王晰朦,杨博逸,陈功博,郭玉明,聂志强,欧艳秋,高向民,吴勇,董光辉,庄建,陈寄梅. 母亲孕期空气污染物混合暴露对子代先天性心脏病的联合作用[J]. 浙江大学学报（医学版）, 2022, 51(3): 326-333.

QU Yanji,ZHOU Xinli,LIU Xiaoqing,WANG Ximeng,YANG Boyi,CHEN Gongbo,GUO Yuming,NIE Zhiqiang,OU Yanqiu,GAO Xiangmin,WU Yong,DONG Guanghui,ZHUANG Jian,CHEN Jimei. Risk of maternal exposure to mixed air pollutants during pregnancy for congenital heart diseases in offspring. J Zhejiang Univ (Med Sci), 2022, 51(3): 326-333.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0073    或    https://www.zjujournals.com/med/CN/Y2022/V51/I3/326

组别

n

母亲35岁及以上

母亲汉族

母亲受教育超过12年

母亲职业为工人/农民/家庭主妇

母亲吸烟

父亲吸烟

母亲接触农药

母亲接触化学制剂

病例组

6038

596（9.87）*

5944（98.44）*

4960（82.15）*

5456（90.36）*

108（1.79）*

1449（24.00）*

21（0.35）*

70（1.16）*

对照组

5227

404（7.73）

5181（99.12）

4138（79.17）

4958（94.85）

19（0.36）

895（17.12）

5（0.10）

104（1.99）

组?别

n

居室半年内装修

居室距主干路50米内

家庭人均月收入不超过3000元

常住地为城市

NO2

PM1

PM2.5

PM10

病例组

6038

261（4.32）*

882（14.61）*

4056（67.17）*

2322（38.46）*

29.5（20.5，37.9）*

38.9（33.6，41.8）*

47.9（41.3，52.5）*

74.3（64.3，80.8）*

对照组

5227

60（1.15）

567（10.85）

3927（75.13）

1872（35.81）

27.7（19.9，36.5）

37.7（33.1，41.2）

46.4（40.4，51.3）

72.1（62.5，79.2）
表 1  两组母亲基本人口社会学特征和孕早期环境暴露情况比较

污染物

NO2

PM1

PM2.5

PM10

NO2

1

0.80*

0.86*

0.85*

PM1

—

1

0.98*

0.98*

PM2.5

—

—

1

0.99*

PM10

—

—

—

1
表 2  空气污染物之间的相关系数
图 1  空气污染物混合暴露对子代先天性心脏病发生风险的影响以X=1，即分位数25%~50%组为参照绘图.

污染物

调整前

调整后*

OR值

95%CI

OR值

95%CI

NO2

1.11

1.07~1.15

1.17

1.13~1.21

PM1

1.12

1.09~1.16

1.16

1.12~1.20

PM2.5

1.14

1.10~1.17

1.17

1.13~1.22

PM10

1.15

1.11~1.18

1.18

1.14~1.23

混合暴露

1.34

1.23~1.45

1.47

1.34~1.61
表 3  母亲孕期污染物及其混合暴露对子代先天性心脏病发生的风险估计

污染物

孕早期

孕中期

孕晚期

OR （95%CI）

P值

OR （95%CI）

P值

OR （95%CI）

P值

NO2、PM1、PM2.5、PM10混合暴露

1.24 （1.13~1.38）

<0.01

1.14 （1.03~1.25）

<0.01

1.22 （1.10~1.36）

<0.01

NO2与PM1混合暴露

1.24 （1.12~1.37）

<0.01

1.14 （1.04~1.25）

<0.01

1.22 （1.10~1.35）

<0.01

NO2与PM2.5混合暴露

1.29 （1.16~1.43）

<0.01

1.14 （1.03~1.25）

<0.01

1.23 （1.11~1.37）

<0.01

NO2与PM10混合暴露

1.29 （1.16~1.42）

<0.01

1.14 （1.04~1.26）

<0.01

1.22 （1.10~1.35）

<0.01
表 4  母亲不同孕期污染物及其混合暴露对子代先天性心脏病发生的风险估计
图 2  NO、PM、PM和PM在混合暴露中对子代先天性心脏病的作用权重212.510NO：二氧化氮；PM：可入肺颗粒物；PM：细颗粒物；PM：可吸入颗粒物.
1 ROTHG A, MENSAHG A, JOHNSONC O, et al.Global burden of cardiovascular diseases and risk factors, 1990—2019[J]J Am College Cardiol, 2020, 76( 25): 2982-3021.
doi: 10.1016/j.jacc.2020.11.010
2 BURCHILLL J, GAOL, KOVACSA H, et al.Hospitalization trends and health resource use for adult congenital heart disease-related heart failure[J/OL]J Am Heart Assoc, 2018, 7( 15): e008775.
doi: 10.1161/JAHA.118.008775
3 PIERPONTM E, BASSONC T, BENSON JRD W, et al.Genetic basis for congenital heart defects: current knowledge[J]Circulation, 2007, 115( 23): 3015-3038.
doi: 10.1161/CIRCULATIONAHA.106.183056
4 PIERPONTM E, BRUECKNERM, CHUNGW K, et al.Genetic basis for congenital heart disease: revisited: a scientific statement from The American Heart Association[J/OL]Circulation, 2018, 138( 21): e653-e711.
doi: 10.1161/CIR.0000000000000606
5 JENKINSK J, CORREAA, FEINSTEINJ A, et al.Noninherited risk factors and congenital cardiovascular defects: current knowledge[J]Circulation, 2007, 115( 23): 2995-3014.
doi: 10.1161/CIRCULATIONAHA.106.183216
6 YANGB Y, QUY, GUOY, et al.Maternal exposure to ambient air pollution and congenital heart defects in China[J]Environ Int, 2021, 106548.
doi: 10.1016/j.envint.2021.106548
7 QUY, LIUX, ZHUANGJ, et al.Incidence of congenital heart disease: the 9-year experience of the guangdong registry of congenital heart disease, China[J/OL]PLoS One, 2016, 11( 7): e0159257.
doi: 10.1371/journal.pone.0159257
8 QUY, LINS, BLOOMM S, et al.Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring[J]Prev Med, 2021, 106319.
doi: 10.1016/j.ypmed.2020.106319
9 LIUX, NIEZ, CHENJ, et al.Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?[J]Environ Pollut, 2018, 214-222.
doi: 10.1016/j.envpol.2017.11.023
10 OUY, MAIJ, ZHUANGJ, et al.Risk factors of different congenital heart defects in Guangdong, China[J]Pediatr Res, 2016, 79( 4): 549-558.
doi: 10.1038/pr.2015.264
11 NIEZ, YANGB, OUY, et al.Maternal residential greenness and congenital heart defects in infants: a large case-control study in southern China[J]Environ Int, 2020, 105859.
doi: 10.1016/j.envint.2020.105859
12 BOYDP A, HAEUSLERM, BARISICI, et al.Paper 1: The EUROCAT network——organization and processes[J]Birth Defects Res Part A Clin Mol Teratol, 2011, 91( S1): S2-S15.
doi: 10.1002/bdra.20780
13 SLAUGHTERJ L, CUAC L, NOTESTINEJ L, et al.Early prediction of spontaneous patent ductus arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation[J]BMC Pediatr, 2019, 19( 1): 333.
doi: 10.1186/s12887-019-1708-z
14 CHENG, KNIBBSL D, ZHANGW, et al.Estimating spatiotemporal distribution of PM1 concentrations in China with satellite remote sensing, meteorology, and land use information[J]Environ Pollution, 2018, 1086-1094.
doi: 10.1016/j.envpol.2017.10.011
15 CHENG, LIS, KNIBBSL D, et al.A machine learning method to estimate PM2.5 concentrations across China with remote sensing, meteorological and land use information[J]Sci Total Environ, 2018, 52-60.
doi: 10.1016/j.scitotenv.2018.04.251
16 OPITZJ M, CLARKE B. Heart development: an introduction[J]Am J Med Genet, 2000, 97( 4): 238-247.
doi: 10.1002/1096-8628(200024)97:4<238::AID-AJMG1274>3.0.CO;2-G
17 GREENLAND S, PEARL J, ROBINS J M. Causal diagrams for epidemiologic research[J]. Epidemiology, 1999, 10(1): 37-48
18 KEILA P, BUCKLEYJ P, O’BRIENK M, et al.A quantile-based g-computation approach to addressing the effects of exposure mixtures[J]Environ Health Perspect, 2020, 128( 4): 047004.
doi: 10.1289/EHP5838
19 SCHMIDTS. Quantile g-computation: a new method for analyzing mixtures of environmental exposures[J]Environ Health Perspect, 2020, 128( 10): 104004.
doi: 10.1289/EHP7342
20 SUNY, LIX, BENMARHNIAT, et al.Exposure to air pollutant mixture and gestational diabetes mellitus in Southern California: results from electronic health record data of a large pregnancy cohort[J]Environ Int, 2022, 106888.
doi: 10.1016/j.envint.2021.106888
21 GITTENBERGER-DE GROOTA C, BARTELINGSM M, DERUITERM C, et al.Basics of cardiac development for the understanding of congenital heart malformations[J]Pediatr Res, 2005, 57( 2): 169-176.
doi: 10.1203/01.PDR.0000148710.69159.61
22 ORNOYA. Embryonic oxidative stress as a mechanism of teratogenesis with special emphasis on diabetic embryopathy[J]Reproductive Toxicol, 2007, 24( 1): 31-41.
doi: 10.1016/j.reprotox.2007.04.004
23 QIW, BIJ, ZHANGX, et al.Damaging effects of multi-walled carbon nanotubes on pregnant mice with different pregnancy times[J]Sci Rep, 2015, 4( 1): 4352.
doi: 10.1038/srep04352
24 VALKONENV P, PÄIVÄH, SALONENJ T, et al.Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine[J]Lancet, 2001, 358( 9299): 2127-2128.
doi: 10.1016/S0140-6736(01)07184-7
25 TENGC, WANGZ, YANB. Fine particle-induced birth defects: impacts of size, payload, and beyond[J]Birth Defect Res C, 2016, 108( 3): 196-206.
doi: 10.1002/bdrc.21136
26 AVISSAR-WHITINGM, VEIGAK R, UHLK M, et al.Bisphenol A exposure leads to specific microRNA alterations in placental cells[J]Reproductive Toxicol, 2010, 29( 4): 401-406.
doi: 10.1016/j.reprotox.2010.04.004
27 BOVÉH, BONGAERTSE, SLENDERSE, et al.Ambient black carbon particles reach the fetal side of human placenta[J]Nat Commun, 2019, 10( 1): 3866.
doi: 10.1038/s41467-019-11654-3
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