Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort Study

The relevance of O<sub>3</sub> exposure in critical congenital heart disease (CCHD) remains uncertain and requires further investigation. The present study aims at quantitatively assessing the association between ambient O<sub>3</sub> exposure during the early pregnancy perio...

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Main Authors: Yanping Ruan, Yaqi Wang, Zhiyong Zou, Jing Li, Yihua He
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Toxics
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Online Access:https://www.mdpi.com/2305-6304/13/6/463
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author Yanping Ruan
Yaqi Wang
Zhiyong Zou
Jing Li
Yihua He
author_facet Yanping Ruan
Yaqi Wang
Zhiyong Zou
Jing Li
Yihua He
author_sort Yanping Ruan
collection DOAJ
description The relevance of O<sub>3</sub> exposure in critical congenital heart disease (CCHD) remains uncertain and requires further investigation. The present study aims at quantitatively assessing the association between ambient O<sub>3</sub> exposure during the early pregnancy period with fetal CCHD and identifying possible susceptible exposure windows. A retrospective cohort study involving 24,516 pregnant women was conducted using data from the Maternal–Fetal Medicine Consultation Network, which encompassed 1313 medical centers across China from 2013 to 2021. We extracted daily O<sub>3</sub> concentrations from a validated grid dataset with a spatial resolution of 0.1° at each participant’s residential county to assess ambient O<sub>3</sub> exposure, followed by calculating the average exposure levels in the periconceptional period, embryonic period, first trimester, and preconception period. The diagnosis of CCHD was based on fetal echocardiography. Exposure–response analyses were carried out using logistic regression models. During the study period, a total of 1541 (17.4%) subjects were diagnosed with fetal CCHD. Each 10 µg/m<sup>3</sup> increase in ambient O<sub>3</sub> exposure in the periconceptional period was associated with a 26.0% increase in the odds of CCHD (odds ratio [OR]: 1.260, 95% confidence interval [CI]: 1.189, 1.335; <i>p</i> < 0.001). Importantly, the association was not modified by factors including maternal age and occupation status, paternal age and smoking status, conception mode, and the presence of risk factors. In the sensitivity analysis, significant associations were observed between O<sub>3</sub> exposure and CCHD in the embryonic period, first trimester, and preconception period, which was consistent with the results of the main analyses. These findings suggest that lowering ambient O<sub>3</sub> exposure in the preconception and early pregnancy periods may be beneficial in reducing the risk of fetal CCHD, especially in regions with elevated O<sub>3</sub> levels.
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spelling doaj-art-b15c6dac6ace4effa6bc66dd685dfe5d2025-08-20T03:32:31ZengMDPI AGToxics2305-63042025-05-0113646310.3390/toxics13060463Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort StudyYanping Ruan0Yaqi Wang1Zhiyong Zou2Jing Li3Yihua He4Echocardiography Medical Center, Maternal-Fetal Medicine Center in Fetal Heart Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaInstitute of Child and Adolescent Health, School of Public Health, Peking University, Beijing 100191, ChinaInstitute of Child and Adolescent Health, School of Public Health, Peking University, Beijing 100191, ChinaInstitute of Child and Adolescent Health, School of Public Health, Peking University, Beijing 100191, ChinaEchocardiography Medical Center, Maternal-Fetal Medicine Center in Fetal Heart Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaThe relevance of O<sub>3</sub> exposure in critical congenital heart disease (CCHD) remains uncertain and requires further investigation. The present study aims at quantitatively assessing the association between ambient O<sub>3</sub> exposure during the early pregnancy period with fetal CCHD and identifying possible susceptible exposure windows. A retrospective cohort study involving 24,516 pregnant women was conducted using data from the Maternal–Fetal Medicine Consultation Network, which encompassed 1313 medical centers across China from 2013 to 2021. We extracted daily O<sub>3</sub> concentrations from a validated grid dataset with a spatial resolution of 0.1° at each participant’s residential county to assess ambient O<sub>3</sub> exposure, followed by calculating the average exposure levels in the periconceptional period, embryonic period, first trimester, and preconception period. The diagnosis of CCHD was based on fetal echocardiography. Exposure–response analyses were carried out using logistic regression models. During the study period, a total of 1541 (17.4%) subjects were diagnosed with fetal CCHD. Each 10 µg/m<sup>3</sup> increase in ambient O<sub>3</sub> exposure in the periconceptional period was associated with a 26.0% increase in the odds of CCHD (odds ratio [OR]: 1.260, 95% confidence interval [CI]: 1.189, 1.335; <i>p</i> < 0.001). Importantly, the association was not modified by factors including maternal age and occupation status, paternal age and smoking status, conception mode, and the presence of risk factors. In the sensitivity analysis, significant associations were observed between O<sub>3</sub> exposure and CCHD in the embryonic period, first trimester, and preconception period, which was consistent with the results of the main analyses. These findings suggest that lowering ambient O<sub>3</sub> exposure in the preconception and early pregnancy periods may be beneficial in reducing the risk of fetal CCHD, especially in regions with elevated O<sub>3</sub> levels.https://www.mdpi.com/2305-6304/13/6/463congenital heart defectscritical congenital heart defectsair pollutionozonepericonceptional period
spellingShingle Yanping Ruan
Yaqi Wang
Zhiyong Zou
Jing Li
Yihua He
Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort Study
Toxics
congenital heart defects
critical congenital heart defects
air pollution
ozone
periconceptional period
title Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort Study
title_full Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort Study
title_fullStr Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort Study
title_full_unstemmed Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort Study
title_short Maternal Exposure to Ambient Ozone and Fetal Critical Congenital Heart Disease in China: A Large Multicenter Retrospective Cohort Study
title_sort maternal exposure to ambient ozone and fetal critical congenital heart disease in china a large multicenter retrospective cohort study
topic congenital heart defects
critical congenital heart defects
air pollution
ozone
periconceptional period
url https://www.mdpi.com/2305-6304/13/6/463
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AT zhiyongzou maternalexposuretoambientozoneandfetalcriticalcongenitalheartdiseaseinchinaalargemulticenterretrospectivecohortstudy
AT jingli maternalexposuretoambientozoneandfetalcriticalcongenitalheartdiseaseinchinaalargemulticenterretrospectivecohortstudy
AT yihuahe maternalexposuretoambientozoneandfetalcriticalcongenitalheartdiseaseinchinaalargemulticenterretrospectivecohortstudy