Open Access

ARTICLE

Unsafe Sanitation and the Global Incidence of Congenital Heart Disease: A Spatial Correlation Analysis

Yi Shen^1,2,3,#, Zeye Liu^4,#, Jing Xie^5,#, Xuanqi An^6,7,8,#, Zeyu Jing^1,2,3, Wenchuan Liao^1,2,3, Yifan Zhu^1,2,3, Chenyu Jiang^1,2,3, Xingliang Zhou^1,2,3, Xu Huang^1,2,3, Tianyu Liu^1,2,3, Jian Liu^1,2,3, Yuxi Ji^1,2,3, Yi Yan^1,3, Bei Feng^1,3, Yiwei Liu^1,2,3, Yi Shi^4,*, Yanjun Sun^2,*, Hao Zhang^1,2,3,*

1 Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children’s Medical Center, National Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
2 Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center, National Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
3 Shanghai Clinical Research Center for Rare Pediatric Diseases, Shanghai Children’s Medical Center, National Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
4 Department of Cardiac Surgery, Peking University People’s Hospital, Peking University, Xicheng District, Beijing, China
5 Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
6 Emergency Department, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
7 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
8 National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China

* Corresponding Authors: Yi Shi. Email: ; Yanjun Sun. Email: ; Hao Zhang. Email:
# These authors contributed equally to this work and are joint first authors

Structural and Congenital Heart Disease 2026, 21(3), 3 https://doi.org/10.32604/schd.2026.085942

Received 21 May 2026; Accepted 27 July 2026; Issue published 31 July 2026

Abstract

Background: Congenital heart disease (CHD) is the most common congenital anomaly worldwide, yet the contribution of environmental factors to its global geographic variation remains incompletely understood. We aimed to systematically identify environmental factors associated with CHD incidence using an integrated framework combining machine learning and spatial epidemiology. Methods: Country-level data were obtained from the Global Burden of Disease (GBD) 2021 study. Boruta algorithm-based feature selection and random forest SHAP value ranking were applied to identify environmental factors associated with CHD incidence. Negative binomial regression was used to evaluate the associations between selected variables and CHD incidence. Spatial clustering was assessed using Global Moran’s I and Local Indicators of Spatial Association (LISA). The population attributable fraction (PAF) associated with unsafe sanitation was further estimated. Results: Boruta identified 28 candidate environmental variables associated with CHD incidence, among which unsafe sanitation consistently ranked as the most influential factor based on SHAP analysis. Negative binomial regression demonstrated a significant association between unsafe sanitation and CHD incidence. Spatial analyses revealed marked geographic concordance between regions with high CHD incidence and high unsafe sanitation exposure, particularly in Sub-Saharan Africa. The estimated PAF suggested that approximately 33% of the global CHD burden could theoretically be attributable to unsafe sanitation under the assumptions of the analytical model. Conclusions: Unsafe sanitation was consistently identified as the environmental factor most strongly associated with global CHD incidence across multiple analytical approaches. These findings provide ecological evidence supporting a potential relationship between sanitation conditions and the geographic distribution of CHD. However, further individual-level epidemiological and mechanistic studies are required to validate these findings and clarify the underlying biological mechanisms.

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