Background: Congenital heart defects (CHDs) are among the most common birth defects and remain a major cause of death in infancy and childhood. The etiology of most congenital heart anomalies is uncertain. Understanding the relationship between environmental tobacco smoke (ETS), socio-economic status, maternal environmental exposures and their joint effects on CHD is important for primary prevention of CHD.
Purpose: This study evaluated the potential interactions among multiple emerging, but modifiable risk factors, such as maternal ETS, environmental and sociodemographic factors during pregnancy on CHDs in China.
Methods: A case-control study of 4,726 pairs of CHD cases and controls was conducted by recruiting subjects from 39 hospitals of the Guangdong Registry of Congenital Heart Disease (GRCHD), an ongoing population-based CHD surveillance system in Southern China in 2004–2014. The CHD defects were defined using a modified code from the International Classification of Diseases (ICD-10: Q20.000-Q28.000). All newborns were evaluated by an obstetrician, pediatrician, or pediatric cardiologist before discharge, or within 72 hours after birth. All echocardiograms of CHDs cases were reviewed by two specialty trained echo doctors. A face-to-face interview was conducted to collect information on demographics, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios (aORs) and 95% confidence intervals (CIs) of CHD and subtypes while simultaneously controlling for other factors. Effect modification with ETS was also evaluated on both additive and multiplicative scales.
Results: 4,726 isolated CHDs were eligible for analysis. Compared to the controls, the case mothers had higher exposures to ETS during the first trimester of pregnancy (aOR=1.44, 95% CI 1.25∼1.66). The associations between maternal socio-demographics, environmental and behavior factors and CHDs are described, the top three factors include low maternal education, migrant status, and household income <2000 RMB per month. All environmental exposures examined were associated with CHD, with the top three risk factors of maternal pregnancy exposure to pesticides, organic solvents, and maternal alcohol drinking. There were considerable additive interactions between maternal ETS and migrant status (Interaction Contrast Ratio, ICR=0.68, 95% CI 0.05∼1.30), low household income (ICR=0.65, 95% CI=0.09∼1.20) and paternal alcohol drinking (ICR=3.06, 95% CI 0.86∼5.26). Maternal low education also modified the ETS - CHD association on the multiplicative scale (P=0.011).
Conclusions: We found that maternal periconceptional ETS exposure independently affected CHD, low socioeconomic factors and behavior synergistically interacted with ETS on CHD risk. These findings will help identify high-risk populations and risk factors for potential intervention strategies and education program to reduce CHD burden.