Environmental Contaminants and Congenital Heart Defects: A Re-Evaluation of the Evidence

Abstract

Congenital heart defects (CHDs) are a common birth defect of largely unknown etiology, with high fetal and neonatal mortality. A review of CHDs and environmental contaminant exposure found that meta-analyses showed only modest associations for smoking, vehicle exhaust components, disinfectant by-products and proximity to incinerators, with stronger results from the newer, larger and better quality studies masked by the typical absence of effect in older studies. Recent studies of exposure to agricultural pesticides, solvents, metals and landfill sites also showed associations. Certain contaminants have been associated with certain CHDs, with septal defects being the most common. Frequent methodological problems include failure to account for potential confounders or maternal/paternal preconception exposure, differences in diagnosing, defining and classifying CHDs, grouping of defects to increase power, grouping of contaminants with dissimilar mechanisms, exclusion of pregnancies that result in death or later life diagnosis, and the assumption that maternal residence at birth is the same as at conception. Furthermore, most studies use measurement estimates of one exposure, ignoring the many additional contaminant exposures in daily life. All these problems can distort and underestimate the true associations. Impaired methylation is a common mechanism, suggesting that supplementary folate may be protective for any birth defect.

Association between preconception paternal smoking and birth defects in offspring: evidence from the database of the National Free Preconception Health Examination Project in China

“…The association between paternal smoking and birth defects in the offspring is unclear, although that of maternal habits on offspring is well recognised. [1][2][3][4][5][6][7] Exposure to paternal cigarette smoke affects the genomic and epigenomic components of sperm via the aryl hydrocarbon receptor (AHR), nuclear factor-E2 related factor 2 (NRF2) and mitogen-activated protein kinase (MARK) pathways, which influences the offspring's development in animal models. 8 Several clinical studies provide evidence of paternal smoking contributing to birth defects.…”

“…First, potential confounders, such as maternal and paternal geographical and genetic factors, environmental exposure and folic acid supplements, which are related to genetic mutation and impaired methylation causing differences in the incidence of birth defects, should be considered. 1,2,12,13 Paternal smoking and alcohol consumption, which often co-exist, have similar toxic effects on germ cells and fetal development, via germ cell mutation, genetic imprinting and epigenetic pathways. To investigate the causal relation between paternal smoking and birth defects, details of paternal and maternal smoking and alcohol consumption, such as exposure timing, frequency and behaviour change after conception, must be considered.…”

Congenital heart diseases and parental occupational exposure in a Hungarian case‐control study in 1997 to 2002

“…The etiology of approximately 20% of CHDs can be linked to known causes, while the rest of cases are the result of complex interactions between genetic, lifestyle, and environmental factors 4,5 . Previous studies explored that maternal antibiotic use (adjusted odds ratio [aOR] = 3.96; 95% CI: 1.78‐8.79), maternal alcohol consumption (aOR = 2.14; 95% CI: 1.64‐2.80), age (aOR = 1.94; 95% CI: 1.12‐3.34), past induced abortion (aOR = 1.58; 95% CI: 1.12‐2.22), education of parents (aOR = 1.47; 95% CI: 1.28‐1.69), the use of assisted reproduction techniques for conception (aOR = 1.45; 95% CI: 1.20‐1.76), higher maternal body mass index (aOR = 1.32; 95% CI: 1.21‐1.43), parity (aOR = 1.18; 95% CI: 1.03‐1.34), and maternal smoking (aOR = 1.11; 95% CI: 1.02‐1.21) may all increase the risk of CHDs, while maternal folate intake (aOR = 0.42; 95% CI: 0.21‐0.86) may have a protective effect 6‐11 . Other studies have also confirmed occupation of parents as a possible causative factor for the development of CHDs.…”

“…Commonly identified occupations include painters, janitors, food service workers, electricians, health care personnel, or plastic workers 5,12,13 . As endocrine disrupting chemicals are often used by people employed in these areas, several studies have focused on this group of chemicals 8 …”

Parental non-hereditary teratogenic exposure factors on the occurrence of congenital heart disease in the offspring in the northeastern Sichuan, China

“…To improve crop yield, chemical fertilizer is widely used 6 . Therefore, in the process of agricultural production, people have more direct contact with pesticides and other harmful substances [6][7][8] . In addition, some non-standard small factories directly discharge factory exhaust gas and wastewater to the environment 9,10 .…”