Paternal Occupational Exposure to Solvents and The Risk of Congenital Heart Defects in Children Using Job Exposure Matrix

Background and aims: Currently, as a result of research on laboratory animals, abundant information has been obtained on the impact of various environmental factors on the occurrence of congenital malformations, but there is still no comprehensive information on the causes of congenital heart malformations (CHD) in human populations. Congenital heart defects (CHDs) constitute the major class of congenital anomalies. Although the incidence of CHDs is close to one percent of live births, its prevalence in the fetus is higher. The prevalence of CHDs is 0.5-0.8% in the live-term neonate, 2% in premature infants and 10-25% in the aborted fetus. The exact causes of CHDs are not clear. About 25% of all CHDs are attributed to the genetic factors. The interaction of genetic and environment is also considered in the etiology of the CHDs. Researchers say occupations such as pharmacy, chemical engineering, dyeing, increase the risk of neonatal eye, heart and intestinal defects and cleft lip and palate. Several studies have shown the effect of non-genetic factors such as environment and lifestyle on the occurrence of CHDs. In the Snijder study, no relationship was found between maternal occupational contact and CHD offspring, whereas fathers' exposure to phthalates increased CHD in neonates. According to the above mentioned content Identify paternal exposure to solvents and its relationship with congenital malformations heart defect can be effective in identifying the factors affecting the incidence of malformations. However, there is no consensus on the role of paternal and maternal exposures and susceptible window of exposure on the CHDs across studies. Additionally, the body of evidence on the association between occupational exposures and congenital malformations especially CHDs are limited. This study aimed to investigate paternal occupational exposure to solvents and congenital heart abnormalities in neonates. Methods: The study was approved by the Ethics Committee of Shahid Sadoughi University of Medical Sciences (Registration Code: ir.ssu.medicine.rec.1359.37). In this case-control study 200 children with congenital heart defect and 400 matched healthy infants were considered as case and control groups respectively. Cases were randomly selected from the medically diagnosed and registered CHDs newborns during 2015-2017 (1393-1395 Persian year) in Yazd, Afshar referral hospital. Controls were selected from healthy newborns of Yazd province referred to the Yazd city health centers for receiving their routine health care services. Controls were matched case by case with the cases in term of age. A researcher-made questionnaire was used to collect the data by the telephone interview. The questionnaire comprised of three sections including a) general items regarding demographic characteristics b) lifestyle of parents and c) occupational and environmental exposures of the parents. Information on paternal occupation of questionnaires and paternal occupational exposure was performed using job exposure matrix. For this purpose, a matrix of occupational exposure assessment of solvents was prepared in Excel software. Exposure ratings of each job were solved based on the opinions of 10 experienced and well-known occupational health professionals. After completing the job matrix, the mean score of solvent exposure was calculated and the mean scores were used as fathers' exposure to solvents. Outcomes definition was performed according to international Classification of Disease version 10 (ICD 10). All refereed children with maximum three years of age which were diagnosed with at least one of CHDs according to the ICD10 classification were entered into the study.  Data were analyzed using SPSS16 software, descriptive and inferential statistics such as frequency and percentage. STATA14 software was used to evaluate job contact and logistic regression tests were used to estimate odds ratios and odds ratios. 95% confidence interval and 0.05 were considered significant. Results: Among the analyzed cases, ventricular septal defect with 31.5% (n = 63) and patent ducts arteriosus with 24% (n= 48), had the highest prevalence. Results showed that mothers of case group had lower level of education compared to control group (p-value <0.001). In this study, the sex ratio of girls to boys was 1/1.06. The BMI in mothers in the case group (26.61± 5.74) was significantly higher than the mothers BMI in the control group (25.06± 3.71). Eight percent increase in the risk of CHDs was found per one unit increase in the BMI in the crude model (95% CI: 1.04:1.13). Eight percent increase in the risk of CHDs was found per one unit increase in the BMI in the crude model (95% CI: 1.04:1.13). About 72% (n=144) of mothers in the case group and 83% (n=332) in the control group reported no history of a diagnosed medical problem during their pregnancy. Significant difference was observed between the frequency of heart problems in the newborns of mothers with and without health problems during pregnancy (OR: 1.83; 95% CI: 1.23: 2.74). 26.5% (n=53) of the mothers in the case group and 21.25% (n=85) in the control group were a passive smoker. However, the risk increase due to passive smoking was not statistically significant (OR: 1.34; 95% CI: 0.90: 1.98). Use of folic acid during pregnancy was associated with 41% lower risk of CHDs (95% CI: 0.30: 0.86). Use of Iron supplement during pregnancy was also associated with 40% lower risk of CHDs (95% CI: 0.36: 0.99). Familial history of other congenital anomalies and also CHDs was associated with increase in the odds of CHDs. The prevalent of Paternal occupational exposure to solvents was 66% and 55% in the case and control groups respectively in which relationship was statistically significant (OR = 1.53, 95% CI = 1.06-2.21). After a removing the effect of confounding factors the significant differences was not observed between paternal exposure to solvents and heart defects in child (AOR = 1.28, 95% CI = 0.84-1.6). Investigation of the relationship between patent ducts arteriosus and occupational exposure to solvents showed that fathers' occupational exposure to solvents was higher in the case group (72%) than in the control group (58%), whereas between arterial openness and occupational exposure to solvents. With and without confounding factors, no significant relationship was observed despite high index ratio (OR: 1.94 4- 95% CI: 0.97-94.09 and OR: 64% CI95: 0.76- 3.55 / 1: AOR)) Conclusion: The limitations of the this study were the small number of samples, the limitation of study to a specific timeframe, use of the job evaluation matrix alone and the lack of evaluation of solvent biomarkers in parental and fetal body tissues and fluids. Despite the limitations of the study, the findings of the study showed that one of the environmental factors affecting the fetal health was occupational exposure Father’s with solvents. therefore father's job may affect the child health.  the results of Studies have also shown that exposure to chemicals reduces the quality of semen and can affect epigenetic planning during sperm cell maturation. These changes may lead to abnormal gene transcription in fetal tissue that may later lead to congenital defects. In addition, occupational exposure to chemicals is generally much higher than exposure to such substances in the diet and the environment, which may further impact such exposure. An animal study has also shown that the cardiovascular system in Fetal growth stage is highly sensitive to many environmental contaminants such as dioxins, polycarbonate biphenyls and some pesticides. In this way, training parents about compliance with occupational safety standards can increase the health of next generation. Also, since this study was conducted as a job and solvents are highly diverse, it is recommended to study the effect of each solvent on the biomarkers and the effect of each solvent.