Occupational exposure to endocrine-disrupting chemicals and other parental risk factors in hypospadias and cryptorchidism development: a case-control study.

Abstract

Summary Aim of the study Endocrine-disrupting chemicals (EDCs) are exogenous agents that are capable of altering the endocrine system functions, including the regulation of developmental processes. The aim of this study was to investigate the association between EDC\xa0exposure and other parental factors in the etiology of hypospadias and cryptorchidism. Methods A case–control study was conducted. Cases (n = 210) were infants aged between 6 months and 14 years diagnosed with hypospadias or cryptorchidism who attended the authors hospital over a period of 18 months, and controls (n = 210) were infants within the same range of age and without any urological disorders who attended the outpatient clinic of the same hospital during the same time period. Their selection was independent of exposures. Data on parental occupational exposure to EDCs and other sociodemographic variables were collected through face-to-face interviews and systematically for both cases and controls. Crude and adjusted odds ratios (ORs) were estimated to control for confounding with their 95% confidence interval (CI) by means of logistic regressions. Specifically, three final models of a dichotomous outcome were constructed: one for cryptorchidism, one for hypospadias, and the third considering both malformations together. The Hosmer-Lemeshow test was used to assess the goodness of fit of the models. Their discriminatory accuracy (DA) was ascertained by estimating their areas under the receiver operating characteristic\xa0curves area under the curve (AUC) along with their 95% CI. Results Associations were found between advanced maternal age (OR adjusted\xa0=\xa01.82; 95% CI: 1.14–2.92), mother s consumption of anti-abortives (OR\xa0=\xa05.40; 95% CI: 1.40–38.5) and other drugs (OR\xa0=\xa02.02; 95% CI: 1.31–3.16) during pregnancy, maternal and paternal occupational exposure to EDCs (OR = 4.08; 95% CI: 2.03–8.96 and OR = 3.90; 95% CI: 2.41–6.48, respectively), fathers smoking (OR\xa0=\xa02.0; 95% CI: 1.33–2.99), and fathers with urological disorders (OR\xa0=\xa02.31; 95% CI: 1.15–4.90). Maternal and paternal high educational level could be protective of cryptorchidism (OR\xa0=\xa00.47; 95% CI: 0.28–0.76\xa0and OR\xa0=\xa00.63; 95% CI: 0.42–0.93, respectively). The DA of the models for the whole sample (AUC\xa0=\xa00.75; 95% CI: 0.70–0.79)\xa0for cryptorchidism (AUC = 0.76; 95% CI: 0.71–0.82)\xa0and for hypospadias (AUC = 0.75; 95% CI: 0.69–0.81) was moderately high. Conclusions Advanced age, some parental occupational exposure to EDCs, some drug\xa0consumption, smoking, and the father s history of urological disorders may increase risk and predict the developments of these malformations. Studies with higher samples sizes are needed to assess associations between individual EDC occupational exposures and drugs and these malformations. Summary table . Adjusted ORs for alleged parental risk factors in the whole sample. Parental variables OR 95% CI Inferior limit Upper limit Advanced maternal age 1.82 1.14 2.92 Maternal EDC exposure 3.48 1.57 7.67 Anti-abortives 5.57 1.08 28.75 Consumption of other drugs 2.22 1.36 3.62 Advanced paternal age 1.36 0.81 2.26 Paternal EDC exposure 4.20 2.48 7.11 Smoking fathers 2.07 1.32 3.26 Father s urological history 2.10 0.95 4.62 Constant 0.26 OR, odds ratio; EDC, endocrine-disrupting chemical; CI, confidence interval. Goodness of fit: Hosmer-Lemeshow chi-squared\xa0=\xa01.10; P\xa0=\xa00.99.