Endocrine Disruptors in the Workplace, Hair Spray, Folate Supplementation, and Risk of Hypospadias: Case-Control Study

Gillian Ormond; Mark J. Nieuwenhuijsen; Paul Nelson; Mireille B. Toledano; Nina Iszatt; Sara Geneletti; Paul Elliott


Environ Health Perspect. 2009;117(2):303-307. 

In This Article


Table 1 shows prevalence of various risk factors and potential confounders for hypospadias. Gestational age and birth weight were correlated (Spearman r = 0.41), as were income and maternal age (r = 0.33) and maternal smoking and environmental tobacco smoke (r = 0.31); no other correlations exceeded ± 0.30. The hypospadias cases were more likely to be born preterm and to have low birth weight ( < 2,500 g) (Table 1). Compared with mothers of control children, mothers of hypospadias cases tended to have lower income (p = 0.001), higher prevalence of smoking (p = 0.02), and lower prevalence of folate supplement use during the first 3 months of pregnancy (p = 0.01) (i.e., the critical period for development of hypospadias) (Harris 1990). For these variables, unadjusted ORs for the association with hypospadias ranged from 1.44 (95% CI, 1.05-1.97) for smokers compared with nonsmokers, to 2.74 (95% CI, 1.55-4.92) for household income < ₤10,000 compared with > ₤50,000, whereas folate supplementation during the first 3 months of pregnancy was associated with significantly reduced risk (OR = 0.64; 95% CI, 0.46-0.89) (Table 1). There was no association with vegetarianism (p = 0.36). Positive family history of hypospadias and previous stillbirth were also significantly associated with risk of hypospadias (not shown).

Among occupational exposures (prevalence ≥ 5%), significantly increased risk was found for self-reported exposure to hair spray (exposed vs. nonexposed unadjusted OR = 2.30; 95% CI, 1.38-3.89) (Table 2). With the job exposure matrix, exposure prevalences were all < 5%; significant excess risk of hypospadias was found for boys of mothers exposed to phthalates (including hairdressers, beauty therapists/those working in beauty/ hairdressing, research chemists, line operators, pharmaceutical operators, electrical assemblers, factory assistants) compared with those with no exposure to phthalates at work (unadjusted OR = 3.65; 95% CI, 1.19-11.20; 14 cases, 4 controls).

After adjustment for multiple potential confounders, the significant positive association with maternal occupational exposure to hair spray was slightly strengthened (exposed vs. unexposed OR = 2.39; 95% CI, 1.40-4.17) (Table 3). Hairdressers as a group had a nonsignificant increased risk (unadjusted OR = 2.73; 95% CI, 0.72-10.38; adjusted OR = 2.59; 95% CI, 0.70-12.32). Folate supplementation during the first 3 months of pregnancy remained inversely associated with risk of hypospadias, with a virtually unchanged risk estimate (OR = 0.64; 95% CI, 0.44-0.93). With phthalates included in the model instead of occupational exposure to hair spray, the risk estimates for folate supplementation and other factors remained essentially unchanged; occupational phthalates exposure was associated with 3-fold elevated risk (OR = 3.12, 95% CI, 1.04-11.46) (Table 3). Inclusion of maternal age did not materially alter the risk estimates for the other variables in the model (data not shown).


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