Endocrine Disruptors in the Workplace, Hair Spray, Folate Supplementation, and Risk of Hypospadias: Case-Control Study
Ormond, Gillian, Nieuwenhuijsen, Mark J., Nelson, Paul, Toledano, Mireille B., Iszatt, Nina, Geneletti, Sara, Elliott, Paul, Environmental Health Perspectives
BACKGROUND: Hypospadias is one of the most common urogenital congenital anomalies affecting baby boys. Prevalence estimates in Europe range from 4 to 24 per 10,000 births, depending on definition, with higher rates reported from the United States. Relatively little is known about potential risk factors, but a role for endocrine-disrupting chemicals (EDCs) has been proposed.
OBJECTIVE: Our goal was to elucidate the risk of hypospadias associated with occupational exposure of the mother to endocrine-disruptor chemicals, use of folate supplementation during pregnancy, and vegetarianism.
DESIGN: We designed a case--control study of 471 hypospadias cases referred to surgeons and 490 randomly selected birth controls, born 1 January 1997-30 September 1998 in southeast England. Telephone interviews of mothers elicited information on folate supplementation during pregnancy and vegetarianism. We used a job exposure matrix to classify occupational exposure.
RESULTS: In multiple logistic regression analysis, there were increased risks for self-reported occupational exposure to hair spray [exposed vs. nonexposed, odds ratio (OR) = 2.39; 95% confidence interval (CI), 1.40-4.17] and phthalate exposure obtained by a job exposure matrix (OR = 3.12; 95% CI, 1.04-11.46). There was a significantly reduced risk of hypospadias associated with of folate use during the first 3 months of pregnancy (OR = 0.64; 95% CI, 0.44-0.93). Vegetarianism was not associated with hypospadias risk.
CONCLUSIONS: Excess risks of hypospadias associated with occupational exposures to phthalates and hair spray suggest that antiandrogenic EDCs may play a role in hypospadias. Folate supplementation in early pregnancy may be protective.
KEY WORDS: endocrine disruptors, hair spray, folate supplementation, hypospadias, occupation. Environ Health Perspect 117:303-307 (2009). doi:10.1289/ehp.11933 available via http://dx.doi.org/[Online 20 November 2008]
Hypospadias is one of the most common urogenital congenital anomalies affecting baby boys (Harris 1990). Prevalence estimates in Europe range from 4 to 24 per 10,000 births, depending on definition (Dolk et al. 2004), with higher rates reported from the United States (Paulozzi 1999). Since the 1960s, prevalence appears first to have increased, then stabilized, along with increasing trends among other male fertility-related disorders (Dolk et al. 2004; Toppari et al. 1996). Little is known about the etiology of hypospadias. A role for endocrine-disrupting chemicals (EDCs) has been proposed, specifically antiandrogens (Baskin et al. 2001). Animal studies suggest association of EDCs with various disorders related to male fertility (Sharpe et al. 2003), but data on humans are largely lacking (Committee on Toxicity 2006). Studies of occupational risk factors have been inconclusive (Aho et al. 2003; Irgens 2000; Kallen 1988; Kristensen et al. 1997; Pierik et al. 2004; Vrijheid et al. 2003; Weidner et al. 1998). Concerning diet and vitamin use, few data are available on effects of folic acid supplementation/antagonists (Brouwers et al. 2007; Czeizel 1996; Czeizel et al. 2001), and two studies reported excess risk related to vegetarianism (Akre et al. 2008; North and Golding 2000). We report here results of a large population-based case-control study of hypospadias in southeast England with primary aims of investigating risk of hypospadias and a) maternal occupational exposures, specifically to EDCs; b) folic acid supplementation during pregnancy; and c) vegetarianism.
Data and Methods
The study region included the health regions of North Thames, South Thames, and the Anglian part of Anglia and Oxford (Figure 1), comprising 120 London boroughs and local authority districts. Surgical centers in the study region and major surgical centers within 50 miles were visited. Hypospadias cases born in the study region over a 21-month period (1 January 1997-30 September 1998) were eligible if there was an abnormally positioned urethral orifice requiring surgery, with no major accompanying anomaly suggesting that it was part of a syndrome. …