1995). The ﬁndings in our case–control study suggest an association between cryptorchidism and hypospadias and lower socioeconomic sta- tus, as reﬂected in low education level and sub- optimal general health status of both parents. The effect of socioeconomic status may be con- founded by selection bias, especially because of differential response between cases and controls. For the impact of education to be spurious, this would require approximately a 2-fold higher response among parents of cases than of controls in subjects with a low education. A similar differential response bias may have contributed to the observed effect of Turkish origin on cryptorchidism and hypo- spadias. Based on the nationalities of all 8,695 examined boys, Moroccan, Turkish, and other minorities were underrepresented by about 40–50% among controls. To exclude confounding by country of origin, we repeated the regression analysis in Dutch subjects only, which did not yield significantly different results, although standard errors increased because of a smaller sample. Among Dutch subjects paternal exposure to pesticides has a similar effect (OR = 3.4; 95% CI, 0.3–43.0) on cryptorchidism but failed to reach the level of conventional significance. Paternal smoking (OR = 6.5; 95% CI, 2.0–21.7) and self- reported paternal exposure to solvents (OR = 3.3; 95% CI, 1.2–9.5) remained signiﬁcant risk factors for hypospadias among Dutch subjects. Previous studies have reported ethnic varia- tions in the occurrence of cryptorchidism and hypospadias (Chia et al. 2003; Fredell et al. 2002). Familial aggregation has been described for both abnormalities, supporting the impor- tance of genetic factors (Fredell et al. 2002; Weidner et al. 1999). The association between Turkish origin and cryptorchidism and hypo- spadias may be the result of a genetic or envi- ronmental factor among Turkish people that predisposes toward these abnormalities. A higher maternal age was a signiﬁcant risk factor within the Turkish minority, but not in the overall group of non-Turkish origin. We can- not exclude the possibility that the response may have been different with age among Turks. In the multifactorial models without adding paternal risk factors, preterm delivery was associated with cryptorchidism (OR = 3.1; Table 3), and being SGA was associated with hypospadias (OR = 7.3; Table 4). These asso- ciations are well known from previous studies Table 3. Multivariate models of the association between maternal and paternal risk factors and the occur- rence of cryptorchidism in a case–control study. Table 4. Multivariate models of the association between maternal and paternal risk factors and the occur- rence of hypospadias in a case–control study. Risk factors Maternal risk factors (n = 443) Education level (low vs. intermediate/high) Premature birth ( > 2 weeks) Interaction age at delivery and country of origin: Non-Turkish mothers < 30 years of age Turkish mothers < 30 years of age Non-Turkish mothers ≥ 30 years of age Turkish mothers ≥ 30 years of age Maternal and paternal risk factors (n = 326) Good general health of mother (no vs. yesa) Vegetable-rich diet of mother (yes vs. noa) Probable exposure to pesticides of father (JEM) Interaction age at delivery and country of origin: Non-Turkish mothers < 30 years of age Turkish mothers < 30 years of age Non-Turkish mothers ≥ 30 years of age Turkish mothers ≥ 30 years of age aReference. *p < 0.05. Risk factors Maternal risk factors (n = 443) Education level (low vs. intermediate/high) SGA (yes vs. no) Turkish origin of mother (vs. non-Turkish) Good general health (no vs. yesa) Maternal and paternal risk factors (n = 326) SGA (yes vs. noa) Current smoker, father (yes vs. noa) Self-reported exposure to solvents of father Time to pregnancy 0 months 1–3 months ≥ 4 months aReference. *p < 0.05. Environmental Health Perspectives • VOLUME 112 | NUMBER 15 | November 2004 Children’s Health | Cryptorchidism and hypospadias study OR (95% CI) 1.9* (1.0–3.4) 3.1* (1.5–6.6) 1.0 2.0 (0.7–5.6) 0.8 (0.5–1.5) 16.3* (3.3–81.2) 3.8* (1.5–9.8) 0.4* (0.2–0.9) 3.8* (1.1–13.4) 1.0 1.6 (0.5–5.6) 1.0 (0.5–2.0) 8.8* (1.2–63.2) OR (95% CI) 2.0* (1.1–3.9) 4.2* (1.2–14.7) 3.0* (1.2–7.7) 3.6* (1.6–8.1) 7.3* (1.7–31.4) 3.8* (1.8–8.2) 2.0 (0.9–4.6) 1.0 3.9* (1.3–11.5) 3.4* (1.1–10.3) (Weidner et al. 1999). Some authors point to reduced placental function as underlying etiol- ogy for low birth weight, cryptorchidism, and hypospadias (Fredell et al. 1998). Some earlier studies looking at large groups of cases have reported ORs ranging from 1.1 to 1.9 for low birth order and a higher maternal age as risk factors for cryptorchidism or hypo- spadias cases (Akre et al. 1999; Biggs et al. 2002; Kallen 2002; Møller and Skakkebaek 1997), although others did not observe these excess risks (Berkowitz et al. 1995; Jones et al. 1998). Birth order and parental age were not signiﬁcantly related to cryptorchidism or hypo- spadias in our study, which may be because of the relatively small effect and limited popu- lation size. Our observation that a longer time to pregnancy was associated with hypospadias (Table 4) may be explained by familial aggre- gation of hypospadias (Fredell et al. 2002) and its association with subfertility (Skakkebaek et al. 2001). Previous studies have reported a higher incidence of hypospadias in boys born after intracytoplasmic sperm injection (Ericson and Kallen 2001; Wennerholm et al. 2000), which may be explained by a lower birth weight that occurs more frequently after ART. In our study, the frequency of ART was too low to evaluate its association with hypospadias or cryptorchidism. This study suggests that paternal environ- mental exposures may increase the risk of cryp- torchidism and hypospadias in newborn boys, which may indicate an effect on the paternal germline. Cryptorchidism was associated with paternal exposure to pesticides, and hypospa- dias was more frequent in fathers that were active smokers. The pregnancy-related risk fac- tors of low birth weight and SGA birth for hypospadias and preterm delivery for cryp- torchidism have consistently been found in pre- vious studies (Weidner et al. 1999). 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