Authors
Pierik, F., Burdof, A., Deddens, J., Juttmann, R., and Weber, R.

Title:
Maternal and Paternal Risk Factors for Cryptorchidism and Hypospadias: A Case-Control Study in Newborn Boys

Source:
Environmental Health Perspectives. 112: 1570-1576. 2004.

Summary:
Cryptorchidism and hypospadias are common congenital abnormalities. Little is known about the environmental risk factors which may contribute to these disorders, however, substances which have estrogen-like or anti-androgenic-like properties have been implicated as potential causal factors. Endocrine disrupting substances are present in some synthetic chemicals and can also occur naturally in food products, such as phytoestrogens in products derived from plants. It has been speculated that maternal exposure during pregnancy contributes to cryptorchidism and hypospadias due to the subsequent exposure to the fetus. Recent studies suggest that paternal environmental factors may also play a role in the development of congenital abnormalities. This may occur through genetic modification of germ cells or through exposure of the oocyte or embryo to contaminated seminal fluid.

Pierik et al. conducted a nested case-control study within a large cohort of newborn boys to evaluate the roles of maternal and paternal occupational and dietary exposures to potential endocrine disruptors in the occurrence of cryptorchidism and hypospadias. The cohort was comprised of newborns examined at their first visit to child health care centers in the Netherlands. A total of 91 cases of cryptorchidism and 67 cases of hypospadias were identified; controls were selected from the remaining newborns. The mother and father (when available) of each case were interviewed using a structured questionnaire. Information was collected on pregnancy parameters, personal characteristics, lifestyle, occupation, and dietary phytoestrogen intake.

Low birth weight was found to be a significant risk factor for hypospadias (odds ratio (OR) = 4.1, 95% confidence interval (CI)= 1.7-9.8), and preterm birth was associated with cryptorchidism (OR = 2.5, CI=1.2-5.1). Mothers with better general health and higher education showed less risk of having offspring with hypospadias or cryptorchidism. Maternal occupational, dietary and lifestyle exposures were not associated with either abnormality. Smoking among fathers was associated with the development of hypospadias (OR = 3.4, CI= 1.7-7.0). Self-reported paternal exposure to solvents was associated with both cryptorchidism (OR= 2.0, CI= 1.0-3.9), and hypospadias (OR= 2.4, CI=1.2-4.8). The odds ratio for cryptorchidism was also significantly elevated for paternal exposure to pesticides (OR = 4.5, CI=1.4-13.9). Information about the parents' country of origin was obtained. Infants born from mothers of Turkish origin had an increased risk for hypospadias as compared to infants born from mothers of non-Turkish origin (OR = 3.0, CI= 1.2-7.7). This association may be a result of genetic or environmental factors related to the development of hypospadias which are more prevalent in the Turkish population compared to other ethnic groups.

The results of this study suggest that paternal environmental exposures may increase the risk of cryptochidism and hypospadias. The design of this study minimized bias in case identification as case status was assessed prospectively. However, it is possible that bias in exposure reporting was present as parents of cases may have been more concerned with and/or knowledgeable about environmental risk factors than were parents of controls. An additional limitation of this study is that the exposure classification of solvents and pesticides were too broad to allow for identification of specific groups of chemicals which may be responsible for the increased risks of these abnormalities. It is also important to note that paternal determinats were missing for 26% of the subjects. In addition, the paternal determinants were reported by the fathers themselves in only 28% of the subjects, when the father was unavailable the mother was responsible for reporting this information. The finding of a potential association between paternal exposures and risk of cryptorchidism and hypospadias has important implications. This information suggests that further studies on environmental risk factors for these disorders should not only focus on maternal exposure during fetal life but also assess paternal exposures.