Risk Factors For Congenital Cryptorchidism In A Prospective Birth Cohort Study

Main Category: Pediatrics / Children's Health
Also Included In: Urology / Nephrology
Article Date: 27 Oct 2008 - 1:00 PDT

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UroToday.com - Although cryptorchidism is the most common urogenital malformation in newborn boys, its etiology remains largely unknown. Genetic factors, e.g. defects in developmental genes such as INSL3 or its receptor may be involved in some cases. Other reported risk factors include low birth weight, prematurity, low parity and twinning.

In Western countries, the condition is occurs in 2-8 % of all full-term newborn boys. Several studies indicate an increase in the prevalence of cryptorchidism in some regions within few generations. It is interesting that the reported geographic and temporal trends seem to follow the same pattern as trends reported for other male reproductive problems such as testicular cancer, hypospadias and poor semen quality. Based on these observations it has been hypothesized that lifestyle and environmental factors may be involved in the etiology of cryptorchidism.

Cryptorchidism is associated with an increased risk of testicular cancer, poor semen quality and subfertility in adulthood, and all these conditions share several risk factors. Thus, it has been hypothesized that the conditions may be interrelated and symptoms of a common underlying entity, the testicular dysgenesis syndrome: TDS. TDS is thought to be caused by disturbances of testicular development during fetal and early postnatal life. This emphasizes the importance of identification of risk factors for cryptorchidism.

Most previous studies of risk factors for cryptorchidism have included data obtained retrospectively, i.e. they may be prone to recall and selection bias. Furthermore, some were based on registry data, which may be hampered by variations in ascertainment of the diagnosis and reporting strategies. We conducted a prospective, population-based cohort study of pregnant women and their newborn boys, in which information on risk factors was obtained antenatally before pregnancy outcome was known, and from birth records. All included boys were examined under standardised conditions in order to ensure a valid diagnosis. The study was performed at the University Hospital of Copenhagen, Denmark, and Turku University Hospital, Finland, in the period from 1997 to 2001. The children were examined at birth (if born preterm then at expected date of delivery) and 3 months old.

We have previously published data describing an association between regular maternal alcohol consumption during pregnancy and cryptorchidism as well as a risk association with persistent organochlorine pesticides. In the current paper, additional infant, maternal and delivery characteristics were investigated. We found that use of nicotine substitutes during pregnancy (n = 40) and infertility treatment by intrauterine insemination (n = 49) were associated with an increased risk for cryptorchidism, adjusted odds ratio (95% confidence interval) (OR (95%CI)) 3.04 (95%CI 1.00-9.27) and 3.01 (95%CI 1.27-7.15), respectively. No association was seen for mothers (n = 79) who had infertility treatment in the form of intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) treatment (OR 0.71 95%CI 0.21-2.38). In total, 728 (29%) mothers reported to have smoked during pregnancy, however, no increased risk among maternal smokers was found. Furthermore, we found statistically significant associations between cryptorchidism and low birth weight, prematurity, being small for gestational age, substantial vaginal bleeding, and breech presentation, which are in accordance with other studies.

The results suggest that cryptorchidism may be of multifactorial origin and not only associated with genetic factors, but also to maternal lifestyle and exposure, either as isolated risk factors or in combination with each other.

Written by Ida Damgaard, MD, as part of Beyond the Abstract on UroToday.com

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