Background: Risk factors for congenital cryptorchidism were investigated in a prospective birth cohort study in Denmark and Finland from 1997 to 2001.
Methodology and principal findings: In total, 2,496 boys were examined for cryptorchidism at birth (cryptorchid/healthy: 128/2,368) and three months old (33/2,215). Information on risk factors was obtained antenatally (questionnaire/interview) or at birth from birth records. 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 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%) 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.
Conclusions and significance: Our study revealed two novel risk factors for cryptorchidism: intrauterine insemination and the use of nicotine substitutes in pregnancy. This suggests that cryptorchidism may not only be associated to genetic factors, but also to maternal lifestyle and exposure.