Abstract
BACKGROUND Recently, over-the-counter mild analgesic use during
pregnancy has been suggested to influence the risk of reproductive disorders in
the offspring. We examined the influence of maternal exposure to mild
analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia
in their offspring.
METHODS Associations between maternal exposure to mild analgesics
during pregnancy and cryptorchidism or hypospadia in the offspring were studied
in 3184 women participating in a large population-based prospective birth
cohort study from early pregnancy onwards in the Netherlands (2002–2006), the
Generation R Study. Cryptorchidism and hypospadia were identified during
routine screening assessments performed in child health care centres by trained
physicians. The use of mild analgesics was assessed in three prenatal
questionnaires in pregnancy, resulting in four periods of use, namely,
periconception period, first 14 weeks of gestation, 14–22 weeks of gestation
and 20–32 weeks of gestation. Logistic regression analyses were used to study
the associations between maternal exposure to mild analgesics and
cryptorchidism and hypospadia.
RESULTS The cumulative prevalence over 30 months of follow
up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics
in the second period of pregnancy (14–22 weeks) increased the risk of
congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence
interval (CI) 1.17–3.83], primarily due to the use of acetaminophen
(paracetamol) (adjusted OR 1.89; 95% CI 1.01–3.51). Among mothers of
cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during
pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia
and 29.9% (926 of 3094) of mothers with healthy boys.
CONCLUSIONS Our results suggest that intrauterine exposure
to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual
differentiation takes place, increases the risk of cryptorchidism.