Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the Generation R Study

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.

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Wikipedia:

Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis. However, about 80% of cryptorchid testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall. Environmental risk factors may include exposure to regular alcohol consumption during pregnancy (5 or more drinks per week, associated with a 3x increase in cryptorchidism, when compared to non-drinking mothers), exposure to pesticides, gestational diabetes, being a twin,^[2] and being born to pregnant women who drink caffeine (at least 3 drinks per day).

A contributing role of environmental chemicals – endocrine disruptors – that interfere with normal fetal hormone balance has been proposed and is rarely possible to implicate a specific chemical exposure for an individual child. One study^[1] reported a significant increase of risk associated with the use of mild painkillers (aspirin, ibuprofen, paracetamol) during pregnancy, especially during the second trimester and if several painkillers were taken simultaneously.

Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus (the opening, or male external urethral orifice). Instead of opening at the tip of the glans of the penis, a hypospadic urethra opens anywhere along a line (the urethral groove) running from the tip along the underside (ventral aspect) of the shaft to the junction of the penis and scrotum or perineum. Hypospadias are among the most common birth defects of the male genitalia (second to cryptorchidism), but widely varying incidences have been reported from different countries, from as low as 1 in 4000 to as high as 1 in 125 boys.

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