Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism.
BACKGROUND
Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout. In humans, aspirin blocks the androgen response to human chorionic gonadotropin (hCG), and, because hCG-stimulated androgen production in utero is crucial for normal testicular descent, exposure to COX inhibitors at vulnerable times during gestation may impair testicular descent. We examined whether prenatal exposure to acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased occurrence of cryptorchidism.


METHODS
Our study used data on 47,400 live-born singleton sons of mothers enrolled in the Danish National Birth Cohort during 1996-2002. Cryptorchidism was identified in 980 boys during childhood, of whom 565 underwent orchiopexy. The use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy was assessed in 3 computer-assisted telephone interviews and 1 self-administered questionnaire. We estimated adjusted hazard ratios (HRs) of cryptorchidism by Cox regression analysis.


RESULTS
Exposure to acetaminophen during both the first and second trimesters was associated with increased occurrence of cryptorchidism (HR = 1.33 [95% confidence interval = 1.00-1.77]). Exposure for more than 4 weeks within the postulated time-window of programming testicular descent (gestational weeks 8-14) was associated with a HR of 1.38 (1.05-1.83) for cryptorchidism. Exposure to ibuprofen and acetylsalicylic acid was not associated with cryptorchidism.


CONCLUSIONS
Maternal intake of acetaminophen for more than 4 weeks during pregnancy, especially during the first and second trimesters, may moderately increase the occurrence of cryptorchidism.
Jensen
Morten Søndergaard
MS
Perinatal Epidemiology Research Unit, Departments of Obstetrics and Pediatrics, Aarhus University Hospital, Skejby, Denmark. morten@sondergaard-jensen.dk
Rebordosa
Cristina
C
Thulstrup
Ane Marie
AM
Toft
Gunnar
G
Sørensen
Henrik Toft
HT
Bonde
Jens Peter
JP
Henriksen
Tine Brink
TB
Olsen
Jørn
J
D000082:Acetaminophen / Q000009:adverse effects*; D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D003456:Cryptorchidism / Q000139:chemically induced* / Q000453:epidemiology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy
D016861:Cyclooxygenase Inhibitors; D000082:Acetaminophen; D001241:Aspirin; D007052:Ibuprofen