Maternal Use of Acetaminophen, Ibuprofen, and Acetylsalicylic Acid During Pregnancy and Risk of Cryptorchidism
Maternal Use of Acetaminophen, Ibuprofen, and Acetylsalicylic Acid During Pregnancy and Risk of Cryptorchidism
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DOI：
10.1097/ede.0b013e3181f20bed
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发表时间：
2010-11-01
期刊：
影响因子：
5.4
通讯作者：
Olsen, Jorn
中科院分区：
文献类型：
--
作者：
Jensen, Morten Sondergaard;Rebordosa, Cristina;Olsen, Jorn
背景：环氧合酶（COX）抑制剂对乙酰氨基酚、布洛芬和乙酰水杨酸在虹鳟鱼中具有内分泌干扰特性。在人类中，阿司匹林阻断了对人绒毛膜促性腺激素（hCG）的雄激素反应，而且，由于hCG刺激的子宫内雄激素产生对正常睾丸下降至关重要，在妊娠期脆弱时期暴露于COX抑制剂可能会损害睾丸下降。我们研究了产前暴露于对乙酰氨基酚、布洛芬和乙酰水杨酸是否与隐睾发生率增加有关。方法：我们的研究使用了1996-2002年期间在丹麦国家出生队列中登记的47,400名母亲活产的独生子女的数据。980名男孩儿童期发现隐睾症，其中565人接受了睾丸切除术。通过3次计算机辅助电话访谈和1份自我调查问卷评估孕妇在妊娠期间对乙酰氨基酚、布洛芬和乙酰水杨酸的使用情况。我们通过Cox回归分析估计隐睾的校正风险比（hr）。结果：妊娠早期和中期暴露于对乙酰氨基酚与隐睾发生率增加相关（HR = 1.33[95%可信区间= 1.00-1.77]）。在设定睾丸下降的时间窗内（妊娠8-14周）暴露超过4周，隐睾的风险比为1.38（1.05-1.83）。暴露于布洛芬和乙酰水杨酸与隐睾症无关。结论：孕妇在妊娠期间，特别是孕早期和中期服用对乙酰氨基酚超过4周，可适度增加隐睾的发生。
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.Conclusion: 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.