Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the Generation R Study
Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the Generation R Study
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DOI：
10.1093/humrep/der474
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发表时间：
2012-04-01
影响因子：
6.1
通讯作者：
Burdorf, Alex
中科院分区：
文献类型：
--
作者：
Snijder, Claudia A.;Kortenkamp, Andreas;Burdorf, Alex
最近，在怀孕期间使用非处方温和止痛剂被认为会影响后代生殖障碍的风险。我们研究了孕妇在怀孕期间暴露于轻度镇痛剂对其后代隐睾和尿道下裂发生率的影响。在荷兰，3184名妇女参加了一项大规模的基于人群的前瞻性出生队列研究，研究了孕妇在怀孕期间暴露于轻度镇痛剂与后代隐睾或尿道下裂之间的关系（2002 - 2006），R世代研究。隐睾症和尿道下裂是在儿童保健中心由训练有素的医生进行的常规筛查评估中确定的。轻度镇痛药的使用进行了评估，在三个产前问卷在怀孕期间，导致四个时期的使用，即围产期，前14周的妊娠，1422周的妊娠和2032周的妊娠。采用Logistic回归分析研究母亲使用轻度镇痛剂与隐睾和尿道下裂的关系，随访30个月的累积患病率隐睾为2.1，尿道下裂为0.7。在妊娠第二阶段（1422周）使用轻度镇痛药增加了先天性隐睾的风险[校正比值比（OR）2.12; 95置信区间（CI）1.173.83]，主要是由于使用对乙酰氨基酚（扑热息痛）（校正OR 1.89; 95 CI 1.013.51）。在隐睾儿子的母亲中，（68例中有23例）在怀孕期间使用轻度镇痛剂，而患有尿道下裂的男孩的母亲为31.8（22例中有7例），（3094例中的926例）。我们的研究结果表明，子宫内接触轻度镇痛药，主要是扑热息痛，在怀孕期间，当男性性别分化发生时，会增加隐睾症的风险。
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.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 (20022006), 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, 1422 weeks of gestation and 2032 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia.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 (1422 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95 confidence interval (CI) 1.173.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95 CI 1.013.51). 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.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.