Analgesia use during pregnancy and risk of cryptorchidism: a systematic review and meta-analysis.
Analgesia use during pregnancy and risk of cryptorchidism: a systematic review and meta-analysis.
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DOI：
10.1093/humrep/dex047
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发表时间：
2017-05-01
期刊：
影响因子：
--
通讯作者：
Sarfati D
中科院分区：
文献类型：
--
作者：
Gurney J;Richiardi L;McGlynn KA;Signal V;Sarfati D
怀孕期间使用镇痛药的母亲所生的男孩与不使用镇痛药的母亲所生的男孩相比，隐睾的风险是否增加？在对10项已发表研究的系统回顾和荟萃分析中，我们仅观察到妊娠期间使用镇痛剂与儿子隐睾风险之间存在关联的微弱证据。与人体接触相关的镇痛浓度被认为会导致发育中的胎儿睾丸内分泌紊乱。然而，当整体来看，似乎有矛盾的证据之间的关联产妇使用镇痛药和隐睾症的发展。对妊娠期间使用镇痛剂与隐睾风险的研究进行了系统回顾和荟萃分析。数据库奥维德Medline、Embase、Scopus和Web of Science中使用的检索词为（analges* 或扑热息痛或对乙酰氨基酚）和（隐睾症或隐睾症或隐睾试验 * 或非隐睾试验 * 或非隐睾试验 *）。检索包括截至2016年5月23日的所有已发表文章，未设定语言限制。摘要由一名评审员筛选，以删除不相关的研究，其中10%的随机样本由第二名评审员验证。所有剩余论文的全文由两名评审员获得并评估，以确定符合我们纳入标准的论文。最终分析中纳入的摘要包括报告暴露（镇痛）和结局（隐睾）之间相关性的研究，对研究设计没有限制。只有提供了可以计算汇总关联（比值比或相对风险）及其95%置信限的数据，或者这些汇总关联由作者自己提供的研究才被纳入。对于每项纳入的研究，两名评审员（JG和VS）根据PRISMA建议独立提取研究元数据。我们使用Newcastle-Ottawa质量评估量表中概述的标准评估了研究质量和偏倚的可能性，但没有确定质量评分。两名评审员根据这些标准独立评估研究质量。在筛选了350篇论文后，10篇被纳入我们的综述（5项病例对照研究，5项队列研究）。我们观察到，曾使用镇痛剂与隐睾风险之间存在关联的证据较弱（合并粗比值比（OR）：1.11，95%CI 1.00-1.23），病例对照研究显示的关联（1.23，95%CI 0.85-1.78）略强于队列研究（1.09，95%CI 0.97-1.22）。我们观察到镇痛暴露周数增加与隐睾风险之间存在剂量-反应关系的微弱证据，以及镇痛暴露时间对隐睾风险的影响的微弱证据。通过Newcastle-Ottawa标准对研究质量进行评估，发现几乎没有（如果有的话）可能对给定研究结果产生有意义影响的实质性偏倚的证据。虽然混淆似乎并不重要，但暴露的错误分类可能是这种情况下测量误差的重要来源。系统性综述对报告偏倚持开放态度。由于数据不足，无法对两个关键问题（与剂量反应和暴露时间相关）进行荟萃分析。药物根据其共同作用进行分组，这对特定类型的镇痛和隐睾症之间的关系几乎没有提供任何见解。最后，假设母亲报告的镇痛剂使用与实际宫内暴露同义也有局限性。在怀孕期间普遍使用镇痛剂，使这种接触从人口健康的角度来看特别重要。10项研究中有9项是在欧洲或美国进行的，这限制了我们观察结果的普遍性。虽然我们的系统评价和荟萃分析的观察结果表明，在怀孕期间使用镇痛药与儿子隐睾的发展没有很强的相关性，他们也强调了需要进一步详细评估产妇镇痛药的使用和隐睾风险之间的关系。本研究由新西兰健康研究理事会资助（参考编号：14/052）。作者没有利益冲突需要声明。CRD42016041414
Are boys who are born to mothers who use analgesics during pregnancy at increased risk of cryptorchidism compared to those born to mothers who do not take analgesia? In this systematic review and meta-analysis of 10 published studies, we observed only weak evidence of an association between analgesia use during pregnancy and risk of cryptorchidism in the son. Concentrations of analgesia relevant to human exposure have been implicated as causing endocrine disturbances in the developing foetal testis. However, when viewed collectively there appears to be conflicting evidence regarding an association between maternal use of analgesics and development of cryptorchidism. A systematic review and meta-analysis of studies on analgesia use during pregnancy and risk of cryptorchidism was performed. The search terms used were (analges* OR paracetamol OR acetaminophen) AND (cryptorchidism OR cryptorchism OR undescended test* OR non-descended test* OR non descended test*) for the databases Ovid Medline, Embase, Scopus and Web of Science. The search included all published articles up until 23rd May 2016 and no limits were set in terms of language. Abstracts were screened by one reviewer to remove irrelevant studies, with a 10% random sample of these verified by a second reviewer. The full text of all remaining papers was obtained and assessed by two reviewers to identify those which met our inclusion criteria. Abstracts included in the final analysis included studies which reported associations between the exposure (analgesia) and the outcome (cryptorchidism), with no limit on study design. Studies were only included if data was provided from which summary associations (odds ratios or relative risks) and their 95% confidence limits could be calculated, or if these summary associations were provided by the authors themselves. For each included study, two reviewers (JG and VS) independently extracted study meta-data in line with PRISMA recommendations. We assessed study quality and potential for bias using the criteria outlined in the Newcastle-Ottawa Quality Assessment Scale, but did not determine a quality score. Two reviewers independently assessed study quality against these criteria. After screening 350 manuscripts, 10 were included in our review (five case-control studies, five cohort studies). We observed weak evidence of an association between ever-use of analgesia and risk of cryptorchidism (pooled crude odds ratio (OR): 1.11, 95% CI 1.00-1.23), with case-control studies revealing a marginally stronger association (1.23, 95% CI 0.85-1.78) than cohort studies (1.09, 95% CI 0.97-1.22). We observed weak evidence of a dose-response relationship between increasing weeks of analgesia exposure and risk of cryptorchidism, as well as weak evidence of an effect of timing on analgesia exposure and risk of cryptorchidism. Assessment of study quality via the Newcastle-Ottawa criteria revealed little (if any) evidence of substantial bias that may have meaningfully affected a given study’s results. While confounding does not appear to be important, misclassification of the exposure is possibly an important source of measurement error in this context. The systematic review is open to reporting bias. Owing to scant data, no meta-analyses for two key questions (relating to dose-response and timing of exposure) could be performed. Medications were grouped based on their common effect and this offers little insight into the relation between specific types of analgesia and cryptorchidism. Finally, there are limitations in assuming that analgesia use reported by mothers is synonymous with actual intrauterine exposure. The ubiquity of analgesia use during pregnancy makes this exposure particularly important from a population health perspective. Nine of the ten studies were conducted in Europe or USA, limiting generalizability of our observations. While the observations from our systematic review and meta-analysis suggest that analgesia use during pregnancy is not strongly associated with cryptorchidism development in the son, they also highlight the need for further detailed assessments of the relationship between maternal analgesia use and risk of cryptorchidism. This study was funded by the Health Research Council of New Zealand (reference #: 14/052). The authors have no conflict of interest to declare. CRD42016041414
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