Association of Gestational Opioid Exposure and Risk of Major and Minor Congenital Malformations.
Association of Gestational Opioid Exposure and Risk of Major and Minor Congenital Malformations.
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DOI：
10.1001/jamanetworkopen.2021.5708
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发表时间：
2021-04-01
影响因子：
13.8
通讯作者：
Meador KJ
中科院分区：
文献类型：
--
作者：
Wen X;Belviso N;Murray E;Lewkowitz AK;Ward KE;Meador KJ
产前处方阿片类药物暴露与重大和轻微先天畸形风险之间是否存在关联？在这项对12424名孕妇进行的队列研究中，891名妇女在怀孕期间接受了处方阿片类药物。第1个孕期的阿片类药物暴露与重大出生缺陷无关，但在第3个孕期分发阿片类药物的妇女，其后代在肌肉骨骼系统中存在轻微出生缺陷的风险较高。研究结果表明，肌肉骨骼系统轻微先天性畸形的风险较高，与妊娠晚期的产前处方阿片类药物暴露相关;这种风险似乎具有剂量依赖性。阿片类药物过量和死亡的迅速增加已成为美国的公共卫生问题。孕妇使用处方类阿片的情况有所增加;致畸性研究的结果仍有争议。评价妊娠期间母体处方阿片类药物使用（不包括阿片类药物使用障碍）与先天性畸形发生率之间的相关性。这项基于人群的回顾性队列研究评估了2008年1月1日至2016年12月31日期间罗得岛医疗补助申请和活产婴儿的生命统计数据。数据分析于2019年5月1日至2020年5月31日进行。在研究期间有活产但没有癌症或阿片类药物使用障碍的妇女，从怀孕前3个月到怀孕结束进行了随访。通过药房索赔获得母亲处方阿片类药物暴露的数据，暴露定义为在妊娠早期、中期或晚期分配至少1种处方阿片类药物。主要结局是总体严重或轻微先天性畸形，定义为1个或多个严重或轻微先天性畸形。次要结局定义为使用国际疾病分类诊断代码按器官系统分类的10种特定类别的先天性畸形。在纳入的12424例妊娠中，891例母亲（7.2%）在妊娠期间接受了处方阿片类药物，3153例婴儿（25.4%）被诊断患有严重或轻微的先天性畸形。比较处方阿片类药物暴露与非暴露，在妊娠1个月内阿片类药物暴露的婴儿中未观察到重大出生缺陷的额外风险（调整后的相对危险度[aRR]，1.40; 95%CI，0.84-2.34），在妊娠3个月内发现总体轻微出生缺陷的风险较高（aRR，1.26; 95%CI，1.04-1.53）和肌肉骨骼系统的轻微出生缺陷在妊娠2（aRR，1.50; 95%CI，1.10-2.03）和妊娠3（aRR，1.65; 95%CI，1.23-2.22）。还确定了特定阿片类药物在选定的轻微畸形和影响中的显著剂量反应。妊娠2期氢可酮（aRR，3.01; 95% CI，1.80-5.03）和妊娠3期羟考酮（aRR，2.43; 95% CI，1.37-4.02）与斜头、多指和其他特定的先天性髋关节畸形相关。这项研究的结果表明，在妊娠3个月使用产前处方阿片类药物相关的轻微先天性畸形的风险较高，这似乎是剂量依赖性的。需要进一步的研究来确定因果关系并探索这种关联的生理学可接受性。这项队列研究检查了在妊娠期间接受阿片类药物治疗的女性所生婴儿的严重和轻微先天性畸形的发生率。
Is there an association between prenatal prescription opioid exposure and the risk of major and minor congenital malformations? In this cohort study of 12 424 pregnancies, 891 women were dispensed prescription opioids during pregnancy. Opioid exposure in trimester 1 was not associated with major birth defects, but women dispensed opioids in trimester 3 had higher risks of offspring with minor birth defects in the musculoskeletal system. The study findings suggest a higher risk of minor congenital malformations in the musculoskeletal system that is associated with prenatal prescription opioid exposure in the third trimester; this risk appears to be dose-dependent. The rapid increase of opioid-related overdoses and deaths has become a public health concern in the US. Use of prescription opioids in pregnant women has increased; results from teratogenicity studies remain controversial. To evaluate the association between maternal prescription opioid use (excluding opioid use disorders) during pregnancy and the incidence of congenital malformations. This retrospective population-based cohort study evaluated linked Rhode Island Medicaid claims and vital statistics data of live births from January 1, 2008, to December 31, 2016. Data analysis was conducted from May 1, 2019, to May 31, 2020. Women who had a live birth during the study period, but no cancer or opioid use disorder, were followed up from 3 months before pregnancy to the end of pregnancy. Data on the mother’s prescription opioid exposure were obtained through pharmacy claims and exposure was defined as dispensing of at least 1 prescription opioid during the first, second, or third trimester. The primary outcome was overall major or minor congenital malformations, defined as 1 or more major or minor congenital malformation. Secondary outcomes were defined as 10 specific categories of congenital malformations classified by organ systems using International Classification of Diseases diagnosis codes. Of 12 424 included pregnancies, 891 mothers (7.2%) received prescription opioids during pregnancy and 3153 infants (25.4%) were diagnosed with major or minor congenital malformations. Comparing prescription opioid exposure vs nonexposure, no excess risk was observed for major birth defects in infants with opioid exposure in trimester 1 (adjusted relative risk [aRR], 1.40; 95% CI, 0.84-2.34), and higher risks were found for overall minor birth defects in trimester 3 (aRR, 1.26; 95% CI, 1.04-1.53) and minor birth defects in the musculoskeletal system in trimester 2 (aRR, 1.50; 95% CI, 1.10-2.03) and trimester 3 (aRR, 1.65; 95% CI, 1.23-2.22). Significant dose responses in selected minor malformations and effects of specific opioids were also identified. Hydrocodone in trimester 2 (aRR, 3.01; 95% CI, 1.80-5.03) and oxycodone in trimester 3 (aRR, 2.43; 95% CI, 1.37-4.02) were associated with plagiocephaly, polydactyly, and other specified congenital deformities of the hip. The findings of this study suggest a higher risk of minor congenital malformations associated with use of prenatal prescription opioids in trimester 3, which seems to be dose-dependent. Further investigation is needed to establish causality and explore the physiologic plausibility of the association. This cohort study examines the incidence of major and minor congenital malformations in infants born to women who receive opioids for medical indications during pregnancy.
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