Pregnancy outcome following opioid exposure: A cohort study
Pregnancy outcome following opioid exposure: A cohort study
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DOI：
10.1371/journal.pone.0219061
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发表时间：
2019-07-01
期刊：
影响因子：
3.7
通讯作者：
Levy, Amalie
中科院分区：
文献类型：
--
作者：
Fishman, Boris;Daniel, Sharon;Levy, Amalie
阿片类药物是镇痛治疗的基石。然而，妊娠期间阿片类药物的安全性尚未得到很好的确定。最近的研究报告了在子宫内阿片类药物暴露和脊柱裂之间的关联。MethodsIn为了进一步评估阿片类药物暴露在怀孕期间与不良妊娠结局的关联，我们进行了一个大型的历史队列，通过连接四个数据库：药物分配，出生，妊娠终止医疗原因和婴儿住院期间的1999-2009年。控制的混杂因素包括母亲年龄、种族、母亲糖尿病、吸烟状况、产次、肥胖、年龄和叶酸摄入量。总的主要畸形和脊柱裂的二次分析进行了使用倾向评分匹配的第一个三个月exposure.ResultsOf的101,586名妇女包括在研究中，3003分发阿片类药物在第一个三个月。宫内暴露于阿片类药物与总体严重畸形（校正比值比（aOR）0.97，95% CI 0.83-1.13）、心血管畸形（aOR = 0.89，95% CI 0.70-1.13）、其他系统畸形或脊柱裂（尤其是）无关。然而，暴露于可待因的新生儿和流产者患脊柱裂的风险是未暴露者的4倍（aOR = 4.42，95%CI 1.60-12.23）。在使用倾向评分匹配的二次分析中，这种关联仍然显著。妊娠晚期暴露于阿片类药物与低出生体重（aOR = 1.08，95%CI 0.77-1.52），围产期死亡（aOR = 1.38，95%CI 0.64-2.99）和其他不良妊娠结局无关。研究发现，妊娠早期暴露于可待因与脊柱裂风险增加有关。然而，这一发现是基于少数案例，需要在今后的工作中加以核实。
IntroductionOpioids constitute a cornerstone of pain relief treatment. However, opioid safety during pregnancy has not been well established. Recent studies reported an association between in utero opioid exposure and spina bifida.MethodsIn order to further evaluate the association of opioids exposure during pregnancy with adverse pregnancy outcomes, we conducted a large historical cohort by linking four data-bases: medications dispensations, births, pregnancy terminations for medical reasons and infant hospitalizations during the years of 1999-2009. Confounders that were controlled for included maternal age, ethnicity, maternal diabetes, smoking status, parity, obesity, year and folic acid intake. A secondary analysis for total major malformations and for spina bifida was performed using propensity score matching for first trimester exposure.ResultsOf the 101,586 women included in the study, 3003 were dispensed opioids during the first trimester. Intrauterine exposure to opioids was not associated with overall major malformations (adjusted odds ratio (aOR) 0.97, 95% CI 0.83-1.13), cardiovascular malformations (aOR = 0.89, 95% CI 0.70-1.13) other malformations by systems or spina bifida in particular. However, the risk for spina bifida among newborns and abortuses who were exposed to codeine was four times higher than that of the unexposed (aOR = 4.42, 95% CI 1.60-12.23). This association remained significant in a secondary analysis using propensity score matching. Third trimester exposure to opioids was not associated with low birth weight (aOR = 1.08, 95% CI 0.77-1.52), perinatal death (aOR = 1.38, 95% CI 0.64-2.99) and other adverse pregnancy outcomes.ConclusionsThese findings suggest that opioids exposure (as a homogenous group) is not a significant risk factor for overall major malformations. Exposure to codeine during the first trimester was found to be associated with increased risk of spina bifida. However, this finding was based on a small number of cases and need to be verified in future work.