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产前阿片类药物暴露与早期生命表观基因组:ECHO研究结果

Prenatal opioid exposure and the early life epigenome: results from ECHO.

作者信息

Schrott Rose, Garrison-Desany Henri, Avalos Lyndsay, Breton Carrie V, Dabelea Dana M, Derefinko Karen, Dunlop Anne, Fang Fang, Gaylord Abigail, Grant Torie, Hivert Marie-France, Karagas Margaret R, Knight Anna K, Lester Barry, Lyall Kristen, McEvoy Cindy, Nguyen Ruby, Page Grier, Paquette Alison, Ruden Douglas, Shorey-Kendrick Lyndsey E, Smith Alicia K, Spindel Eliot, Volk Heather E, Ladd-Acosta Christine

机构信息

Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

出版信息

J Subst Use. 2025;30(3):484-491. doi: 10.1080/14659891.2024.2356569. Epub 2024 May 27.

Abstract

BACKGROUND

Prenatal opioid exposure has been associated with adverse child health outcomes. Changes to the epigenome provide a plausible mechanism through which effects may be elicited. We investigated whether prenatal opioid exposure was associated with locus-specific changes in umbilical cord blood DNA methylation (DNAm) and gestational epigenetic age.

METHODS

We leveraged data from the Environmental influences on Child Health Outcomes cohort. Prenatal opioid data was obtained from maternal self-report and/or medical record data. DNAm measures were generated from blood biospecimens collected at birth. Linear regression models tested associations between prenatal maternal opioid exposure and epigenetic outcomes in crude and fully adjusted models.

RESULTS

We tested the association between prenatal opioid exposure and cord blood DNAm at 15 CpG sites in 385 ( = 25 exposed, = 360 unexposed) individuals from three cohorts. We identified a single CpG site (cg14303187) that was nominally associated with prenatal opioid exposure ( = 0.02, β = -0.012; 95% CI, -0.023 to -0.0012). No significant associations between exposure and gestational epigenetic age were found ( = 716 individuals from eight cohorts; = 29 exposed, = 687 unexposed).

CONCLUSIONS

We identified a nominally significant association between prenatal opioid exposure and DNAm at one CpG site. Future studies should continue investigating the effect of this exposure on the epigenome.

摘要

背景

产前阿片类药物暴露与儿童健康不良后果有关。表观基因组的变化提供了一种可能引发这些影响的机制。我们研究了产前阿片类药物暴露是否与脐带血DNA甲基化(DNAm)的位点特异性变化以及妊娠表观遗传年龄有关。

方法

我们利用了环境对儿童健康结果队列研究的数据。产前阿片类药物数据来自母亲的自我报告和/或医疗记录数据。DNAm测量值是从出生时采集的血液生物样本中生成的。线性回归模型在粗模型和完全调整模型中测试了产前母亲阿片类药物暴露与表观遗传结果之间的关联。

结果

我们在来自三个队列的385名个体(暴露组 = 25名,未暴露组 = 360名)中测试了产前阿片类药物暴露与15个CpG位点的脐带血DNAm之间的关联。我们确定了一个单一的CpG位点(cg14303187),该位点与产前阿片类药物暴露名义上相关(P = 0.02,β = -0.012;95% CI,-0.023至-0.0012)。未发现暴露与妊娠表观遗传年龄之间存在显著关联(来自八个队列的716名个体;暴露组 = 29名,未暴露组 = 687名)。

结论

我们确定了产前阿片类药物暴露与一个CpG位点的DNAm之间存在名义上的显著关联。未来的研究应继续调查这种暴露对表观基因组的影响。

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