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Prenatal medication exposure and epigenetic outcomes: a systematic literature review and recommendations for prenatal pharmacoepigenetic studies
Epigenetics ( IF 2.9 ) Pub Date : 2021-04-29 , DOI: 10.1080/15592294.2021.1903376
Emilie Willoch Olstad 1, 2 , Hedvig Marie Egeland Nordeng 1, 2, 3 , Kristina Gervin 1, 2, 4
Affiliation  

ABSTRACT

When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such modifications occur and whether they disrupt normal foetal developme nt, are currently unanswered questions. This field of prenatal pharmacoepigenetics has received increasing attention, with several studies reporting associations between in utero medication exposure and offspring epigenetic outcomes. Nevertheless, no recent systematic review of the literature is available. Therefore, the objectives of this review were to (i) provide an overview of the literature on the association of prenatal exposure to psychotropics a nd analgesics with epigenetic outcomes, and (ii) suggest recommendations for future studies within prenatal pharmacoepigenetics. We performed systematic literature searches in five databases. The eligible studies assessed human prenatal exposure to psychotropics or analgesics, with epigenetic analyses of offspring tissue as an outcome. We identified 18 eligible studies including 4,419 neonates exposed to either antidepressants, antiepileptic drugs, paracetamol, acetylsalicylic acid, or methadone. The epigenetic outcome in all studies was DNA methylation in cord blood, placental tissue or buccal cells. Although most studies found significant differences in DNA methylation upon medication exposure, almost no differences were persistent across studies for similar medications and sequencing methods. The reviewed studies were challenging to compare due to poor transparency in reporting, and heterogeneous methodology, design, genome coverage, and statistical modelling. We propose 10 recommendations for future prenatal pharmacoepigenetic studies considering both epidemiological and epigenetic perspectives. These recommendations may improve the quality, comparability, and clinical relevance of such studies. PROSPERO registration ID: CRD42020166675.



中文翻译:

产前药物暴露和表观遗传结果:产前药物表观遗传学研究的系统文献回顾和建议

摘要

在怀孕期间使用时,镇痛药和精神药物会通过胎盘进入胎儿循环,并可能诱导表观遗传修饰。这种改变发生在哪里以及它们是否会破坏正常的胎儿发育,目前仍是悬而未决的问题。这一产前药物表观遗传学领域受到越来越多的关注,一些研究报告了子宫内药物暴露和后代表观遗传结果。然而,最近没有文献的系统评价可用。因此,本综述的目的是 (i) 概述有关产前接触精神药物和镇痛剂与表观遗传结果之间的关系的文献,以及 (ii) 为产前药物表观遗传学的未来研究提出建议。我们在五个数据库中进行了系统的文献检索。符合条件的研究评估了人类产前对精神药物或镇痛药的暴露,并将后代组织的表观遗传分析作为结果。我们确定了 18 项符合条件的研究,包括 4,419 名接触抗抑郁药、抗癫痫药、扑热息痛、乙酰水杨酸或美沙酮的新生儿。所有研究的表观遗传结果都是脐带血中的 DNA 甲基化,胎盘组织或颊细胞。尽管大多数研究发现药物暴露后 DNA 甲基化存在显着差异,但在类似药物和测序方法的研究中几乎没有持续存在差异。由于报告的透明度差、方法学、设计、基因组覆盖率和统计建模的异质性,审查的研究难以比较。考虑到流行病学和表观遗传学的观点,我们为未来的产前药物表观遗传学研究提出了 10 条建议。这些建议可能会提高此类研究的质量、可比性和临床相关性。PROSPERO 注册 ID:CRD42020166675。在类似药物和测序方法的研究中,几乎没有持续存在差异。由于报告的透明度差、方法学、设计、基因组覆盖率和统计建模的异质性,审查的研究难以比较。考虑到流行病学和表观遗传学的观点,我们为未来的产前药物表观遗传学研究提出了 10 条建议。这些建议可能会提高此类研究的质量、可比性和临床相关性。PROSPERO 注册 ID:CRD42020166675。在类似药物和测序方法的研究中,几乎没有持续存在差异。由于报告的透明度差、方法学、设计、基因组覆盖率和统计建模的异质性,审查的研究难以比较。考虑到流行病学和表观遗传学的观点,我们为未来的产前药物表观遗传学研究提出了 10 条建议。这些建议可能会提高此类研究的质量、可比性和临床相关性。PROSPERO 注册 ID:CRD42020166675。考虑到流行病学和表观遗传学的观点,我们为未来的产前药物表观遗传学研究提出了 10 条建议。这些建议可能会提高此类研究的质量、可比性和临床相关性。PROSPERO 注册 ID:CRD42020166675。考虑到流行病学和表观遗传学的观点,我们为未来的产前药物表观遗传学研究提出了 10 条建议。这些建议可能会提高此类研究的质量、可比性和临床相关性。PROSPERO 注册 ID:CRD42020166675。

更新日期:2021-04-30
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