Table5_Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome.XLSX

Introduction: The neonate exposed to opioids in utero faces a constellation of withdrawal symptoms postpartum commonly called neonatal opioid withdrawal syndrome (NOWS). The incidence of NOWS has increased in recent years due to the opioid epidemic. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. Epigenetic variations in microRNAs (miRNAs) and their impact on addiction-related processes is a rapidly evolving area of research.Methods: The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls.Results: The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis.Conclusion: This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well.

引言：在子宫内暴露于阿片类药物的新生儿在出生后常出现一系列称为新生儿阿片类药物戒断综合征（NOWS）的戒断症状。近年来，由于阿片类药物的流行，NOWS的发病率有所上升。微RNA（miRNA）是参与基因调控的关键作用的微小非编码RNA分子。微RNA（miRNA）的表观遗传变异及其对成瘾相关过程的影响是研究迅速发展的领域。方法：本研究采用Illumina Infinium Methylation EPIC BeadChip分析96个人胎盘组织中miRNA编码基因的DNA甲基化水平，以识别与NOWS相关的miRNA基因甲基化谱：32例为母亲孕期阿片类药物暴露的婴儿需要药物治疗NOWS的病例，32例为母亲孕期阿片类药物暴露的婴儿无需治疗NOWS的病例，以及32例未暴露的对照组。结果：研究鉴定出46个与47个独特miRNA相关的显著差异甲基化（FDR p值≤0.05）的CpG位点，其中ROC曲线下面积（AUC）≥0.75的包括28个低甲基化和18个高甲基化的CpG位点，可能与其相关。这些失调的微RNA甲基化模式可能是NOWS发病机制的一个促成因素。结论：这是首次分析NOWS婴儿miRNA甲基化谱的研究，揭示了miRNA在诊断和治疗疾病中的独特作用。此外，这些数据可能为NOWS婴儿的可行精准医学提供一步。