Effects of Opioid Use Disorder in Pregnancy on Long-Term Maternal and Child Outcomes

妊娠期阿片类药物使用障碍对母婴长期结局的影响

• 批准号: 10499023
• 负责人: Senthilkumar Sadhasivam
• 金额: $ 54.53万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10499023
• 关键词: Effects; Opioid; Use; Disorder; Pregnancy

Project Summary: In the US, 14-21% of pregnant women are exposed to opioids during pregnancy. This re- flects a doubling of prescribed opioid use and opioid use disorder (OUD) in pregnancy in the past dec- ade. Opioid relapse during pregnancy and after delivery is high due to post-partum depression and other psy- chosocial factors. In parallel, neonatal abstinence syndrome (NAS) rates have increased more than 3 to 20 fold since 2000. Every 25 minutes, a baby is born dependent to opioids in the US. Children exposed to opioids pre- natally and in the neonatal period are at risk of opioid misuse later in life, and may develop cognitive, behavior- al and neurodevelopmental problems. All these preventable public health crises confer a significant societal and economic burden, with loss of productive life. Despite the high prevalence of exposure to opioids, little is known about the factors predisposing to poor maternal outcomes, and neurodevelopmental outcomes in chil- dren with maternal OUD. Further, the effect of in-utero opioid exposure on placental function, fetal maturation and neonatal brain activity are unknown. Tackling maternal opioid misuse and NAS requires a comprehensive understanding of multiple maternal-infant factors. There is a critical need for early and targeted identification of pregnant women with OUD at risk for relapse and poor long term maternal and childhood outcomes. Our long- term goals are to reduce future maternal OUD and relapse on opioid maintenance therapy, decrease severity of NAS, personalize NAS treatment, and improve neurodevelopment in children with in-utero opioid exposure. The objective of this proposal is to determine multi-factorial genetic, psychosocial predictors of opioid related maternal and infant outcomes using rigorous prospective longitudinal design, innovative combinatorial phar- macogenetic approach, fetal MRI and neonatal brain resting state functional MRI analysis. Our earlier work showed that maternal/neonatal genetic variations and opioid-pharmacogenetics were associated with NAS se- verity and adverse effects of opioids. Our preliminary data show that children treated for NAS had significantly worse cognitive function at two years of life. Based on our previous results, we hypothesize that a combination of maternal and infant genetic profile, maternal psychosocial factors, maternal opioid treatment response, fetal and neonatal neurodevelopment and NAS treatment will affect maternal and childhood outcomes with prenatal opioid exposure.The specific aims are to: 1) Identify high-risk genetic profiles and psychosocial factors in preg- nant women with opioid use disorder, and predisposing to poor maternal opioid maintenance treatment out- comes; 2) Determine maternal-infant genetic profiles and maternal opioid treatment factors predicting adverse fetal development, severity of NAS, and neonatal brain function; and 3) Develop predictive models for maternal opioid relapse, and poor long-term neuro-developmental outcomes in children with in-utero opioid exposure. Critical new knowledge from this research will enable safe, effective treatment of maternal-infant opioid expo- sure and neurodevelopmental outcomes by enabling proactive risk predictions and personalized interventions.

项目摘要：在美国，14-21％的孕妇在怀孕期间接触阿片类药物。这个重新 在过去的怀孕期间，折断规定的阿片类药物使用和阿片类药物使用障碍（OUD）的触觉 - 阿德。由于产后抑郁症和其他PSY- chosocial因子。同时，新生儿禁欲综合征（NAS）的速率增加了3至20倍 自2000年以来。每25分钟，一个婴儿天生就取决于美国的阿片类药物。暴露于阿片类药物的儿童 出生时期和新生儿时期有滥用阿片类药物的风险，并可能发展认知，行为 - AL和神经发育问题。所有这些可预防的公共卫生危机赋予了一个重要的社会 和经济负担，失去生产力。尽管接触阿片类药物的患病率很高，但几乎没有 知道偏见的孕产妇结局的因素以及CHIL-的神经发育结局 用母亲阵风。此外，局内阿片类药物暴露对胎盘功能，胎儿成熟的影响 和新生儿大脑活动尚不清楚。解决母体阿片类药物滥用，NAS需要全面 了解多种产妇因素。迫切需要早期和针对性的识别 OUD有复发风险和长期母亲和儿童期的孕妇。我们的长期 定期目标是减少未来的母亲口气和阿片类药物维持治疗的复发，减少严重程度 NAS，个性化NAS治疗，并改善阿片类药物内接触儿童的神经发育。 该提案的目的是确定阿片类药物相关的多因素遗传，社会心理预测指标 使用严格的前瞻性纵向设计，创新的组合法 - 促麦克诺遗传学方法，胎儿MRI和新生儿脑静息状态功能性MRI分析。我们的早期工作 结果表明，母亲/新生儿遗传变异和阿片类药物遗传学与NAS Se-相关 阿片类药物的真实性和不良影响。我们的初步数据表明，接受过NAS治疗的儿童有明显的 在两年的生活中，认知功能较差。根据我们以前的结果，我们假设一个组合 母体和婴儿遗传特征，母性心理因素，孕产妇阿片类药物治疗反应，胎儿 和新生儿神经发育和NAS治疗将影响产前的母亲和儿童期望 阿片类药物的暴露。具体目的是：1）确定preg-中的高风险遗传特征和社会心理因素 南特妇女患有阿片类药物使用障碍，并且易于遭受较差的母体阿片类药物维护治疗 来2）确定产妇遗传特征和产妇阿片类药物治疗因素预测不良 胎儿发育，NAS的严重程度和新生儿大脑功能； 3）开发孕产妇的预测模型 阿片类阿片类药物内暴露儿童的阿片类药物复发和长期神经发展结局。 来自这项研究的批判新知识将使您可以安全有效地治疗产妇的阿片类药物博览会 - 当然，通过实现主动的风险预测和个性化干预措施来实现神经发育结果。