Fentanyl use during pregnancy: impact on dam, placenta, and offspring development.

摘要 对孕妇或一般育龄妇女滥用阿片类药物是一个紧迫的公共卫生问题。 在过去的几年里，在分娩和分娩时使用阿片类药物的妇女人数增加了四倍多 十年。而怀孕期间使用阿片类药物的直接影响，即新生儿阿片类药物的戒断 综合症，都有很好的描述，对阿片类药物滥用的有害影响只有有限的了解 怀孕对产妇健康、胎盘功能和胎儿发育的影响。这项提案旨在调查 孕期使用芬太尼对母体生理、应激反应的影响 胎盘功能和后代发育，使用翻译相关的方法，其中大鼠自体 在怀孕前和整个怀孕期间，在扩大接触条件下静脉注射芬太尼。在三年内 目的：我们将测试以下假设：怀孕前和怀孕期间芬太尼自我给药会影响 母体心血管系统、呼吸和应激反应，2)在 胎盘功能，以及3)诱导新生儿阿片类药物戒断，损害后代发育并增加 后代的应激反应能力。 我们将全面评估健康、血压、呼吸频率、应激激素水平和氧化 怀孕、芬太尼自我给药女性的压力和胎盘功能。在后代中，我们将评估 新生儿阿片类药物戒断的总体健康状况、发生率和严重程度以及年龄适当性的实现 后代的躯体和行为发育里程碑。与带轭的生理盐水和假的 控制水坝，我们假设芬太尼自我给药会导致血压下降， 呼吸抑制和应激反应增加。我们还预计胎盘的充分性会降低， 以及新生儿阿片类药物戒断症状、后代发育障碍和后代应激 反应性。拟议研究的结果将提供有关芬太尼疗效的必要信息 对怀孕雌性的生理和行为及后代发育的影响。最终，我们的研究应该 掌握对确定产前和产后治疗机会至关重要的知识。

ABSTRACT Opioid abuse of pregnant women or women of childbearing age in general is an urgent public health concern. The number of women using opioids presenting at labor and delivery has more than quadrupled in the last decade. While the imminent effects of opioid use during pregnancy, namely neonatal opiate withdrawal syndrome, are well described, there is only limited knowledge about harmful effect of opioid abuse during pregnancy on maternal health, placental function, and the developing child. This proposal aims to investigate the effects of fentanyl use during pregnancy and its consequences on maternal physiology, stress reactivity, placental function, and offspring development using a translationally relevant approach in which rat dams self - administer fentanyl intravenously under extended-access conditions prior and throughout pregnancy. In three Aims we will test the hypotheses that fentanyl self-administration before and throughout pregnancy will 1) affect the maternal cardiovascular system, respiration and stress reactivity, 2) induce profound impairments in placental function, and 3) induces neonatal opioid withdrawal, impairs offspring development and increases stress reactivity in the offspring. We will assess comprehensively health, blood pressure, respiration rate, stress hormone levels and oxidative stress, and placental function in pregnant, fentanyl self-administering females. In the offspring, we will assess the overall health, occurrence and severity of neonatal opiate withdrawal and achievement of ag e-appropriate somatic and behavioral developmental milestones by the offspring. In comparison to yoked saline and sham control dams, we hypothesize that fentanyl self-administration of dams will lead to decreased blood pressure, respiratory depression and an increase in stress reactivity. We also expect a reduced sufficiency of the placenta, as well as neonatal opioid withdrawal symptoms, impairments in offspring development, and offspring stre ss reactivity. The results fromthe proposed studies will provide needed information regarding the effects of fentanyl on the pregnant female physiology and behavior and on offspring development. Ultimately, our studies should lead to knowledge that is vital for the identification of treatment opportunities, both pre- and postpartum.