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

摘要 孕妇或一般育龄妇女滥用类阿片是一个紧迫的公共卫生问题。 去年，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。 十年虽然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戒断， 综合征，有很好的描述，只有有限的知识阿片类药物滥用的有害影响， 妊娠对产妇健康、胎盘功能和胎儿发育的影响。该提案旨在调查 在怀孕期间使用芬太尼的影响及其对母体生理，应激反应， 胎盘功能，和后代的发展，使用一个相关的方法，其中大鼠大坝自我， 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 目的：我们将测试以下假设：在怀孕前和整个怀孕期间芬太尼自我给药将1）影响 母亲的心血管系统，呼吸和应激反应，2）引起严重的损害， 胎盘功能，和3）诱导新生儿阿片类药物戒断，损害后代发育和增加 后代的应激反应。 我们将全面评估健康，血压，呼吸率，应激激素水平和氧化 压力和胎盘功能在怀孕，芬太尼自我管理的女性。在后代中，我们将评估 新生儿总体健康状况、阿片类戒断发生率和严重程度及年龄适应性 后代的身体和行为发育里程碑。与轭式生理盐水和假手术相比 对照母鼠，我们假设母鼠的芬太尼自我给药将导致血压降低， 呼吸抑制和应激反应增加。我们还预计胎盘功能会下降， 以及新生儿阿片类戒断症状、后代发育障碍和后代压力 反应性从拟议的研究结果将提供有关芬太尼的影响所需的信息 对怀孕雌性的生理和行为以及对后代发育的影响。最终，我们的研究应该 获得对于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.