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

怀孕期间使用芬太尼：对母鼠、胎盘和后代发育的影响。

基本信息

批准号：
10750077
负责人：
Daniela Rüedi-Bettschen
金额：
$ 150.95万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10750077
关键词：
Achievement Affect Analgesics Behavior Behavioral Blood Pressure Cardiovascular system Caring Child Consensus Development Developmental Delay Disorders Drug Exposure Elements Environment Female Female of child bearing age Fentanyl Fetal Growth Retardation Fetus Future Health Hormones Impairment Intake Intravenous Investigation Knowledge Lead Low Birth Weight Infant Maternal Health Maternal Physiology Measures Modeling Mothers Neonatal Neonatal Abstinence Syndrome Outcome Overdose Oxidative Stress Pain Patients Personal Satisfaction Pharmaceutical Preparations Physiological Physiology Placenta Postpartum Period Pregnancy Pregnancy Complications Pregnancy Outcome Pregnant Women Premature Birth Public Health Rattus Respiration Risk Rodent Model Role Saline Self Administration Severities Stress Substance Withdrawal Syndrome Testing Time Ventilatory Depression Withdrawal Withdrawal Symptom Woman behavioral impairment biological adaptation to stress clinically relevant delivery complications effective intervention experimental study fentanyl abuse fentanyl exposure fentanyl self-administration fentanyl use fetal opioid exposure human model improved in utero interest maternal stress offspring opioid abuse opioid exposure opioid use opioid use disorder opioid withdrawal postnatal preclinical study pregnant statistics stress reactivity treatment strategy

项目摘要

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.

抽象的孕妇或育龄妇女滥用阿片类药物是一个紧迫的公共卫生问题。去年，临产时使用阿片类药物的女性人数增加了四倍多十年。怀孕期间使用阿片类药物的直接影响，即新生儿阿片戒断综合征，已得到很好的描述，但对于阿片类药物滥用的有害影响知之甚少。怀孕对孕产妇健康、胎盘功能和发育中的儿童的影响。本提案旨在调查怀孕期间使用芬太尼的影响及其对母亲生理机能、应激反应性的影响，胎盘功能和后代发育使用翻译相关的方法，其中大鼠自我在怀孕前和整个怀孕期间在长期使用条件下静脉注射芬太尼。三分之内目的我们将测试以下假设：在怀孕前和整个怀孕期间自行服用芬太尼会 1) 影响母体心血管系统、呼吸和应激反应性，2) 引起严重损伤胎盘功能，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。我们将全面评估健康状况、血压、呼吸频率、应激激素水平和氧化水平自我服用芬太尼的怀孕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整体健康状况、发生情况和严重程度以及达到适当年龄后代的躯体和行为发育里程碑。与轭盐水和假手术相比对照水坝，我们假设水坝自我施用芬太尼会导致血压下降，呼吸抑制和应激反应性增加。我们还预计胎盘的充足性会减少，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影响的所需信息对怀孕女性生理和行为以及后代发育的影响。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。