Monitoring in utero drug exposure

子宫内药物暴露监测

• 批准号: 6414306
• 负责人: Marilyn Huestis
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6414306
• 关键词: buprenorphine; clinical research; cocaine; drug abuse; embryo /fetus drug adverse effect; embryo /fetus monitoring; embryo /fetus toxicology; gestational age; heroin; human pregnant subject; human subject; membrane permeability; methadone; method development; vertical transmission

Drug-abusing women have higher rates of pregnancy complications and an increased incidence of infants with lower birth weights and higher rates of congenital malformations and mortality than are seen with the general populations. In addition, there is an increased prevalence for longer hospitalization due to neonatal abstinence syndrome. The risk of adverse events in drug-exposed infants can be directly influenced by dose, class of abused substance and time of intrauterine exposure. In addition, poly-drug use may also have an effect on the developmental outcome of the fetus. To better understand the role illicit and licit substances have on the developing fetus, it is necessary that we develop improved methods of detection and gain a better understanding of the transport process involved in the transfer of drug across the placental membrane. Limited data are available correlating the relationship between maternal concentration as seen in plasma, urine, saliva, sweat and hair to amniotic fluid, cord blood, fetal urine, meconium and fetal hair. We have designed and are working in collaboration on several studies to investigate the relationship of maternal and fetal disposition of a variety of substances. Each maternal specimen gives a history of drug exposure at different stages of gestation. Fetal specimens offer the opportunity to examine the occurrence of drugs at different time points. Since it is known that meconium starts developing in the 13th week of gestation and hair in the last trimester, you would not expect to see any substance the mother stopped using in the second trimester in fetal hair only in meconium. Each matrix offers the unique opportunity to examine the disposition of drugs exposed in utero. In addition, due to the low concentrations of drugs in fetal matrices, it is necessary to develop sensitive and selective methods for detecting these compounds. Analytical methods are being improved to offer more sensitive and reliable methods of detecting the parent drug and metabolites of opiates, including buprenorphine and methadone, cocaine, methamphetamine, cannabinoids and nicotine in a variety of maternal and infant specimens. One of the analytical challenges in measurement of drugs following in utero exposure is the finding that drug and metabolite profiles in neonatal specimens may be quite different than those found in adult biological fluids. This is especially true with premature infants.

与一般人口相比，滥用药物的妇女怀孕并发症的发生率较高，婴儿出生体重较轻的发生率较高，先天畸形和死亡率较高。 此外，由于新生儿禁欲综合征而延长住院时间的流行率也有所增加。 药物暴露的婴儿不良事件的风险可直接受到剂量、滥用物质的类别和宫内暴露时间的影响。 此外，多种药物的使用也可能对胎儿的发育结果产生影响。 为了更好地了解非法和合法物质对发育中的胎儿的作用，我们有必要开发改进的检测方法，并更好地了解药物穿过胎盘膜的转运过程。在血浆、尿液、唾液、汗液和毛发中观察到的母体浓度与羊水、脐带血、胎儿尿液、胎粪和胎儿毛发之间的关系方面，可用的数据有限。 我们已经设计并正在合作进行几项研究，以调查各种物质的母体和胎儿处置的关系。 每个母体样本都提供了妊娠不同阶段的药物暴露史。 胎儿标本提供了在不同时间点检查药物发生的机会。 由于已知胎粪在妊娠的第13周开始发育，而毛发在最后三个月开始发育，因此您不会期望在胎粪中看到母亲在第二个三个月停止使用的任何物质。 每个矩阵提供了独特的机会，检查药物暴露在子宫内的处置。 此外，由于胎儿基质中药物浓度低，因此有必要开发灵敏和选择性的方法来检测这些化合物。 正在改进分析方法，以提供更灵敏、更可靠的方法来检测各种产妇和婴儿样本中的阿片类药物的母体药物和代谢物，包括丁丙诺啡和美沙酮、可卡因、甲基苯丙胺、大麻素和尼古丁。 在子宫内暴露后测量药物的分析挑战之一是发现新生儿样本中的药物和代谢物谱可能与成人生物体液中的药物和代谢物谱完全不同。 对于早产儿来说尤其如此。