Monitoring In Utero Drug Exposure

子宫内药物暴露监测

• 批准号: 6535673
• 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/6535673
• 关键词: buprenorphine; cannabinoids; clinical research; cocaine; diagnosis design /evaluation; drug abuse; embryo /fetus toxicology; female; gestational age; heroin; human pregnant subject; human tissue; methadone; nicotine; pregnancy disorder; prenatal diagnosis; women's health

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.

与一般人群相比，吸毒妇女的妊娠并发症发生率更高，出生体重较低的婴儿发生率更高，先天畸形和死亡率更高。此外，由于新生儿戒断综合症，住院时间较长的患病率也有所增加。药物暴露婴儿发生不良事件的风险可能直接受到剂量、滥用物质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。将血浆、尿液、唾液、汗液和头发中的母体浓度与羊水、脐带血、胎儿尿液、胎便和胎儿毛发中的浓度关联起来的数据有限。我们已经设计并正在合作开展几项研究，以调查母体和胎儿对各种物质的处置之间的关系。每个母体样本均提供了不同妊娠阶段的药物暴露史。胎儿标本提供了检查不同时间点药物发生情况的机会。由于众所周知，胎便在妊娠第 13 周开始形成，毛发则在妊娠最后三个月开始形成，因此您不会期望在胎毛中仅在胎便中看到母亲在妊娠中期停止使用的任何物质。每个矩阵都提供了独特的机会来检查子宫内暴露的药物的处置情况。此外，由于胎儿基质中的药物浓度较低，因此有必要开发灵敏且选择性的方法来检测这些化合物。分析方法正在不断改进，以提供更灵敏、更可靠的方法来检测各种母婴样本中的阿片类药物和代谢物，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。测量子宫内暴露后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有很大不同。对于早产儿尤其如此。