Monitoring In Utero Drug Exposure

子宫内药物暴露监测

• 批准号: 7593266
• 负责人: Marilyn Huestis
• 金额: $ 63.01万
• 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/7593266
• 关键词: Adult; Adverse event; Amniotic Fluid; Biological; Buprenorphine; Cannabinoids; Class; Cocaine; Congenital Abnormality; Data; Detection; Development; Dose; Drug Exposure; Drug usage; Evaluation; Fetal Hair; Fetus; General Population; Goals; Hair; Hospitalization; Incidence; Infant; Liquid substance; Low Birth Weight Infant; Measurement; Measures; Meconium; Methadone; Methamphetamine; Methods; Monitor; Neonatal; Neonatal Abstinence Syndrome; Nicotine; Opiates; Outcome; Outcome Measure; Parents; Perinatal Exposure; Pharmaceutical Preparations; Plasma; Pregnancy; Pregnancy Complications; Premature Infant; Prevalence; Rate; Recording of previous events; Risk; Role; Saliva; Specimen; Staging; Sweat; Sweating; Third Pregnancy Trimester; Time; Tissues; Transport Process; Umbilical Cord Blood; Urine; Week; Woman; analytical method; design; drug exposure in utero; fetal; fetal drug exposure; improved; mortality; placental membrane

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 within the general population. 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 relationships between maternaldrug concentration in plasma, urine, saliva, sweat and hair to amniotic fluid, cord blood, fetal urine, meconium and fetal hair. We have designed several studies to investigate maternal and fetal drug disposition in a variety of biological fluid and tissues. Each maternal specimen provides a history of drug exposure at different stages of gestation. Fetal specimens offer unique information about prenatal drug exposure. Meconium begins to be formed in the 13th week of gestation and hair in the last trimester. Each matrix offers the opportunity to determine if drug concentrations in different matrices relate to maternal and neonatal outcome measures. 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 that drug and metabolite profiles in neonatal specimens may be quite different than those found in adult biological fluids. This may be especially true for premature infants.

与一般人口相比，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，先天性畸形和死亡率也更高。此外，由于新生儿戒断综合征，住院时间较长的患病率也在增加。药物暴露婴儿发生不良事件的风险可直接受到药物剂量、滥用药物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，并更好地了解药物在胎盘膜上转移的运输过程。关于孕妇血浆、尿液、唾液、汗液和毛发中药物浓度与羊水、脐带血、胎儿尿液、胎粪和胎儿毛发之间关系的资料有限。我们设计了几项研究来调查各种生物液体和组织中母体和胎儿的药物处置。每个母体标本都提供了妊娠不同阶段的药物暴露史。胎儿标本提供了关于产前药物暴露的独特信息。胎便在妊娠的第13周开始形成，在妊娠的最后三个月开始长毛。每个矩阵提供了机会，以确定是否药物浓度在不同的矩阵与产妇和新生儿的结局措施。此外，由于药物在胎儿基质中的浓度较低，有必要开发敏感和选择性的方法来检测这些化合物。正在改进分析方法，以提供更敏感和可靠的方法来检测母体药物和阿片类药物的代谢物，包括各种母婴标本中的丁丙诺啡和美沙酮、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新生儿标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大不相同。对于早产儿来说尤其如此。