Monitoring In Utero Drug Exposure

与普通人群相比，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，由于新生儿禁欲综合征，延长住院时间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直接受剂量、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，并更好地了解药物通过胎盘膜的转运过程。关于母体血浆、尿液、唾液、汗液和头发中的药物浓度与羊水、脐带血、胎儿尿液、胎粪和胎儿毛发之间的关系，现有的数据有限。我们设计了几项研究来调查母体和胎儿药物在各种生物液和组织中的处置情况。每个孕妇样本都提供了怀孕不同阶段的药物暴露史。胎儿样本提供了有关产前药物暴露的独特信息。胎粪在妊娠第13周开始形成，毛发在最后三个月开始形成。每个母体提供了机会来确定不同母体中的药物浓度是否与母体和新生儿结局指标有关。此外，由于药物在胎儿体内的浓度很低，有必要开发灵敏和选择性的方法来检测这些化合物。分析方法正在改进，以提供更灵敏和可靠的方法来检测母体药物和鸦片类药物的代谢物，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。在子宫暴露后测量药物的分析挑战之一是，新生儿样本中的药物和代谢物可能与成人生物液中的药物和代谢物特征有很大不同。对于早产儿来说，情况可能尤其如此。 对我们来说，一项主要的新举措是结合儿科艾滋病毒/艾滋病队列研究(PHACS)对胎粪中的抗逆转录病毒药物进行量化。儿科艾滋病毒/艾滋病队列研究(PHACS)是一项纵向研究，始于2007年，评估婴儿期和青春期因宫内和/或生命头两个月暴露于抗逆转录病毒(ARV)而发生的多个领域的异常，包括代谢、生长、心脏、神经、神经发育、行为、语言和听力领域。在PHACS队列中，ARV毒性监测(SMARTT)研究正在检查艾滋病毒感染妇女所生的未感染艾滋病毒的儿童的临床和实验室数据，以评估与妊娠ARV暴露有关的不良事件的潜在信号。人们对一些新生儿暴露于妊娠期ARV的潜在毒性表示担忧，包括线粒体功能障碍、骨孔率增加以及听力和语言障碍。准确地量化胎儿ARV暴露是非常有必要的。我们正在与该小组合作，提供20种分析物的胎粪ARV测量；胎粪中的浓度可能更好地预测婴儿可能发生ARV相关毒性。目的是确定胎粪抗逆转录病毒分析是否比母体用药史更能预测发育异常。 目前，我们还在研究胎粪中乙基葡萄糖醛酸乙酯、硫酸乙酯和脂肪酸乙酯浓度在检测怀孕期间母亲饮酒方面的应用。关于哪个标记物(S)最能预测母亲饮酒行为，哪个标记物(S)应该用来筛查婴儿潜在的酒精相关问题，该领域存在很大争议。我们正在与大型临床研究合作，包括PHACS和产前酒精在SIDS中的应用，以及静产(PASS，安全通道)研究，以评估这些目标。

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. A major new inititative for us is the quantification of anti-retroviral drugs in meconium in conjunction with the Pediatric HIV/AIDS Cohort Study (PHACS). The Pediatric HIV/AIDS Cohort Study (PHACS) is a longitudinal study, beginning in 2007, assessing occurrences of abnormalities from antiretroviral (ARV) exposure in utero and/or in the first two months of life in multiple domains, including metabolic, growth, cardiac, neurologic, neurodevelopmental, behavior, language, and hearing domains, during infancy and adolescence. Within the PHACS cohort, the Surveillance Monitoring for ARV Toxicities (SMARTT) study is examining clinical and laboratory data from HIV-uninfected children born to HIV-infected women to assess potential signals for adverse events related to gestational ARV exposure. Concerns are being raised about the potential toxicity in some neonates to gestational ARV exposure, including mitochondrial dysfunction, increased bone porosity, and hearing and language impairment. There is a strong need to accurately quantify fetal ARV exposure. We are collaborating with this group to provide meconium ARV measurements of 20 analytes; concentrations in meconium may better predict infants likely to develop ARV-related toxicities. The goal is to determine if meconium ARV analysis better predicts developmental abnormalities than maternal drug history. Currently we are also investigating the utility of ethyl glucuronide, ethyl sulfate and fatty acid ethyl ester concentrations in meconium to detect maternal alcohol consumption during pregnancy. There is great debate in the field about which marker(s) best predict maternal drinking behavior and which marker(s) should be used to screen infants for potential alcohol-related problems. We are collaborating with large clinical studies including PHACS and Prenatal Alcohol in SIDS and Stillbirth (PASS, Safe Passage) study to evaluate these objectives.