Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Pharmacy, Faculty of Health Sciences, Universidade de Brasília, Brasília, Brazil.
Am J Perinatol. 2021 Jul;38(9):968-975. doi: 10.1055/s-0040-1701505. Epub 2020 Feb 12.
This pilot study evaluated the relationship between maternal and neonatal R- and S-methadone and R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) exposure and the severity of neonatal abstinence syndrome (NAS). The use of dried blood spots (DBS) as an alternative for plasma in assessing methadone and EDDP was also assessed.
Women receiving methadone for medication assisted treatment of opioid use disorder during pregnancy were eligible for recruitment. Plasma and DBS samples were collected from mothers during labor, from cord blood, and from newborns during genetic screen. R-/S-methadone and EDDP were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). Associations between methadone exposure, neonatal morphine requirements, and severity of NAS were examined.
Twenty women and infants completed the study. Maternal methadone dose at delivery was 112 mg/day (range = 60-180 mg/day). Sixteen neonates experienced NAS requiring morphine; three also required phenobarbital. Higher cord blood concentrations of R-methadone, R- and S-EDDP were associated with higher maximum doses of morphine ( < 0.05).
Maternal methadone and cord blood concentration at delivery are variable and may be potential markers of neonatal abstinence syndrome.
本初步研究评估了母体和新生儿 R-和 S-美沙酮与 R-和 S-2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷（EDDP）暴露与新生儿戒断综合征（NAS）严重程度之间的关系。还评估了使用干血斑（DBS）代替血浆来评估美沙酮和 EDDP 的情况。
接受美沙酮进行药物辅助治疗妊娠期间阿片类药物使用障碍的女性有资格入组。在分娩期间从母亲、脐带血中采集血浆和 DBS 样本，并在新生儿进行基因筛查时采集。通过高效液相色谱串联质谱法（HPLC/MS/MS）测量 R-/S-美沙酮和 EDDP。研究了美沙酮暴露、新生儿吗啡需求与 NAS 严重程度之间的关系。
共有 20 名女性及其婴儿完成了研究。分娩时的母体美沙酮剂量为 112mg/天（范围= 60-180mg/天）。16 名新生儿出现需要吗啡治疗的 NAS；3 名新生儿还需要苯巴比妥。脐带血中 R-美沙酮、R-和 S-EDDP 浓度较高与较高的吗啡最大剂量相关（<0.05）。
分娩时母体美沙酮和脐带血浓度变化不定，可能是新生儿戒断综合征的潜在标志物。
