Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
Pharmacotherapy. 2024 Jan;44(1):22-27. doi: 10.1002/phar.2863. Epub 2023 Aug 23.
Neonatal opioid withdrawal syndrome (NOWS) is a condition that often occurs in neonates born to mothers who received methadone treatment for opioid use disorder during pregnancy. Early identification and treatment of infants at risk of NOWS may improve clinical outcomes. The purpose of this study was to evaluate whether maternal and umbilical cord plasma concentrations of methadone and its metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), could predict the need for NOWS treatment.
Single-center prospective study.
University of Michigan Neonatal Intensive Care Unit.
The study included 11 opioid-dependent mother-infant dyads, where the mothers were treated with methadone at 34 weeks' gestation or later.
Maternal and cord blood samples were collected from the study participants.
Maternal and cord plasma concentrations of methadone and EDDP were determined. Six out of the 11 infants required treatment for NOWS. Maternal methadone plasma concentrations were comparable between infants requiring and not requiring NOWS treatment (329.1 ± 229.7 ng/mL vs. 413.2 ± 329.8 ng/mL). However, the average cord plasma methadone concentration in infants who did not require NOWS treatment was 2.9-fold higher than in those who required the treatment (120.0 ± 88.6 ng/mL vs. 40.9 ± 24.4 ng/mL), although the difference was not statistically significant. The ratios of maternal-to-cord methadone plasma concentrations were significantly higher in patients who required treatment for NOWS compared with those who did not (7.7 ± 1.9 vs. 3.5 ± 1.6, p = 0.003). Maternal and cord plasma EDDP concentrations and the maternal-to-cord plasma EDDP concentration ratios did not differ between patients who required and did not require treatment for NOWS.
The results suggest that methadone permeability across the blood-placental barrier may affect in utero exposure to methadone, and the maternal-to-cord methadone plasma concentration ratio could be a potential biomarker for predicting the need for NOWS treatment.
新生儿阿片类戒断综合征（NOWS）是一种经常发生在母亲在怀孕期间接受美沙酮治疗阿片类药物使用障碍的新生儿的疾病。早期识别和治疗有 NOWS 风险的婴儿可能会改善临床结局。本研究的目的是评估产妇和脐带血浆中美沙酮及其代谢物 2-乙基-1,5-二甲基-3,3-二苯基吡咯烷（EDDP）的浓度是否可以预测 NOWS 治疗的需要。
单中心前瞻性研究。
密歇根大学新生儿重症监护病房。
本研究纳入了 11 例阿片类药物依赖的母婴对，其中母亲在妊娠 34 周或以后接受美沙酮治疗。
从研究对象中采集产妇和脐带血样。
测定了产妇和脐带血浆中美沙酮和 EDDP 的浓度。11 例婴儿中有 6 例需要治疗 NOWS。需要和不需要 NOWS 治疗的婴儿的产妇美沙酮血浆浓度相似（329.1±229.7ng/ml 比 413.2±329.8ng/ml）。然而，不需要 NOWS 治疗的婴儿脐带血浆中美沙酮的平均浓度是需要治疗的婴儿的 2.9 倍（120.0±88.6ng/ml 比 40.9±24.4ng/ml），尽管差异无统计学意义。与不需要 NOWS 治疗的患者相比，需要治疗 NOWS 的患者的母体-脐带美沙酮血浆浓度比值显著更高（7.7±1.9 比 3.5±1.6，p=0.003）。需要和不需要 NOWS 治疗的患者的产妇和脐带血浆 EDDP 浓度以及母体-脐带血浆 EDDP 浓度比值无差异。
结果表明，美沙酮穿过血胎盘屏障的通透性可能会影响胎儿暴露于美沙酮的情况，而母体-脐带美沙酮血浆浓度比值可能是预测需要 NOWS 治疗的潜在生物标志物。
