Supplementary Material for: MR Spectroscopy Shows Long Propylene Glycol Half-Life in Neonatal Brain

Introduction: Neonatal propylene glycol (PG) clearance is low with long plasma half-life. We hypothesized that neonatal brain PG clearance is diminished and may be related to perinatal asphyxia, infection, or stroke, via different blood-brain barrier permeability. This study aimed to estimate cerebral PG half-life with a clearance model including PG measured with MR spectroscopy (MRS) in neonates that received phenobarbital as the only PG source and to evaluate whether PG clearance was related to intracerebral pathology, for example, perinatal asphyxia, infection, or stroke. Methods: In this retrospective cohort study, 45 neonates receiving any dose of phenobarbital underwent MRS (short echo time single-voxel MRS at 1.5 T). Cumulative phenobarbital/PG doses were calculated. MRS indications were perinatal asphyxia (n = 22), infection (n = 4), stroke (n = 10), metabolic disease (n = 4), and others (n = 5). Results: Medians (interquartile range) included gestational age 39.4 (3.1) weeks, birth weight 3,146 (1,340) g, and cumulative PG dose 700 (1,120) mg/kg. First-order kinetics with mono-exponential decay showed cerebral PG half-life of 40.7 h and volume of distribution of 1.6 L/kg. Zero-order kinetics showed a rate constant of 0.048 mM/h and a volume of distribution of 2.3 L/kg, but the fit had larger residuals than the first-order model. There were no differences in ΔPG (i.e., PG estimated with clearance model minus PG observed with MRS) in infants with perinatal asphyxia, infection, or stroke. Discussion/Conclusion: This study showed a long cerebral PG half-life of 40.7 h in neonates, unrelated to perinatal asphyxia, infection, or stroke. These findings should increase awareness of possible toxic PG concentrations in neonatal brain due to intravenous PG-containing drugs.引言：新生儿丙二醇（propylene glycol, PG）的清除率较低，血浆半衰期较长。我们推测新生儿脑部PG清除能力受损，且该损伤可能因血脑屏障通透性改变，与围产期窒息、感染或脑卒中相关。本研究旨在通过清除率模型，以苯巴比妥（phenobarbital）作为PG唯一来源的新生儿的磁共振波谱（MR spectroscopy, MRS）检测所得PG浓度为基础，估算其脑部PG半衰期，并评估PG清除能力是否与围产期窒息、感染或脑卒中等颅内病变相关。方法：本研究为回顾性队列研究，共纳入45名接受任意剂量苯巴比妥的新生儿，所有受试者均接受了MRS检测（1.5T场强下的短回波单体素磁共振波谱）。研究人员计算了苯巴比妥/PG的累计给药剂量。本次MRS检测的指征包括围产期窒息（n=22）、感染（n=4）、脑卒中（n=10）、代谢性疾病（n=4）及其他（n=5）。结果：受试者的中位数（四分位间距）分别为：胎龄39.4（3.1）周，出生体重3146（1340）g，累计PG给药剂量700（1120）mg/kg。采用单指数衰减的一级动力学模型分析显示，脑部PG的半衰期为40.7小时，分布容积为1.6 L/kg。零级动力学模型则得出速率常数为0.048 mM/h，分布容积为2.3 L/kg，但该拟合的残差大于一级动力学模型。围产期窒息、感染或脑卒中患儿的ΔPG（即通过清除率模型估算的PG浓度减去MRS检测得到的实际PG浓度）无显著组间差异。讨论与结论：本研究显示新生儿脑部PG半衰期长达40.7小时，且该半衰期与围产期窒息、感染或脑卒中无关联。上述研究结果应提高临床对静脉输注含PG药物可能导致新生儿脑部PG毒性浓度的警惕性。