Bogen Debra L, Hanusa Barbara H, Perel James M, Sherman Frederick, Mendelson Marla A, Wisner Katherine L
University of Pittsburgh School of Medicine, Division of General Academic Pediatrics, Children's Hospital of Pittsburgh, 3414 Fifth Ave, CHOB 3rd floor, Pittsburgh, PA 15213.
Department of Pediatrics, University of Pittsburgh School of Medicine, Division of General Academic Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Clin Psychiatry. 2017 Sep-Oct;78(8):e1013-e1019. doi: 10.4088/JCP.16m11318.
Methadone is a standard treatment for opioid dependence in pregnancy; however, its impact on maternal corrected QT interval (QTc) has not been evaluated. We studied the association between methadone dose and enantiomer-specific plasma concentrations and QTc among pregnant and postpartum women and newborns. We assessed the relevance of QTc screening guidelines for pregnant women and infants.
From 2006 to 2008, plasma methadone concentrations were measured during pregnancy, postpartum, and in cord blood in women treated for opioid dependence at a single treatment program. Electrocardiograms (ECGs) were obtained at peak methadone concentrations in mothers and within 48 hours of birth for infants. Pearson correlations were performed at each time point for QTc and R-methadone, S-methadone, and total methadone concentrations and ratio of R-methadone/S-methadone concentrations.
Mean (SD) daily methadone dose for the 25 women was 94.2 (39.1) mg during pregnancy and 112.5 (46.6) mg postpartum. During the third trimester, higher methadone dose and R-methadone concentration correlated with longer QTc (Pearson r = 0.67, P < .001 and Pearson r = 0.49, P = .02, respectively), while S-methadone concentration, R-methadone/S-methadone concentration ratio, and total methadone concentration did not. Postpartum, QTc did not significantly correlate with dose or enantiomer concentrations. Infant QTc did not correlate with maternal dose at delivery or enantiomer-specific cord methadone concentrations. In pregnant and postpartum women, 13% and 17%, respectively, had QTc ≥ 450 ms, as did 19% of infants.
QTc correlated with dose and R-methadone concentration during the third trimester. However, longer QTc was common among women during and after pregnancy. Given the relatively high rate of QTc > 450 ms, an ECG before and after methadone initiation is advisable for pregnant and postpartum women.
美沙酮是孕期阿片类药物依赖的标准治疗药物；然而，其对母亲校正QT间期（QTc）的影响尚未得到评估。我们研究了美沙酮剂量、对映体特异性血浆浓度与孕妇、产后妇女及新生儿QTc之间的关联。我们评估了孕妇和婴儿QTc筛查指南的相关性。
2006年至2008年期间，在单一治疗项目中，对接受阿片类药物依赖治疗的妇女在孕期、产后及脐带血中测量血浆美沙酮浓度。在母亲美沙酮浓度峰值时以及婴儿出生后48小时内获取心电图（ECG）。在每个时间点对QTc与R-美沙酮、S-美沙酮、总美沙酮浓度以及R-美沙酮/S-美沙酮浓度比值进行Pearson相关性分析。
25名妇女孕期美沙酮平均（标准差）日剂量为94.2（39.1）mg，产后为112.5（46.6）mg。在孕晚期，较高的美沙酮剂量和R-美沙酮浓度与更长的QTc相关（Pearson相关系数分别为r = 0.67，P <.001和r = 0.49，P =.02），而S-美沙酮浓度、R-美沙酮/S-美沙酮浓度比值以及总美沙酮浓度则无此关联。产后，QTc与剂量或对映体浓度无显著相关性。婴儿QTc与分娩时母亲剂量或脐带血中对映体特异性美沙酮浓度无相关性。孕期和产后妇女中，分别有13%和17%的人QTc≥450 ms，婴儿中这一比例为19%。
孕晚期QTc与剂量和R-美沙酮浓度相关。然而，孕期及产后妇女中QTc延长较为常见。鉴于QTc>450 ms的发生率相对较高，建议对孕妇和产后妇女在开始使用美沙酮前后进行心电图检查。
