Michel Holger, Potapow Antonia, Dechant Markus-Johann, Brandstetter Susanne, Wellmann Sven, Köninger Angela, Melter Michael, Apfelbacher Christian, Kabesch Michael, Gerling Stephan
University Children's Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of John, University of Regensburg, Regensburg, Germany.
Member of the Research and Development Campus Regensburg (WECARE), Hospital St. Hedwig of the Order of St. John, Regensburg, Germany.
Front Pharmacol. 2023 Aug 7;14:1193317. doi: 10.3389/fphar.2023.1193317. eCollection 2023.
Acquired QT interval prolongations due to drug side effects can result in detrimental arrhythmia. Maternal use of placenta-permeable drugs may lead to fetal exposure, thus leading to an increased risk of neonatal QT prolongation and arrhythmia. This study aimed to evaluate the influence of maternal QT-prolonging medication on the neonatal QT interval. In the prospective KUNO-Kids health study, an ongoing population-based birth cohort, we classified maternal medications according to the known risk of QT interval prolongation. Effects on the neonatal QT interval were tested by linear regression analyses, correcting for perinatal confounders (birth weight, gestational age, birth mode, and age at ECG recording). Subgroup analyses were performed for selective serotonin reuptake inhibitors, proton pump inhibitors, and antihistamine dimenhydrinate. Logistic regression analysis was performed using a QTc of 450 ms as the cut-off value. A total of 2,550 pregnant women received a total of 3,990 medications, of which 315 were known to increase the risk of QT prolongation, resulting in 105 (4.1%) neonates exposed in the last month of pregnancy. Overall, the mean age of the neonates at ECG was 1.9 days and the mean QTc (Bazett) was 414 ms. Univariate (regression coefficient -2.62, = 0.288) and multivariate (regression coefficient -3.55, = 0.146) regression analyses showed no significant effect of fetal medication exposure on the neonatal QT interval, neither in the overall nor in the subgroup analysis. Logistic regression analysis showed no association of exposure to maternal medication with an increased risk of neonatal QT interval prolongation (OR (odds ratio) 0.34, = 0.14). The currently used maternal medication results in a relevant number of fetuses exposed to QT interval-prolonging drugs. In our cohort, exposure was found to have no effect on the neonatal QT interval.
药物副作用导致的获得性QT间期延长可引发有害的心律失常。母亲使用可透过胎盘的药物可能会使胎儿接触到这些药物,从而增加新生儿QT间期延长和心律失常的风险。本研究旨在评估母亲使用延长QT间期的药物对新生儿QT间期的影响。在一项正在进行的基于人群的出生队列研究——KUNO-Kids健康研究中,我们根据已知的QT间期延长风险对母亲使用的药物进行了分类。通过线性回归分析测试对新生儿QT间期的影响,并对围产期混杂因素(出生体重、孕周、分娩方式和心电图记录时的年龄)进行校正。对选择性5-羟色胺再摄取抑制剂、质子泵抑制剂和抗组胺药茶苯海明进行了亚组分析。以QTc 450毫秒为临界值进行逻辑回归分析。共有2550名孕妇使用了总共3990种药物,其中315种已知会增加QT延长的风险,导致105名(4.1%)新生儿在妊娠最后一个月接触到这些药物。总体而言,新生儿心电图检查时的平均年龄为1.9天,平均QTc(Bazett法)为414毫秒。单变量(回归系数-2.62,P=0.288)和多变量(回归系数-3.55,P=0.146)回归分析显示,无论是在总体分析还是亚组分析中,胎儿药物暴露对新生儿QT间期均无显著影响。逻辑回归分析显示,母亲用药暴露与新生儿QT间期延长风险增加无关(优势比(OR)0.34,P=0.14)。目前母亲使用的药物导致相当数量的胎儿接触到延长QT间期的药物。在我们的队列中,发现这种暴露对新生儿QT间期没有影响。