Pediatric Pharmacology and Pharmacometrics, University Children's Hospital of Basel, (UKBB), University of Basel, Basel, Switzerland.
Pediatric Cardiology, University Children's Hospital of Basel (UKBB), University of Basel, Basel, Switzerland.
Neonatology. 2021;118(4):406-415. doi: 10.1159/000516845. Epub 2021 Jun 29.
Pregnant women with inherited long QT syndrome (iLQTS) are at an increased risk for preterm delivery and intrauterine growth retardation (IUGR) due to their underlying disease. Additionally, they are at a risk of arrhythmogenic events, particularly during the postpartum period because of physiological changes and increased emotional/physical stress. β-receptor blockers can effectively prevent life-threatening Torsades de Pointes ventricular tachycardia and they are the treatment of choice in iLQTS. Use of β-receptor blockers in pregnancy is recommended, although IUGR is commonly reported for prenatally exposed infants. IUGR, particularly in preterm infants, can result in adverse neonatal outcomes. This review was performed to support clinicians in their selection of β-receptor blocker treatment for their pregnant iLQTS women by (i) summarizing the available literature addressing the impact of different β-receptor blockers on IUGR and (ii) reporting additional aspects which might influence the β-receptor blocker selection. In general, experts recommend to use nonselective β-receptor blockers, such as nadolol and propranolol, for iLQTS management as these drugs seem to be superior in effectiveness. However, β-1-selective receptor blockers, such as bisoprolol or metoprolol, seem to affect less likely uterine contraction, peripheral vasodilation, and are associated with lower IUGR rates and fetal hypoglycemia. They are therefore recommended, except atenolol, as first-line therapy for pregnant women. Additionally, maternal factors such as iLQTS genotype, other underlying comorbidities (e.g., diabetes mellitus type 1, asthma bronchiale), and uteroplacental dysfunction or fetal factors have to be taken into account. Therefore, each woman with iLQTS who wants to become pregnant should be well-advised for a personalized β-receptor blocker therapy according to the individual risk-benefit evaluation by a multidisciplinary team of cardiologists, gynecologists, pediatric cardiologists, neonatologists, and clinical pharmacologists. During pregnancy, a close monitoring of IUGR and, after birth, monitoring of bradycardia, hypoglycemia, and respiratory depression in the neonate is mandatory. This review summarizes available data on β-receptor blocker-related risk for IUGR in prenatally exposed infants and illustrates which factors might influence β-receptor blocker selection with the aim to support clinicians in their pharmacological management of their pregnant iLQTS patients.
患有遗传性长 QT 综合征 (iLQTS) 的孕妇由于其潜在疾病，早产和宫内生长迟缓 (IUGR) 的风险增加。此外，由于生理变化和情绪/身体压力增加，她们还存在心律失常事件的风险，特别是在产后期间。β-受体阻滞剂可有效预防危及生命的尖端扭转型室性心动过速，是 iLQTS 的首选治疗方法。尽管在产前暴露的婴儿中常报告 IUGR，但在怀孕期间推荐使用β-受体阻滞剂。IUGR，特别是早产儿，可导致不良的新生儿结局。进行这项综述是为了通过以下方式支持临床医生在为患有 iLQTS 的孕妇选择β-受体阻滞剂治疗时做出决策：(i) 总结现有文献中关于不同β-受体阻滞剂对 IUGR 的影响，以及 (ii) 报告可能影响β-受体阻滞剂选择的其他方面。一般来说，专家建议使用非选择性β-受体阻滞剂，如纳多洛尔和普萘洛尔，用于 iLQTS 管理，因为这些药物在有效性方面似乎更优。然而，β-1-选择性受体阻滞剂，如比索洛尔或美托洛尔，似乎不太可能影响子宫收缩、外周血管扩张，并且与较低的 IUGR 发生率和胎儿低血糖相关。因此，除了阿替洛尔外，它们被推荐作为孕妇的一线治疗药物。此外，还需要考虑母体因素，如 iLQTS 基因型、其他潜在合并症（例如，1 型糖尿病、支气管哮喘）、胎盘功能障碍或胎儿因素。因此，每个想要怀孕的 iLQTS 女性都应该在由心脏病专家、妇科医生、儿科心脏病专家、新生儿科医生和临床药理学家组成的多学科团队的个体化风险效益评估的基础上，获得有关β-受体阻滞剂治疗的充分建议。怀孕期间，必须密切监测 IUGR，出生后，必须监测新生儿的心动过缓、低血糖和呼吸抑制。本综述总结了有关产前暴露的婴儿中与β-受体阻滞剂相关的 IUGR 风险的现有数据，并说明了哪些因素可能影响β-受体阻滞剂的选择，旨在为临床医生提供支持，以帮助他们对患有 iLQTS 的孕妇进行药理学管理。
