Intrauterine Growth Retardation in Pregnant Women with Long QT Syndrome Treated with Beta-Receptor Blockers

Abstract

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.

The use of erenumab for migraine prophylaxis during pregnancy: A case report and narrative review

“…[1][2][3][4][5][6][7][8] Gabapentin, lamotrigine, levetiracetam, zonisamide, metoprolol, propranolol, and onabotulinumtoxinA should only be used in pregnant women if the potential benefits outweigh the risks due to the potential for fetal harm in animal studies. [9][10][11][12][13][14][15][16] Pregnancy information is limited with calcitonin gene-related peptide (CGRP) receptor or ligand-directed therapies.…”

Assessment of Severity of Long QT Syndrome Phenotype and Risk of Fetal Death

“…Atenolol is a Food and Drug Administration category D drug and is currently not recommended in pregnancy due to higher risk of IUGR. 23 Nadolol has been associated with IUGR, 24 neonatal hypoglycemia, and bradycardia, and it should be used for high‐risk patients; 30% of babies born with IUGR were exposed to nadolol in our cohort. There is evidence suggesting that metoprolol is less effective in arrhythmia prevention 25 ; thus, it is not considered as a first‐line BB; bisoprolol is a valuable option in pregnancy, 23 as no IUGR has been reported with its use, 26 although data are limited.…”

“…BBs remain the cornerstone of LQTS treatment; however, our study confirms that they can cause lower birth weight compared with untreated women. 24 , 26 , 27 …”

Metoprolol Inhibits Developmental Brain Sterol Biosynthesis in Mice

“…MTP is the fifth most commonly utilized medication in the US, with >75 M yearly prescriptions [ 50 ]. It is often prescribed to pregnant women [ 37 , 39 , 40 , 41 , 42 , 48 , 51 , 52 , 53 , 54 ]. In the preliminary experiments MTP exposure resulted in a 50–100-fold elevation of 7-DHC in neurons and astrocytes.…”

“…At the same time, maternal exposure to medications must be considered to avoid potential adverse effects on the developing fetus. The utilization of antihypertensive drugs during pregnancy, and the potential effect on the developing fetus have been topics of considerable debate: some studies found no negative effect on fetal development [ 39 , 40 ], while others reported increased risk for intrauterine growth restriction, small for gestational age, and preterm delivery [ 41 , 42 , 43 ]. As a result, we embarked on assessing the effects of six commonly used beta-blockers on sterol biosynthesis, utilizing cell lines, neuronal and astroglial cultures, and an in vivo mouse model.…”