Neonatal effects of intrauterine metoprolol/bisoprolol exposure during the second and third trimester: a cohort study with two comparison groups

Kayser, Angela; Beck, Evelin; Hoeltzenbein, Maria; Zinke, Sandra; Meister, Reinhard; Weber-Schoendorfer, Corinna; Schaefer, Christof

doi:10.1097/hjh.0000000000002256

Cited by 15 publications

(16 citation statements)

References 28 publications

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“…There is a growing body of evidence that adrenergic beta-blockers are associated with an increased birth rate of neonates SGA ( 144 – 148 ) with a mean effect estimated at ≤200 g at term ( 149 ). A similar but less pronounced effect has also been reported for Alfa-MethylDopa ( 145 , 150 ) but not for calcium channel blockers ( 145 ). A possible explanation for this differential effect is that beta-blockers partially exert their effects via a reduction of CO ( 151 ), whereas calcium channel blockers mainly function via reduced peripheral resistance with a compensatory rise of CO ( 152 ).…”

Section: Clinical Implications Of Maternal Low Volume Circulation In ...supporting

confidence: 74%

Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction

Gyselaers

Lees

2022

Front. Med.

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This narrative review summarizes current evidence on the association between maternal low volume circulation and poor fetal growth. Though much work has been devoted to the study of cardiac output and peripheral vascular resistance, a low intravascular volume may explain why high vascular resistance causes hypertension in women with preeclampsia (PE) that is associated with fetal growth restriction (FGR) and, at the same time, presents with normotension in FGR itself. Normotensive women with small for gestational age babies show normal gestational blood volume expansion superimposed upon a constitutionally low intravascular volume. Early onset preeclampsia (EPE; occurring before 32 weeks) is commonly associated with FGR, and poor plasma volume expandability may already be present before conception, thus preceding gestational volume expansion. Experimentally induced low plasma volume in rodents predisposes to poor fetal growth and interventions that enhance plasma volume expansion in FGR have shown beneficial effects on intrauterine fetal condition, prolongation of gestation and birth weight. This review makes the case for elevating the maternal intravascular volume with physical exercise with or without Nitric Oxide Donors in FGR and EPE, and evaluating its role as a potential target for prevention and/or management of these conditions.

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Section: Clinical Implications Of Maternal Low Volume Circulation In ...supporting

confidence: 74%

Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction

Gyselaers

Lees

2022

Front. Med.

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“…Amongst the 13 non-RCTs, four had critical [ 32 , 39 , 54 , 60 ], six had serious [ 31 , 34 , 43 , 49 , 52 , 58 ] and three had a moderate risk of overall bias [ 30 , 35 , 37 ]. Most of the studies had issues of confounding, selection bias, bias in classification of interventions and selective reporting.…”

Section: Resultsmentioning

confidence: 99%

The Risk for Neonatal Hypoglycemia and Bradycardia after Beta-Blocker Use during Pregnancy or Lactation: A Systematic Review and Meta-Analysis

Bruin

Dalen

Franx

et al. 2022

IJERPH

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Beta-blockers are often used during pregnancy to treat cardiovascular diseases. The described neonatal side effects of maternal beta-blocker use are hypoglycemia and bradycardia, but the evidence base for these is yet to be evaluated comprehensively. Hence, this systematic review and meta-analysis was performed to evaluate the potential increased risk for hypoglycemia and bradycardia in neonates exposed to beta-blockers in utero or during lactation. A systematic search of English-language human studies was conducted until 21 April 2021. Both observational studies and randomized controlled trials investigating hypoglycemia and/or bradycardia in neonates following beta-blocker exposure during pregnancy and lactation were included. All articles were screened by two authors independently and eligible studies were included. Pair-wise and proportion-based meta-analysis was conducted and the certainty of evidence (CoE) was performed by standard methodologies. Of the 1.043 screened articles, 55 were included in this systematic review. Our meta-analysis showed a probable risk of hypoglycemia (CoE—Moderate) and possible risk of bradycardia (CoE—Low) in neonates upon fetal beta-blocker exposure. Therefore, we suggest the monitoring of glucose levels in exposed neonates until 24 h after birth. Due to the limited clinical implication, monitoring of the heart rate could be considered for 24 h. We call for future studies to substantiate our findings.

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“…The mean birth weight and percentage low birth weight (<2,500 g) were 3,058 ± 748 g and 18.0% for atenolol, 3,163 ± 702 g and 13.3% for metoprolol, 3,286 ± 651 g and 7.6% for propranolol, and 3,353 ± 554 g and 5.2% for nonexposed controls [30]. Kayser et al [31] analyzed 294 neonates of hypertensive mothers treated with metoprolol or bisoprolol during the second and/or third trimester and compared these infants with 225 methyldopa-exposed infants and 588 infants of non-hypertensive mothers. The rate of IUGR was significantly higher in infants who had long-term β-receptor blocker exposure (24.1%) as compared to those exposed to methyldopa (10.2%, OR 2.5, 95% CI 1.2–5.2) and the non-hypertensive ones (9.9%, OR 4.3, 95% CI 2.6–7.1) [31].…”

Section: Resultsmentioning

confidence: 99%

“…Kayser et al [31] analyzed 294 neonates of hypertensive mothers treated with metoprolol or bisoprolol during the second and/or third trimester and compared these infants with 225 methyldopa-exposed infants and 588 infants of non-hypertensive mothers. The rate of IUGR was significantly higher in infants who had long-term β-receptor blocker exposure (24.1%) as compared to those exposed to methyldopa (10.2%, OR 2.5, 95% CI 1.2–5.2) and the non-hypertensive ones (9.9%, OR 4.3, 95% CI 2.6–7.1) [31]. Lydakis et al [27] performed a study in 312 pregnancies of 223 women.…”

Section: Resultsmentioning

confidence: 99%

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

2021

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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.

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Neonatal effects of intrauterine metoprolol/bisoprolol exposure during the second and third trimester: a cohort study with two comparison groups

Cited by 15 publications

References 28 publications

Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction

Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction

The Risk for Neonatal Hypoglycemia and Bradycardia after Beta-Blocker Use during Pregnancy or Lactation: A Systematic Review and Meta-Analysis

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

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