Philip Stoutenbeek

Sotalol in the Treatment of Fetal Dysrhythmias

BACKGROUND Fetal tachycardia may cause hydrops fetalis and lead to fetal death. No unanimity of opinion exists regarding the optimum treatment. This study evaluates our experience with transplacental sotalol therapy to treat fetal tachycardias in terms of safety and efficacy. METHODS AND RESULTS The charts of 21 patients who were treated with sotalol for fetal tachycardia were reviewed. Ten fetuses had atrial flutter (AF), 10 had supraventricular tachycardia (SVT), and 1 had VT. Hydrops fetalis was present in 9 fetuses. Drug treatment was successful in establishing sinus rhythm in 8 of 10 fetuses with AF and in 6 of 10 fetuses with SVT. The mortality rate in this study was 19% (4 of 21 fetuses; 3 had SVT and 1 had AF); 3 deaths occurred just days after the initiation of sotalol therapy, and 1 occurred after a dosage increase. At birth, tachycardia was present in 6 infants. Two patients who converted to sinus rhythm in utero suffered from neurologic pathology postnatally. CONCLUSIONS Fetal tachycardia is a serious condition in which treatment should be initiated, especially in the presence of hydrops fetalis. The high success rate in fetuses with AF suggests that sotalol should be considered a drug of first choice to treat fetal AF. The low conversion rate and the fact that 3 of the 4 deaths in this study occurred in fetuses with SVT indicate that the risks of sotalol therapy outweigh the benefits in this group and that sotalol should, therefore, be limited in the treatment of fetal SVT.

Treatment of fetal tachycardia with sotalol: transplacental pharmacokinetics and pharmacodynamics

OBJECTIVES The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of sotalol in the treatment of fetal tachycardia. BACKGROUND Maternally administered, intrauterine therapy of fetal tachycardia is dependent on the transplacental passage of the antiarrhythmic agent. METHODS In a prospective study of patients treated for fetal tachycardia with sotalol, concentrations of sotalol were determined in maternal and umbilical blood and in amniotic fluid, and the relationship between these concentrations and the occurrence of conversion to sinus rhythm was investigated. RESULTS Eighteen fetal patients were studied, nine with atrial flutter and nine with supraventricular tachycardia. Fourteen were treated with sotalol; 13 converted to sinus rhythm, of whom 2 relapsed. There was one intrauterine death. Four patients were treated with sotalol and digoxin, of whom two were treated successfully. Mean birth weight was 3,266 g. The daily maternal sotalol dose was linearly related to the maternal plasma concentration. The mean fetal/maternal sotalol plasma concentration was 1.1 (range 0.67 to 2.87, SD 0.63), and the mean amniotic fluid/fetal blood ratio of sotalol was 3.2 (range 1.28 to 5.8, SD 1.4). The effectiveness of sotalol therapy could not be extrapolated from maternal blood levels. CONCLUSIONS Sotalol is a potent antiarrhythmic agent in the treatment of fetal tachycardia. The placental transfer is excellent. Sotalol accumulates in amniotic fluid but not in the fetus itself. Therefore it seems that renal excretion in the fetus is efficient and greater than the oral absorption by fetal swallowing. The maternal blood level is not a reliable predictor of the chances of success of therapy. Sotalol is not associated with fetal growth restriction.

Drug Treatment of Fetal Tachycardias

The pharmacological treatment of fetal tachycardia (FT) has been described in various publications. We present a study reviewing the necessity for treatment of FT, the regimens of drugs used in the last two decades and their mode of administration.The absence of reliable predictors of fetal hydrops (FH) has led most centers to initiate treatment as soon as the diagnosis of FT has been established, although a small minority advocate nonintervention. As the primary form of pharmacological intervention, oral maternal transplacental therapy is generally preferred.Digoxin is the most common drug used to treat FT; however, effectiveness remains a point of discussion. After digoxin, sotalol seems to be the most promising agent, specifically in atrial flutter and nonhydropic supraventricular tachycardia (SVT). Flecainide is a very effective drug in the treatment of fetal SVT, although concerns about possible pro-arrhythmic effects have limited its use. Amiodarone has been described favorably, but is frequently excluded due to its poor tolerability. Verapamil is contraindicated as it may increase mortality. Conclusions on other less frequently used drugs cannot be drawn.In severely hydropic fetuses and/or therapy-resistant FT, direct fetal therapy is sometimes initiated. To minimize the number of invasive procedures, fetal intramuscular or intraperitoneal injections that provide a more sustained release are preferred.Based on these data we propose a drug protocol of sotalol 160mg twice daily orally, increased to a maximum of 480mg daily. Whenever sinus rhythm is not achieved, the addition of digoxin 0.25mg three times daily is recommended, increased to a maximum of 0.5mg three times daily. Only in SVT complicated by FH, either maternal digoxin 1 to 2mg IV in 24 hours, and subsequently 0.5 to 1 mg/day IV, or flecainide 200 to 400 mg/day orally is proposed. Initiating direct fetal therapy may follow failure of transplacental therapy.

Idiopathic polyhydramnios and postnatal findings

Objective. Our objective was to investigate the outcome of neonates with idiopathic polyhydramnios in the first year after birth. Methods. All patients diagnosed in the Erasmus Medical Centre Rotterdam and the University Medical Centre Utrecht between January 2000 and April 2005 with idiopathic polyhydramnios were studied. The outcome variables included mode of delivery, pre-term delivery, birth weight, macrosomia, large-for-gestational-age (weight > p90), neonatal or infant mortality and infant morbidity at 1 year after delivery. These were related to antenatal findings, including the onset of polyhydramnios and ultrasonographic evidence of macrosomia (estimated fetal weight > p90). Results. Polyhydramnios was diagnosed at a mean gestational age (± s.d.) of 31.0 ± 4.9 weeks. The mean gestational age at birth (± s.d.) was 37.9 ± 3.7 weeks. Macrosomia at birth was present in 25.3% (22/88). Sixty-three of 88 infants were in good health 1 year after birth; 20 infants had an abnormality and 5 children had died. Macrosomia and detection of polyhydramnios in the third trimester was associated significantly with a good outcome. Conclusion. In neonates with idiopathic polyhydramnios, abnormalities were detected during the first year of life in 28.4%. Detection of polyhydramnios in the second trimester and low or normal birth weight are risk factors for associated abnormalities.

Lactate in the foetal brain: detection and implications

Background and methods: In six hydrocephalic foetuses (gestational age 29–38 wk), proton MR spectroscopy (1H‐MRS) was performed in the basal ganglia for detection of lactate in vivo. Results: Lactate was present in two foetal brains, absent in two and not detectable because of movement in two.

Trends in the utilization of invasive prenatal diagnosis in The Netherlands during 2000-2009.

To analyze trends in the number and type of invasive procedure, reasons for referral, maternal age and chromosomal abnormalities over a 10‐year period and correlate the trends to changes in the national prenatal screening policy.

Prenatal Diagnosis of the Fetus with Hypoplastic Left Heart Syndrome

Abstract.Objectives: To review our 13-year experience with prenatally detected hypoplastic left heart syndrome (HLHS) of which management remains controversial. Material and Methods: Retrospective study of the management and outcome in all cases of HLHS diagnosed prenatally in a tertiary referral center for pediatric cardiology and cardiac surgery between January 1988 and July 2001. Results: The diagnosis of HLHS was made in 32 fetuses. One mother had two pregnancies associated with HLHS. In 16 cases parents opted for termination of pregnancy and in five for compassionate care. Four fetuses died in utero, and seven patients received a palliative reconstructive Norwood procedure. In seven fetuses, associated anomalies were detected: three chromosomal and structural and four only structural. In six fetuses, other associated intracardiac anomalies were detected. Of seven infants operated, six had no associated anomalies and only one is alive at an age of 17 months. Conclusion: The low percentage of intention to treat among patients in our center (34%) is in accordance with the percentage found in another study from the UK (36.2%), but differs significantly from reported series across the Atlantic (67%). Prenatal diagnosis of the HLHS provides opportunities not only for getting patients in optimal preoperative condition when surgery is offered, but also for in-depth counseling of the parents on this severe malformation. A minority of parents faced with the difficult decision of possible termination of pregnancy, compassionate care or the Norwood strategy, choose surgical treatment which might be based on socioreligious differences and the interpretation of the long-term quality of life.Zusammenfassung.Hintergrund: Das hypoplastische Linksherzsyndrom (HLHS) umfasst ein Spektrum struktureller Herzfehlbildungen, die durch eine schwerwiegende Unterentwicklung der Strukturen im Herz-Aorta-Komplex des linken Ventrikels charakterisiert sind. Bei einer geschätzten Häufigkeit von 1–4/10 000 Lebendgeborene ist das HLHS für 7–8% der angeborenen Herzerkrankungen verantwortlich und die häufigste kardiale Todesursache in der Neugeborenenperiode. Die Einführung der Norwood-Operation im Jahr 1985 führte zu einer steigenden Anzahl von Eingriffen bei Säuglingen mit HLHS. Das HLHS lässt sich innerhalb von 20 Wochen nach Beginn der Schwangerschaft mit einer echokardiographischen Untersuchung des fetalen Herzens nachweisen und gehört zu den häufigsten in utero entdeckten Anomalien. Eine chirurgische Behandlung des Säuglings war bis vor kurzem unmöglich. Doch obwohl das HLHS inzwischen operativ behandelbar ist, sind die Ergebnisse enttäuschend. Außerdem müssen die nachteiligen neurologischen Folgerscheinungen und die zukünftige Lebensqualität berücksichtigt werden. Ziel: Ziel dieser Untersuchung war, unsere Erfahrung mit dem pränatal entdeckten HLHS, dessen Behandlungsmethoden umstritten sind, zusammenzufassen. Material und Methodik: Die medizinischen Unterlagen von 31 Müttern, bei deren Kindern mit Hilfe einer Echokardiographie Karyotypdes fetalen Herzens ein HLHS diagnostiziert worden war, wurden retrospektiv aufgearbeitet. Die Untersuchungen fanden vom 01.01.1988 bis 30.06.2001 am Medizinischen Zentrum der Universität Utrecht, Niederlande, statt. Die Diagnose des HLHS basierte auf einem zweidimensionalen Echokardiogramm des Fetus. Dabei wurde zwischen dem klassischen HLHS und einem mit anderen intrakardialen, extrakardialen oder chromosomalen Anomalien assoziierten HLHS unterschieden. Die eigenen Daten wurden mit Daten aus der angloamerikanischen Literatur verglichen. Ergebnisse: Bei 32 Feten wurde die Diagnose HLHS gestellt. Bei einer Mutter fanden sich zwei Feten, die ein HLHS aufwiesen. In 16 Fällen entschieden sich die Eltern für einen Schwangerschaftsabbruch, in fünf für das Austragen des Kindes. Vier Feten verstarben in utero, sieben erhielten eine rekonstruktive Norwood-Operation. Bei sieben Feten wurden extrakardiale Anomalien festgestellt: drei chromosomale und vier strukturelle Veränderungen. Bei sechs Feten wurden intrakardiale Anomalien dokumentiert. Bei sechs der sieben operierten Säuglingen fanden sich extrakardiale Anomalien. Nur ein Säugling überlebt das Alter von 17 Monaten. Diskussion: Es gibt einen bemerkenswerten Unterschied bei der Behandlung pränatal entdeckter HLHS zwischen unseren Zentrum und der veröffentlichten angloamerikanischen Literatur. Der prozentale Anteil der Säuglinge, die in den Niederlanden operiert werden, beträgt 34%, während er in den USA bei 67% liegt (p < 0,05). In den Niederlanden sprechen sich 50% der Eltern für einen Schwangerschaftsabbruch aus, in den USA nur 13% (p < 0,05). Für das Austragen des Kindes entscheiden sich in den Niederlanden 16%, in den Vereinigten Staaten 20% (sechs von 30). In einer angelsächsischen Studie ergaben sich dagegen mit 36,2%, 60,3% und 3,5% vergleichbare Verhältnisse wie in den Niederlanden. Die unterschiedliche Behandlung des HLHS in Europa und den USA dürfte der verschiedenen sozioreligiösen Einstellung zuschreiben sein. Schlussfolgerung: Ärzte und Eltern in Europa legen mehr Wert auf die Lebensqualität der Kinder und sehen aufgrund der schlechten Prognose von einer operativen Behandlung ab. Dies könnte sich in Zukunft ändern, weil sich die Überlebensraten nach dem Norwood-Verfahren verbessern, das kurzfristige neurologische Defizit abnimmt und positive Verlaufsbeobachtungen über die neurologischen Folgen und die Lebensqualität der Säuglinge nach diesem Eingriff verfügbar sein werden.

Modeling Down syndrome screening performance using first-trimester serum markers

To evaluate the modeled predictive value of three current screening markers (pregnancy‐associated plasma protein‐A (PAPP‐A), free β‐human chorionic gonadotropin (free β‐hCG), and nuchal translucency (NT)) and four potential screening markers (a disintegrin and metalloprotease 12 (ADAM12), total hCG, placental protein 13 (PP13), and placental growth factor (PlGF)) for Down syndrome using different screening strategies.

Methods of sonographic cervical length measurement in pregnancy: A review of the literature

In this review we give an overview of the methods and pitfalls in cervical length measurements. We compared the different techniques and investigated factors that influence visualization of the cervix. The data in this overview may be used to establish guidelines in clinical practice.

Neurological Outcome in Isolated Congenital Heart Block and Hydrops Fetalis

Objective: Isolated fetal heart block (HB), a condition associated with fetal hydrops, carries a high mortality rate and may result in neurodevelopmental sequelae. To the best of our knowledge, no data exist regarding the long-term outcome of such hydropic fetuses. We reviewed our experience with this condition to determine the neurodevelopmental outcome of prenatally diagnosed cases with isolated HB complicated by hydrops fetalis. Methods: Neurodevelopmental assessment of 5 children presented prenatally with isolated HB associated with hydrops fetalis. Results: During the last 18 years, 10 cases were detected prenatally with isolated HB and hydrops fetalis. 3 of the 10 fetuses died in utero, and 2 died postnatally, due to a dilated cardiomyopathy, at the age of 9 months and 4 years, respectively. Neurodevelopmental studies done on the 5 remaining children were normal. Conclusion: Long-term neurodevelopmental assessments of 5 surviving cases presented prenatally with isolated HB and hydrops fetalis are reassuring.