Brain and CSF Volumes in Fetuses and Neonates with Antenatal Diagnosis of Critical Congenital Heart Disease: A Longitudinal MRI Study.

BACKGROUND AND PURPOSE: Fetuses and neonates with critical congenital heart disease are at risk of delayed brain development and neurodevelopmental impairments. Our aim was to investigate the association between fetal and neonatal brain volumes and neonatal brain injury in a longitudinally scanned cohort with an antenatal diagnosis of critical congenital heart disease and to relate fetal and neonatal brain volumes to postmenstrual age and type of congenital heart disease. MATERIALS AND METHODS: This was a prospective, longitudinal study including 61 neonates with critical congenital heart disease undergoing surgery with cardiopulmonary bypass <30 days after birth and MR imaging of the brain; antenatally (33 weeks postmenstrual age), neonatal preoperatively (first week), and postoperatively (7 days postoperatively). Twenty-six had 3 MR imaging scans; 61 had at least 1 fetal and/or neonatal MR imaging scan. Volumes (cubic centimeters) were calculated for total brain volume, unmyelinated white matter, cortical gray matter, cerebellum, extracerebral CSF, and ventricular CSF. MR images were reviewed for ischemic brain injury. RESULTS: Total fetal brain volume, cortical gray matter, and unmyelinated white matter positively correlated with preoperative neonatal total brain volume, cortical gray matter, and unmyelinated white matter (r = 0.5-0.58); fetal ventricular CSF and extracerebral CSF correlated with neonatal ventricular CSF and extracerebral CSF (r = 0.64 and 0.82). Fetal cortical gray matter, unmyelinated white matter, and the cerebellum were negatively correlated with neonatal ischemic injury (r = -0.46 to -0.41); fetal extracerebral CSF and ventricular CSF were positively correlated with neonatal ischemic injury (r = 0.40 and 0.23). Unmyelinated white matter:total brain volume ratio decreased with increasing postmenstrual age, with a parallel increase of cortical gray matter:total brain volume and cerebellum:total brain volume. Fetal ventricular CSF:intracranial volume and extracerebral CSF:intracranial volume ratios decreased with increasing postmenstrual age; however, neonatal ventricular CSF:intracranial volume and extracerebral CSF:intracranial volume ratios increased with postmenstrual age. CONCLUSIONS: This study reveals that fetal brain volumes relate to neonatal brain volumes in critical congenital heart disease, with a negative correlation between fetal brain volumes and neonatal ischemic injury. Fetal brain imaging has the potential to provide early neurologic biomarkers.

Congenital posterior pole cataract and adult onset dilating cardiomyopathy: expanding the phenotype of αB-crystallinopathies.

Mutations in the αB-crystallin gene (CRYAB) have been reported in desmin-related myopathies, with or without cardiac involvement. Mutations in this gene have also been documented in large multi-generation families with autosomal dominant congenital posterior pole cataract (CPPC). In these congenital cataract families no cardiac or muscular phenotype was reported. This report describes a family with an unusual read-through mutation in CRYAB, leading to the elongation of the normal αB-crystallin protein with 19 amino acid residues. Affected family members combine a CPPC with an adult onset dilated cardiomyopathy (DCM), thereby expanding the αB-crystallinopathy phenotype. Repolarisation abnormalities preceded the onset of cardiomyopathy and were already present in childhood. No skeletal myopathy was observed. This report illustrates that congenital cataract can be a prelude to more severe disease even outside the context of inborn errors of metabolism. The identification of a CRYAB mutation in this family supports the notion that mutations in this gene are a rare cause of genetically determined DCM. The combined congenital cataract/cardiomyopathy phenotype adds to our understanding of the complex phenotypic spectrum of αB-crystallinopathies.

Sotalol as first-line treatment for fetal tachycardia and neonatal follow-up.

OBJECTIVES: In fetal tachycardia, pharmacological therapy with digoxin, flecainide and sotalol has been reported to be effective. In a recent retrospective multicenter study, sotalol was considered to be less effective than the other drugs in treatment of fetal supraventricular tachycardia (SVT). The aim of this study was to re-evaluate the efficacy and safety of maternally administered sotalol in the treatment of fetal tachycardia. METHODS: This was a retrospective review of the records of 30 consecutive fetuses with tachycardia documented on M-mode echocardiography between January 2004 and December 2010 at Wilhelmina Children's Hospital, a tertiary referral university hospital. Patients were subdivided into those diagnosed with supraventricular tachycardia and those with atrial flutter (AF) and presence of hydrops was noted. Other variables investigated included QTc interval measured on maternal electrocardiogram before and after initiation of antiarrhythmic therapy, fetal heart rhythm and heart rate pre- and postnatally, oral maternal drug therapy used, time to conversion to sinus rhythm (SR), percentage of fetuses converted following transplacental treatment, maternal adverse effects, presence or absence of tachycardia as noted on postnatal ECG, postnatal therapy or prophylaxis and neonatal outcome. Findings are discussed with reference to the literature. RESULTS: A total of 28 patients (18 with SVT, 10 with AF) were treated with sotalol as first-line therapy. Fetal hydrops was present in six patients (five with SVT, one with AF). All hydropic patients converted antenatally to SR (67% with sotalol as a single-drug therapy, 33% after addition of flecainide). Of the non-hydropic patients, 91% converted to SR (90% with sotalol only, 10% after addition of flecainide or digoxin). In 9% (with AF) rate control was achieved. There was no mortality. No serious drug-related adverse events were observed. Postnatally, rhythm disturbances were detected in 10 patients, two of whom still had AF. In eight, SVT was observed within 3 weeks postnatally, and in five of these within 72 hours. CONCLUSIONS: Sotalol can be recommended as the drug of first choice for treatment of fetal AF and has been shown to be an effective and safe first-line treatment option for SVT, at least in the absence of hydrops. Postnatal maintenance therapy after successful prenatal therapy is not necessarily indicated, as the risk of recurrence is low beyond 72 hours of age.

Aortico-right ventricular tunnel: prenatal diagnosis leading to neonatal survival.

In the 36th week of gestation a large aortico-right ventricular tunnel with an otherwise structurally normal heart was diagnosed by fetal echocardiography. This report describes for the first time the impact of the timely prenatal diagnosis of an aortico-right ventricular tunnel followed by successful management in early infancy.

Poor sensitivity of routine fetal anomaly ultrasound screening for antenatal detection of atrioventricular septal defect.

OBJECTIVE: To report the antenatal detection rate in a consecutive series of liveborn infants with atrioventricular septal defect (AVSD). DESIGN: Review and analysis of referrals for detailed fetal echocardiography and postnatal diagnosis of AVSD. SETTING: Tertiary referral centre for congenital heart disease centre with data prospectively collected between 1996 to 2001. RESULTS: 92 consecutively liveborn infants with AVSDs were identified of which 27 (29%) were detected by routine obstetric antenatal ultrasound. The antenatal diagnosis rate was worse for liveborn infants with trisomy 21 (12 of 49 (25%) v 15 of 43 (35%) chromosomally normal children) and for infants with AVSD without other structural heart disease (18 of 74 (24%) v 9 of 18 (50%) infants with associated structural heart disease). CONCLUSION: Despite the potential ability of fetal ultrasound to detect AVSDs, the antenatal diagnosis rate is poor. This is particularly true for infants with trisomy 21 and is of importance when counselling parents with an apparently normal fetal ultrasound scan.

Are children with cystic fibrosis who are treated with a proton-pump inhibitor at risk for vitamin B(12) deficiency?

BACKGROUND: In a recent study, the authors demonstrated the beneficial effect of proton-pump inhibitors (PPI) on fat malabsorption and bone mineral content in children with cystic fibrosis (CF). Prolonged use of PPI could result in vitamin B(12) deficiency as a consequence of impaired release of vitamin B(12) from food in a nonacid environment. The aim of this study was to evaluate the vitamin B 12 status of CF patients either treated with a PPI or not by measuring vitamin B(12) and homocysteine blood levels, the latter being a sensitive indicator of vitamin B(12) deficiency. METHODS: The study population consisted of 20 CF patients, 11 patients treated with a PPI for at least 2 years and 9 patients not treated with a PPI, and 10 healthy, age-matched control participants. Homocysteine blood levels were measured by high-performance liquid chromatography, and vitamin B(12) levels were measured by a competitive protein-binding assay. RESULTS: Vitamin B(12) levels were significantly higher in both CF groups compared with the control participants (PPI+, P = 0.02; PPI-, P = 0.009). There was no significant difference in vitamin B(12) levels between both CF groups. Homocysteine levels were normal and similar in all groups. CONCLUSIONS: Cystic fibrosis patients treated with a PPI for at least 2 years show no signs of vitamin B(12) deficiency.

Future population distribution in the past and present.

"There is at present much public interest in the future geography of the Netherlands. Plans for new infrastructure to accommodate rail, road and air traffic are hotly debated. The location of new residential areas and the disposition of economic activity are also frequently discussed. Supply and demand of employment and housing show diverging trends in various parts of the country. For planners this raises the question as to the likely or advisable future population distribution."