R. Gendron

Prenatal Head Growth and White Matter Injury in Hypoplastic Left Heart Syndrome

Children with hypoplastic left heart syndrome (HLHS) have an increased prevalence of central nervous system (CNS) abnormalities. The extent to which this problem is due to CNS maldevelopment, prenatal ischemia, postnatal chronic cyanosis and/or multiple exposures to cardiopulmonary bypass is unknown. To better understand the etiology of CNS abnormalities in HLHS, we evaluated 68 neonates with HLHS; in 28 cases, both fetal ultrasound and echocardiogram data were available to assess head size, head growth and aortic valve anatomy (atresia or stenosis). In addition, we evaluated neuropathology in 11 electively aborted HLHS fetuses. The mean head circumference percentile in HLHS neonates was significantly smaller than HLHS fetuses (22 ± 2% versus 40 ± 4%, p < 0.001). A significant decrease in head growth, defined as a 50% reduction in head circumference percentile, was observed in half (14/28) of HLHS fetuses and nearly a quarter (6/28) were already growth restricted (≤10%) at the time of initial evaluation. Brains from HLHS fetuses demonstrated chronic diffuse white matter injury of varying severity. These patterns of prenatal head growth and brain histopathology identify a spectrum of abnormal CNS development and/or injury in HLHS fetuses.

A phase II, open-label study of the efficacy and safety of imiquimod in the treatment of superficial and mixed infantile hemangioma.

Abstract:  Objectives:  To explore the efficacy and safety of imiquimod 5% cream as a treatment for infantile hemangioma.

Age-Dependent Recombination Rates in Human Pedigrees

In humans, chromosome-number abnormalities have been associated with altered recombination and increased maternal age. Therefore, age-related effects on recombination are of major importance, especially in relation to the mechanisms involved in human trisomies. Here, we examine the relationship between maternal age and recombination rate in humans. We localized crossovers at high resolution by using over 600,000 markers genotyped in a panel of 69 French-Canadian pedigrees, revealing recombination events in 195 maternal meioses. Overall, we observed the general patterns of variation in fine-scale recombination rates previously reported in humans. However, we make the first observation of a significant decrease in recombination rates with advancing maternal age in humans, likely driven by chromosome-specific effects. The effect appears to be localized in the middle section of chromosomal arms and near subtelomeric regions. We postulate that, for some chromosomes, protection against non-disjunction provided by recombination becomes less efficient with advancing maternal age, which can be partly responsible for the higher rates of aneuploidy in older women. We propose a model that reconciles our findings with reported associations between maternal age and recombination in cases of trisomies.

Cytokine Tissue Levels as Markers of Disease Activity in Pediatric Crohn Disease

The mucosal immune system is overactivated in Crohn disease (CD) and viral infections have been associated with clinical exacerbations. To investigate the potential association between mucosal inflammation and the cytokines involved in the early response to viruses, we analyzed colonic tissue levels of IL-2Rα, interferon-α, and IL-15 in CD. Patients undergoing diagnostic colonoscopy were classified into controls (n = 22) and three CD groups based on the histologic severity of inflammation and clinical activity: a) severely active CD (n = 3); b) mild to moderately active CD (n = 14); and c) quiescent CD (n = 23). Rectal biopsies (two per patient) were homogenized and cytokine levels determined by ELISA kits. Statistical analysis was performed by ANOVA with Tukey and Scheffé tests. IL-2Rα levels were increased in the active CD group compared with the quiescent CD group: a) 405 ± 87, b) 159 ± 31, and c) 33 ± 15 pg/mg DNA (p < 0.001). The latter group was similar to controls (39 ± 20 pg/mg DNA). Furthermore, a linear correlation (r = 0.98) between IL-2Rα and disease activity (Van Hees index) was observed. IL-15 levels were also higher in active compared with quiescent CD and controls: a) 0.69 ± 0.23 and b) 0.72 ± 0.31 versus c) 0.28 ± 0.21 and 0.28 ± 0.14 pg/mg DNA for controls (p < 0.05). Interferon-α levels were undetectable in all samples. Our data suggest that IL-2Rα tissue levels correlate with CD activity. IL-15 is also overproduced in inflamed CD tissue. The lack of a parallel elevation of interferon-α does not support a role for viral induction of IL-15 in inflamed CD samples.

Profiling left and right ventricular proportional output during fetal life with a novel systolic index in the aortic isthmus

Left ventricular ejection causes forward flow in the fetal aortic isthmus while the right ventricle has a retrograde influence. The aim of this study was to create reference values for an isthmic systolic index (ISI) reflecting the changing influence of right and left ventricular performance on Doppler flow velocity waveforms of the aortic isthmus throughout normal pregnancy.

Ventricular outputs, central blood flow distribution and flow pattern through the aortic isthmus of fetuses with simple transposition of the great arteries

Our objective was to determine the impact of simple transposition of the great arteries (TGA) on fetal left ventricular (LV) and right ventricular (RV) performances and central circulatory dynamics including the aortic isthmus.

Aortic Isthmus Flow Recording Predicts the Outcome of the Recipient Twin after Laser Coagulation in Twin-Twin Transfusion Syndrome

Introduction: The objective was to assess the prognostic value of the systolic flow through the aortic isthmus in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated by placental laser ablation. Material and Methods: Fetal echocardiography and outcome data of 105 cases of TTTS treated by laser photocoagulation of placental anastomoses were reviewed. Hemodynamic parameters were collected before and after treatment. The isthmic systolic index (ISI) was calculated as the peak systolic velocity/systolic nadir ratio. Results: A total of 105 laser coagulations were studied. Fetal echocardiography pre- and post-laser were available in 68 cases, including 55 with data on aortic isthmic Doppler. Survival rates were 17, 22, and 61% for 0, 1, or 2 twins, respectively. At least 1 twin was delivered alive in 83% of the pregnancies. The mean gestational age at surgery was 21 weeks (range 16-26). Median ISI values were similar for donor and recipient twins, before and after laser ablation (all p > 0.05). A lower recipient ISI before laser was related to early recipient demise within 24 h (p = 0.04). Discussion: A lower ISI before placental laser ablation for TTTS is associated with postoperative demise of the recipient twin.

Prenatal diagnosis and prognosis of accelerated idioventricular rhythm

As postnatal identification of accelerated idioventricular rhythm (AIVR) relies on specific electrocardiographic patterns, prenatal diagnosis of this condition is challenging and its true incidence is unknown. The objectives of this study were to evaluate the performance of prenatal ultrasonography in identifying intrauterine cardiocirculatory events linked to specific electrocardiographic signs of postnatal AIVR, including left or right ventricular origin, and to assess the prenatal prognosis of this arrhythmia.

OC26.06: Fetal circulatory dynamics in presence of simple TGA

Objectives: The increased nuchal translucency (NT) is a marker for trisomy 21 (Tri21) and for cardiac defects (CHDs), Cardiac dysfunction has been postulated in Tri21 fetuses. We aimed to study cardiac function throughout gestation in these fetuses. Methods: Echocardiography was performed on 49 trisomy 21 fetuses and 190 eukaryotic controls with normal hearts, (86 with a normal NT and 104 with a NT ≥ 95th percentile), between 11 and 35 weeks’ gestation. Measurements included: Eand Awave peak velocity, E/A velocity ratio and E/TVI ratio over the atrioventricular valves, myocardial performance index, semilunar valves peak velocity (PVel)and acceleration time (AT), stroke volume (SV) and cardiac output (C) and the ductus venosus pulsatility index for veins at 11–14 weeks’ gestation (DVPIV). Results: 11–13.9 weeks’ gestation: In Tri21 fetuses the semilunar valve PVels and tricuspid valve (TV) A-wave velocity were significantly reduced and TV E/A ratio and DVPIV significantly increased compared to normal NT controls. 14 and 21.9 weeks’ gestation: Aortic PVel, mitral (MV) and TV Eand A-wave velocities and MV E/TVI were significantly reduced in Tri21 fetuses without CHD compared to controls. 22 and 35 weeks’ gestation: In Tri21 fetuses with normal hearts the TV Eand A-wave velocity, right ventricular SV, aortic PVel and left ventricular CO were significantly reduced compared to normal NT controls. Conclusions: Tri21 fetuses have abnormal cardiac function irrespective of the NT thickness or presence of CHD. We found evidence for increased preload in early gestation with increased afterload thereafter along with biventricular systolic and diastolic dysfunction.