Rapid cardiovascular effects of growth hormone treatment in short prepubertal children: impact of treatment duration.

OBJECTIVE: Previous studies show that growth hormone (GH) treatment increases cardiac dimensions in short children with GH deficiency (GHD) and has diverse cardiac effects in children with idiopathic short stature (ISS). This study was performed to assess the effect of GH on the cardiovascular system in short children with a broad range of GH secretion and GH sensitivity/responsiveness. DESIGN AND PATIENTS: In this prospective, multicentre study, short prepubertal children diagnosed with isolated GHD (89) or ISS (38) were followed during 2 years of GH treatment. They were randomized to receive either a standard (43 µg/kg/day) or an individualized GH dose (range 17-100 µg/kg/day) based on GH responsiveness estimated by a prediction model and distance to target height. Echocardiography, blood pressure and electrocardiography were performed at baseline, 3, 12 and 24 months. RESULTS: Left ventricular mass (LVM) indexed to body surface area increased significantly during 2 years of GH treatment in both GHD and ISS irrespective of randomized dose. This change was already apparent at 3 months, when standard deviation scores (SDS) of wall thickness and diameter were increased. At 24 months, left ventricular diameter SDS remained increased, whereas myocardial thickness SDS returned to baseline values. There was no impairment of systolic or diastolic function. There was no correlation with treatment dose and LVM SDS at 24 months. CONCLUSIONS: Irrespective of GH status, there was a rapid increase in LVM during GH treatment in short children. At 3 months, wall thickness and diameter were increased, whereas only diameter remained increased at 24 months.

Transition from acenocoumarol to warfarin in a 12-year-old child.

The types of coumadin anticoagulants registered and available for use differ between countries. Most frequently used coumadin anticoagulants are warfarin and acenocoumarol. Under several specific conditions, transition from one coumarin to another is required. Because of different pharmacokinetic and pharmacodynamic characteristics, the transition from one type of coumarol to another type can be challenging. There are no studies that address this issue in children. We present the case report of transition treatment between acenocoumarol and warfarin in a 12-year-old child with prosthetic mitral valve.

Array based characterization of a terminal deletion involving chromosome subband 15q26.2: an emerging syndrome associated with growth retardation, cardiac defects and developmental delay.

BACKGROUND: Subtelomeric regions are gene rich and deletions in these chromosomal segments have been demonstrated to account for approximately 2.5% of patients displaying mental retardation with or without association of dysmorphic features. However, cases that report de novo terminal deletions on chromosome arm 15q are rare. METHODS: In this study we present the first example of a detailed molecular genetic mapping of a de novo deletion in involving 15q26.2-qter, caused by the formation of a dicentric chromosome 15, using metaphase FISH and tiling resolution (32 k) genome-wide array-based comparative genomic hybridization (CGH). RESULTS: After an initial characterization of the dicentric chromosome by metaphase FISH, array CGH analysis mapped the terminal deletion to encompass a 6.48 megabase (Mb) region, ranging from 93.86-100.34 Mb on chromosome 15. CONCLUSION: In conclusion, we present an additional case to the growing family of reported cases with 15q26-deletion, thoroughly characterized at the molecular cytogenetic level. In the deleted regions, four candidate genes responsible for the phenotype of the patient could be delineated: IGFR1, MEF2A, CHSY1, and TM2D3. Further characterization of additional patients harboring similar 15q-aberrations might hopefully in the future lead to the description of a clear cut clinically recognizable syndrome.

Prenatal diagnosis of congenital heart defects - a population based study.

AIM: The aim of this study was to describe the efficiency of routine prenatal ultrasound screening for the detection of cardiac defects in a Swedish region and to study the effect of prenatal diagnosis on the survival and outcome of the child. METHODS: We identified all fetuses and infants with a diagnosed major cardiac defect born in 1999-2003 in a region of Sweden using a register of the regional paediatric cardiac clinic, various health-care registers and registers of prenatally detected malformations. The outcome of newborns with and without a prenatal diagnosis of a cardiac defect was compared. RESULTS: During the study period, 77,241 infants were born in the area. Among 145 major cardiac defects, 21% were detected prenatally. For the two university departments the detection rate was 38%. Of the major cardiac defects diagnosed <23 gestational weeks, 30% were terminated. No significant difference in the outcome was found between children with and without a prenatal diagnosis of a major cardiac defect. CONCLUSIONS: It could not be shown that survival and outcome for children with major cardiac defects was better when the defect was known prenatally than if it was detected postnatally. The size of the study prohibits conclusions on moderate differences.

Long-term survival in children with atrioventricular septal defect and common atrioventricular valvar orifice in Sweden.

BACKGROUND: The survival for patients with atrioventricular septal defect has improved markedly over the last decades and, during the same period, the survival of children with Down's syndrome has also increased. The aim of our study was to investigate long-term survival in patients having atrioventricular septal defect with common valvar orifice, but without associated significant congenital heart defects, in the setting of Down's syndrome, comparing the findings to those in chromosomally normal children with the same malformation. METHODS AND RESULTS: In a population-based retrospective study, we scrutinised the medical records from 801 liveborn children with atrioventricular septal defect born in Sweden during the period 1973 through 1997. Data on gender, presence or absence of Down's syndrome, associated congenital heart defects, date of birth, operation and death were recorded and followed up until 2001. An isolated atrioventricular septal defect with common atrioventricular valvar orifice was present in 502 children, of whom 86% had Down's syndrome. We found a significant reduc tion over time in age at operation, and in postoperative mortality at 30 days, from 28 to 1%. Using a multiple logistic regression model, we found no significant differences in mortality between genders, nor between those with or without Down's syndrome. Early corrective surgery could not be identified as a significant independent factor for survival. The 5-year postoperative survival in patients with Down's syndrome increased from 65% over the period from 1973 through 1977, to about 90% in the period 1993 through 1997, and the same trend was observed in chromosomally normal patients. CONCLUSIONS: Survival in uncomplicated atrioventricular septal defect with common atrioventricular valvar orifice has greatly increased, and surgical correction is now equally successful in patients with Down's syndrome and chromosomally normal patients, and for both genders. Death in connection with surgery is no longer the major threat, and focus must now be on long-term follow-up.