Down’s syndrome (DS) is the most common form of intellectual disability. The syndrome is characterized by congenital malformations, especially of the heart and gastrointestinal tract, which can result in high mortality rates in the affected population. Many improvements have been made in the medical treatment of this syndrome during the past few decades and the survival of individuals with DS has increased in the industrial world. The aim of the present study was to investigate mortality in relation to congenital malformations. Medical records from all liveborn children with DS delivered between 1973 and 1980 in northern Sweden were studied, and malformations and causes of death were recorded. Out of the 219 children included in the study, a congenital heart defect was reported in 47.5% of subjects, 42.1% of whom had complete atrioventricular septal defect. Gastrointestinal tract malformations were present in 7.3% of subjects, and was frequently associated with a cardiac malformation and a very high mortality rate. Other major and minor congenital anomalies were present in 5.5% and 5.5% of subjects, respectively. In the 14.5‐year follow‐up of 213 children, the rate of survival was 75.6%. Mortality rates within one and 10 years after birth were 14.6% and 23.5%, respectively. Mortality within 10 years differed significantly between children with (44.1%) and without (4.5%) a congenital heart defect. A very high mortality rate was observed among children with a congenital heart defect, especially when it was combined with a gastrointestinal malformation.

We believe that an individualised endurance training programme for Fontan patients improves submaximal exercise capacity and quality of life in Fontan patients and the effect on quality of life appears to be long-lasting.

In spite of similar measured total activity, Fontan patients reported less time engaged in regular physical exercise than healthy controls and their quality of life was lower than the controls. We speculate that promoting structured regular physical exercise could improve the quality of life of Fontan patients.

SUMMARY Lung function was measured at 30 minutes and again at 2 hours after birth in 12 infants delivered vaginally, in 15 infants delivered by elective caesarean section under general anaesthesia (GA), and in 15 delivered under epidural anaesthesia (EDA). Umbilical arterial blood was analysed for pH and for concentrations of catecholamines and cortisol. No important differences in gestational age, birthweight, Apgar scores, or haematocrit were found among the three groups. Tidal volume and minute ventilation measured 30 minutes after birth were lower in infants delivered by caesarean section than in those delivered vaginally and at 2 hours the tidal volume was still lower in the babies delivered by caesarean section than in those delivered vaginally. Dynamic compliance was lower at 30 minutes in the group that had a caesarean section than in the vaginal group, and this difference was significant at two hours. Tidal volume, minute ventilation, and dynamic compliance in the GA and EDA groups did not differ. The catecholamine and cortisol concentrations at birth were higher in the vaginal group than in the group delivered by caesarean section. Two hours after birth there was a significant correlation (r= 084) between the catecholamine concentrations of the infants born vaginally and lung compliance. The lower dynamic lung compliance in infants delivered by elective caesarean section might be explained by delayed absorption of liquid in the lung due to lack of catecholamine surge. PatientsAll the infants in the study were born at term in uncomplicated deliveries, and their mothers had normal pregnancies. Their development, assessed according to a modified Dubowitz score, was appropriate for gestational age, but infants with an umbilical arterial pH <7-24 at birth were excluded.

Twenty-two smoking mothers and their healthy newborn infants (mean postnatal age of 3.7 days) were studied in the maternity ward. A close correlation was found (r = 0.94) between nicotine concentrations in the mothers' plasma and milk after smoking, the milk: plasma ratio being 2.9. The amount of nicotine transferred to the infant increased from 0.09 to 1.03 micrograms/kg infant body weight when mothers smoked before breast-feeding. The daily dose of nicotine via the mothers' milk was 6 micrograms per kg infant body weight. Cotinine but not nicotine concentrations in the plasma and milk of the mothers and the urine of the infants reflected the smoking habits of the mothers during pregnancy. There was no correlation between nicotine and cotinine concentrations in the infant's urine and the amount of nicotine given to the infant via the mother's milk.

The immediate postnatal metabolic adaptation and sympatho-adrenal activation were studied in infants delivered vaginally or by elective caesarean section. Vaginally delivered infants showed high catecholamine levels at birth compared to infants born by caesarean section under epidural or general anaesthesia. Umbilical arterial glucose levels were significantly higher in the vaginal group than in both caesarean section groups. At 30 min, all groups showed a marked decrease with several infants showing asymptomatic hypoglycaemia in the caesarean section group. C-peptide levels showed no difference at birth but later became significantly higher in the vaginal group. Although the levels of free fatty acids and glycerol were low at birth, they were significantly higher in the vaginal group. In all groups they increased substantially with time. Considering the marked differences in catecholamine levels, the differences in metabolic adaptation were unexpectedly small. This implies an attenuated metabolic response to sympatho-adrenal stimulation in the newborn.

The transition must be carefully planned to ensure that adolescents can master new skills to manage the transfer to adult cardiologic healthcare. A structured program may facilitate and fulfill the needs of the adolescents and their parents, taking into consideration the aspects of trust, safety, and control. However, the content and performance of such a program must also be examined. We plan to undertake an extensive research project in the area, and this study will be a baseline for further research.

PurposeNumerous studies have investigated causes of warfarin dose variability in adults, whereas studies in children are limited both in numbers and size. Mechanism-based population modelling provides an opportunity to condense and propagate prior knowledge from one population to another. The main objectives with this study were to evaluate the predictive performance of a theoretically bridged adult warfarin model in children, and to compare accuracy in dose prediction relative to published warfarin algorithms for children.MethodAn adult population pharmacokinetic/pharmacodynamic (PK/PD) model for warfarin, with CYP2C9 and VKORC1 genotype, age and target international normalized ratio (INR) as dose predictors, was bridged to children using allometric scaling methods. Its predictive properties were evaluated in an external data set of children 0–18 years old, including comparison of dose prediction accuracy with three pharmacogenetics-based algorithms for children.ResultsOverall, the bridged model predicted INR response well in 64 warfarin-treated Swedish children (median age 4.3 years), but with a tendency to overpredict INR in children ≤2 years old. The bridged model predicted 20 of 49 children (41 %) within ± 20 % of actual maintenance dose (median age 7.2 years). In comparison, the published dosing algorithms predicted 33–41 % of the children within ±20 % of actual dose. Dose optimization with the bridged model based on up to three individual INR observations increased the proportion within ±20 % of actual dose to 70 %.ConclusionA mechanism-based population model developed on adult data provides a promising first step towards more individualized warfarin therapy in children.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-012-1466-4) contains supplementary material, which is available to authorized users.