Maternal and neonatal factors and mortality in children with Down syndrome born in 1973-1980 and 1995-1998.

AIMS: To investigate maternal and neonatal factors in Down syndrome (DS) at birth, the impact of a congenital heart defect (CHD) on these factors and changes over time. METHODS: Medical data of children with DS born in northern Sweden in the periods 1973-1980 (n = 219) and 1995-1998 (n = 88) obtained from the Swedish Medical Birth Register were compared. A comparison with the general population on a group level was also made. RESULTS: The main finding was a reduction in infant mortality in DS, from 14.2% to 2.3% in 1995-1998 (p < 0.001), but this was still significantly higher than in the general population. The rate of Caesarean sections increased over time (from 14.5% to 27.3%, p < 0.05) even after adjustment for increased maternal age. No change over time was detected in the following rates: premature birth (gestational age < or = 36) (25%); asphyxia (5-min Apgar score < or = 6) (8%); low birthweight (< 2500 g) (14%); or small for gestational age (SGA) (14%); all rates were significantly higher than those of the general population. A CHD did not seem to influence the rates of these factors in a logistic regression model. CONCLUSION: Infant mortality decreased substantially over time in the DS group, whereas there was no reduction in the rate of asphyxia, SGA, low birthweight or prematurity. The presence of a CHD did not influence any of the neonatal factors studied.

Utilization of medical care among children with Down's syndrome.

BACKGROUND: The present authors have previously found an increased mortality rate in children with Down's syndrome (DS) and a congenital heart defect (CHD). The aim of the present study was to investigate the utilization of medical care in relation to congenital malformations in DS. METHOD: Retrospectively, 211 children with DS born between 1973 and 1980 in the northern part of Sweden were followed up for at least 17 years (1973-1997). The duration of neonatal care was compared with that of children with DS born between 1995 and 1998 in the same region. RESULTS: Neonatal care was reduced over time. Almost 50% of the children had CHD, and before 10 years of age, these subjects were admitted for inpatient care twice as often as children with DS who did not have malformations, and had more than 12 times as many inpatient days per month. The existence of a gastrointestinal or other malformation increased inpatient days per month four and two times, respectively, compared to healthy children with DS. During the first 10 years of life, children with DS and a CHD accounted for 71% of all inpatient days caused by infections. No gender differences were observed. CONCLUSIONS: At a group level, the presence of a CHD was the most important congenital abnormality in determining utilization of medical care and the burden of infections in the population of children with DS.

Informal parental traffic education and children's bicycling behaviour.

The aim of this study was to analyze the relation between traffic intensity and traffic hazards in the local traffic environment, the parents' view of their child's traffic situation and the actions taken by the parents to cope with these hazards. 58 parents were interviewed. The traffic intensity in the vicinity of the home was estimated. 19% of the parents lived in inner city areas, 62% in suburbs and 19% in the countryside. Suburban children had a safe traffic environment. Inner city- and countryside children predominately lived in high-intensity traffic environment. Inner city- and suburb children frequently used the bike, in inner city as a tool for play and in the suburbs mainly as a means of transport. Countryside children seldom used their bicycle. In inner city areas carefulness in traffic and in the other two independence was emphasized. Only 16% reported cooperation between home and school on traffic matters. Traffic accidents were concentrated to children living in suburbs (p<0.01). 81% of accidents were reported by parents having independence as a goal for traffic training (p<0.01). The results underline that traffic accident risk is strongly contingent on the local traffic environment and informal parenteral education in traffic safety.

Mortality in Down's syndrome in relation to congenital malformations.

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.

Vitamin A exerts potential therapeutic effects in the endotoxaemic pig.

BACKGROUND: Pretreatment with an injection of vitamin A has beneficial effects on cardiac and pulmonary functions in normally bred endotoxaemic pigs. The present study was performed in order to elucidate whether the response of an ongoing infusion of E. coli can be modulated by a single injection of vitamin A. METHODS: Sixteen healthy (not vitamin A-depleted) pigs were anaesthetized, monitored, mechanically ventilated and subjected to an infusion of E. coli endotoxin (10 micrograms.kg-1.h-1). This infusion resulted within 30 min in a progressive haemodynamic derangement. When the mean pressure in the pulmonary artery was twice the baseline value, vitamin A (460 IU.kg-1) or a corresponding volume of vehicle was injected intravenously. After sacrificing the animals, the right lung was excised and weighed, and biopsy specimens were taken from the left lung for microscopical examination. RESULTS: Mean arterial blood pressure was significantly less affected (P < 0.01) between the 1st and 6th hour in endotoxaemic pigs treated with vitamin A than in those given vehicle. The mean lung weight in the vitamin A-treated pigs was significantly lower than that in the vehicle group (164 +/- 5.3 vs 199 +/- 19.8 g; P < 0.01). Microscopical examination showed significantly less oedema (0.93 +/- 0.17 vs 2.00 +/- 0.26; P < 0.01) and microatelectasis (0.56 +/- 0.17 vs 1.75 +/- 0.31; P < 0.01) in the vitamin A group. Endotoxaemia was also accompanied by an initial, steep decline in neutrophil counts in all animals; this decrease was significantly less pronounced (P < 0.05) in vitamin A-injected pigs than in the vehicle-injected group. The major difference was a more rapid restitution in the vitamin A group. CONCLUSION: Several manifestations of endotoxaemia were expressed less in the vitamin A group. Thus, vitamin A may turn out to be a tool in the management of endotoxaemia.

Beneficial effects of pre-treatment with vitamin A on cardiac and pulmonary functions in endotoxaemic pigs.

BACKGROUND: Septic shock is associated with high mortality despite the development of new antibiotics. Since Vitamin A has an immunomodulating ability and is able to lower the concentrations of endotoxin and some cytokines, we decided to study whether supplementation with vitamin A may have a beneficial effect in experimental endotoxaemia. METHODS: A porcine model was used, in which normally bred (i.e., not vitamin A depleted) animals were anaesthetised, monitored and injected intramuscularly with a non-toxic dose of vitamin A (230 IU.kg-1) (n = 9) or the corresponding volume of vehicle (n = 9) 1 hour before an infusion of purified E. coli endotoxin was given in a dose of 10 micrograms.kg-1.h-1 over 6 hours. Another 3 pigs also injected with vitamin A, but not endotoxin, served as controls. RESULTS: Vitamin A- and endotoxin-injected pigs were significantly less affected in several circulatory and respiratory variables as compared to vehicle-and endotoxin-injected animals (e.g., blood pressure; heart rate; cardiac index; pulmonary capillary wedge pressure; left and right ventricular stroke work indices; pH; base excess; oxygen delivery; and oxygen extraction). Vitamin A did not per se significantly affect these variables. Hb increased significantly in the vehicle group, indicating a more pronounced capillary permeability. Urinary output or fluid supply did not differ between the groups. Myocardial production of metabolites of prostacyclin or thromboxane A2 did not differ between the groups. CONCLUSION: Pre-treatment with vitamin A had a beneficial effect on several variables, such as oxygen delivery and metabolic acidosis in the endotoxaemic pig. Improvement of these variables is associated with increased survival in septic shock and may indicate reduced tissue hypoxia. Thus, vitamin A may turn out to be useful as a prophylactic agent in conditions where septic shock is apt to occur.

Interactions of vitamins A and E and retinol-binding protein in healthy Swedish children--evidence of thresholds of essentiality and toxicity.

The serum levels of vitamins A and E and retinol-binding protein (RBP) were determined and their relationships investigated in 144 healthy Swedish children between the ages of 1 month and 16 years. The median level for vitamin A was 540 micrograms l-1 (range 181-1720 micrograms l-1); for vitamin E 6.8 mg l-1 (range 1.0-14.0 mg l-1) and for RBP 0.030 g l-1 (0.018-0.045 g l-1). Retinol-binding protein levels rose steeply in relation to vitamin A levels of up to approximately 800 micrograms l-1. However, RBP levels remained constant when vitamin A levels were between 800 and 1600 micrograms l-1 but displayed a further steep rise for vitamin A levels above this range. Fourteen individuals had levels that did not follow this pattern but fell rather neatly below the correlation line. These individuals were also found to have significantly higher mean levels of acute phase reactants than the rest of the study group, suggesting the possibility of subclinical infection or inflammation in these subjects. Vitamins A and E showed an inverse curvilinear relationship. This is the first report of an interaction between vitamins A and E and RBP in healthy Swedish children. The study demonstrates that a linear one-to-one relationship between RBP and vitamin A may not be of regular occurrence as previously assumed. The pattern described suggests the existence of thresholds of essentiality and toxicity in the interaction between the two vitamins and RBP.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma levels of fat-soluble vitamins A and E in neonates, after administration of two different vitamin solutions.

The aim of this study was to compare the effects of 2 different vitamin solutions on plasma levels of vitamin A and E during and after short term total parenteral nutrition (TPN), after neonatal surgery. 2 compounds were compared, one with a higher vitamin A content (100 mu g/ml) and no vitamin E and one with vitamin E (0.64 mg/ml) and a lower vitamin A content (69 mu g/ml). 2 randomly chosen groups of 10 neonates were studied each with gastrointestinal malformations. The groups were comparable regarding gestational age (GA), weight and length. Diagnoses within the groups were similar. TPN was given after corrective surgery for a median time of 6.5 days to both groups. Vitamin A and retinol binding protein (RBP) levels increased significantly (p < 0.05) above the pre-treatment level in patients receiving supplementation with a higher dosage of vitamin A (100 mu g/ml). In patients receiving the lower dose of vitamin A (69 mu g/ml) plasma levels of this vitamin were unchanged but RBP levels fell significantly (p < 0.05). There was no significant difference in plasma vitamin E levels in the group of patients receiving vitamin E supplementation as compared with the unsupplemented group. In both groups vitamin E levels increased significantly (p < 0.005) after introduction of oral feeding. The results indicate that even during short term TPN endogenous stores of vitamin A might become depleted. In spite of the fact that no vitamin A deficiency was noted it seems obvious that a higher vitamin A intake is advisable which is in accordance with the recommendations from the Subcommittee on Paediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of The American Society for Clinical Nutrition.

Plasma concentrations of fat-soluble vitamins A and E in neonates with myelomeningocele.

A group of newborn infants with myelomeningocele was compared with a group of neonates suffering from gastrointestinal malformations and a group of healthy children less than one year of age. The parameters studied were prealbumin, retinol-binding protein and the fat-soluble vitamins A and E. There were no significant differences between the groups in the plasma levels of the proteins or vitamin E. Vitamin A levels in newborn infants with myelomeningocele were found to be significantly lower compared to both the other groups.

Clinical adsorption and photodegradation of the fatsoluble vitamins A and E.

The adsorption of the fat-soluble vitamins A and E to administration sets and their photodegradation was studied under varying conditions. Infusion bottles with or without photoprotectors (red plastic bags) were studied, as were systems exposed to the blue light, used in the treatment of hyperbilirubinaemia, which has a maximum emission spectrum at 450 nm. An IV bag containing lipids, carbohydrates, amino-acids, minerals and vitamins was also studied. Vitamin levels in all administration sets decreased by approximately 30% during the first 3h, except for those in the IV bag. Vitamins were best preserved in the IV bag, where 85-90% of both vitamins remained after 20h. Vitamin E appeared to suffer from both adsorption and photodegradation but to a lesser extent than vitamin A. Vitamin A displayed a greater tendency for adsorption. In order to avoid loss of vitamins during parenteral administration, we recommend that they should be administered as a bolus or during a limited period of 1 h, and that the system be protected from light.

Effects of vitamin A on endotoxaemia in rats.

OBJECTIVES: To find out if survival after peritonitis induced by caecal puncture and injection of endotoxin is correlated with serum endotoxin concentrations in rats; whether this study could be carried out by studying the effects of vitamin A in rats with peritonitis; and if it was possible to differentiate between local and systemic effects of vitamin A on endotoxaemia in rats. DESIGN: Prospective randomised study. MATERIAL: Sixty adult male Sprague-Dawley rats. INTERVENTIONS: Rats were kept on a diet containing no vitamin A for six days; 30 were given vitamin A 1,380 IU/kg/day intramuscularly and 30 were given peanut oil. Peritonitis was then induced in 16 rats by caecal puncture (treated n = 10, untreated n = 6) and the remainder received intraperitoneal injections of either 0.5 mg/kg endotoxin, or 2.0 mg/kg endotoxin. MAIN OUTCOME MEASURES: Plasma concentrations of vitamin A, vitamin E, and serum concentrations of endotoxin, estimation of erythrocyte volume fraction and leucocyte particle concentrations, and survival. RESULTS: Rats that were given 2 mg of endotoxin had higher mortality and did generally less well than others. Serum endotoxin concentrations were lower in those groups that had been pretreated with vitamin A. No animal developed vitamin A deficiency and there were no differences in erythrocyte volume fraction or leucocyte particle concentration between those that did and did not receive vitamin A. CONCLUSION: Vitamin A lowered the concentration of endotoxin in the circulation, it has a central function in the host's defence against endotoxin, and the experimental model seems suitable for the study of the effect of vitamin A or endotoxemia and peritonitis.