Effect of daily low dose of vitamin A compared with single high dose on morbidity and mortality of hospitalized mainly malnourished children in senegal: a randomized controlled clinical trial.

BACKGROUND: In vitamin A-deficient populations, children hospitalized with infections and/or malnutrition are at particular risk of developing severe vitamin A (VA) deficiency. High-dose VA supplements are recommended as part of the treatment but results on its effect on recovery from morbidity and on prevention from nosocomial morbidity are conflicting. OBJECTIVE: We aimed to assess the effect of a single high dose and daily low dose of VA on hospitalized malnourished children's morbidity. DESIGN: We carried out a double-blind, randomized trial in 604 and 610 Senegalese hospitalized children. The first mentioned batch received a high-dose VA supplement (200,000 IU) on admission, the second a daily low-dose VA supplement (5000 IU per day) during hospitalization. Children were followed up until discharged. Data on all-cause morbidity were collected daily. RESULTS: Survival analysis showed that the incidence of respiratory disease was significantly lower in the low-dose group than in the high-dose group, hazard ratios (HR): 0.26, 95% CI: 0.07-0.92. The duration of respiratory infection was also significantly lower in the low-dose group than in the high-dose group (HR of cure: 1.41, 95% CI: 1.05-1.89). Duration and incidence of diarrhoea were not significantly different between treatment groups. In children with oedema on admission, mortality was significantly lower in the low-dose group (Adjusted odds ratio: 0.21; 95% CI: 0.05-0.99). CONCLUSIONS: Daily low dose of VA compared with single high dose significantly reduced duration and incidence of respiratory infection but not of diarrhoea in hospitalized children.

Costs associated with hospital-acquired bacteraemia in a Belgian hospital.

Studies from around the world have shown that hospital-acquired infections increase the costs of medical care due to prolongation of hospital stay, and increased morbidity and mortality. The aim of this study was to determine the extra costs associated with hospital-acquired bacteraemias in a Belgian hospital in 2001 using administrative databases and, in particular, coded discharge data. The incidence was 6.6 per 10000 patient days. Patients with a hospital-acquired bacteraemia experienced a significantly longer stay (average 21.1 days, P<0.001), a significantly higher mortality (average 32.2%, P<0.01), and cost significantly more (average 12853 euro, P<0.001) than similar patients without bacteraemia. At present, the Belgian healthcare system covers most extra costs; however, in the future, these outcomes of hospital-acquired bacteraemia will not be funded and prevention will be a major concern for hospital management.

Iodine deficiency during infancy and early childhood in Belgium: does it pose a risk to brain development?

Iodine deficiency is well documented in Belgium in adults including pregnant women, adolescents, schoolchildren, and neonates, but no data are available in the age group 6 months-3 years. We investigated the status of iodine nutrition in 111 healthy subjects in this age group in an attempt to evaluate the risk of brain damage due to iodine deficiency in Belgium. In 244 causal urine samples collected in these subjects, the median concentration of iodine was 101 micrograms/l vs 180-220 micrograms/l under normal conditions. The daily supplementation of the subjects with a physiological dose of 90 micrograms iodine was followed by a slow and progressive increase of urinary iodine, which reached a normal level only after a delay of about 30 weeks of therapy. This observation suggests that part of the supplement of iodine offered to the children was stored in their thyroid glands until the iodine content of the gland had reverted to normal, reflecting the state of hyperavidity of the thyroid for iodide characteristic of iodine deficiency. In conclusion, infants and young children in Belgium are as iodine deficient as all other age groups of the population and, consequently, are at risk of brain damage. This works further illustrates the need for systematic iodine supplementation of the population in Belgium.

The molar ratio of serum retinol-binding protein (RBP) to transthyretin (TTR) is not useful to assess vitamin A status during infection in hospitalised children.

OBJECTIVE: To assess the usefulness of the molar ratio of serum retinol-binding protein (RBP) to transthyretin (TTR) to determine vitamin A (VA) status during infection. DESIGN: We took advantage of previously collected data during a randomised double-blind, placebo-controlled clinical trial to conduct a secondary analysis of the RBP/TTR ratio and its relationship to infection and VA status. In this clinical trial, children were randomly assigned to one of three groups and received either one single oral high dose of VA (200 000 IU) on the day of admission and subsequently a placebo daily until discharge or daily oral low doses of VA (5000 IU) from admission until discharge or a placebo daily from admission until discharge. SETTING: Lwiro pediatric hospital, Province of South Kivu, Democratic Republic of Congo. SUBJECTS: A total of 900 children aged 0-72 months hospitalised consecutively between March 1994 and March 1996. MAIN OUTCOME MEASURES: RBP/TTR molar ratio after 7 days hospitalisation. RESULTS: After 7 days hospitalisation, molar RBP:TTR ratio (mean+/-s.d.) of infected children (C-reactive proteins>10 mg/l) was 0.67+/-0.31 in the high-dose group (n=81), 0.74+/-0.44 in the low dose group (n=71) and 0.73+/-0.39 in the placebo group (n=81). These values did not differ significantly (one-way ANOVA P=0.472). In patients with baseline serum retinol concentrations<0.70 micromol/l, changes in RBP:TTR ratio between admission and day 7 were not statistically different in the three groups (one-way ANOVA P=0.548). CONCLUSIONS: In this population of malnourished hospitalised children, molar RBP:TTR ratio does not appear to be useful to assess VA status during infection. SPONSORSHIP: Our research was partially supported by a grant from the Fonds de la Recherche Scientifique et Médicale (contract 3.4505.94) and the David and Alice Van Buuren Foundation.

Silent iodine prophylaxis in Western Europe only partly corrects iodine deficiency; the case of Belgium.

OBJECTIVE: Belgium is one of the Western European countries in which no program of iodine-deficiency correction using iodized salt has been implemented, in spite of well-documented mild iodine deficiency. In 1995, the median urinary iodine concentration was 55 microg/l (normal: 100-200) and the prevalence of goiter was 11% (normal: below 5%) in representative samples of schoolchildren aged 6-12 years. Based on these results, the authors of the present study and others had emphasized to health professionals and to the public the necessity for iodine supplementation. The objective of this study was to evaluate as to whether these efforts had resulted in an improvement in the status of iodine nutrition. DESIGN: We performed a national survey of the status of iodine nutrition in Belgium based on the determination of thyroid volume, obtained by ultrasonography, and urinary iodine concentrations in schoolchildren. METHODS: A mobile van equipped with an ultrasound instrument, a computer and a deep-freeze visited 23 schools selected from across the country. The sample included 2855 schoolchildren (1365 boys and 1490 girls) aged 6-12 years. RESULTS: The results show a homogeneous situation in the whole country, with a median urinary iodine concentration of 80 microg/l and a goiter prevalence of 5.7%. Urinary iodine slightly decreases with age in girls and reaches a critical value of 59 microg/l at the age of 12 years, together with a goiter prevalence of 18.4%. CONCLUSION: Iodine nutrition has improved slightly in Belgium but mild iodine deficiency continues, with public-health consequences. The improvement indicates silent iodine prophylaxis, as no official salt-iodization measures have been taken. Silent iodine prophylaxis only partly corrects iodine deficiency in Western Europe. Active measures, including the implementation of a program of salt iodization, are urgently required.

Randomized placebo-controlled clinical trial of the effect of a single high dose or daily low doses of vitamin A on the morbidity of hospitalized, malnourished children.

The effect of high-dose vitamin A supplementation on recovery from morbidity and on recovery from nosocomial morbidity of hospitalized children has been poorly studied and results are conflicting. The effect of daily, low doses has never been assessed. We investigated the effect of a single high dose and daily, low doses of vitamin A on diarrhea, acute lower respiratory tract infections (ALRIs), and all-cause fevers in 900 hospitalized preschool-age children in the Democratic Republic of Congo in a randomized, double-blind, placebo-controlled clinical trial. The high-dose treatment group received 200,000 IU vitamin A (100,000 IU if aged <12 mo) orally on the day of admission, the low-dose treatment group received 5000 IU vitamin A/d until discharge. Data on all-cause morbidity were collected daily. Mortality rates were not significantly different among the 3 groups. High-dose vitamin A supplementation had no significant effect on the duration of moderate or severe diarrhea nor on the duration and incidence of ALRIs and all-cause fevers. Children in the high-dose group with no edema had an increased risk of severe nosocomial diarrhea (relative risk: 2.42; 95% CI: 1.15, 5.11). Low-dose vitamin A supplementation significantly reduced the incidence of severe diarrhea in severely malnourished children (relative risk: 0.21; 95% CI: 0.07, 0.62) but showed no significant effect on the duration of moderate or severe diarrhea or on the duration and incidence of ALRIs and all-cause fevers. Supplementation with high doses of vitamin A did not reduce morbidity in this population of malnourished and subclinically vitamin A-deficient children; daily, low doses appeared more beneficial for severely malnourished children.

Vitamin A supplementation but not deworming improves growth of malnourished preschool children in eastern Zaire.

A randomized controlled trial was conducted in eastern Zaire to assess the effects of high dose vitamin A supplementation and regular deparasitation on the growth of 358 moderately malnourished preschool children, discharged from the hospital. The treatment groups received either vitamin A (60 mg of oily solution of retinyl palmitate, 30 mg if aged <12 mo) every 6 mo or mebendazole (500 mg) every 3 mo; the control group received no supplementation. Anthropometric data were gathered at baseline and after 6 and 12 mo of follow-up. Serum retinol concentrations were measured at baseline and after 3 mo. The three groups did not differ in sociodemographic indicators, age and sex composition, nutritional status and serum retinol concentrations at baseline. In children who were vitamin A deficient at baseline, adjusted mean weight and mid-upper arm circumference (MUAC) increments were higher in the vitamin A-supplemented group than in the control group [annual increment in weight and MUAC in vitamin A vs. control group: 2.088 vs. 1.179 kg (P = 0.029) and 2.24 vs. 0.95 cm (P = 0.012), respectively], whereas growth increment did not differ between the dewormed group and the control group. In children who were not vitamin A deficient at baseline, growth increment did not differ between the vitamin A-supplemented and control groups, whereas weight gain was lower in the dewormed group than in the control group. Vitamin A-supplemented boys gained more weight and height than control boys, whereas vitamin A-supplemented girls gained less height than control girls. Dewormed boys and girls gained less weight than control boys and girls. Programs to improve vitamin A status by high dose vitamin A supplementation may improve growth of preschool children who are vitamin A deficient, whereas deworming does not.

Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast.

The effect of selenium supplementation on plasma selenium concentrations and lymphocyte-proliferation responses to mitogens was investigated in 22 elderly institutionalized subjects. Subjects were assigned to a 6-mo trial with either 100 micrograms Se/d (as selenium-enriched yeast) or a placebo. Plasma selenium concentrations of the selenium-supplemented group increased from 0.84 +/- 0.26 to 1.55 +/- 0.33 mumol/L (mean +/- SD) after 2 mo and the values plateaued thereafter. The mean response of lymphocytes to mitogens in elderly subjects tended to be lower than responses in healthy adults, although responses remained within the 5-95% confidence-interval limit for healthy adults. During selenium supplementation the proliferative response to pokeweed mitogen increased significantly (+79% of baseline concentrations after 4 mo, P less than 0.01) and reached the upper limit of the usual range for adults after 6 mo (+138%, P less than 0.001). In accordance with previous studies in animals and in vitro, this investigation demonstrates for the first time immunostimulatory properties of selenium-enriched yeast in elderly humans.

Endemic infantile hypothyroidism in a severe endemic goitre area of central Africa.

Thyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goitre area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 +/- 4 nmol/l) and stayed at that level during the first year of life (123 +/- 9) (NS), but decreased to 75 +/- 8 (P less than 0.001) at 2-4 years and to 62 +/- 6 (P less than 0.001) at 5-7 years of age. Mean serum FT4 decreased from 10.4 +/- 0.9 pmol/l during the first year to 8.2 +/- 1.0 (NS) at 2-4 years (NS) and to 7.7 +/- 0.9 (P less than 0.05) at 5-7 years. Mean serum TSH was 10.4 (8.4-12.9) mU/l (geometric mean +/- 1 SEM) during the first year, 10.1 (7.5-13.7) (NS) at 2-4 years and 24.3 (18.5-31.9) (P less than 0.05) at 5-7 years. Mean serum T3 was 3.23 +/- 0.12 nmol/l during the first year and remained stable thereafter. The frequencies of low T4 (T4 less than 77 nmol/l), high TSH TSH (TSH greater than 50 mU/l), and low T4 and T3 (T3 less than 1.69 nmol/l) were twice as high at 5-7 years as in the first year (respectively 65%, 42% and 15%). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 +/- 5 mumol/l) decreased to normal values between 3 and 12 months of age and increased again during and after weaning (1 to 3 years of age) to reach a value of 138 mumol/l which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 +/- 7 mumol/l) in the mothers' serum but low in the mothers' milk (57 +/- 3 mumol/l) (P less than 0.001). Multivariate analysis showed that both iodine deficiency and thiocyanate overload were explanatory factors of the serum levels of T4, FT4 and TSH in children. In conclusion, our results show that infantile hypothyroidism is much more frequent at 5-7 years of age than at birth or during the first year of life. The deterioration in thyroid function during and after weaning is linked to persistent iodine deficiency accompanied by an increase in thiocyanate overload. The variability in the age of onset, the severity, and the duration of infantile hypothyroidism might explain the wide range of psychomotor and physical abnormalities observed in a large proportion of subjects in this area.

PIP: Thyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goiter area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 +or- 4 nmol/1) and stayed at that level during the 1st year of life (123 +or- 9) (NS), but decreased to 75 +or- 8 (P0.001) at 2-4 years and to 62 +or- 6 (P.001) at 5-7 years of age. Mean serum FT4 decreased from 10.4 +or- 0.9 pmol/1 during the 1st year to 8.2 +or- 1.0 (NS) at 2-4 years (NS) and to 7.7 +or- 0.9 (P0.05) at 5-7 years. Mean serum TSH was 10.4 (8.4-12.9) mU/1 (geometric mean +or- 1 SEM) during the 1st year, 10.1 (7.5-13.7) (NS) at 2-4 years, and 24.3 (18.5-31.9) (P0.05) at 5-7 years. Mean serum T3 was 3.23 +or- 0.12 nmol/1 during the 1st year and remained stable thereafter. The frequencies of low T4 (T477 nmol/1), high TSH TSH (TSH50 mU/1), and low T4 and T3 (T31.69 nmol/1) were twice as high at 5-7 years as in the 1st year 65%, 42%, and 15%, respectively). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 +or- 5 cmol/1) decreased to normal values between 3-12 months of age and increased again during and after weaning (1-3 years of age) to reach a value of 138 umol/1 which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 +or- 7 umol/1) in the mothers' serum but low in the mothers' milk (57 +or- 3 umol/1) (P0.001). Multivariate analysis showed that both iodine deficiency and thiocyanate overload were explanatory factors of the serum levels of T4, FT4, and TSH in children. The results show that infantile hypothyroidism is more frequent at 5-7 years of age than at birth or during the 1st year of life. The deterioration in thyroid function during and after weaning is linked to persistent iodine deficiency accompanied by an increase in thiocyanate overload. Variability in age at onset, severity, and duration of infantile hypothyroidism might explain the wide range of psychomotor and physical abnormalities observed in a lage proportion of subject, in this area.