Association between vitamin D receptor gene polymorphism and sex-dependent growth during the first two years of life.

An association between vitamin D receptor (VDR) gene polymorphisms and bone mass variance has been observed in adult populations. To analyze possible association between VDR genotype and growth, we studied 589 healthy infants who were homogeneous for age, diet, and vitamin D status. The Bsm I, TaqI, and ApaI alleles' frequencies and genotypes were similar to those reported for Caucasian populations. Variations in Bsm I polymorphism were not associated with calcium intakes nor with serum levels of calcium, 25-hydroxyvitamin D, 1, 25-dihydroxyvitamin D, or alkaline phosphatase activity. But, they were associated with differences in body size. At 2 yr, homozygote BB (BsmI site absent) girls had higher length, weight and body surface area, and inversely, BB boys had lower weight, body mass index and body surface area, than their respective bb counterparts. As a result, gender-related differences were observed in Bb and bb, but not in BB populations. This VDR genotypic effect was observed also at birth and at 10 months in the longitudinal analysis of 145 selected full-term babies homozygous for the Bsm I polymorphism. These findings provide support for the hypothesis that VDR genotype influences intrauterine and early postnatal growth, directly or via interactions with gender-related growth regulators.

Vitamin D prophylaxis during infancy: comparison of the long-term effects of three intermittent doses (15, 5, or 2.5 mg) on 25-hydroxyvitamin D concentrations.

Serum 25-hydroxyvitamin D [25(OH)D], calcium, phosphorus, and alkaline phosphatase activities were measured from birth to 6-9 mo of age in 60 healthy neonates to assess the effectiveness and potential toxicity of three intermittent oral doses of cholecalciferol. Two weeks after a first dose of 15, 5, or 2.5 mg, 25(OH)D concentrations reached 307 +/- 160, 150 +/- 55, and 92 +/- 42 nmol/L, respectively. Prolonged vitamin D overload, up to 6 mo, was found in 50% of the children given 15 mg, but not in the other infants. Serum calcium transiently increased 2 wk after 15 mg but not after the lower doses. Oral doses of 2.5 mg given every 3 mo appear to provide the best protection against vitamin D deficiency and vitamin D overload in high-risk infant populations that are unsuitable for daily vitamin D supplementation.

Subclinical vitamin D deficiency in neonates: definition and response to vitamin D supplements.

To determine the biological criteria for neonatal vitamin D deficiency, serum 25-hydroxyvitamin D (calcidiol), parathyroid hormone (PTH), calcium, phosphates, and alkaline phosphatase (ALP) activity were measured during the winter-spring period in 80 healthy neonates and their mothers 3-6 d after delivery. A longitudinal 3-mo survey of the serum biology of 52 of these neonates consuming formula was also performed to test the influence of their neonatal vitamin D status on the effects of two oral ergocalciferol supplements (500 and 1000 IU or 12.5 and 25 micrograms/d). At birth, 63.7% of the infants had calcidiol concentrations < or = 30 nmol/L. Most of them had no other biological sign evocative of vitamin D deficiency, but 14 neonates had low calcidiol concentrations and serum PTH concentrations > 60 ng/L, the upper limit of the adult normal range. They also had a significantly lower mean serum calcium concentration than did neonates with calcidiol concentrations > 30 nmol/L. On the basis of the association of low calcidiol concentrations (< or = 30 nmol/L) and high PTH concentrations (> 60 ng/L) as criteria for vitamin D deficiency, 24% of the neonates born to unsupplemented mothers were found to be vitamin D-deficient. Neonatal vitamin D status influenced the response of the infants to vitamin D supplements. Neonates with no sign of vitamin D deficiency showed similar changes in their serum calcidiol, calcium, phosphate, and PTH concentrations and ALP activity and no toxic effect (hypercalcemia or highly elevated calcidiol concentration) was observed whatever their vitamin D intake. In contrast, neonates with subclinical vitamin D deficiency had normalized serum PTH within 1 mo only when they were given 1000 IU ergocalciferol (25 micrograms)/d in addition to their formula.

[Fortified milk and supplements of oral vitamin D. Comparison of the effect of two doses of vitamin D (500 and 1,000 UI/d) during the first trimester of life]. / Laits enrichis et suppléments oraux en vitamine D. Comparison de l'effet de deux doses de vitamine D (500 et 1,000 UI/j) pendent le premier trimestre de la vie.

BACKGROUND: Administration of oral vitamin D supplements has been the usual strategy used in France for the prevention of rickets. But this strategy needs reevaluation since the fortification of infant formulas with vitamin D is authorized in this country. We report the effects of oral daily supplements of vitamin D on the calcium metabolism and vitamin D status of infants receiving or not fortified milk during the first trimester of life. POPULATION AND METHODS: Circulating levels of 25-hydroxyvitamin D (25-(OH)D) were measured: 1) in 64 infants aged 1 to 4 months, seen as outpatients between February and October, given oral vitamin D2 (theoretically 1,000 IU/d) and fed infant formulas, fortified or not with vitamin D; 2) in healthy neonates born to unsupplemented (n = 48) or supplemented vitamin D mothers (n = 22), between April and July, followed from birth (n = 70) to 3 months of age (n = 52), fed fortified milk, and given either 500 or 1,000 IU/D of vitamin D2. Serum calcium, phosphate, intact parathyroid hormone levels and alkaline phosphatase activities were simultaneously measured in this second study. RESULTS: In the first study, the infants who had been seen during the summer and fed fortified milk had 25-(OH)D levels higher than those seen during the winter and fed the unfortified formulas (37.0 +/- 11.2 ng/mL vs 29.1 +/- 9.7 ng/mL, P = 0.013). But when daily supplements of vitamin D2 were strictly controlled (second study), all infants fed the fortified milk had 25-(OH)D levels within the adult range (10 to 37 ng/mL) at 1 and 3 months of age, whatever their vitamin D status at birth and although these infants were seen during the summer. No difference was found between infants given 500 or 1,000 IU/d as regards their mean serum calcium, phosphate and alkaline phosphatase activities. In addition, the percentage of infants with calcemia above 2.60 mM/L was even lower with the 1,000 IU/d vitamin D dosage than with the 500 IU/d dosage. CONCLUSIONS: Daily supplements of vitamin D2 (500 to 1,000 IU/d) during the first trimester of life do not appear to induce a significant vitamin D overload when fortified milk is given to the infants. These supplementations may thus be maintained, especially when neonates are at risk of vitamin D deficiency.

[Vitamin D and pubertal maturation. Value and tolerance of vitamin D supplementation during the winter season]. / Vitamine D et maturation pubertaire. Intérêt et tolérance d'une supplémentation vitaminique D en période hivernale.

BACKGROUND: In France, several cases of vitamin D-deficiency rickets among adolescents have been reported, but no prophylaxis measure has been systematically recommended at this age. The aim of this study was to measure 25-hydroxyvitamin D (25-(OH)D) levels and to search for biological signs of vitamin D deficiency during adolescence. Moreover, the effects of a unique oral dose of 100,000 IU of vitamin D3, given during the winter, were analysed. POPULATION AND METHODS: Circulating levels of 25-(OH)D, 1,25-dihydroxyvitamin D, intact parathyroid hormone (iPTH), alkaline phosphatase activities, calcium and phosphate were measured in 53 adolescents aged 10-17 years (81% of metropolitan origin), seen during the winter. The effect of a single oral dose of 100,000 IU of vitamin D3 or of placebo was studied in 15 of these subjects. RESULTS: 24.5% of the adolescents had low 25-(OH)D concentrations (< 6 ng/ml), this frequency being even more elevated (38%) at the end of pubertal maturation (stages 4 and 5). An increase in iPTH concentrations was found in subjects with lowest 25-(OH)D levels (< 3 ng/ml). An oral dose of 100,000 IU of vitamin D3 resulted in a significant increase in the 25-(OH)D levels; yet, these levels remained within the normal range during the 1-2 month follow-up of the nine treated subjects. This dosage made it possible to correct the low calcium concentrations (2.20-2.24 mmol/l) found before treatment in three adolescents. CONCLUSIONS: The high frequency of low vitamin D status observed during puberty and its normalization after a 100,000 IU vitamin D3 supplementation show the interest and safety of this intermittent 100,000 IU vitamin D3 supplementation to adolescents during the winter season.

[Prevention of vitamin D deficiency in adolescents and pre-adolescents. An interventional multicenter study on the biological effect of repeated doses of 100,000 IU of vitamin D3]. / Prophylaxie de la carence en vitamine D chez l'adolescent et le préadolescent. Etude interventionnelle multicentrique sur les effets biologiques d'un apport répété de 100,000 UI de vitamin D3.

UNLABELLED: Recent studies have shown a high prevalence of calcium and vitamin D deficiencies in adolescents. The aim of this present study was to follow the changes in calcium status and 25 hydroxyvitamin D (25[OH]D) and parathyroid hormone (iPTH) levels during winter in preadolescents and adolescents from four university hospitals in northern France. SUBJECTS AND METHODS: Two groups of teenagers and adolescents (range: 10-15 years) were followed from October 1996 to June 1997. They were given either 100,000 IU of vitamin D (treated group n = 33) or a placebo (control group n = 35) in October, January and April. Serum calcium, phosphate, 25(OH)D and iPTH levels were measured at inclusion and every three months thereafter. RESULTS: At inclusion, plasma or serum 25(OH)D levels were < or = 10 ng/mL in 16 subjects and < 6 ng/mL in six. In control children, no significant change in 25(OH)D occurred during the study, while plasma or serum iPTH levels increased to 34 +/- 11 pg/mL. In the treated groups, 25(OH)D levels remained > 20 ng/mL in every subject; no hypercalcemia was observed; and the mean plasma or serum iPTH level was 25 +/- 14 pg/mL at the end of the study. CONCLUSION: Teenagers presented with a high prevalence of biological vitamin D deficiency at the end of summer. The increase of iPTH during winter in the unsupplemented group suggests that this has secondary consequences on their calcium homeostasis unless they are supplemented with vitamin D. We advocate a sufficient calcium supply and a 100,000 IU vitamin D supplement given two or three times during winter to preadolescents and adolescents living in northern France.

[Administration of a single dose of 100,000 U.I. of vitamin D3 in the pregnant woman in winter. The effect on blood calcium level of the newborn infant]. / Administration d'une dose unique de 100,000 U.I. de vitamine D3 chez la femme enceinte en hiver. Incidence sur la calcémie du nouveau-né.

Serum levels of 25-hydroxyvitamin D [25-(OH)D], calcium, phosphate and alkaline phosphatase activity were measured between December and July in 110 pregnant women during the last trimester of pregnancy, and in their infants on the fifth day of life. This study showed a fall, during spring, below 6 ng/ml, of the maternal 25-(OH)D concentration at the time of delivery, and a fall of the 25-(OH)D and calcium concentrations in newborns. The existence of a positive correlation between calcium and 25-(OH)D levels in the newborns suggests that the low calcium concentrations found in the infants born in spring is related to a vitamin D deficiency of the infant and therefore of the mother. The administration of a single low dose of vitamin D3 (100,000 I.U.) on the sixth or seventh month of pregnancy allowed to prevent the seasonal fall in serum calcium and 25-(OH)D concentrations. This dosage appears therefore to be sufficient to reduce the risk of vitamin D deficiency of the newborn and the occurrence of neonatal hypocalcemia.

[Effects of sunlight exposure on vitamin D status in pregnant women in France]. / Effet de l'ensoleillement sur le statut vitaminique D de la femme enceinte en France.

The concentration of 25-(OH)D in the blood were measured in 61 pregnant women between the ages of 16 and 45 who were living in three towns that had different amounts of sun (Lyon, Chambery, Nice). The reason for doing this was to find out the influence of exposure or non-exposure to sun on the vitamin D status of these women. A subclinical lack of vitamin D was found in a number of women where ever they lived, seemingly linked to too little exposure to sun (5% of women exposed to sunshine and 59% of women who were not exposed to sunshine had concentrations of 25-(OH)D (less than 10 ng/ml). In the women who were not exposed to sunshine there was a higher frequency of low concentrations of 25-hydroxy vitamin D (less than 10 ng/ml) in Lyon in winter and in women who came from South Europe, Africa or the Middle East. But 39% of the caucasian women who did not go out into the sun, also had low levels of 25-(OH)D (less than 10 ng/ml). There was a positive correlation between the concentrations of 25-(OH)D in the mothers and in the new born (p less than 0.001) which confirmed the dependence of the infant on his mother to build up reserves of vitamin D. Vitamin D supplements should be given to all women in the last trimester of pregnancy who cannot have enough sunshine, where ever they are living in France, in order to avoid the repercussions of low maternal vitamin D levels for the mother and her new-born infant.

[Vitamin D supplementation in institutionalized elderly. Effects of vitamin D3 (100,000 IU) orally administered every 3 months on serum levels of 25-hydroxyvitamin D]. / Supplémentation vitaminique D chez des sujets âgés placés en institution. Effets sur les concentrations sériques en 25-hydroxyvitamine D d'une administration orale trimestrielle de vitamine D3 (100,000 UI).

A clinical trial carried out during the autumn/winter season in 46 institutionalized elderly subjects (35 women, 11 men) (group mean age = 83 +/- 2 years) revealed a severe deficiency in vitamin D in these subjects (25-hydroxyvitamin D level less than or equal to 3 ng/ml). After oral administration of 100,000 IU of vitamin D3, an increase in 25-hydroxyvitamin D levels above the 10 ng/ml threshold was observed and maintained for three months. A second dose, administered after 3 months, made it possible to sustain this level. No sign of toxicity was detected, notably no trace of hypercalcemia. In contrast, no change in the deficit (25-hydroxyvitamin D level less than or equal to 3 ng/ml) was seen in the placebo population. Three-monthly administration of the moderate dosage of 100,000 IU of vitamin D3 all year round would offer a simple, effective and risk-free system to counteract vitamin D deficiency in the elderly and of preventing the risk of osteomalacia, thus reducing the incidence of fractures.

Serum osteocalcin regulation in protein-energy malnourished children.

To evaluate bone turnover changes occurring during protein-energy malnutrition, serum osteocalcin, a marker of bone formation, has been studied in healthy control, stunted, and severely malnourished (kwashiorkor and marasmus) Senegalese children. Serum osteocalcin levels were dramatically reduced in stunted, kwashiorkor, and marasmic children compared with control children. In addition serum osteocalcin levels of control children living in Senegal were lower (-46%) than those of African children living in France. Interestingly, serum osteocalcin level was not related to its major known regulators (1 alpha,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, and PTH) nor to stunting, but was related to serum transthyretin and thyroid hormones concentrations. These data suggest that serum osteocalcin level is related to protein-energy status and that bone formation was affected in apparently healthy and in malnourished Senegalese children. Serum osteocalcin could be a potent tool in the study of the alterations of bone formation in malnutrition.