Role of vitamin D in acquired immune and autoimmune diseases.

Vitamin D has been attributed roles in the pathogenesis and prevention of several diseases such as cancer, cardiovascular disease, multiple sclerosis, diabetes, autism and autoimmune diseases. The concomitant expression of the 25-hydroxyvitamin D3-1α-hydroxylase and of the vitamin D3 receptor in animal and human tissues and organs other than bone supports this paradigm. Translated into the clinical field, meta-analyses and systematic reviews have also revealed an association between vitamin D insufficiency or deficiency and non-osseous diseases. Although relying on the large databases, they are diverse in nature and involve participants of varying age and evolving in different environments. Furthermore, they do not allow any analysis of a possible causal relationship between vitamin D supplementation and clinical outcomes. Following a brief historical account, this review addresses these caveats, and gives examples of randomized controlled trials conducted in the fields of acquired immune and autoimmune diseases.

[Neonatal medicine, past and present]. / Néonatologie: passé et present.

This review deals with early neonatal medicine and its rapid development as a medical specialty, starting with the birth of neonatology in the early 19th century. Shaffer first used the term neonatology in 1963 to cover neonatal disorders and their treatment. Between the early 19th century and the 1950s, neonatal care was ensured by obstetricians, whose main goal was to reduce neonatal mortality. After the second world war, and especially the 1960s, the development of neonatal physiology and pathophysiology provided insights into neonatal diseases and their treatment, including respiratory distress, jaundice, malnutrition, and prevention of respiratory distress and brain complications, etc. Currently, neonatal mortality, regardless of birth weight, is below 2/1000, and the survival rate of premature infants, regardless of gestational age and birth weight, exceeds 85%. This represents a resounding success, despite the associated costs, ethical issues, and inevitable morbidity.

[Infant nutrition]. / Alimentation du nouveau-né et du nourrisson.

Nutritional quality during the first weeks of life can influence health during both infancy and adulthood. Exclusive long-term breast feeding is strongly recommended, particularly for infants at risk of allergy. It protects against gastrointestinal and respiratory infections, and has been shown to enhance cognitive and intellectual development. Breast-feeding is also associated with a lower risk of obesity and type 1 diabetes in infants and of cardiovascular disease in adults. Breast-feeding is rarely contraindicated. Multiple European and French guidelines and regulations govern the composition of infant formulas, which may be given during the first year of life when breast-feeding is unavailable. Hypoallergenic and soy-based formulas are not recommended for healthy infants.

[Newborn and infant nutrition in France in 2007]. / L'alimentation du nouveau-né et du nourrisson. Etat des lieux en France en 2007.

Newborns and infants are mainly fed with maternal and/or formula milk. In France, breast-feeding is abandoned about 8 weeks after delivery on average, even though it is well known that it is best for growth and sensory development. Several formulas are claimed to mimic maternal milk, but their large number is a source of confusion. Up to three years of age, formula milk and cow's milk are important for growth and skeletal mineralization.

Bone mineralization and growth are enhanced in preterm infants fed an isocaloric, nutrient-enriched preterm formula through term.

BACKGROUND: Because recent data on the effects of mineral concentrations in preterm infant formula on bone mineralization are lacking, recommendations for the mineral content of preterm infant formula differ greatly between committees. OBJECTIVE: The goal of the study was to assess the effects of an isocaloric, nutrient-enriched preterm formula, which was fed from the age when full enteral feedings were tolerated through expected term, on bone mineralization in preterm infants. DESIGN: We conducted a prospective, randomized, double-blind study in healthy, preterm infants (gestational age of 28-32 wk) who were fed either a control preterm formula (n=20) or an isocaloric, nutrient-enriched preterm formula (n=21) until 3 mo of age (ie, approximate expected term). Serum calcium indexes were taken throughout the study, and bone mass was determined by using dual-energy X-ray absorptiometry at hospital discharge and expected term. RESULTS: A total of 37 infants (experimental formula, n=19; control formula, n=18) completed the study. Compared with control subjects, infants fed the experimental formula had 25% and 40% higher intakes of calcium and phosphorus, respectively. Serum calcium, phosphorus, osteocalcin, and alkaline phosphatase concentrations and urinary collagen type I cross-linked N-telopetide concentrations were not significantly different between the groups at any time point. The bone mineral content of infants fed the experimental formula was 23% (P=0.039) and 35% (P=0.002) higher at hospital discharge and expected term, respectively. CONCLUSIONS: Bone mineralization at hospital discharge and expected term was significantly higher in preterm infants fed the isocaloric, nutrient-enriched formula than in those fed control formula. Continuation of the experimental formula beyond hospital discharge, through expected term, further improved bone mineralization.

Nitrogen utilization and bone mineralization in very low birth weight infants fed partially hydrolyzed preterm formula.

Partialy hydrolyzed formulas have been proposed for term and preterm infants, but decreased nitrogen and calcium intestinal absorption rates, together with plasma amino acid imbalances have been reported in preterm infants. We evaluated a new formula with modified nitrogen and calcium sources (glycerophosphate). During their second week of life, 16 preterm infants were randomly assigned to 1 of 2 groups: 9 were fed the new partially hydrolyzed formula and 7 a conventional formula. A nutrient balance was performed at the end of the first month of life. Amino acid concentrations and whole-body mineralization were measured at the end of study period (theoretical term). Birth weight and gestational age (mean +/- SD) were similar in the 2 groups (28.9 +/- 7.0 wks and 1,183 +/- 242 g v 27.7 +/- 1.0 wks and 1,139 +/- 162 g). Median nitrogen absorption rate (85% v 89%; P = .03) was lower in infants fed the new formula than in those fed the conventional one. After correction for difference in nitrogen intake, there was no significant difference in N retained between the 2 groups (P = .11). Plasma amino acid concentrations were also similar in the 2 groups. At theoretical term, median bone mineral content was not significantly different between the 2 groups (50 g/kg v 55 g/kg; P = .17) and it was close to the reference values obtained in term neonates just after birth. As long as nitrogen content is 10% higher in protein hydrolyzed formula than in entire protein formula, appropriate nitrogen retention, plasma amino acid profile can be achieved with the new partially hydrolyzed formula. In both groups, bone mineralization at theoretical term was close to the mineralization observed term neonates just after birth.

First all-solid pediatric phantom for dual X-ray absorptiometry measurements in infants.

Manufacturer-supplied lumbar spine phantoms are normally used for quality control of dual X-ray absorptiometry (DXA) instruments. Presently, there is no pediatric phantom for whole-body mineralization and softtissue composition DXA measurements. We designed blocks of acrylic (for fat mass), polyvinyl chloride (for lean mass), and aluminum (for bone mass) whose combination provides five whole-body phantoms ("Inphants") that mimic body weight and composition during the first year of life and help solve problems that require repeated scans in stable conditions. Inphants were scanned using an Hologic QDR 2000. Comparisons were made between values obtained with and without the table pad, using infant software. Then we compared data obtained using infant and adult softwares successively in the same phantoms. The table pad significantly influenced DXA measurements. We observed significant differences in fat mass (p = 0.04) and lean mass (p = 0.03) with the smaller Inphant (3 kg) and in bone mineral content (BMC) (p = 0.02) with the larger Inphant (13 kg). BMC was three to five times lower with adult than with infant software. Adult software yielded systematically significantly lower fat masses but higher lean masses than infant software. Because there was no overlap with larger Inphants, we calculated conversion formulae between values of infant and adult software. The results suggest guidelines for scan acquisition and analysis in young subjects.

[Vitamin D and pregnancy]. / Vitamine D et grossesse.

During pregnancy maternal serum concentrations of 25 hydroxyvitamin D correlate with dietary vitamin D intake. Maternal serum concentrations of 1.25-dihydroxyvitamin D the hormonal circulating and active form of vitamin D are elevated, during pregnancy. 1.25-dihydoxyvitamin D is synthesized mainly by the décidual cells of the placenta and allows for increased calcium absorption. The fetus is entirely dependent on the mother for its supply of 25 (OH) D which is believed to cross easily the placenta. Vitamin D deficiency during pregnancy affects the fetus and the newborn. Birth weight is decreased, bone mineralization is impaired and neonatal hypocalcemia is frequent. In countries where dairy products are not routinely supplemented in vitamin D maternal vitamin D supplementation during pregnancy is necessary.

[Mortality and morbidity of low-birth-weight infants. Current prognosis and future perspectives]. / Mortalité et morbidité des enfants de faible poids de naissance. Pronostic actuel: quel avenir?

In a retrospective epidemiologic study conducted from January 1996 to December 2002, 2555 low-birth-weight infants (less than 2500 g) were admitted to the neonatal intensive care unit of E Herriot Hospital in Lyon, France. Very low birth weight (795 infants) was defined as a birth weight below 1500 g. The total mortality rate among these latter infants was 8%. The mortality rate was less than 25% among infants with a gestational age of at least 25 weeks. Neonatal morbidity mainly consisted of respiratory distress syndrome and cerebral hemorrhage. Sequelae at age 2 years (corrected) affected less than 10% of surviving in very-low-birth-weight infants. Gestational age is thus an important predictor of survival and functional outcome in very-low-birth-weight infants.

Enteral calcium, phosphate and vitamin D requirements and bone mineralization in preterm infants.

UNLABELLED: With major advances in life-support measures, nutrition has become one of the most debated issues in the care of very low birth-weight (VLBW) infants. Current nutritional recommendations are based on healthy premature infants and designed to provide postnatal nutrient retention during the 'stable-growing' period equivalent to the intrauterine gain of a normal foetus. However, this reference is still a matter of discussion, especially in the field of the mineral requirements. After birth, there are dramatic physiological changes in bone metabolism resulting from various factors: disruption in maternal mineral supply, stimulation of calciotropic hormone secretion, change in hormonal environment and relative reduction in mechanical stress. These events stimulate the remodelling process leading to an increase in endosteal bone resorption and a decrease in bone density. In preterm infants, these adaptation processes modify the mineral requirement, since, by itself, the increased remodelling provides a part of the mineral requirement necessary for postnatal bone growth and turnover. The care of newly born premature infants should not necessarily aim to achieve intrauterine calcium accretion rates. CONCLUSION: Considering that a calcium retention level ranging from 60 to 90 mg/kg/day assures appropriate mineralization, and decreases the risk of fracture and diminishes the clinical symptoms of osteopenia, an intake of 100 to 160 mg/kg/day of highly bioavailable calcium salts, 60 to 90 mg/kg/day of phosphorus and 800 to 1000 IU of vitamin D per day is recommended.

Oral vitamin A, E and D supplementation of pre-term newborns either breast-fed or formula-fed: a 3-month longitudinal study.

BACKGROUND: In contrast to the studies of vitamin A and E status in children, adolescents and adults, information on preterm infants is scarce. In the present investigation we examined the vitamin A, D and E status of pre-term infants at birth, and verified whether, at 1 and 3 months, breast or formula feeding affected the plasma concentration of those vitamins while being supplemented with Uvesterol ADEC. PATIENTS AND METHODS: In this prospective study, 2 groups of consecutively recruited preterm newborns fed either breast milk or formula received 3000 IU of vitamin A, 5 IU of vitamin E and 1000 IU of vitamin D daily. Vitamin A and E were measured by high performance liquid chromatography and spectrophotometry. 25-hydroxyvitamin D, a surrogate marker for vitamin D status, was measured by radioimmunoassay, and retinol binding-protein concentration was measured by immunonephelometry. RESULTS: At birth, formula-fed and breast-milk fed infants had similar plasma concentrations of vitamin A (0.75 +/- 0.20 and 0.64 +/- 0.21 micromol/L, ns), 25-hydroxyvitamin D (34.4 +/- 25.6 and 47.5 +/- 26.7 nmol/L, ns) and vitamin E (9.5 +/- 3.2 and 8.4 +/- 3.3 micromol/L, ns). Vitamins A and E, and retinol binding-protein concentrations steadily increased with time in both groups of infants without attaining, at 3 months, values considered normal in term infants and in young children. At 3 months of age, concentrations of 25-hydroxyvitamin D reached values comparable to those observed in term infants. CONCLUSION: Plasma concentrations of vitamins A and E and of retinol binding-protein steadily increased during the the study without reaching full repletion values. At the conclusion of the study, the type of nutrition did not affect plasma vitamin concentrations.

Urinary excretion of cross-linked N-telopeptides of type 1 collagen to assess bone resorption in infants from birth to 1 year of age.

OBJECTIVES: To evaluate noninvasively bone resorption in infants and more specifically, to assess the accuracy of urinary collagen type 1 cross-linked N-telopeptide (NTX) excretion normalized to creatinine (NTX/Cr) in a spot urine sample as a reflection of daily NTX production in infants and to compute normative values for NTX excretion from birth to 1 year of age. METHODS: NTX/Cr values obtained from a single spot urine sample were compared with daily urinary NTX excretion and NTX/Cr obtained in 24-hour urine collected from 8 hospitalized infants. Normative values for NTX excretion were collated with a cross-sectional study in 70 healthy French infants (42 boys, 28 girls) aged 0 to 374 days (weight: 2700-11 340 g; length: 46-76.5 cm) and free of diseases or treatments that could influence growth, bone mineralization, or renal function. RESULTS: NTX/Cr values from single spot urine sample were significantly and linearly correlated with both daily NTX excretion (r = 0.783) and daily NTX/Cr (r = 0.952). In healthy infants, NTX excretion is low at birth, increases dramatically and significantly during the first 10 days of life, remains significantly elevated for approximately 3 months, and then decreases progressively to return to values similar to that observed at birth by 1 year of age. CONCLUSIONS: These data provide new insights regarding the use of spot urine analysis for assessing NTX excretion during the first year of life. The normative data demonstrate significant age-related variations in this marker, which probably reflect adaptation to extrauterine life and accelerated bone turnover in infancy and which should be considered for the interpretation of this noninvasive bone resorption marker in the clinical setting.

Influence of dietary cholesterol on vitamin d metabolism in formula-fed preterm neonates.

OBJECTIVES: Supplementation of preterm formulas with cholesterol could help to mimic the fat composition of human milk. However, this could possibly influence vitamin D 25-hydroxylation because this reaction is catalyzed in part by the mitochondrial cytochrome P-450, the enzyme responsible for the 27-hydroxylation of cholesterol. The purpose of this study was to verify whether the addition of cholesterol to preterm formulas could interfere with vitamin D metabolism in preterm neonates. METHODS: In a prospective study, 30 preterm neonates were randomly assigned to a low (< 0.03 g/L), medium (0.15 g/L), or high (0.30 g/L) cholesterol-content preterm formula until theoretical term (i.e., 40 weeks post-conceptional age). Anthropometric data and serum hydroxy-vitamin D and 1,25 dihydroxy-vitamin D concentrations were measured at study entry and theoretical term. In a subgroup of 14 subjects, serum cholesterol and lymphocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA were also assessed. RESULTS: (median [25, 75 centiles]): At theoretical term, there were no significant differences in serum hydroxy-vitamin D concentrations among the three groups, even after adjustment for confounding variables (65 [50, 78] nmol/L, 79 [59, 86] nmol/L, and 67 [43, 103] nmol/L, respectively, = 0.65) or 1,25 dihydroxy-vitamin D ( = 0.88). Furthermore, there were no significant differences in 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA copy numbers. CONCLUSIONS: In preterm neonates fed formulas with a cholesterol content similar to or higher than that of human milk, we did not observe deleterious effects on vitamin D metabolism. However, long-term effects of cholesterol supplementation require further studies.