[Is it justifiable to administrate vitamin A, E and D for 6 months in the premature infants?]. / Est-il légitime d'administrer des vitamines liposolubles (A, E et D) chez le prématuré pendant 6 mois?

UNLABELLED: Information on the vitamin A and E nutritional status in preterm infants is scarce. POPULATION AND METHODS: In the present prospective and longitudinal study, we measured the plasma concentrations of vitamins A, E, D and of retinol binding protein (RBP) in preterm infants (32-34 weeks of gestation) at birth, and verified whether oral supplementation with these 3 vitamins for 1, 3 and 6 months affected their plasma concentrations. The 17 consecutively recruited premature infants received daily 3000 IU of vitamin A, 5 mg of vitamin E and 1000 IU of vitamin D. RESULTS: At birth, premature infants exhibited a low plasma concentrations of vitamin A (0.66 [0.41-0.96]) micromol/l, vitamin E (8.1 [4.2-16.9] micromol/l), RBP (0.45 [0.22-0.71] micromol/l) and 25 hydroxyvitamine D (25 OHD) (20 [20-40] nmol/l). Plasma vitamin A, E , D and RBP concentrations increased with time, but vitamin A at 1, 3 and 6 months did not attain values considered normal in term infants or adolescents. At 6 months, the plasma 25 OHD was at 92 (71-116) nmol/l, a concentration considered normal and non-toxic. CONCLUSION: We recommend to increase oral administration of vitamin A to 5000 IU/day, at least for the first month of life and, thereafter to administer 3000 IU for 5 months. As for vitamin E and vitamin D, the doses used in this study are sufficient but should be administered for 6 months.

[Fat-soluble vitamins in infants]. / Vitamines liposolubles chez le nourrisson.

Vitamins are micronutrients not synthesised by the human body and should be provided by the nutrition. Liposoluble vitamins include vitamins A, E, D and K. Vitamins A and E are two potent antioxidant nutrients and play a significant role in immune function. Vitamin D plays a major role in intestinal calcium absorption and bone mineralization. Vitamin K intervenes in the synthesis of coagulation factors particularly in the prothrombin synthesis. Vitamin metabolism, placental transfer, vitamin status in newborns and infants are reported. Finally requirements of these vitamins are defined.

The use of low-EPA fish oil for long-chain polyunsaturated fatty acid supplementation of preterm infants.

Because docosahexaenoic acid (DHA) may be an essential nutrient for the visual and early cognitive development of preterm infants, DHA enrichment of preterm formulas has been recommended. This randomized trial was designed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a standard formula. A reference group of breast-fed infants was studied concurrently. The fatty acid content of red blood cell (RBC) phospholipid was assessed at enrollment, hospital discharge, expected term, and 3 and 6 mo postterm. The DHA content of RBC phospholipid was higher in infants fed the enriched versus the standard formula at hospital discharge, expected term, and 3 and 6 mo postterm. However, compared with infants fed the standard formula, infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content (0.69 +/- 0.15% versus 0.25 +/- 0.12%, p < 0.001), and lower RBC phospholipid arachidonic acid content (15.1 +/- 0.93% versus 18.8 +/- 0.89%; p < 0.001). We conclude that supplementing preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status, but results in worsening of n-6 fatty acid status. We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved.

Perinatal metabolism of vitamin D.

During pregnancy, maternal serum concentrations of 25-hydroxyvitamin D, the circulating form of vitamin 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-dihydroxyvitamin D is synthesized mainly by the decidual cells of the placenta and allows for increased calcium absorption. The fetus is entirely dependent on the mother for its supply of 25-hydroxyvitamin D, which is believed to cross the placenta. Hypocalcemia and increased parathyroid hormone secretion induce synthesis of 1,25-dihydroxyvitamin D after birth in both full-term and preterm neonates. Nevertheless, serum concentrations of 25-hydroxyvitamin D are a rate-limiting factor in the synthesis of 1,25-dihydroxyvitamin D. In vitamin D-replete infants, circulating 1,25-dihydroxyvitamin D concentrations are higher than those observed in older infants. In countries where dairy products are not routinely supplemented with vitamin D, maternal vitamin D supplementation during pregnancy is necessary. However, there is no indication for the use of pharmacologic doses of vitamin D or its metabolites in the perinatal period.

Bone mineral metabolism in the micropremie.

Environmental factors, nutritional supplies, hormonal status, diseases, and treatments appear to affect postnatal skeletal growth and mineralization in VLBW infants. Compared with their term counterparts, ELBW infants are at risk of postnatal growth deficiency and osteopenia at the time of hospital discharge. From recent data, DXA is becoming one of the reference techniques to evaluate mineral status, whole-body composition, and effects of dietary manipulations on weight gain composition and mineral accretion in preterm infants. Weight gain and length increases need to be evaluated carefully during the first weeks of life, in the intensive care unit and out of it, in the step down unit. Nutritional survey is required to improve the nutritional supply and to maximize linear growth. As the critical epoch of growth extends, during the first weeks or months after discharge, follow-up and nutritional support need to be provided during the first years to promote early catch-up growth and mineralization. Further studies need to determine precisely the most optimal feeding regimen during this period but also need to evaluate the long-term implications of such a policy on stature, peak bone mass, and general health at adulthood.

Erythrocyte fatty acid composition in term infants fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months.

UNLABELLED: When term infants are fed standard formula that does not contain long-chain polyunsaturated fatty acids (LC-PUFA), they still show lower levels of docosahexaenoic acid (DHA) in red blood cell (RBC) phospholipids by several weeks or months postnatally. This study was designed in order to evaluate a potential alternative for supplementing term infant formulas with DHA by adding a high-DHA/low-eicosapentanoic acid fish oil to levels similar to that in human milk (0.3%). A total of 37 term infants were included in the study at 3 days of life. DHA concentrations remained stable between inclusion and 4 months of life at around 8% of the RBC phospholipids in the LC-PUFA enriched formula-fed group whereas it decreased significantly in the standard formula-fed group. In the human milk-fed group, RBC DHA concentrations at 4 months of age were significantly lower than that at birth and were significantly correlated with the duration of breast feeding (r = 0.85; P = 0.0002). A significant decrease of arachidonic acid between inclusion and 4 months of age was observed in the enriched formula-fed group and reached a mean value at 4 months, which was significantly lower than that observed in the human milk or standard formula-fed groups (P<0.0001). CONCLUSION: Supplementing term formulas with a high-docosahexaenoic acid/low-eicosapentanoic acid fish oil up to 4 months of age is efficient in improving docosahexaenoic acid status, however it increases the risk of impaired n-6 fatty acid status.

Vitamin A and E supplementation in breast-fed newborns.

BACKGROUND: Vitamins A and E are two potent antioxidant nutrients that play a significant role in immune function. In contrast to the numerous studies of vitamin A and E status in children, adolescents, and adults, information on term infants, particularly breast-fed infants, is scarce. The goals of the present investigation were to examine the vitamins A and E nutritional status of term breast-fed infants at birth and to assess retinol and tocopherol plasma levels during a 3-month supplementation trial. METHODS: The study was a prospective, blinded comparison of a supplementation protocol with a placebo in a group of consecutively recruited term newborns. The supplemented group received 3000 IU vitamin A and 5 IU vitamin E orally. The placebo group received a solution of similar viscosity and organoleptic characteristics. Vitamin A and E were separated by reverse-phase high-performance liquid chromatography on a C18 Spectrasyl column and quantified by ultraviolet spectrophotometry. RESULTS: Vitamin A and E levels steadily increased with age in both groups of infants. However, levels at 3 months were higher in the supplemented than in the control group. CONCLUSION: The data show that supplementation with 3000 IU vitamin A and 5 IU vitamin E for 3 months increases circulating vitamin levels in newborn term babies compared with those in nonsupplemented infants.

[Iron supplementation in preterm infants treated with erythropoietin]. / Supplémentation en fer chez les enfants prématurés traités par érythropoïétine.

Anemia in premature infants can be prevented by prophylactic treatment with recombinant human erythroprotein (r-huEPO). r-HuEPO as been used for a long time in patients with end-stage renal failure. The main factor which can limit r-HuEPO efficiency is limited iron bioavailability. Adapted iron supplementation is needed when preterm infants receive r-HuEPO in order to avoid the depletion of iron stores. Oral iron supplementation is simple but indigestibility is frequent. Furthermore, the intestinal absorption and utilization of oral iron is limited. Parenteral iron supplementation is possible in infants who are very pre-term as they are parenterally fed during the first weeks of life. There are various preparations of intravenous iron with different physicochemical properties. Toxicity and side-effects of parenteral iron preparations depend on these properties. Two parenteral iron preparations are available in France: iron-saccharate (Venofer) and iron-dextrin (Maltofer). Iron delivery and possible side-effects of these preparations are different and need to be considered before use in preterm infants.

High-versus low-dose erythropoietin in extremely low birth weight infants. The European Multicenter rhEPO Study Group.

OBJECTIVE: To investigate whether a weekly 1500 IU/kg dose of recombinant human erythropoietin (rhEPO) is more effective than a dose of 750 IU/kg/week in preventing anemia and reducing the transfusion need in infants with birth weights less than 1000 gm. STUDY DESIGN: In a randomized, double-blind, multicenter trial, 184 infants with birth weights between 500 and 999 gm were treated with either rhEPO 750 (low-dose group) or 1500 IU/kg/week (high-dose group) from day 3 of life until 37 weeks' corrected age. RESULTS: Thirty-two percent of the infants in each group did not receive any transfusion during the treatment period. The total volume of erythrocytes received was similar in each group. The success rate, defined as no transfusion needed and hematocrit value 0.30 L/L or greater, was 27.6% in the low-dose and 29.5% in the high-dose group (p = 0.96). CONCLUSION: Doubling the rhEPO dose of 750 IU/kg/week is not indicated in infants with birth weights less than 1000 gm.

Nutritional evaluation of protein hydrolysate formulas.

Growth parameters, biochemical indice of protein metabolism and plasma Amino acid (AA) concentrations were investigated during the first month of life in term infants (n = 61) fed various protein hydrolysate formulas (whey (WHF, n = 3), soy collagen (SCHF, n = 1) and whey-casein hydrolysate formulas (WCHF, n = 1)). In addition, metabolic balance studies were performed in 10 infants fed WHF and in 5 fed WCHF. Comparatively to breast fed infants, growth reduction and decrease in plasma protein concentrations were observed with the use of one of the WHF and in a lesser extent with the SCHF and the WCHF. Plasma amino acid pattern reflected the AA content of the formulas. Whey hydrolysate formulas induced mainly an increase in threonine and a decrease in tyrosine concentrations. Soy-collagen hydrolysate formula led to an increase of non-essential amino acids, such as glycine and hydroxyproline and a decrease in plasma lysine and cystine. Whey-casein hydrolysate formula induced a plasma amino acid pattern close to the profile observed in breast fed infant. Metabolic balance studies showed a relative reduction in nitrogen absorption and utilisation in the infants fed the WHF and the WCHF. In addition a drastic reduction in fat, calcium and phosphorus absorption was also observed with the use of the WCHF. In preterm infants (n = 19) fed whey predominant hydrolysed preterm formulas (n = 3), metabolic balance studies an plasma AA concentration were evaluated at the end of the first month of life at 34 weeks of gestation age. Comparatively to similar preterm infants fed conventional preterm formulas, a relative reduction in nitrogen absorption (83% vs 90%) and retention (64 vs 70%) as well as in phosphorus absorption (78 vs 89%) was observed. Calcium retention was similar (48 vs 45 mg/kg/d) but calcium intake was significantly higher in infants fed hydrolysate formulas 120 vs 91 mg/kg/d. Plasma amino acid concentrations were related to amino acid composition of the formulas. Compared with the standard preterm formulas, all three protein hydrolysate formulas led to a significant increase in plasma threonine and a decrease in tyrosine and phenylalanine concentrations. In addition, there was a reduction in plasma histidine, valine, leucine, cystine, methionine and/or tryptophane with some of the hydrolysate formulas used. In conclusion, these studies provide evidence that protein hydrolysed formulas are not equivalent to whole protein formulas in terms of nutritional efficiency for preterm and term infants. Therefore further extensive nutritional studies on growth, biochemical indices of protein metabolism and metabolic balance, including minerals and trace elements, appear to be necessary before maintaining and promoting the use of such formulas for teh potential benefits on atopic disease in preterm and in full-term newborn infants.

Mineral balance and whole body bone mineral content in very low-birth-weight infants.

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants (< or = 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100 mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65 +/- 14 and 62 +/- 9 mg/kg/day versus 55 +/- 12 and 47 +/- 7 mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5 +/- 0.4 g/kg/day and 88 +/- 4% versus 4.2 +/- 1 g/kg/day, 79 +/- 6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3 +/- 30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6 +/- 36.6 g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Red blood cell fatty acid composition in low-birth-weight infants fed either human milk or formula during the first months of life.

The fatty acid composition of red blood cell (RBC) phospholipids in low-birth-weight infants was determined immediately after delivery and during the first 3 months of life. In the first study, infants were fed either human milk or two formulas with different fatty acid compositions but no long chain polyunsaturated fatty acids (LCPUFA). Both groups of formula-fed infants had significantly lower levels of docosahexaenoic acid (DHA) in RBC phospholipids compared with breast-fed infants. RBC phospholipid DHA was similar in the two formula groups at all ages. In the second study, infants received either a non-supplemented or a LCPUFA-supplemented formula. DHA remained stable in RBC phospholipids of infants supplemented with LCPUFA, whereas DHA decreased in RBC phospholipids of unsupplemented infants. These results confirm that adding DHA to formulas is more effective than increasing 18:3 n-3 content, in maintaining RBC phospholipid DHA levels.

Nutritional evaluation of various protein hydrolysate formulae in term infants during the first month of life.

The aim of the study was to compare, during the first month of life, growth parameters, biochemical indices of protein metabolism and plasma amino acid concentrations in newborn infants fed either human milk (n = 23), three different whey hydrolysate formulae (WHF 1, n = 13; WHF 2, n = 10; WHF 3, n = 13), a soy-collagen hydrolysate formula (SCHF n = 18) or a whey-casein hydrolysate formula (WCHF, n = 20). Growth parameters and the various protein concentrations determined in the infants fed WHF 1 and WHF 2 were similar to the values observed with human milk. With WHF 3, growth in weight, length and head circumference and serum total protein concentrations were reduced significantly whereas blood urea nitrogen was increased. With SCHF, growth in weight and length as well as serum total protein and transferrin concentration were decreased significantly, whereas serum IgG concentration was increased. With WCHF growth in length and serum transferrin concentration were decreased compared to the human milk group. In the various groups, the plasma amino acid pattern reflected the amino acid content of the formula. Whey hydrolysate formula induced mainly an increase in threonine and a decrease in tyrosine concentrations. Soy-collagen hydrolysate formula led to an increase of non-essential amino acids, such as glycine and hydroxyproline, and a decrease in plasma lysine and cystine. Whey-casein hydrolysate formula induced a plasma amino acid pattern close to the profile observed with human milk. Nevertheless, the plasma concentrations of most of the various amino acids were higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Net calcium absorption in premature infants: results of 103 metabolic balance studies.

Net calcium absorption was evaluated in 103 low-birth-weight preterm infants by a 72-h balance technique. At birth the infants had a mean (+/- SE) gestational age of 30.9 +/- 0.2 wk and weighed 1.43 +/- 0.03 kg. When tested 3 wk later, their net calcium absorption averaged 58 +/- 1% with an intake of 80 +/- 2 mg Ca.kg body wt-1.d-1. Of the 103 infants, 58 had been fed low-birth-weight formulas supplemented with vitamin D. The remainder received banked human milk, of whom 34 were supplemented with vitamin D and calcium; 11 infants received no supplementation. Calcium absorption in the four subgroups did not differ significantly, with neither vitamin D supplementation nor supplementation with vitamin D and calcium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-130 mg Ca.kg body wt-1.d-1) with a zero intercept. Because vitamin D supplementation did not increase net calcium absorption, it is concluded that in preterm low-birth-weight infants calcium absorption proceeds by a nonsaturable route, with the transcellular, vitamin D-regulated mechanism not yet expressed.

[Late neonatal hypocalcemia. Apropos of 33 cases treated with 1 alpha-hydroxycholecalciferol]. / Etude de l'hypocalcémie néo-natale tardive. A propos de 33 observations traitées par le 1 alpha-hydroxycholécalciférol.

Thirty-three observations of late-onset neonatal hypocalcemia were reviewed retrospectively. Their etiological, clinical and biological features were consistent with a transient congenital hypoparathyroidism, associated with a materno-foetal vitamin D deficiency. 1 alpha-hydroxycholecalciferol was used for rapid correction of calcemia and proved to be satisfactorily metabolized after its oral administration.

Vitamin D metabolism in preterm infants.

Perinatal metabolism of vitamin D was studied in premature babies with the aim of: (1) reporting the relationship between the pregnant mother and her preterm infant and the metabolism of vitamin D during the first weeks of life, and (2) assessing the effect of vitamin D metabolites on phosphorus calcium and magnesium intestinal absorption. There was only a positive correlation between plasma cord calcium and 25-hydroxyvitamin D levels and the mother's plasma levels at birth. During the hypocalcemic episode observed during the first week of life, vitamin D activation did occur, but later on rickets or osteomalacia cannot be due to the low levels of vitamin D metabolites in the preterm receiving an adequate dose of vitamin D (1,000-1,200 IU of D2). Calcitriol, the major metabolite of vitamin D, is acting on the intestine and promotes calcium absorption even in very tiny prematures. The pathogenesis of hypomineralization in the preterm infant is due to the low intake of calcium or phosphorus and/or poor absorption of calcium in the case of vitamin D deficiency.

Vitamin D supplementation during pregnancy: effect on neonatal calcium homeostasis.

We assessed whether modification of vitamin D nutritional status during the last trimester of pregnancy affects maternal and neonatal calcium homeostasis. At the end of the first trimester, 40 pregnant women were randomly assigned to either of two groups, and blood taken to assess the basal values of Ca, Pi, Mg, iPTH, 25-OHD, and 1,25(OH)2D. From the sixth month on, group 1 (+D) received 1000 IU vitamin D3 daily; group 2 (-D) served as control. At the time of delivery, maternal serum 25-OHD was higher in the +D group (P less than 0.0005). Ca, Pi, iPTH, and 1,25(OH)2D were not affected. At term, venous cord 25-OHD levels were also higher in the +D group (P less than 0.0005), and 1,25(OH)2D levels slightly lower (P less than 0.05), but neither Ca, Pi, nor iPTH differed between the two groups. Serum CaT dropped significantly (P less than 0.002) at 4 days of age in the infants from both groups, although to a lesser extent in these from the +D group (P less than 0.05). Circulating iPTH increased in both groups. Serum 25-OHD remained low in the -D group, and dropped slightly in the +D group; 1,25(OH)2D remained stable during the first 4 days of life in the -D group, and increased in the +D group (P less than 0.001). Our data demonstrate the importance of providing adequate maternal vitamin D stores to ensure better perinatal handling of calcium. This is of particular importance for populations at risk for hypovitaminosis D.