[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.

Perinatal serum bone Gla-protein and vitamin D metabolites in preterm and fullterm neonates.

Whether the hypocalcemia often found in premature neonates results from an adaptation to extrauterine life or an expression of imbalanced mineral homeostasis has yet to be established. We compared serum levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25-(OH)2D], and bone Gla-protein (BGP), a specific marker of bone formation during the first month of life in fullterm and preterm neonates. Measurements were performed in cord blood and on days 1, 5, and 30 of life. In maternal blood, mean serum 1,25-(OH)2D concentrations were higher in the mothers of premature than in those of fullterm neonates, and serum BGP concentrations were lower than those in nonpregnant women. In cord blood mean serum BGP levels were 2-3 times higher than in adults. Serum BGP increased significantly on days 5 and 30 in fullterm infants. In preterm infants, and increase was found only on day 30. Mean serum 25-hydroxyvitamin D and 1,25-(OH)2D concentrations were lower in neonates than in mothers, but not different in fullterm and preterm neonates. In fullterm infants serum 1,25-(OH)2D increased rapidly from birth to day 5 and decreased on day 30. The pattern was similar in preterm infants, but 1,25-(OH)2D was higher than in fullterm infants on day 30. No sustained correlation between serum BGP and 1,25-(OH)2D levels was found. These data support the contention that changes in 1,25-(OH)2D reflect the perinatal equilibration of calcium homeostasis. Serum BGP may be a potential marker of bone growth in premature neonates.

Diabetes during pregnancy does not alter whole body bone mineral content in infants.

A previous study using single photon absorptiometry has reported low bone mineral density of the radius in infants of diabetic mothers. The aim of this study was to assess by dual x-ray absorptiometry the whole body bone mineral content (WbBMC) and the body composition of 40 infants of diabetic mothers at birth (mean gestational age +/- SD, 37.5 +/- 1.3 weeks; mean birth weight +/- SD, 3815 +/- 641 g). WbBMC was not correlated with gestational age, but was well correlated with birth weight (r = 0.73; P = 0.0001) and also with fat mass (r = 0.87; P = 0.0001) and lean mass (r = 0.42; P = 0.008). The z-scores +/- SD adjusted for weight for WbBMC and fat mass were significantly increased (1.3 +/- 0.9 and 2.6 +/- 1.3, respectively (P < 0.0001), but were not significantly influenced either by in utero growth or by the type of the diabetes mellitus of the mother. Bone mineralization and fat mass studied by whole body dual x-ray absorptiometry are increased at birth in these infants compared with reference curves.

Hypoparathyroidism during pregnancy: treatment with calcitriol.

A pregnant woman suffering from idiopathic hypoparathyroidism was treated with calcitriol [0.5-2 micrograms/day 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)]. Her twin infants were delivered by cesarian section at 37 weeks of gestation. Laboratory investigations in the perinatal period disclosed: 1) normal serum calcium and phosphorus levels in the mother, 2) normal babies with no clinical or biochemical signs of hyperparathyroidism, 3) a low serum level of 25-hydroxyvitamin D despite a normal serum level of 1,25-(OH)2D in the mother, and 4) a low level of 25-hydroxyvitamin D and a high level of 1,25-(OH)2D in cord serum in both infants. It is suggested that calcitriol is an effective treatment of hypoparathyroidism during pregnancy and produces no ill effects on the baby.

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.

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.

Dynamic histomorphometric evaluation of human fetal bone formation.

We have evaluated dynamic and static parameters of bone formation in femoral metaphyses collected from two human fetuses at 19 weeks of gestation. Tetracycline was administered to the mother at set intervals (2-5-2 day schedule) before interruption of pregnancy. Labels were distinct and sharply linear, suggesting a well organized calcification front at this early stage of mineralization. Mineral apposition rate (MAR) was fastest (4.1 +/- 0.3 microns/d) in the periosteal (Ps) envelope, and about half that value in the endosteal envelopes (endocortical: 2.5 +/- 0.1, cancellous 2.1 +/- 0.1 microns/d). Because cellular activities may vary throughout the metaphyseal area, sections were arbitrarily separated in 0.75 mm layers starting from the growth plate. Three measured parameters decreased rapidly with increasing distance from the physis: Ps MAR: 4.9 to 2.3 microns/d, trabecular osteoid thickness: 5.9 to 1.2 microns, and cartilage volume (CgV/TV): 5.4% to 1.2%. Others did not vary significantly along the metaphysis. Comparison of several static parameters with those measured in five autopsy specimens from full-term infants showed that bone and cartilage volume, and trabecular thickness increased while osteoid thickness and parameters of resorption decreased in the second half of the gestation period. The study indicates that fetal bone matrix mineralization is already highly organized at mid-gestation, and validates the use of histomorphometry to assess bone maturation during early skeletal development.

Human fetal bone development: histomorphometric evaluation of the proximal femoral metaphysis.

Quantitative data on metaphyseal bone histology during early human development are scarce. In the present study the proximal femoral metaphysis of 35 fetuses and newborns (gestational age 16-35 weeks) was analyzed by histomorphometry. Averaged over the entire metaphyseal area, the relative amount of bone and cartilage was higher in the third compared to the second trimester. Osteoid thickness increased with gestational age, whereas indices of bone resorption decreased. The relative amount of cartilage decreased with increasing distance from the growth plate, whereas the relative amount of bone increased. This was due to trabecular thickening, which occurred at an estimated rate of 3 microm/day in areas close to the growth plate. Despite this rapid rate of net bone gain, osteoid indices were relatively low, indicating that mineralization occurred very rapidly after bone deposition. These observations suggest that modeling, not remodeling, is the predominant mechanism responsible for the development of femoral metaphyseal cancellous bone in utero.

An analysis of the microbial flora of premature neonates.

An analysis of the microbial flora of 10 premature neonates hospitalized in a neonatal intensive care unit (NICU) was made. The babies had received neither antibiotics nor antiseptics and nine out of 10 were born by caesarean section. Samples were collected on the fourth or fifth day of life from 18 skin or mucosal sites. Detailed bacterial counts were obtained by plating out suitable dilutions of the samples on to selective media. Representative samples of each colony type were then subcultured and identified, using standard laboratory methods. Two hundred and fifty-six isolates of staphylococci were obtained and their susceptibility to 23 antibiotics tested. Only 11% of the samples were sterile. Coagulase-negative staphylococci (CNS) were the commonest species isolated and were predominant in every site studied. They were found in 79% of the samples and represented almost 81% of the neonates' flora. Eight species and biotypes of CNS were identified. In decreasing order of frequency, they comprised S. epidermidis (biotypes 1 and 2), S. hominis (biotype 1), S. warneri, S. haemolyticus, S. capitis, S. cohnii and S. hominis (biotype 2). CNS distribution appeared to be highly heterogeneous with no significant specificity of any species for a particular body site. The main quantitative and qualitative variations seemed to relate to the method of delivery, and the intensity and nature of exposure of the neonate to its local environment. A high level of antibiotic resistance was found among the CNS isolates (especially S. epidermidis and S. haemolyticus): penicillin G (96%), oxacillin (31%), erythromycin (52%) and gentamicin (28%). Moreover, multiresistant strains were numerous, supporting the nosocomial origin of CNS.

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.

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.

Methods for measuring body composition in newborns--a comparative analysis.

The complexity of nutritional support in infants now makes it necessary to use body-composition methods for accurate nutritional assessment. For this goal a variety of methods of determining body composition have been introduced in research on human nutrition. The purpose of this paper is to review the background and to describe the precision of established techniques, focusing on the results obtained in newborns and infants. The ideal method for assessing newborns' and infants' body composition should be non-invasive, reproducible, accurate, and also relatively inexpensive. In addition, we summarize in this paper data on body composition obtained in normal and pathological newborns by using dual X-ray absorptiometry, one of the reference techniques.

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)

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.

Metabolic and energy balance in small- and appropriate-for-gestational-age, very low-birth-weight infants.

This study compared nutrient utilization and postnatal weight gain composition in eight appropriate for gestational age (AGA: birth weight 1293 +/- 107 g; gestational age 28.8 +/- 1.4 weeks) and eight symmetrically growth-retarded (SGA: birth weight 1110 +/- 230 g; gestational age 32.7 +/- 1.9 weeks), very low-birth-weight (VLBW) infants. There was no significant difference in protein, mineral and energy intake between AGA and SGA infants. Nitrogen absorption (84 +/- 3 and 83 +/- 4%) and nitrogen retention (356 +/- 48 and 352 +/- 43 mg/kg/day) were similar in both groups. Fat absorption tended to be lower in AGA (78 +/- 15%) than in SGA (87 +/- 4%) infants. Calcium, phosphorus and magnesium absorptions were similar in AGA and SGA infants. Metabolizable energy utilization was similar in both groups; about 55% was expended and 45% stored in new tissues. Energy expenditure was 58 +/- 4 kcal/kg/day in SGA infants and 61 +/- 9 kcal/kg/day in AGA infants. Weight gain and its composition were similar in both groups. We conclude that nutrient and energy utilization are similar in AGA and symmetrically growth-retarded, VLBW infants.

Aetiology, morphology and body composition of infants born small for gestational age.

Infants born small for gestational age (SGA) are a heterogeneous group. Both the timing and duration of the intrauterine insult determine the physical condition and body composition of the infant at birth. Infants with symmetrical intrauterine growth retardation (IUGR) have a similar body composition at birth to weight-matched infants born appropriate for gestational age. However, these infants are more likely to remain shorter and lighter than normal infants. In contrast, infants with asymmetrical IUGR have reduced fat deposition but are more likely to exhibit catch-up growth during the first few months of life. The low mortality and morbidity rates in infants born SGA observed in recent studies are linked to their appropriate perinatal management, including adequate early nutritional support.

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)

[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.

[New technique of nasal continuous positive pressure in neonatology]. / Nouvelle technique de pression positive continue par voie nasale en néonatologie.

BACKGROUND: Early treatment with nasal continuous positive airway pressure (CPAP) in newborns with respiratory distress syndrome is useful, by recruiting alveoli and restoring the functional residual capacity. POPULATION AND METHODS: Nasal CPAP was supplied by the Infant Flow Driver (Electro Medical Equipment). From 15 June 1994 to 15 December 1994, 42 neonates received nasal CPAP. Their mean birthweight and gestational age were 1511 +/- 411 g and 30.9 +/- 2.5 weeks, respectively. Fifteen infants had been ventilated for hyaline membrane disease and nasal CPAP was applied immediately after extubation. In the other 27 infants, nasal CPAP was given soon after birth (respiratory distress syndrome: 20 neonates; apneic spells: seven neonates). RESULTS: Three infants needed subsequent mechanical ventilation because of the severity of the disease (one had spontaneous pneumothorax); four infants received exogenous surfactant (Curosurf, one single dose) within a brief period of mechanical ventilation (30-45 min). There were no failure of extubation, and no intracranial lesions. Excess of pharyngeal secretion and abdominal distension were common. CONCLUSION: Early treatment with nasal CPAP reduces the need for mechanical ventilation. Furthermore, surfactant therapy required by a moderate to severe disease is possible with a rather short period of artificial ventilation.