Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial.

OBJECTIVES: Infants of

Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants. The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials. METHODS: We performed a multicenter, blinded, randomized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth. The mean birth weight was 770 g in the vitamin A group and 769 g in the control group, and the respective gestational ages were 26.8 and 26.7 weeks. RESULTS: By 36 weeks' postmenstrual age, 59 of the 405 infants (15 percent) in the vitamin A group and 55 of the 402 infants (14 percent) in the control group had died. The primary outcome - death or chronic lung disease at 36 weeks' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group (55 percent vs. 62 percent; relative risk, 0.89; 95 percent confidence interval, 0.80 to 0.99). Overall, 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements. The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar. The proportion of infants with serum retinol values below 20 microg per deciliter (0.70 micromol per liter) was lower in the vitamin A group than in the control group (25 percent vs. 54 percent, P<0.001). CONCLUSIONS: Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants.

Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network.

OBJECTIVE: Inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia have been reported. Meta-analysis of these reports resulted in a relative risk of 0.69-1.02 for death or bronchopulmonary dysplasia associated with vitamin A supplementation. Effective dosage regimens or serum retinol concentrations have not been determined in previous reports. The purpose of this pilot study was to define a vitamin A regimen that produces serum retinol concentrations of 25-55 micrograms/dl. STUDY DESIGN: In this three-phase study, 91 infants (mean birth weight 799-864 g) were enrolled. Vitamin A was administered three times/week for 4 weeks at an average daily dose of 986-2143 IU/day. Physical examinations were performed and serum retinol specimens were collected weekly to assess clinical signs of toxicity. RESULTS: The majority of serum retinol concentrations remained < 25 micrograms/dl until an intramuscular vitamin A dose of 5000 IU/dose three times/week was used. No clinical signs of toxicity were associated with the higher dosage and higher serum concentrations of vitamin A. CONCLUSION: A large clinical trial of vitamin A supplementation with 5000 IU/dose three times/week (25-114% more than the dose used in the three published clinical trials) is needed to assess whether vitamin A supplementation safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight infants.

Composition of the fetal and maternal guinea pig throughout gestation.

The guinea pig is a small animal species in which the conceptus constitutes a large proportion of maternal weight at term, thereby imposing a major metabolic demand on the mother during pregnancy. In addition the neonatal fat concentration is similar to the human making the guinea pig an interesting model for comparative physiologic study. The purpose of our study was to describe the fetal and maternal physical/chemical growth characteristics of the Hartley albino guinea pig throughout the latter half of gestation. Forty-eight pregnant adult and 122 fetal guinea pigs were sacrificed at intervals throughout gestation and the carcasses analyzed for a variety of growth parameters. The fetal growth rate during the last 8 days of gestation (5.8 g/day) was 9.7 times faster than from 30 to 40 days of gestation (0.6 g/day). The fetal mass comprised 55.4% of the maternal weight gain at term. Fetal energy increased from 403 cal/g at 30 days to 1950 cal/g at term and was paralleled by an increase in fetal fat concentration from 0.3 to 9.8% (wet weight). Nitrogen concentration increased from 0.9% wet weight at 30 days to 2.6% at term. An increasing carbon concentration and carbon:nitrogen ratio was also evident. Fetal water concentration declined from 91.6 to 67.8% during latter gestation. On a wet weight basis, the concentration of fetal sodium remained stable throughout the latter half of pregnancy; potassium, magnesium, iron, calcium, and phosphorus concentrations increased. In contrast to the changes in fetal composition, maternal energy, fat, protein, water, sodium, potassium, calcium, phosphorus, magnesium, and iron concentrations remained relatively constant throughout pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum vitamin E levels in the very low birth weight infant during oral supplementation.

A prospective study was initiated to monitor serum tocopherol levels in all infants admitted to Indiana University Medical Center with birth weights less than 1,500 g. These infants routinely receive 100 mg/kg/d of oral vitamin E (Aquasol E tocopherol acetate) every six hours. Levels are determined weekly or semiweekly using a modification of the fluorometric method of Hanson and Warwick. Vitamin E dosage is adjusted regularly to achieve levels greater than or equal to 3.5 mg/dL. During the 6 months of this study, a total of 76 patients had 567 serum measurements. Of these, 220 levels (38%) were greater than or equal to 3.5 mg/dL, 71 (13%) were greater than or equal to 5.5 mg/dL, and 15 (2.7%) were greater than 8 mg/dL. Serum tocopherol levels often (1) remained greater than or equal to 3.5 mg/dL for several days after oral supplementation was discontinued or (2) again became greater than or equal to 3.5 mg/dL on a reduced dosage of 25 to 50 mg/kg/d. These data indicate that infants weighing less than 1,500 g at birth who are receiving oral vitamin E supplementation at 100 mg/kg/d will have varied serum levels with a significant percentage exceeding 3.5 mg/dL.

Breast-feeding the premature infant.

Although some controversy persists regarding the nutritional adequacy of breast milk for the very low birth weight infant, most authorities agree that milk expressed from the infant's biologic mother and fortified with additional minerals and protein is a proper source of nutrition. Proper support of the preterm infant and mother during expression of breast milk and during the transition to nursing requires a broad knowledge base and familiarity with the practical aspects of breast-feeding.

Nitrogen sources for parenteral nutrition in the newborn infant.

Protein requirements for the preterm and term infant have been determined by a variety of methods. The parenteral protein needs of the very low birth weight infant are around 3 gm/kg/day and of the term infant approximately 2.2 gm/kg/day for maintenance of normal growth. These values are averages and may need to be modified for individuals depending upon a variety of potentially complicating factors. In this regard, many neonatologists recommend the provision of a maximum of 2 to 2.5 gm/kg/day of protein to newborns under most clinical situations. Whereas excessive administration of protein may result in adverse consequences, the tolerance of young infants to infusion of amino acid solutions is not well defined. Based upon animal studies of fetal amino acid utilization, the preterm infant may be capable of appropriately modifying its supply of amino acids over a relatively broad concentration range. It would appear that the supply of individual amino acids is adequately met by a number of amino acid solutions. The newer preparations appear to be more ideally suited to the special needs of the very low birth weight.

Formulas and human milk for premature infants: a review and update.

New methods of feeding low-birth-weight infants have been developed as a result of improved knowledge concerning the nutritional requirements of the premature infant. Breast milk may offer certain nutritional and non-nutritional advantages for immature babies. Preterm milk is theoretically more appropriate than term or pooled mature breast milk. However, some nutrients may be inadequate to support intrauterine rates of growth in small premature infants. New formulas specifically designed for preterm babies appear to be safe and to promote improved weight gain, fat absorption, bone mineralization, and nitrogen retention. Nutritional needs of growing preterm infants are better met by preamture formulas than by formulas designed for term babies.

Differences in the composition of preterm and term human milk during early lactation.

The composition of human milk from mothers delivering prematurely (PT) and at term (T) was studied over the first weeks of lactation. Complete 24 h milk expressions were obtained by electric pump at weekly or biweekly intervals through 44 wk conceptual age (120 samples from 20 PT mothers and 28 samples from 7 T mothers). PT milk was found to contain significantly higher concentrations than T milk of the following nutrients: total nitrogen, protein nitrogen, sodium, chloride, magnesium and iron. No differences were found between T and PT milk for nonprotein nitrogen, volume, solids, total calories, lactose, fat, fatty acids, potassium or calcium. The nutrients supplied to a 33 wk preterm infant fed 200 ml/kg/day of "average" PT milk were in excess of theoretic intrauterine requirements for all substrates except calcium and phosphorus. PT human milk is theoretically more suitable for the premature infant than either mature or term human milk, but may be deficient in specific nutrients for the very low birth weight baby.