Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study.

OBJECTIVE: To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development. DESIGN: A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at

Nutritional follow-up of the breastfeeding premature infant after hospital discharge.

In summary, fortification of human milk may be beneficial in preterm infants, particularly those born at less than 34 weeks' gestation or less than 1800 g birth weight, during and after initial hospitalization. This fortification after hospital discharge is more crucial for infants who cannot consume ad libitum quantities of breast milk, have poor growth, or have abnormalities in the biochemical screen of nutritional status. Although data indicate that in-hospital, short-term gains in growth and mineral status are achieved, information is fragmentary regarding the influence on long-term growth and neurodevelopmental outcomes of feeding supplemented human milk. Also, no data are available on outcomes when providing these mixtures to premature infants after hospital discharge. It is recommended that a nutritional survey be accomplished before and approximately 1 month after discharge and that fortification or supplementation be initiated if an infant is failing to achieve normal growth and biochemical measures of nutrition.

Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge.

OBJECTIVE: At hospital discharge, preterm infants may have low body stores of nutrients, deficient bone mineralization, and an accumulated energy deficit. This double-blind, randomized study evaluated the growth of premature infants with birth weights <1800 g who were fed a 22 kcal/fl oz nutrient-enriched postdischarge formula (PDF) or a 20 kcal/fl oz term-infant formula (TF) from hospital discharge to 12 months' corrected age (CA). METHODS: Infants were randomized to PDF or TF a few days before hospital discharge with stratification by gender and birth weight (<1250 g or >/=1250 g). The formulas were fed to 12 months' CA. Growth was evaluated using analysis of variance controlling for site, feeding, gender, and birth weight group. Interaction effects were also assessed. Secondary analyses included a repeated measures analysis and growth modeling. RESULTS: One hundred twenty-five infants were randomized; 74 completed to 6 months' CA and 53 to 12 months' CA. PDF-fed infants weighed more than TF-fed infants at 1 and 2 months' CA, gained more weight from study day 1 to 1 and 2 months' CA, and were longer at 3 months' CA. There were significant interactions between feeding and birth weight group-among infants with birth weights <1250 g, those fed PDF weighed more at 6 months' CA, were longer at 6 months' CA, had larger head circumferences at term 1, 3, 6, and 12 months' CA, and gained more in head circumference from study day 1 to term and to 1 month CA. The repeated measures and growth modeling analyses confirmed the analysis of variance results. The PDF formula seemed to be of particular benefit for the growth of male infants. Infants fed the PDF consumed less formula and had higher protein intakes at several time points. Energy intakes, however, were not different. CONCLUSIONS: Growth was improved in preterm infants fed a nutrient-enriched postdischarge formula after hospital discharge to 12 months' CA. Beneficial effects were most evident among infants with birth weights <1250 g, particularly for head circumference measurements.

Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial.

OBJECTIVE: A prospective, double-blind, randomized, controlled trial was conducted to evaluate the growth and nutritional status of preterm infants receiving preterm human milk supplemented with a newly formulated powdered human milk fortifier (HMF), study fortifier (SF), or a powdered commercial HMF (CF). METHODS: Infants (n = 144) with a birth weight

Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study.

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants < 7 d old were randomized to be fed formulas containing linoleic acid (approximately 10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP within approximately 10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.

Salt supplementation, growth, and nephrocalcinosis in the furosemide-treated weanling rat.

OBJECTIVE: Furosemide treatment in the human neonate is associated with sodium depletion, growth retardation, hypercalciuria and nephrocalcinosis. Dietary sodium intake is known to directly influence urinary calcium excretion. The objectives of this study were to create a rat model of furosemide-induced nephrocalcinosis and to test the effects of dietary sodium supplementation on growth, electrolyte balance, calciuria, and renal calcifications. METHODS: Initially, 18 weanling Sprague-Dawley rats were randomly divided into three groups. Groups A (control) and B were fed a basal diet. Group C was fed a sodium-enriched diet. Groups B and C received furosemide (40 mg/kg) intraperitoneally daily for 28 days. At the end of the study, serum, urine, and kidney samples were obtained for biochemical and histologic analyses. The three groups were then compared for differences in growth, electrolyte homeostasis, calcium excretion and nephrocalcinosis. Subsequently an additional 15 rats were studied to confirm our findings regarding urinary calcium excretion and kidney calcifications. RESULTS: Treatment with furosemide without sodium supplementation (group B) resulted in decreased weight gain compared with group A (137.5 +/- 12.9 vs 154.0 +/- 10.6 g; p < 0.05), hypokalemia (3.7 +/- 0.1 vs. 4.4 +/- 0.4 mEq/l; p < 0.05), and nephrocalcinosis (187.1 +/- 155 vs. 18.8 +/- 6.9 micrograms Ca/g dry kidney; p < 0.05). Sodium supplementation (group C) normalized weight gain and corrected electrolyte abnormalities without increasing calciuria or nephrocalcinosis. CONCLUSIONS: We conclude that in this animal model, chronic furosemide treatment results in growth failure and development of nephrocalcinosis. Sodium supplementation protects against the deleterious effects of furosemide on weight gain and electrolyte homeostasis with no adverse effect on nephrocalcinosis.

Feeding of premature infant formula after hospital discharge of infants weighing less than 1800 grams at birth.

A randomized, double-blind study was conducted to determine whether continued feeding of premature infant formula after hospital discharge improve biochemical measures of bone mineral or protein status and anthropometrics during the first 8 and 12 weeks, respectively, after initial hospital discharge. Forty-three subjects were randomized to receive either a 20 kcal/ounce standard cow's milk-based formula with iron or a 20 kcal/ounce premature infant formula with iron for 8 weeks after hospital discharge. Sixteen exclusively breast-fed infants (mother's own milk) who received a multivitamin supplement with iron were compared with infants in both formula groups. There were no differences among the three groups in gender, birth weight, gestational age, or weight and age at the time of study entry. Alkaline phosphatase values were lower in infants receiving premature infant formula than in those receiving standard formula 8 weeks after discharge. Phosphorus values were lower and alkaline phosphatase values higher in the human milk-fed group than in both formula groups 8 weeks after discharge despite supplementation with calcium, phosphorus, and vitamin D before and during the study. At 8 weeks after discharge, human milk-fed infants also had lower transferrin levels than infants fed formulas. Infants in both formula groups grew similarly in weight, whereas the infants fed human milk weighed less throughout the study. The group fed premature infant formula had greater mean length and head circumference than the standard formula or human milk-fed groups. These data indicate that premature infants weighing < 1800 gm at birth may benefit from the continuation of premature infant formula during the first 8 weeks after initial hospital discharge.

Feeding iron-fortified premature formula during initial hospitalization to infants less than 1800 grams birth weight.

OBJECTIVE: A randomized, double-blind study was conducted comparing high-iron content (15 mg/L) with low-iron content (3 mg/L) premature formula given during initial hospitalization to infants with birth weights less than 1800 g to determine the influence of these differing intakes on the iron nutritional status during the first 4 months of life. A third group of similar infants received human milk mixed with an equal volume of liquid fortifier resulting in an iron content of approximately 1.7 mg/L. PATIENTS AND METHODS: Mean birth weight, gestational age, age at study entry, volume of blood removed for studies, and volume of red cells transfused were not different among the three groups. After hospitalization both formula-fed groups were given a cow milk formula with an iron content of 12 mg/L, and breast-fed infants were given an iron-containing multivitamin with a resulting iron intake of 10 mg/d. Infants were observed to 8 weeks after discharge. RESULTS: There were no differences in serum iron, ferritin, transferrin, transferrin saturation, hemoglobin, hematocrit, or reticulocyte count among the three groups at study entry, although mean corpuscular hemoglobin and mean corpuscular volume were lower in infants in the low-iron formula group. Mean plasma ferritin was significantly lower in infants receiving low-iron content premature formula at the time of hospital discharge compared with the other two groups. The incidence of anemia (hemoglobin < 9.0 g/dL) and low transferrin saturation (< 24%) was also greater in the low-iron content formula group. Eight weeks after discharge, the incidence of low plasma ferritin (< 19 ng/mL) remained greater in infants receiving low-iron content formula than in the other two groups. No adverse effects of iron intake were observed. Growth was not different among the three groups. CONCLUSIONS: These data indicate that preterm infants with < 1800 g birth weight receiving premature infant formula benefit from formula given during initial hospitalization containing 15 mg/L iron compared with that containing 3 mg/L.

Calcium and phosphorus supplementation after initial hospital discharge in breast-fed infants of less than 1800 grams birth weight.

This study evaluated whether calcium and phosphorus supplementation after initial hospital discharge was advisable in infants of < 1800 gm birth weight who were being breast fed. Twenty-seven infants (15 without any illness affecting nutritional intake and 12 with medical illness) received breast milk plus a liquid human milk fortifier mixed 1:1 and 400 IU vitamin D daily during initial hospitalization. At discharge, 12 infants (6 without and 6 with previous illness) were randomly assigned to receive calcium and phosphorus supplementation, and 15 infants (9 without illness and 6 with previous illness) received no mineral supplementation. A third group of seven healthy infants received a formula for premature infants during initial hospitalization and a standard cow's milk formula (20 calories per ounce) after discharge. The mean plasma calcium, phosphorus, and alkaline phosphatase levels did not differ among the three groups at study entry. Eight weeks after discharge, eight infants (four without illness and four with illness) had hypophosphatemia < 4.5 mg/dl. All were breast fed, and seven of eight had not received posthospitalization calcium and phosphorus supplementation. The incidence of hypophosphatemia in infants with or without illness was significantly greater in infants who did not receive supplementation (p = 0.038). These data indicate that calcium, phosphorus, and vitamin D supplementation may be necessary in approximately 50% of breast-fed infants of < 1800 gm birth weight after hospital discharge. It is recommended that serum calcium, phosphorus, and alkaline phosphatase be measured 4 to 8 weeks after discharge to identify those infants who require supplementation.

Hypophosphatemia in breast-fed low-birth-weight infants following initial hospital discharge.

The present study evaluated 12 infants with birth weights less than 2000 g who received human milk plus a multivitamin supplement and 20 similar infants who received standard cow's milk formula for 16 weeks from the time of initial hospital discharge. Examination at birth, at hospital discharge (study entry), at 4 and 16 weeks after hospitalization, and at 52 weeks of age revealed no intergroup differences in body weight, length, and head circumference. Hypophosphatemia (plasma phosphorus concentration less than or equal to 1.45 mmol/L) developed in 6 infants fed human milk (5 infants at 4 weeks and 1 infant at 16 weeks of study). Mean vitamin D intakes, but not calcium and phosphorus intakes, were significantly lower during hospitalization in human milk-fed infants with hypophosphatemia (44 [25, SD] IU/d) compared with those without hypophosphatemia (322 [180] IU/d). These data indicate that human milk-fed, low-birth-weight infants are at risk for hypophosphatemia following initial hospital discharge. Plasma calcium, phosphorus, and alkaline phosphatase concentrations at hospital discharge may not predict the infants at risk. Vitamin D supplementation early in the infants' hospital course may prevent hypophosphatemia.

Comparison of calcium- and phosphorus-supplemented soy isolate formula with whey-predominant premature formula in very low birth weight infants.

In a random, controlled study of very low birth weight (VLBW) infants from 3 to 8 weeks of age, 17 infants were fed soy isolate formula supplemented with calcium (92 mg/kg/day), phosphorus (44 mg/kg/day), and vitamin D (500 IU/kg/day), and 15 were fed a new whey-predominant, low osmolality formula designed for small preterm infants. Mean birth weight (1,206 g, SD 178) and gestational age (30 weeks, SD 1.9) of the soy-fed group were not significantly different from the whey formula group (1,143 g, SD 158, and 30 weeks, SD 1.8, respectively). Caloric and protein intakes were not different between the formula groups throughout the study period. However, mean weight gain in g/kg/day was significantly greater for the whey formula group: 15.3 g, SD 2.5, vs. 11.3 g, SD 2.3, p less than 0.0001. Serum protein and albumin were higher in the whey formula-fed group during the latter 2 weeks of the study (p less than 0.05). The incidence of vomiting, gastric residual, abdominal distension, diarrhea, and constipation was low and not different between the two groups. No infant developed necrotizing enterocolitis. Serum calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D and parathyroid hormone were similar in both groups, and no infant developed radiographic evidence of rickets. Although soy isolate formula supplemented with calcium, phosphorus, and vitamin D was not associated with rickets, no fewer complications were observed with this lactose-free, low solute formula.(ABSTRACT TRUNCATED AT 250 WORDS)

Etiologic factors in rickets of very low-birth-weight infants.

The incidence of rickets was found to be 32% (39/125) in a retrospective review of consecutive survivors of very low birth weight in whom serial radiographic and biochemical data were obtained. A higher proportion of these infants were black, had a greater initial weight loss, and had a longer hospitalization; there was a prevalence of births in the spring. Soy formula, supplemented with calcium and vitamin D but not phosphorus, was used predominantly in both groups; cumulative calcium, phosphorus, vitamin D, and caloric intakes were the same. We believe that the etiology of rickets in VLBW infants is multifactorial; however, nutritional deficiency is of central importance. Soy isolate formula, as well as human milk and many other commercially available formulas, do not provide sufficient calcium and phosphorus to keep pace with rates of intrauterine accretion. Supplementation with calcium, phosphorus, and vitamin D, beginning as soon as possible after birth, is indicated.