Intrauterine Accretion Rates Research Articles

Gestational age dependent content, composition and intrauterine accretion rates of fatty acids in fetal white adipose tissue

Background Little is known about the gestational age (GA) dependent content, composition and intrauterine accretion rates of fatty acids (FA) in fetal white adipose tissue (WAT). Objective & design To acquire this information, we collected abdominal subcutaneous WAT samples from 40 preterm and term fetuses. Their GA ranged from 22 to 43 weeks. FA were expressed as mg/g wet WAT and g/100 g FA (g%). Intrauterine WAT FA accretion rates were estimated for appropriate (AGA) and large (LGA) for gestational age infants. Results From 25 to 40 weeks gestation, saturated-FA (SAFA) increased from 83 to 298 mg/g WAT and monounsaturated-FA (MUFA) from 83 to 226 mg/g WAT, while polyunsaturated-FA (PUFA) increased insignificantly from 18.0 to 23.2 mg/g WAT. As percentages of total FA, SAFA increased from 46 to 55 g%, MUFA decreased from 44 to 41 g%, and PUFA from 10.3 to 4.26 g%. Docosahexaenoic (DHA) and arachidonic acid (AA) accretion rates in WAT during the 3rd trimester for AGA infants were 88 and 193 mg/week, respectively. Contemporaneous DHA and AA accretion rates for 4500 g LGA infants were 184 and 402 mg/week, respectively. Compared to the whole 3rd trimester, increment rates during the last 5 weeks of gestation were about 2-fold higher. Conclusion FA accretion rates, notably those of DHA and AA, may be important for designing nutritional regiments for preterm infants. The current WAT-DHA and WAT-AA accretion rates are considerably lower than previously reported in the literature.

Higher dose of docosahexaenoic acid in the neonatal period improves visual acuity of preterm infants: results of a randomized controlled trial

Background: Preterm infants have improved visual outcomes when fed a formula containing 0.2–0.4% docosahexaenoic acid (DHA) compared with infants fed no DHA, but the optimal DHA dose is unknown.Objective: We assessed visual responses of preterm infants fed human milk (HM) and formula with a DHA concentration estimated to match the intrauterine accretion rate (high-DHA group) compared with infants fed HM and formula containing DHA at current concentrations.Design: A double-blind randomized controlled trial studied preterm infants born at <33 wk gestation and fed HM or formula containing 1% DHA (high-DHA group) or ≈0.3% DHA (current practice; control group) until reaching their estimated due date (EDD). Both groups received the same concentration of arachidonic acid. Sweep visual evoked potential (VEP) acuity and latency were assessed at 2 and 4 mo corrected age (CA). Weight, length, and head circumference were assessed at EDD and at 2 and 4 mo CA.Results: At 2 mo CA, acuity of the high-DHA group did not differ from the control group [high-DHA group (x̄ ± SD): 5.6 ± 2.4 cycles per degree (cpd), n = 54; control group: 5.6 ± 2.4 cpd, n = 61; P = 0.96]. By 4 mo CA, the high-DHA group exhibited an acuity that was 1.4 cpd higher than the control group (high-DHA: 9.6 ± 3.7 cpd, n = 44; control: 8.2 ± 1.8 cpd; n = 51; P = 0.025). VEP latencies and anthropometric measurements were not different between the high-DHA and control groups.Conclusion: The DHA requirement of preterm infants may be higher than currently provided by preterm formula or HM of Australian women.

14 Individualized Fortification of Human Milk: Does it Make the Difference?

Background: Inadequate nutrition leading to growth failure is common among premature infants. Although fortified breast milk is the preferred feeding, nutrient intakes achieved with fortified breast milk fall short of meeting nutrient needs consistently. This is mainly due inadequate protein content of fortifiers and high inter- and intra-individual variation in composition of expressed breast milk. Objective: To test a new adjustable fortification regimen designed to ensure that protein needs of premature infants are met all the time. The new regimen encompassed increasing the amount of fortifier and the addition of extra protein to breast milk. These periodic adjustments of fortification were guided by determinations of BUN. The study tested the hypothesis that the new regimen leads to higher protein intake and to improved weight gain compared to standard fortification. Methods: In a prospective, controlled trial, preterm infants with birth weights of 600–1750 grams and gestational ages between 26–34 weeks were fed their own mother's milk, or banked donor milk, or both. Infants were randomly assigned to either the new (adjustable) fortification regimen or the standard regimen. The study period began when feeding volume reached 150 ml/kg/day and ended when infants reached 2000 g. The standard fortification regimen (STD) consisted in the addition of the recommended amount of HMF. The adjustable regimen (ADJ) consisted of standard fortification, but with addition of extra HMF and supplemental protein guided by twice-weekly BUN determinations. Primary outcome was growth, serum biochemical indicators and nutrient intakes were secondary outcomes. Results: Thirty-two infants completed the study as planned (16 ADJ, 16 STD). Infants receiving the ADJ regimen had mean protein intakes of 2.9, 3.2, 3.4 g/kg/d, respectively, in weeks 1, 2 and 3, whereas infants receiving the STD regimen had intakes of 2.9, 2.9, 2.8 g/kg/d, respectively. Infants on the ADJ regimen showed significantly greater gain in weight (17.5 ± 3.0 g/kg/d vs 14.4 ± 3.0 g/kg/d, p<0.01) and greater gain in head circumference (1.4 ± 0.3 vs 1.0 ± 0.3; p<0.05) than infants on the STD regimen. Weight and head circumference gain were significantly correlated with average protein intake (r=0.39, p<0.05 for both). No significant correlations were found between growth parameters and intake of fat and energy. In the ADJ group BUN concentrations increased significantly (p<0.001) over time but were not significantly higher than in the STD group. Conclusion: Premature infants managed with the new adjustable fortification regimen had significantly higher weight and head circumference gains than infants managed with standard fortification. Higher protein intake appears to have been primarily responsible for the improved growth with the adjustable regimen. With the new regimen protein intakes approached intrauterine accretion rates without evidence of metabolic stress. The new fortification method seems to be a promising approach to solving the problem of undernutrition among premature infants fed human milk.

Nutrient Requirements For Preterm Infant Formulas

Achieving appropriate growth and nutrient accretion of preterm and low birth weight (LBW) infants is often difficult during hospitalization because of metabolic and gastrointestinal immaturity and other complicating medical conditions. Advances in the care of preterm-LBW infants, including improved nutrition, have reduced mortality rates for these infants from 9.6 to 6.2% from 1983 to 1997. The Food and Drug Administration (FDA) has responsibility for ensuring the safety and nutritional quality of infant formulas based on current scientific knowledge. Consequently, under FDA contract, an ad hoc Expert Panel was convened by the Life Sciences Research Office of the American Society for Nutritional Sciences to make recommendations for the nutrient content of formulas for preterm-LBW infants based on current scientific knowledge and expert opinion. Recommendations were developed from different criteria than that used for recommendations for term infant formula. To ensure nutrient adequacy, the Panel considered intrauterine accretion rate, organ development, factorial estimates of requirements, nutrient interactions and supplemental feeding studies. Consideration was also given to long-term developmental outcome. Some recommendations were based on current use in domestic preterm formula. Included were recommendations for nutrients not required in formula for term infants such as lactose and arginine. Recommendations, examples, and sample calculations were based on a 1000 g preterm infant consuming 120 kcal/kg and 150 mL/d of an 810 kcal/L formula. A summary of recommendations for energy and 45 nutrient components of enteral formulas for preterm-LBW infants are presented. Recommendations for five nutrient:nutrient ratios are also presented. In addition, critical areas for future research on the nutritional requirements specific for preterm-LBW infants are identified.

Calcium, magnesium and phosphorus in the nutrition of the newborn.

Several factors have been suggested to contribute to inadequate bone mineralization in infants. Calcium and phosphorus intakes in preterm infants are below the intrauterine accretion rates. Calcium retention is influenced by the types of calcium salts used and by alterations in dietary phosphorus, fat and carbohydrates. Dietary intakes of vitamin D, and modifications in the protein base of infant formula, e.g., soy base vs cow milk base, may impact bone mineralization. The major hormonal mechanisms involved in the regulation of bone mineralization are parathyroid hormone, calcitonin and vitamin D. From recent animal studies, it has been suggested that parathyroid hormone related peptide (PTH-rp) may also play a role in perinatal calcium homeostasis.

Postnatal attainment of intrauterine macromineral accretion rates in low birth weight infants fed fortified human milk

Hypothesis: Provision of more bioavailable mineral sources as human milk supplements enables very low birth weight (VLBW) infants to meet the intrauterine accretion rate for calcium and phosphorus. Design: Comparison of currently formulated human milk fortifier with previous formulation. Setting: Neonatal level II and III nurseries Patients: Twenty-six healthy, VLBW infants, whose mothers chose to breast-feed. Interventions: We tested the effects of two formulations designed for VLBW infants as human milk supplements and differing primarily in their quantity and source of Ca, P, and magnesium. The study interval began with a milk intake of 100 ml · kg -1 · day -1 and ended when a body weight reached 2.0 kg. Main outcome measures: Net absorption and retention of Ca, P, and Mg during a nutritional balance study conducted once during the study interval, growth during the entire study interval, and bone mineral content of the radius were measured at the beginning and end of the study interval. Results: The newer Ca gluconate-glycerophosphate preparation (given to group CaGP) resulted in greater net absorption and retention of Ca and P ( p <0.01) than in infants given Ca phosphate (group CaTB). Mg retention was greater than (in group CaGP) or equivalent to (in group CaTB) the intrauterine accretion rate. Radius bone mineral content was significantly greater in group CaGP than in group CaTB ( p <0.001). Volumes of the fortified human milk preparation needed to meet the needs for gain in body weight were higher in group CaGP than in group CaTB ( p <0.001). Conclusions: Intrauterine accretion rates for Ca and P can be achieved when VLBW infants are fed human milk supplemented with Ca gluconate-glycerophosphate. Supplementation of human milk with Mg may not be indicated. In this study, greater intakes of Ca and P, and not improvements in bioavailability, result in improved net retention and bone mineral content of VLBW infants. (J P ediatr 1995;126:441-7)

Glycero‐ vs Glucose‐Phosphate in Parenteral Nutrition of Premature Infants: A Comparative in Vitro Evaluation of Calcium/Phosphorus Compatibility

In total parenteral nutrition (TPN) of premature infants, glycero- and glucose-phosphate have been recommended, and clinically used, because of their considerable compatibility with calcium. However, a systematic comparative in vitro assessment of the therapeutic potential and safety of these substances has not yet been provided. We investigated the stability of TPN solutions containing calcium-gluconate and glycero- or glucose-phosphate in high concentrations. Evaluation was performed by visual inspection, absorptiometry, light microscopy, measurement of pH, and determination of calcium concentration before and after microfiltration. Even under circumstances promoting precipitation of calcium and phosphate--such as body temperature, relatively high pH, and concentrations of calcium and phosphorus exceeding those necessary to provide intrauterine accretion rates, all but one of the examined TPN admixtures remained stable. Our data suggest that the use of glycero-phosphate, and particularly glucose-phosphate, together with calcium-gluconate, is an uncomplicated and safe procedure to administer simultaneously high amounts of calcium and phosphorus in TPN of premature infants.

HYDROGEN ION [H]+ LOAD AND CALCIUM-PHOSPHATE SOLUBILITY IN IV NUTRITION AND THE PRETERM INFANT (PTI)

Significant osteopenia occurs in circa 30% of PTI. Inadequate mineral substrate intake to match intrauterine accretion rates is thought to be a major cause. Calcium (Ca) and Phosphate (iP) intake in IV feeding is restricted by solution solubility to less than half the desired intake. 17 PTI (median wt 1.20kg, gest 28w) were entered into a cross-over study comparing Addiphos (KabiVitrum) and K2 HPO4 as the iP source, while keeping amino acid intake standard. Results: (i) An increase in Ca - iP solubility and increased Ca and iP intake (P<0.001) can be achieved by lowering solution pH using Addiphos instead of K2 HPO4. (ii) Plasma Ca and iP is significantly increased with Addiphos (P<0.01). (iii) To match intrauterine Ca and iP accretion there was a 2x increase in [H]+ load. (iv) With (iii) there was no significant change in blood acid-base parameters, but there was an increase in urine titratable acidity excretion. Conclusion: Intravenous Ca and iP concentration of infusion can be increased by lowering pH of parenteral solution using Addiphos. This increased [H]+ load is well tolerated by PTI.

Achievement of in utero retention of calcium and phosphorus accompanied by high calcium excretion in very low birth weight infants fed a fortified formula

Calcium and phosphorus retention was evaluated in 13 very low birth weight infants who were fed an experimental formula designed to deliver quantities of calcium and phosphorus sufficient to meet the intrauterine accretion rates for these minerals. Retention of calcium and phosphorus in slight excess of these rates was achieved without any apparent difficulties for the infants. Biochemical measurements demonstrated normal serum calcium (9.8 +/- 8 mg/dL) and alkaline phosphatase (242 +/- 51.6 IU) values. However, there was evidence of high tubular reabsorption of phosphate (98.1% +/- 3.3%), hypercalciuria (7.2 +/- 3.8 mg/kg/d), and a relatively low serum phosphorus concentration (5.7 +/- 0.6 mg/dL). This biochemical picture is similar to that seen in phosphorus deficiency except for the low alkaline phosphatase activity. The latter finding, in concert with the high retention of calcium and phosphorus in these balance studies, makes such a diagnosis unlikely. We speculate that this biochemical picture is the result of an inappropriately high calcium/phosphorus ratio.

Sequential calcium and phosphorus balance studies in preterm infants

Forty-six infant boys less than 1500 g at birth and less than 32 weeks gestation were fed enterally from birth until day 47. Cohorts were given milk formula varying in calcium and phosphorus content: group A, calcium 45 mg/dL, phosphorus 33 mg/dL; group B, calcium 85 mg/dL, phosphorus 33 mg/dL; group C, calcium 125 mg/dL, phosphorus 33 mg/dL; group D, calcium 125 mg/dL, phosphorus 50 mg/dL; and group E, calcium 125 mg/dL, phosphorus 64 mg/dL. Three-day balance studies were begun at days 10, 20, 30, and 40. Calcium net absorption and retention were influenced by postnatal age and calcium intake. Calcium retention best approached intrauterine accretion rates in group C. Phosphorus was well absorbed irrespective of the calcium content of the milk. Phosphorus retention increased with increments in the calcium content of the milk. Increasing the phosphorus content of the milk (groups D and E) resulted in no overall change in calcium absorption and retention but some increments in phosphorus retention.

99 ASSESSMENT OF CA AND P REQUIREMENTS AND PREVENTION OF OSTEOPENIA IN VLBW INFANTS

Severe postnatal bone demineralization has now been recognized to be a common event in the VLBW infant because of calcium (Ca) and phosphorus (P) deficiency. Formula supplemented with Ca and P may not prevent this condition which is due to the wide variation in net calcium absorption. Hypothesis: Intrauterine bone mineral accretion rate will be achieved in VLBW infants postnatally when Ca and P are administered in sufficient quantity to result in a urinary excretion of both elements. Methods: To test this hypothesis we studied 18 periods of 3 weeks in 12 VLBW infants who were fed BM or formula supplemented with Ca-gluconate and Ca-glycerophosphate to produce a urinary excretion of 2-5 mmol/L Ca and P. The increase in bone mineral content (BMC, mg/cm) of the mid humerus measured by photonabsorptiondensitometry was assessed with respect to weight gain. Results: The median increase of BMC was 5.5 mg/cm per 100 g weight gain (range 2.7-9.9). This value is similar to the intrauterine accretion rate (4.6) which we have calculated from the BMC of newborn infants with birthweights between 800 and 4000 g (1). The mineral accretion rate, however was higher than the intrauterine rate in half of the study periods. Conclusion: Measurement of Ca and P in urine is a simple method by which individual requirements of Ca and P supplementation in VLBW may be accessed. Catch up mineralisation was observed in 9 of the babies. (1) Bone mineral content in appropriate and small for gestational infants: a reference for the evaluation of postnatal bone mineralization. Pediat Res 19:1116 (abstr.) (1985).

THE EFFECT OF DIET COMPOSITION ON ENERGY METABOLISM, SUBSTRATE UTILISATION AND GROWTH IN THE VLBW INFANT

Medium-chain-triglycerides (MCT) induce a decrease in fat storage in adult animals. To study the effect of MCT on quality of growth in the VLBW infant, oxidation (ox) and accretion (accr) of energy, protein, fat and carbohydrate have been measured in 20 growing VLBW infants, fed either an MCT enriched formula (gp 1; n=8) or an LCT formula (gp 2; n=12). 16 studies were performed in each group, combining indirect calorimetry, macronutrient balance and anthropometry. Weight and length gain simulated intra-uterine growth rate in both groups. Subscapular skinfolds and calculated body fat were similar in both groups, but higher than in the fetus of comparable postconceptional age. CONCLUSIONS: 1) The similar energy expenditure and fat oxidation indicate that MCT are not preferentially oxidised. 2) Consequently, MCT have to be chain elongated before storage. 3) The improvement of protein accretion to a level exceeding the intra-uterine accretion rate and improved absorption for MCT vs LCT indicate that body composition can be manipulated by isocalorically altering diet composition.

CALCIUM (Ca), PHOSPHORUS (P), ZINC (Zn), AND COPPER (Cu) CONTENT OF PRETERM HUMAN MILK (PTHM)

The Ca, P, Zn, and Cu content of PTHM was determined on cross-sectional and longitudinal samples of PTHM collected on days 1-2, 4±1, 7±1, 14±2, 28±2, 42±2, 56±2, and 70±2 of lactation from 74 women who delivered at or before 34 wks of gestation. Ca, Zn, and Cu were analyzed by atomic absorption spectroscopy. P was analyzed by the spectrophotometric method of Bartlett. The findings are displayed in the Table. Changes in content over time were tested by analysis of variance. Zn content decreased significantly with duration of lactation. The content of Ca, P, and Cu increased slightly during the early days of lactation, but then decreased slightly with the duration of lactation. Comparing these data with the estimated third trimester intrauterine accretion rates for these 4 minerals suggests that although the Zn content of PTHM might meet those rates, the content of Ca, P, and Cu does not.

Plasma concentrations of vitamin D metabolites in premature infants.

The plasma concentrations of 25-hydroxyvitamin D (OHD), 1,25-(OH)2D and 24,25-(OH)2D were determined in 28 healthy premature infants (median gestational age 33, range 28-36 wk; and median birth weight 1880, range 900-2350 g) during the first 5-10 wk of life, and in a reference group of 17 young adults. The infants received a vitamin D supplement of 500 IU/d and a diet low in calcium (Ca) and phosphorus (P) compared with that of corresponding intrauterine accretion rates. The median 25-OHD concentration increased from 11 (range 6-30) ng/ml at 1 d to 27 (range, 15-41) ng/ml by 5-10 wk of age (P less than 0.01). 1,25-(OH)2D concentrations at age 1 d were similar to the adult levels (median 37, range 8-64 versus 35, range 18-58 pg/ml), but increased significantly within 1 wk to 48 (26-156) pg/ml (P = 0.01), and between 1 and 3-4 wk of age to 104 (58-203) pg/ml (P less than 0.01). The levels at 5-10 wk were similar to the 3-4 wk value. 24,25-(OH)2D concentrations were persistently low compared with the adult levels (medians 0.4-0.5, range less than 0.3-2.1 versus 1.7, range 0.4-2.0 ng/ml, P less than 0.01). The relative concentrations, expressed as the ratio of 24,25-(OH)2D to 25-OHD, were comparable to those of the adults at birth, but decreased significantly within 2 wk. The data demonstrate that healthy premature infants can produce high plasma levels of 1,25-(OH)2D.

Growth, metabolic response, and development in very-low-birth-weight infants fed banked human milk or enriched formula. I. Neonatal findings

Banked human milk has been widely used, although its composition and nutritional adequacy for preterm infants are uncertain. We randomized 76 healthy infants of less than or equal to 1500 gm birth weight to ad lib feedings of frozen BHM or a protein-mineral-calorie-enriched formula (Similac Special Care) designed to sustain intrauterine accretion rates; BHM contained 2.2 gm fat/100 ml and 60 kcal/100 ml (gross energy). Infants fed BHM ingested more milk (197 vs 165 ml/kg/day) but less gross energy (118 vs 143 kcal/kg/day); grew less rapidly in weight (15 vs 30 gm/day), length (0.7 vs 1.1 cm/wk), and head circumference (0.8 vs 1.2 cm/wk); and were discharged at a lower weight (2200 vs 2348 gm) and older age (61 vs 47 day) than infants fed formula (P less than 0.02). At 37 weeks' postmenstrual age, infants fed BHM were less responsive to Brazelton inanimate stimuli (mean total score 5.0 vs 7.5; P less than 0.02). With few exceptions, blood amino acids, pH, and serum electrolyte values were similar in both groups. The different caloric intake of our feeding groups may explain only part of the large difference in growth rate. Donor milk should not be fed to preterm infants unless it has been analyzed and the feedings shown to provide a nutrient intake considered appropriate to the needs of these infants.

655 ACHIEVEMENT OF HIGH CA AND P CONCENTRATIONS IN PARENTERAL NUTRITION SOLUTIONS FOR NEONATES

Supply of nutrients approximating intrauterine accretion rates is a goal for total parenteral nutrition. In prematures it has been difficult to achieve high levels of Ca and P in parenteral nutrition solutions because of incompatibility of these minerals. We determined the amounts of these ions held in stable solution in Dextrose 5 or 10% and Amino acid 1.25% or 2.5% solution containing Zn, Cu, Mg, multivitamins, folic acid, Vit. K and Vit. B12. The appearance of the solutions was noted immediately and after 24 and 48 hrs at 4°C. When 10% Ca gluconate (9.4mgCa/ml) was added first to the base solution followed by K phosphate (P 93 mg/ml) precipitates occurred on addition of 1-2 drops of K phosphate. When P was diluted and then added, larger amounts of Ca and P were held in stable solution. However when the order of addition was reversed, i.e., P added first followed by Ca, optimal amounts of Ca and P were held in stable solution. The solubility of Ca and P in D 10% AA 2.5% was greater than in D 5% AA 1.25%, and at least 25% more P could be added. With D 5% AA 1.25% no precipitates were observed at 4°C in 48 hrs at Ca 150 mg/dl with P ≤50 mgm/dl; at Ca 100 mg/dl with P ≤75mgm/dl, at Ca 50 mgm/dl with P ≤ 100 mgm/dl. With D 10% AA 2.5% no precipitates occurred at 4°C in 48 hours at Ca 150 mg/dl with P ≤100 mgm/dl; at Ca 100mgm/dl with P 100 ≤mgm/dl; at Ca 50 mgm/dl with P ≤125 mgm/dl. Thus, when the order of addition of P and Ca in D-AA solutions is optimal it is possible to achieve high levels of these minerals exceeding that needed to approximate intrauterine requirements.