Distribution of plasma Vitamin E levels in supplemented very low birthweight infants

Abstract The distribution of plasma Vitamin E (VE) was determined in 25 very low birthweight (VLBW) infants who were supplemented with 100 mg/kg per day of α-tocopherol acetate, given intragastrically. Their mean birthweight was 917 g and mean gestational age was 28 weeks. Mean plasma VE levels after 1 and 6 weeks' supplementation were 2.7 mg/dL (s.e.m. = 1.0) and 6.4 mg/dL (s.e.m. = 1.4), respectively (the difference was not significant). There was wide variability in plasma VE levels in these infants despite being on an identical dose of tocopherol. Plasma VE was < 0.5 mg/dL in 12% of samples, 0.5–3.0 mg/dL in 32%, 3.1–5.0 mg/dL in 18%, and 5.1–20 mg/dL in 38%. Fifteen of the 25 infants had at least one level in the range which has been associated with an increased incidence of septicaemia and necrotizing enterocolitis (> 5.0 mg/dL).
These data suggest that if a policy of VE supplementation for VLBW infants is chosen, monitoring of plasma VE levels appears necessary so that the dosage can be adjusted in order to maintain plasma VE within the optimal range. This study's dosage regimen of supplementing infants with 100 mg/kg per day of VE was associated with a high incidence of elevated plasma VE levels and it is concluded that it is not advisable to use such large doses of VE in the premature newborn.     

Effect of recombinant human erythropoietin on transfusion needs in preterm infants

OBJECTIVE: To study the efficacy, safety and cost effectiveness of recombinant human erythropoietin (r-HuEPO) in reducing erythrocyte transfusion needs in very low birthweight (VLBW) infants. METHODS: We conducted a non-blind randomized controlled trial and assigned 100 VLBW infants, less than 33 weeks gestation, to receive either r-HuEPO 750 U/kg per week subcutaneously from day 5 to day 40 or no erythropoietin (EPO). Infants received oral iron 3-6 mg/kg per day from day 10. Transfusion needs were analysed for all enrolled infants and in five weight subgroups: birthweight of less than 600 g, 600-799 g, 800-999 g, 1000-1199 g and infants more than 1200 g. RESULTS: VLBW infants on r-HuEPO attained higher reticulocyte counts and haematocrit than control infants but the mean number of transfusions and volume of erythrocyte transfused per infant were not statistically different. Of infants 800-999 g at birth, the mean number of transfusions per infant was 2.1 compared with 3.5 transfusions per control infant (P = 0.04). Volume of erythrocytes transfused was 34.9 +/- 32.1 mL/kg in r-HuEPO-treated infants and 56.6 +/- 25.8 mL/kg in control infants (P = 0.03). The cost per patient for transfusion and EPO was S$388 for r-HuEPO recipient and S$438 for control infant. Blood pressure, neutrophil count, platelet count and complications of prematurity were not significantly different in both groups of VLBW infants. CONCLUSION: r-HuEPO at 750 U/kg per week stimulates erythropoiesis in VLBW infants but significantly reduces the need for erythrocyte transfusion only in infants weighing 800-999 g at birth.     

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.     

Vitamin E levels in premature infants during and after intravenous multivitamin supplementation

Serum vitamin E levels were measured in 19 infants weighing 1.0 to 1.5 kg, in 16 infants weighing less than 1 kg who received 65% of a vial (4.6 mg of vitamin E) of multivitamins (MVI Pediatric) daily, and in another group of 16 infants weighing less than 1 kg who received 30% of a vial (2.1 mg of vitamin E) daily. Supplementation was started within 12 hours of birth. Serum vitamin E levels were also measured after supplementation was discontinued in infants who had received 65% of a vial daily. Vitamin E sufficiency (levels equal to or greater than 0.5 mg/dL) was attained after 48 hours of supplementation in all infants receiving 65% of a vial daily and after 72 hours of supplementation in all infants receiving 30% of a vial daily. Vitamin E sufficiency was not maintained in all infants receiving 30% of a vial daily. Of the infants weighing less than 1 kg who received 65% of a vial daily, 31% had serum levels greater than 3.5 mg/dL, whereas no infant weighing less than 1 kg who received 30% of a vial daily had a level greater than 3.5 mg/dL (P less than .05). Of the infants weighing less than 1 kg who received 30% of a vial daily, 56% had levels less than 1 mg/dL v 6% of infants less than 1 kg who received 65% of a vial daily (P less than .01). Vitamin E levels decreased after MVI Pediatric supplementation with 65% of a vial was discontinued (P less than .05). After MVI Pediatric was discontinued, some infants became vitamin E insufficient.     

Stool water loss in very-low-birth-weight neonates

Fluid requirements in very-low-birth-weight (VLBW) infants include compensation for renal, insensible (skin and lung), and stool losses and provision for fluid retained for growth. Current estimates of stool water losses in VLBW infants are based on measurements established in term neonates. Therefore, the water content of 24-hour stool collections were determined in 11 healthy VLBW male infants on full enteral feeds and compared to the working norms. The neonates in this study were less than 2 weeks old with a mean +/- SD birth weight and gestational age of 1,311 +/- 112 g and 30.8 +/- 1.5 weeks, respectively. They were receiving only enteral formula feedings of 100 ml/kg/day or more with no parenteral fluid supplementation. The mean +/- SD number of stools and water content of the stools was 2.7 +/- 2.0/day and 7.2 +/- 4.0 ml/kg/day, respectively. There was a significant correlation (r = 0.696, p less than 0.02) between gestational age at birth and number of stools per day, but the correlation between stool water loss per day, gestational age, volume of feedings per day, and birthweight was not significant. Based on this study, 7 ml/kg/day is a reasonable estimate of daily stool water loss in VLBW babies.     

Plasma zinc concentrations in iron supplemented low birthweight infants.

We investigated the effect of prolonged iron supplementation of low birthweight infants on plasma zinc concentrations. Thirty infants (neonatal weight 820-2000 g) were examined at 6 or 12 months of life to assess their iron state and plasma zinc concentration. All of them were feeding on iron fortified formulas, which supply about 1 mg/kg/day of iron. In addition, 14 of them had been receiving 2 mg/kg/day of medicinal ferrous salts for at least five months. The other 16 were not given medicinal iron supplementation. Whereas iron state significantly differed in the two groups, plasma zinc concentrations were similar. Moreover, no zinc values below 75 micrograms/100 ml were found in any case. The results suggest that long term iron supplementation of low birthweight infants, at the recommended doses, does not influence zinc plasma concentrations unfavourably.     

Oral iron supplementation in preterm infants treated with erythropoietin

BACKGROUND: It is not known whether a moderate dose of oral iron supplementation would further enhance erythropoiesis in recombinant human erythropoietin (EPO)-treated very low-birthweight (VLBW) infants. METHODS: In total, 24 preterm infants with birthweights 750-1499 g were enrolled at the age of 14-28 days to receive 400 IU/kg per week EPO subcutaneously for 8 weeks. The infants were randomly allocated either to receive oral iron supplementation 4 mg/kg per day or to serve as controls. RESULTS: Hemoglobin and the absolute reticulocyte count in the iron supplementation and the control groups remained identical throughout the study period, whereas serum ferritin was significantly lower in the control group at study exit and follow up. Rates of treatment success (no need for transfusion and hemoglobin never below 8 g/dL) also did not differ between the groups. CONCLUSIONS: In this study we did not find a clear advantage in a moderate dose of oral iron supplementation on erythropoiesis in EPO-treated VLBW infants. Whether a higher dose would lead to enhanced erythropoiesis remains to be answered.     

Preventive management of hypoglycemia in very low-birthweight infants following indomethacin therapy for patent ductus arteriosus

BACKGROUND: To evaluate the effects of an increase in glucose infusion rate of 2 mg/kg per min from the basal infusion rate on the prevention of hypoglycemia in very low-birthweight (VLBW) infants, following indomethacin therapy for patent ductus arteriosus (PDA). METHODS: Forty VLBW infants with PDA were given indomethacin 0.2 mg/kg intravenously up to three doses. In 15 of the 40 infants (supplemented group: between April 1995 and March 1996) the glucose infusion rate was increased in 2 mg/kg per min increments from the basal rate just before the initial indomethacin administration, compared with 25 historical control infants who received a fixed glucose infusion rate during the first 12 h after the initial dose. We evaluated the changes in blood glucose levels and glucose infusion rates in both groups. RESULTS: In the control group 11 of 25 (44%) infants had a blood glucose value below 40 mg/dL between 12 and 60 h (mean 32.7 h). In contrast only two out of 15 infants in the supplemented group reached the glucose level below 40 mg/dL between 72 and 96 h but both two were light-for-dates infants (defined as birthweight below the 10th percentile for gestational age on the standard intrauterine growth curve). Blood glucose values in the supplemented group were significantly higher than those in the control group between 12 and 96 h. However, glucose infusion rates were similar before and between 72 and 96 h. CONCLUSIONS: This retrospective study shows that an increase in glucose infusion rate of 2 mg/kg per min, in addition to the pre-existing stable maintenance glucose intake, might prevent against the occurrence of unexpected hypoglycemia in VLBW infants following indomethacin therapy.     

Plasma and urine riboflavin during riboflavin-free nutrition in very-low-birth-weight infants

BACKGROUND: Very-low-birth-weight (VLBW; birth weight <1500 g) infants receive enteral and parenteral nutriture that provides greater daily riboflavin (vitamin B2) than does term infant nutriture, and elevated plasma riboflavin develops in these infants after birth. The purpose of this study was to measure plasma and urine riboflavin concentrations in VLBW infants during riboflavin-free nutrition. Our hypothesis was that elevated plasma riboflavin develops in VLBW infants because of high daily intake and immature renal riboflavin elimination. METHODS: Eighteen clinically healthy VLBW infants received parenteral nutrition and preterm infant formula during the first postnatal month. On postnatal days 10 and 28, the infants received specially prepared riboflavin-free enteral and parenteral nutrition for the 24-hour study period. Serial collections of plasma were made at time 0 and at 12 and 24 hours. Urine was collected continuously for the 24-hour period in 4-hour aliquots. Samples were analyzed for riboflavin concentration. RESULTS: During the 24-hour riboflavin-free study period on postnatal day 10, plasma riboflavin decreased 56% from 185 +/- 37 ng/mL (mean +/- SEM), and urine riboflavin decreased 75% from 3112 +/- 960 mg/mL. Similarly, on postnatal day 28, plasma riboflavin decreased 79% from 184 +/- 32 ng/mL, and urine riboflavin concentration decreased 91% from 5092 +/- 743 ng/mL during the 24-hour riboflavin-free study period. Riboflavin half-life (t(1/2)) was 18.5 hours on postnatal day 10 and decreased 48% by postnatal day 28. Riboflavin elimination was 145.1 +/- 20.6 mg/kg per day on postnatal day 10 and increased 40% by postnatal day 28. CONCLUSION: The VLBW infants who received parenteral nutrition and preterm infant formula had elevated plasma riboflavin on postnatal days 10 and 28. Plasma riboflavin t(1,2) was shorter and renal riboflavin elimination was greater on postnatal day 28 than on postnatal day 10. Plasma riboflavin was normal after 24 hours of riboflavin-free nutrition. The pattern of plasma and urine riboflavin in VLBW infants suggests a lower daily intake would maintain plasma riboflavin close to normal.     

A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants

INTRODUCTION: Very-low-birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. METHODS: Preterm infants with birth weight < or =1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, chi, and analysis of variance. RESULTS: The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 +/- 29 g and 25.5 +/- 0.3 weeks (mean +/- SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 +/- 0.009 mg/kg/day), 35% more vitamin A (318.3 +/- 11.4 microg/kg/day), and 14% more vitamin E (3.17 +/- 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 +/- 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 +/- 0.022 microg/mL) and vitamin E (22.26 +/- 1.61 /mL) concentrations were greater in the modified group. CONCLUSIONS: The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.     

A randomized controlled trial of enteral glutamine supplementation in very low birth weight infants: plasma amino acid concentrations

OBJECTIVE: Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants are susceptible to glutamine depletion, as enteral nutrition is limited in the first weeks of life. Enteral glutamine supplementation may have a positive effect on feeding tolerance, infectious morbidity and short-term outcome. The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations, reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants. METHODS: In a double-blind placebo-controlled randomized controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of life. Supplementation was added to breast milk or to preterm formula. Plasma amino acid concentrations were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. RESULTS: Baseline patient and nutritional characteristics were not different in glutamine (n = 52) and control (n = 50) groups. Plasma concentrations of most essential and non-essential amino acids increased throughout the study period. There was no effect of enteral glutamine supplementation. In particular, the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups (P = 0.49 and P = 0.34 respectively, day 30). CONCLUSIONS: Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine, glutamate or other amino acids. Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants.     

Effect of Bifidobacterium administration on very‐low‐birthweight infants

Background: The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 (B. bifidum) on accelerating enteral feeding and bacterial colonization in very‐low‐birthweight (VLBW) infants. Methods: We conducted a single‐center prospective pilot study. Thirty‐six VLBW infants were randomly divided into two groups: group E, wherein B. bifidum was supplemented within 48 h of birth, and group L, wherein it was supplemented more than 48 h after birth. Results: Group E and group L reached a total feeding volume of 100 mL/(kg/day) after 10 [7–13] days and 11 [10–15] days, respectively (median [quartile]). The daily bodyweight gain in group E was significantly higher (21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day, P < 0.02; 11.1 ± 1.5 g/kg/day vs 10.4 ± 1.2 g/kg/day, P < 0.04). No significant differences were found in the fecal Bifidobacterium level between the groups quantitated with a real‐time polymerase chain reaction assay at 1 and 4 weeks of age. However, the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth. The incidence of morbidities between the groups was similar. Conclusion: The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity. Furthermore, the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth.     

Late-onset neutropenia in very low birthweight infants

AIM: To evaluate the incidence and duration of late-onset neutropenia (defined as an absolute neutrophil count (ANC) <1500 mm(-3) at a postnatal age of >3 wk) in a population of infants with birthweight <2000 g, and to determine whether copper deficiency, a possible cause of both anemia and neutropenia, may be associated with this complication. METHODS: Complete blood cell count and differential were assessed in 247 low (LBW) and very low birthweight (VLBW) infants who were discharged after 3 wk of life. In neutropenic infants plasma copper and ceruloplasmin levels were also measured. RESULTS: Late-onset neutropenia was detected in 11 out of 147 VLBW infants (7.5%) and in 7 out of 127 LBW infants (5.5%). A neutrophil count of <1000 mm(-3) was observed in 14 infants (5.1%). A significantly lower gestational age was found in neutropenic infants compared with non-neutropenic infants. In neutropenic infants ANCs were significantly correlated with hemoglobin and hematocrit. In addition, a significant negative correlation was found between neutrophil and reticulocyte counts. Plasma copper concentration was significantly correlated with birthweight. Oral copper sulfate was administered to infants with plasma copper concentration <50 microg dl(-1), and did not seem to affect ANC, hemoglobin, hematocrit or reticulocyte counts. CONCLUSION: Late-onset neutropenia appears to be a benign condition that is not associated with any particular complication and does not require specific treatment. Reference ranges after the early neonatal period and during the first few months of life in LBW and VLBW infants should probably be set at lower values.     

HFE gene mutation and transferrin saturation in very low birthweight infants.

AIM: To determine if there is an association between high transferrin saturation and the C282Y HFE gene mutation in very low birthweight (VLBW) infants. METHODS: One hundred and forty three VLBW infants receiving recombinant erythropoietin and 3 to 9 mg/kg/day of enteral iron were studied. Genomic DNA was extracted from filter paper cards. The C282Y mutation was determined by restriction fragment length polymorphism analysis. RESULTS: Six infants were heterozygous for the mutation; none was homozygous. Ten infants had a transferrin saturation above 80% at least once. No infant was positive for both transferrin saturation above 80% and the mutation. CONCLUSIONS: The data strongly suggest that there is no association between high transferrin saturation and the HFE gene mutation in VLBW infants during the first weeks of life.     

Determination of Serum Unbound Bilirubin for Prediction of Kernicterus in Low Birthweight infants

Serum unbound bilirubin concentrations (UBC) and serum total bilirubin concentrations (TBC) were measured serially in 138 low birthweight (LBW) infants treated with phototherapy for non-hemolytic hyperbilirubinemia. We attempted to assign the suitable critical UBC levels for predicting bilirubin encephalopathy into two different birthweight groups: a very low birthweight (VLBW) group (birthweight < 1,500 g) and an LBW group (birthweight between 1,500 g and 2,499 g). Twelve infants were diagnosed as 'at risk' for kernicterus, of whom 11 had signs of acute bilirubin encephalopathy and exchange transfusion. One VLBW infant had neurological sequelae at a 3 year follow-up, although exchange transfusion was not carried out because of low TBC.
Sensitivity and specificity for predicting kernicterus were calculated at different UBC levels between 0.6μg/dl and 1.5μg/dl and TBC levels between 8 mg/dl and 26 mg/dl. The receiver-operating characteristic (ROC) curves plotted for UBC as a predictor of kernicterus were clearly shifted up and to the left compared with the curves for TBC in the VLBW and LBW groups. Thus, the UBC measurement may well provide a more rational basis for evaluating the risk of kernicterus in LBW infants. The optimal cut-off points were derived from these curves. In the VLBW group, the sensitivity was 100% and the specificity was 96% for a UBC of 0.8μg/dl, and 80% and 64% for a TBC of 11 mg/dl. In the LBW group, the sensitivity was 100% and the specificity was 98% for a UBC of 1.0μg/dl and 71% and 78% for a TBC of 16 mg/dl. These results suggest that UBC determination is more suitable for predicting kernicterus than TBC in LBW infants with non-hemolytic hyperbilirubinemia.     

Factors related to transfusion in very low birthweight infants treated with erythropoietin.

The need for red cell transfusions is reduced but not eliminated by recombinant human erythropoietin (rhEPO) in very low birthweight (VLBW) infants. To detect factors associated with the decision to transfuse VLBW infants during rhEPO treatment and to explain rhEPO ''non-responders'', the subgroup of those 120 VLBW infants who were treated with rhEPO 750 IU/kg per week in the second European Multicentre rhEPO Trial was evaluated. Sixty (50%) infants received at least one transfusion during erythropoietin treatment. Transfusion was frequent in infants with extremely low birthweight (79% for 750-999 g), low gestational age (70% for < or = 28 weeks), low initial haematocrit or low initial reticulocyte count (61% for haematocrit < or = 0.48 and reticulocytes < or = 9%, respectively). Considerable differences among centres were found for sampling blood loss, iron supply, and transfusion rate, which ranged from 13% to 73% and was related to the volume of diagnostic blood loss (19% vs 80% for blood loss < 1 vs > or = 1 ml/kg per day). The prognostic variables birthweight, initial haematocrit, and gestational age were found to be most predictive for transfusion. To improve rhEPO response in VLBW infants, there is a need to minimise diagnostic blood loss, to prevent iron deficiency, and to develop rational criteria for transfusion in preterm infants.     

Postnatal changes in calcium-regulating hormones in very-low-birth-weight infants. Effect of early neonatal hypocalcemia and intravenous calcium infusion on serum parathyroid hormone and calcitonin homeostasis

In very-low-birth-weight (VLBW) infants, we studied the hypotheses that in early neonatal hypocalcemia the serum parathyroid hormone (PTH) concentration would rise; the serum calcitonin (CT) concentration would decline; and, in response to intravenous (IV) calcium (Ca) infusion, the serum PTH concentration would be lowered; and the serum CT concentration would rise. Fifteen infants appropriate for gestational age (age, less than 32 weeks; birth weight, less than 1,500 g) were enrolled in the study. In eight infants in whom the serum Ca level declined to less than 6.0 mg/dL, changes in serum magnesium, phosphorus, PTH, CT, and whole blood ionized calcium (iCa) were evaluated on entry into the study, when serum Ca declined to less than 6.0 mg/dL, immediately after infusion of 18 mg/kg of elemental calcium as calcium gluconate, and at eight hours post-Ca infusion (+ 8 hr). The serum Ca concentration declined from 7.9 +/- 0.6 baseline (mean +/- SE) to 5.2 +/- 0.2 mg/dL pre-Ca infusion and rose to 9.17 +/- 0.74 mg/dL post-Ca infusion and 7.1 +/- 0.5 mg/dL at +8 hr post-Ca infusion. Whole blood iCa declined from 4.82 +/- 0.24 to 3.72 +/- 0.19 mg/dL pre-Ca infusion, rose to 6.68 +/- 0.32 mg/dL post-Ca infusion, and was 4.12 +/- 0.21 mg/dL at + 8 hr post-Ca infusion. The serum P concentration did not change significantly. The serum PTH concentration rose from 116 +/- 17 to 204 +/- 34 pmole/L pre-Ca infusion, declined to 149 +/- 22 pmole/L post-Ca infusion, and was 187 +/- 28 pmole/L at + 8 hr post-Ca infusion. The serum CT concentration was elevated and did not change significantly. Thus, in infants less than 32 weeks' gestation, the serum PTH level rises in early neonatal hypocalcemia and is suppressed by IV Ca infusion; the serum CT level is markedly elevated and is not altered in early neonatal hypocalcemia and does not rise further in response to IV Ca infusion in VLBW infants. We suggest that hypercalcitoninemia occurs in VLBW infants and that serum CT concentrations are unresponsive to changes in serum Ca.     

Effect of high calcium and phosphorus intake on mineral retention in very low birth weight infants chronically treated with furosemide

The treatment of premature infants with the diuretic furosemide appears to be a contributory factor in the development of metabolic bone disease presumably because of furosemide-induced hypercalciuria. In this study, we measured calcium and phosphorus balance in furosemide-treated very low birth weight infants (VLBW) infants with bronchopulmonary dysplasia (BPD) who were fed a specialized premature formula containing increased amounts of calcium and phosphorus. Furosemide-treated infants received 166 +/- 37 mg/kg/day and retained 80 +/- 34 mg/kg/day of calcium, and 87 +/- 19 mg/kg/day and retained 52 +/- 14 mg/kg/day of phosphorus. The amounts retained were approximately 65% of the calcium and 72% of the phosphorus requirements for in utero mineral accretion. Compared to a group of similarly fed VLBW infants without BPD and not treated with the diuretic, the furosemide-treated infants excreted a larger percent of the calcium intake in the urine but had similar total urinary calcium and phosphorus losses (mg/kg/day) and serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) levels. From the latter two findings, we suggest that the extra mineral content of the formula may have promoted bone mineralization and prevented the occurrence of secondary hyperparathyroidism.     

Late-onset neutropenia in very low birthweight infants

Aim : To evaluate the incidence and duration of late-onset neutropenia (defined as an absolute neutrophil count (ANC) <1500 mm⁻³ at a postnatal age of >3 wk) in a population of infants with birthweight <2000 g, and to determine whether copper deficiency, a possible cause of both anemia and neutropenia, may be associated with this complication. Methods : Complete blood cell count and differential were assessed in 247 low (LBW) and very low birthweight (VLBW) infants who were discharged after 3 wk of life. In neutropenic infants plasma copper and ceruloplasmin levels were also measured. Results : Late-onset neutropenia was detected in 11 out of 147 VLBW infants (7.5%) and in 7 out of 127 LBW infants (5.5%). A neutrophil count of <1000 mm⁻³ was observed in 14 infants (5.1%). A significantly lower gestational age was found in neutropenic infants compared with non-neutropenic infants. In neutropenic infants ANCs were significantly correlated with hemoglobin and hematocrit. In addition, a significant negative correlation was found between neutrophil and reticulocyte counts. Plasma copper concentration was significantly correlated with birthweight. Oral copper sulfate was administered to infants with plasma copper concentration <50 μg dl⁻¹, and did not seem to affect ANC, hemoglobin, hematocrit or reticulocyte counts.
Conclusion : Late-onset neutropenia appears to be a benign condition that is not associated with any particular complication and does not require specific treatment. Reference ranges after the early neonatal period and during the first few months of life in LBW and VLBW infants should probably be set at lower values.     

Growth effects of systemic versus inhaled steroids in chronic lung disease

AIM: To compare the effects of inhaled and systemic steroids on growth in very low birthweight (VLBW) infants with chronic lung disease (CLD). METHODS: Sixteen babies with CLD randomly received inhaled budesonide (100 microg four times daily for 10 days via Aerochamber) or systemic steroids (dexamethasone 0.5 mg/kg/day, reducing over nine days). Linear growth (lower leg length, LLL) was measured by knemometry twice weekly. RESULTS: The gestational age, birth weight, postnatal age, and LLL velocity (LLLvel) were similar between the two groups at the start of treatment. At the end of the treatment period, LLLvel was reduced in the dexamethasone group (mean -0.01 mm/day) but had increased in the budesonide group (mean 0.48 mm/day). Mean weight gain was non-significantly lower in the dexamethasone group (5.8 g/kg/day) compared to the budesonide group (mean 12.7 g/kg/day). CONCLUSION: Inhaled budesonide has less short term effects on growth than systemically administered dexamethasone.