Insulin infusion with parenteral nutrition in extremely low birth weight infants with hyperglycemia

From Nov. 7, 1983, to Nov. 6, 1986, all infants with birth weight less than or equal to 1000 gm admitted to Oregon Health Sciences University who had persistent hyperglycemia and glycosuria were treated with graded insulin infusion while energy intake was increased to at least 100 kcal/kg/day (419 kilojoules/kg/day). The records of these infants were reviewed to define the clinical characteristics of infants likely to develop hyperglycemia and to see whether insulin administration would allow goals for energy intake to be met. There were 76 surviving infants; 34 received insulin and 42 did not. Treated infants were smaller (767 +/- 161 vs 872 +/- 98 gm; p = 0.0004), were more immature (26.8 +/- 1.4 vs 27.7 +/- 2.0 weeks; p = 0.0115), and required mechanical ventilation longer (28 +/- 19 vs 17 +/- 15 days; p = 0.0196). There were no significant differences between the groups at 3, 7, 10, or 14 days for intravenously administered glucose or for total nonprotein energy intake at 3, 7, 10, 14, 28, or 56 days. Treated infants achieved an intake of 100 kcal/kg/day (419 kilojoules/kg/day) at 15 +/- 8 vs 17 +/- 11 days and regained birth weight at 12 +/- 6 vs 13 +/- 6 days (NS). There was no difference in percent change from birth weight at 7, 14, 28, or 56 days. Treated infants had a glucose concentration of 195 +/- 60 mg/dl (10.8 +/- 3.3 mmol/L) while receiving 7.9 +/- 3.0 mg/kg/min (43 +/- 17 mumol/kg/min) of glucose at the start of insulin infusion on days 1 to 14. Insulin was given for 1 to 58 days. The initial dose was 40 to 100 mU/gm of dextrose infused (57 to 142 nmol/mol) and then gradually decreased. Less than 0.5% of blood glucose values were 25 to 40 mg/dl (1.4 to 2.2 mmol/L). We conclude that insulin infusion improves glucose tolerance in extremely low birth weight infants and allows hyperglycemic infants to achieve adequate energy intake similar to that of infants who do not become hyperglycemic.     

Energy expenditure in premature newborns with bronchopulmonary dysplasia.

Five premature newborns (birth weight, mean +/- SD, 960 +/- 145 g; gestational age 28 +/- 1 weeks) with bronchopulmonary dysplasia (BPD) according to the criteria of Bancalari, and 6 controls (birth weight 1,320 +/- 210 g; gestational age 30 +/- 2 weeks) were studied for energy expenditure (EE) by indirect calorimetry. The measurement of total EE was performed when the intake of the infants in both groups was the same and when the respiratory condition had stabilized (control group: postnatal age 31 +/- 6 days, 1,950 +/- 200 g; BPD group: postnatal age 105 +/- 45, postnatal weight 2,440 +/- 380). The BPD group had a higher VO2 (11.15 vs. 8.04 ml/kg/min, p less than 0.01), VCO2 (9.13 vs. 7.74 ml/kg/min, p less than 0.02) and total EE (76 vs. 61 kcal/kg/day, p less than 0.02). The highest values were encountered in the 3 more severely ill infants: mean VO2 11.03 ml/kg/min, mean EE 82 kcal/kg/min. In these cases, administration of medium chain triglycerides limits the increase in VCO2 and lowers the respiratory quotient (0.87 vs. 0.96 in controls.     

Prophylactic intravenous administration of immune globulin in preterm infants: effect on serum immunoglobulin concentrations during the first year of life

In a prospective study, serum IgG, IgA, IgM, and IgG subclass levels of 66 preterm infants (gestational age less than or equal to 34 weeks) were measured sequentially from birth to 12 months of life. Infants were divided into two groups, comparable for gestational age, birth weight, sex, and intensive care, on the basis of admission order: the treatment group, consisting of 33 infants who received intravenous immune globulin therapy (0.5 gm/kg at 10-day intervals) prophylactically, and the control group, consisting of 33 infants who did not receive. Twenty of the 33 treated infants received only one infusion and the remaining 13 received two to five infusions. The mean number of infusions per neonate was 1.96. Immunoglobulin measurements showed that the proportion of infants with an IgG level of greater than or equal to 7 gm/L on the tenth and thirtieth days of life was significantly higher in the treatment than in the control group (p less than 0.01). At the same ages, mean serum IgG, IgG1, and IgG2 concentrations were significantly higher in the treatment group (p less than 0.001). Thereafter levels in both groups fell progressively, reaching their lowest point between 3 and 5 months of age. During this period, profound hypogammaglobulinemia (IgG less than 2 gm/L) was observed in 3 of 33 treated and 11 of 33 untreated infants (p less than 0.05). By 3 months of age, mean serum total IgG concentrations were still significantly higher in treated than in untreated infants (p less than 0.05), but the IgG subclass concentrations were not. After the third month, no significant differences between the two groups were observed. Moreover, the sequentially measured serum IgA and IgM levels in the two groups remained comparable from birth to age 12 months. The IgG level at different ages from 3 to 12 months was not correlated with either birth weight or the number of infusions performed during the neonatal period (p greater than 0.1). We conclude that prophylactic intravenous administration of immune globulin to preterm infants with a birth weight of 1000 to 2000 gm, at a dose of 0.5 gm/kg every 10 days, results in maintenance of a satisfactory serum IgG level throughout the high-risk period for infections. Such treatment does not have a suppressive effect on subsequent serum immunoglobulin concentrations.     

Insulin infusions in infants of birthweight less than 1250 g and with glucose intolerance

Fifteen preterm babies (mean gestation: 26.7 weeks; mean birthweight 860 g) with significant glucose intolerance were treated with insulin infusions. During the insulin infusions there was a significant increase in both the mean energy intake (60.8 +/- 25.1 cal/kg per day to 79.9 +/- 24.5 cal/kg per day; P less than 0.001) and the mean amount of intravenous dextrose tolerated (7.0 +/- 2.7 mg/kg per min to 9.2 +/- 2.6 mg/kg per min; P less than 0.01). The infusions were initiated at a mean postnatal age of 5.3 days (range: 2-12 days) and were continued for 1.5-17.5 days. Of the 998 blood glucose estimations performed during the insulin infusions, 28 (2.8%) were less than 2 mmol/l and 216 (21.6%) greater than 8 mmol/l. We conclude that continuous insulin infusion is a safe and effective way of managing glucose intolerance in very low birthweight infants, provided adequate means for continuous monitoring of blood glucose are available.     

Decreased plasma glucose following indomethacin therapy in premature infants with patent ductus arteriosus

The effect of indomethacin on carbohydrate metabolism was studied in six premature infants with significant patent ductus arteriosus (mean +/- S.D., birth weight 1,066 +/- 244 gm, gestational age 30 +/- 1.6 weeks). All infants were in a glucose steady state between 50 and 100 mg/dl over a 2-hour period before indomethacin administration. There was a significant fall in plasma glucose at 1, 6, 12, and 24 hours following intravenous indomethacin infusion. Since there was no significant change in insulin levels from the baseline, the mechanism of indomethacin-mediated lack of prostaglandin inhibition of insulin release was not substantiated. Based on this study, plasma glucose levels should be followed closely in the first 24 hours following intravenous indomethacin administration.     

Ontogeny of glucose homeostasis in low birth weight infants

Suppression of the endogenous glucose production rate (Ra) is the adult response to glucose infusion. Persistent Ra (greater than or equal to 1 mg.kg-1min-1 or less than 80% decrease in basal Ra) in response to glucose infusion is evidence of a transitional homeostatic state in the neonate during the first days after birth. To determine whether postnatal development produces an adultlike response, Ra was measured in 11 infants (birth weight 1716 +/- 48 g, gestational age 33 +/- 0.3 weeks) at 2 to 5 weeks of age. In these paired studies, 4 micrograms.kg-1min-1 D-(U-13C)glucose tracer was infused by prime constant infusion to determine Ra, during infusion of either saline solution or glucose, the latter at a rate of 5.3 +/- 0.2 mg.kg-1min-1 (mean +/- SEM). When the results of the saline infusion turnover period were compared with those of the glucose infusion turnover period, plasma glucose concentration increased significantly, from 88 +/- 3 mg/dL to 101 +/- 4 mg/dL (P less than 0.001). Plasma insulin concentration remained unchanged (12 +/- 5 microU/mL vs 8 +/- 3 microU/mL). Ra was heterogenous during glucose infusion, and persistent Ra was present in six of 11 infants. Of the five infants who had decreased Ra during glucose infusion, three received glucose at a rate exceeding basal Ra. Of the remaining six infants who evidenced persistent Ra during glucose infusion, three received glucose at a rate equal to or in excess of basal Ra. We conclude that glucose homeostasis in low birth weight infants is transitional throughout the neonatal period.     

Insulin pump therapy in the very low birth weight infant

Ten critically ill, very low birth weight infants less than 30 weeks' gestation were treated with exogenous insulin administered through a continuous insulin infusion pump (Betatron II, Cardiac Pacemaker, Inc). Infants were hyperglycemic to dextrose infusions greater than 6 mg/kg/min. The blood glucose concentration became normal in all infants within two to four hours, with varying requirements for continued insulin treatment. Tolerance to intravenous dextrose increased from a mean of 7.4 mg/kg/min to 11.2 mg/kg/min with glycosuria. Energy intake increased from 49.5 calories/kg/d prior to insulin pump therapy to 70.4 calories/kg/d afterward (P less than .01) with weight gain changed from -23 g/d to +13 g/d (P less than .01). One unexpected observation was the apparent normalization of blood glucose homeostasis on higher dextrose doses among some infants after only one three- to six-hour treatment with insulin. The continuous insulin infusion pump is a flexible tool that allows insulin infusion rates to be changed as dictated by blood glucose values without altering other parenteral infusions.     

Metabolic rate and energy balance in infants with bronchopulmonary dysplasia

To determine energy use and growth of infants with bronchopulmonary dysplasia (BPD), we studied metabolic rate and energy balance in five infants with stage III-IV BPD (birth weight 1309 +/- 530 gm, gestational age 32 +/- 3 weeks, postnatal age 59.8 +/- 14.2 days) and in five control infants (birth weight 1540 +/- 213 gm, gestational age 33 +/- 2 weeks, postnatal age 42.0 +/- 4.2 days). Infants with BPD had significantly lower energy intake but higher energy expenditure than did control infants. Weight gain and energy cost of growth were significantly less in BPD infants than in control infants, as were urine output and output/intake ratio. We conclude that infants with BPD (1) absorbed caloric intake as well as did normal control infants, (2) had low energy intake and high energy expenditure, resulting in poor weight gain, and (3) had low energy cost of growth, suggesting an alteration in composition of tissue gain, with relatively high water content.     

Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin

Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful.     

Effect of hydrocortisone on intravenous glucose tolerance in small-for-gestational-age infants

The effects of hydrocortisone (H) hemisuccinate (10 mg/kg) on intravenous glucose tolerance (1 g/kg) was studied in eight full term small-for-gestational-age (SGA) infants and compared to seven control infants at mean age of 41 h. After H, the rate of glucose disappearance was (mean +/- SD) 0.92 +/- 0.27 vs 1.24 +/- 0.31% min in controls (p less than 0.01). Glucose space was similar after H: 449 +/- 62 ml/kg and in the control group 468 +/- 75 ml/kg. At 5 and 15 min, although higher in the H group, mean plasma glucose was not significantly different. The difference became significant at 30 min (t = 2.00; p = 0.05), 45 (t = 2.298; p less than 0.05) and 60 min (t = 2.48; p less than 0.02). Plasma insulin concentration did not change after glucose injection in the control group. After H administration, plasma insulin increased: the basal median value was less than 5 mU/ml (range less than 5-18) and at 60 min it rose to 30 mU/ml (range 7.5-89). These data suggest that in newborn infants corticoids induce a reduced peripheral uptake of glucose independent of insulin secretion.     

Determinants of arm muscle and fat accretion during the first postnatal month in preterm newborn infants

We measured arm muscle and fat areas in 22 preterm appropriate for gestational age infants at birth (mean +/- 1 SD birth weight: 1,640 +/- 484 g; gestational age: 31 +/- 2 weeks). Birth arm muscle and fat areas correlated significantly with gestational age (arm muscle: r = 0.86; p less than 0.001; arm fat: r = 0.75; p less than 0.001) and with birth weight. Deviations of birth weights from gestational age means (birth weight z-scores) were related more to variations in arm muscle area (r = 0.69; p less than 0.001) rather than arm fat area (r = 0.44; p = 0.04). Sixteen infants were followed over 4 weeks. They were most physiologically unstable (mean Physiologic Stability Index score = 5.3 +/- 3.5) during the first postnatal week when they also all lost weight. Their mean arm muscle area decreased significantly during the first week by greater than 10%, whereas the mean arm fat area remained unchanged. First week arm muscle losses were directly correlated with the lack of protein intake (r = 0.52; p less than 0.05). The regression equation predicted a protein intake of 4.06 g/kg/day (95% confidence interval: 2.3-6.4) to prevent first week muscle loss. Enteral intake and weight gain were established after week 1, accompanied by a significant reduction in physiologic instability (PSI score = 1.9 +/- 1.9; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity

To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity, we randomly assigned 19 anemic preterm infants (birth weight 988 +/- 227 gm; gestational age 27.6 +/- 1.2 weeks; age 41 +/- 15 days; all values mean +/- SD) to receive either transfusion or subcutaneously administered erythropoietin (200 units/kg every other day for 10 doses). In the 10 erythropoietin recipients, corrected reticulocyte counts increased from 2% +/- 1% to 7% +/- 2% (p less than 0.001) and hematocrits increased from 27% +/- 2% to 30% +/- 4% (p less than 0.05). In the nine infants who underwent transfusion, reticulocyte counts did not increase, but hematocrits increased from 28% +/- 4% to 41% +/- 2% after initial transfusion (p less than 0.001) and had decreased to 34% +/- 5% by day 20. Signs attributed to anemia (tachycardia, apnea with bradycardia, and poor weight gain) declined in both the erythropoietin recipients and those who underwent transfusion. However, five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions. Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors (p less than 0.01), greater concentrations of mature erythroid progenitors (p less than 0.001), and higher cycling rates of erythroid progenitors (p less than 0.001). The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group, resulting in an inverse myeloid/erythroid ratio (0.5:1 vs 6.2:1; p less than 0.001). After 20 days, absolute blood neutrophil counts were lower in the erythropoietin recipients (1.8 +/- 0.9 x 10(3) cells/microliters) than in the infants who underwent transfusion (3.9 +/- 1.9 x 10(3) cells/microliters; p less than 0.05). Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia; the significance of the relative neutropenia remains to be determined. We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity.     

Optimization of gentamicin therapy in very low birth weight infants

In order to optimize gentamicin (G) therapy we studied G pharmacokinetics in 48 preterm infants (gest. age 31.6 +/- 3.4, range 25-37 wk; birth weight 1.5 +/- 0.5 kg, range 0.7-2.5 kg). They received IV G twice daily (5.2 +/- 0.6 mg/kg/day). After at least 2 days of treatment trough and peak levels were measured for 2 successive doses. Trough levels were significantly higher in infants less than 1 kg receiving 5 mg/kg/day than in other infants (1-2.5 kg) who received the same dose (3.1 +/- 1.0 vs. 2.3 +/- 0.5 micrograms/ml; p less than 0.01). Mean G t 1/2 was significantly longer in infants under 1 kg than in those weighing 1-2.5 kg (7.9 +/- 1.9 and 6.5 +/- 1.6 hr, respectively; p less than 0.01). These differences could be attributed to lower G clearance in infants less than 1 kg (31 +/- 6 vs. 39 +/- 8 ml/kg/hr; p less than 0.005). There was no difference in G distribution volume between less than 1 kg and 1-2.5 kg infants (0.35 +/- 0.07 and 0.38 +/- 0.13 L/kg, respectively). A correlation was found between clearance and t 1/2 for the total group (r = 0.57, p less than 0.01). No correlation was detected between BUN and clearance or between gestational age and clearance. Our data suggest that G dose in infants less than 1 kg should be reduced to 3.5-4 mg/kg/day in order to avoid excessive levels associated with nephrotoxicity.     

Introduction of intravenous lipid administration on the first day of life in the very low birth weight neonate

OBJECTIVE: To investigate lipid tolerance in sick, ventilator-dependent, very low birth weight infants from the first day of life and the effects of early introduction of intravenously administered lipid (IVL) on glucose homeostasis. METHOD: Twenty-nine infants in the neonatal intensive care unit with birth weight less than 1500 gm received isocaloric, isonitrogenous parenteral feedings from day 1 with either IVL, 1 gm/kg from day 1 to 3 gm/kg from day 4 (group I; n = 16), or IVL added only from day 8 (group II; n = 13). Possible adverse clinical effects were monitored. Blood metabolites, nonesterified fatty acids, serum triglycerides, and insulin levels were determined daily. Arterial blood gases were measured and changes in partial pressures of oxygen and of carbon dioxide in arterial blood were compared between the two groups. RESULTS: Early lipid infusion did not appear to have deleterious effects on blood gas tensions or to increase respiratory morbidity. The incidence of other adverse clinical effects that may be associated with IVL was not increased by earlier introduction of lipid. Serum lipid values were comparable to those of preterm infants receiving IVL at a later postnatal age. Blood glucose concentrations were higher in group II (mean, 7.50 (SEM 0.43) mmol/L) than in group I (mean, 6.01 (SEM 0.28) mmol/L; p less than 0.05). There was no evidence of increased gluconeogenesis in infants in group I and no correlation between blood glucose concentrations and serum nonesterified fatty acid concentrations. CONCLUSION: When given infusion rates not exceeding 0.15 gm/kg/hr, sick, very low birth weight infants can tolerate IVL with stepwise dose increases from the first day of life without an increased incidence of possible adverse effects.     

Total parenteral nutrition with intralipid in premature infants receiving TPN with heparin: effect on plasma lipolytic enzymes, lipids, and glucose

Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic and clinical consequences of changing from high-glucose to high-fat regimens in parenterally fed newborn infants

To evaluate the metabolic and clinical consequences of changing from high-glucose to high-fat regimens during initiation of parenteral nutrition, we performed 22 studies in 11 newborn infants (birth weight (mean +/- SD) 2.54 +/- 0.54 kg, gestational age 37 +/- 3 weeks, postnatal age 8 +/- 3 days) maintained in a constant thermal environment. In a paired design, two isoproteinic (2.4 +/- 0.2 gm/kg/day) and isocaloric (64 +/- 6 kcal/kg/day) regimens differing by source of energy (high glucose vs high lipid) were infused on consecutive days. Environmental and body temperatures were recorded during a 4-hour period, and 24-hour urinary excretions of catecholamines, nitrogen, and C peptide were measured. Despite constant incubator and average skin temperatures, the rectal and interscapular temperatures rose significantly when the high-glucose regimen was changed to a high-lipid regimen. The specific locations of these changes in body temperature suggested brown fat activation. A significant drop in nitrogen retention (63 +/- 9% vs 56 +/- 10%) during the lipid infusion could be further evidence of a metabolic adaptation to the rapid change in energy substrates.     

Role of glucose in the regulation of endogenous glucose production in the human newborn

The role of plasma glucose concentration in the regulation of endogenous glucose production in the human newborn was examined by infusing glucose at 2.6-4.6 mg/kg . min as a continuous infusion to eight normal term appropriate for gestational age infants, five preterm, and six small for gestational age infants. All infants were healthy, had no overt clinical problems and were studied 6 h after their last feed. Glucose production rates were measured during the basal state and during glucose infusion by tracer dilution using [6,6(2)H2]glucose. The rate of glucose production during the basal state was similar in preterm and term appropriate for gestational age infants (appropriate for gestational age 3.53 +/- 0.32, preterm 3.49 +/- 0.38 mg/kg . min, mean +/- SD), while it was higher in the small for gestational age infants (4.25 +/- 0.98, p less than 0.03) as compared with appropriate for gestational age. During glucose infusion, the peak glucose concentration was related to the rate of glucose infusion. The endogenous glucose production rates during glucose infusion were variable in the three groups. However, a negative correlation between peak glucose concentration and endogenous glucose production rate was observed (r = 0.59, p = 0.006). The insulin response to glucose infusion was comparable in all infants. In addition, three small gestational age and one preterm infants, who had become hypoglycemic in the immediate newborn period, were studied while they were receiving parenteral glucose and their plasma glucose had stabilized at 55.5 +/- 10.25 mg/dl. Tracer kinetic studies showed persistence of endogenous glucose production in these infants even though they were receiving high rates of exogenous glucose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers.

Infants of diabetic mothers frequently have polycythemia, elevated serum erythropoietin concentrations, and decreased serum iron and ferritin concentrations, likely representing a redistribution of fetal iron into erythrocytes to support augmented fetal hemoglobin synthesis. We hypothesized that fetal liver, heart, and brain iron concentrations are also reduced in these infants. After obtaining autopsy tissue from infants who had died before 7 days of age, we measured liver, heart, and brain iron concentrations using atomic absorption spectrophotometry. Seven infants of diabetic mothers and seven gestational age-matched control infants were studied. All infants of diabetic mothers had pancreatic islet cell hyperplasia, indicating fetal hyperglycemia and hyperinsulinemia. Liver iron concentrations in the infants of diabetic mothers were 6.6% of control values (489.0 +/- 154.4 vs 7379.7 +/- 1473.8 micrograms/gm dry tissue weight (mean +/- SEM); p less than 0.001), heart iron concentrations were 43.9% of control values (124.7 +/- 20.5 vs 284.1 +/- 34.8 micrograms/gm dry tissue weight; p less than 0.002), and brain iron concentrations were 60.6% of control values (106.1 +/- 13.7 vs 175.2 +/- 10.7 micrograms/gm dry tissue weight; p less than 0.003). Heart and brain iron concentrations were directly correlated with liver iron concentrations (r = 0.80 for both; p less than 0.001) and indicated that hepatic iron was greater than 75% depleted before heart and brain iron reduction. We conclude that severely affected infants of diabetic mothers have reduced liver, heart, and brain iron concentrations. The role of tissue iron deficiency in the genesis of the abnormal clinical findings in these infants deserves further consideration.     

Glucagon and insulin secretion in low birthweight preterm infants. The effect of glucose infusion

The effect of the intravenous glucose on plasma levels of glucagon and insulin were evaluated in thirty-five LBW preterm infants who were appropriate for gestational age. Their mean birthweight and gestational age were 1220 +/- 55 g (range 750-1730 g) and 29 +/- 1 weeks (range 25-35 weeks), respectively. A 30 min glucose infusion in 16 infants (1 g/kg b.w. in 30 min) caused a prompt and sustained suppression of plasma glucagon and a delayed but significant insulin release. The mean of the sum of maximal plasma glucagon decrements below the baseline was 173 +/- 42 pg/ml. In another 12 infants a significant fall in plasma glucagon and a variable but significant plasma insulin release also occurred throughout the 24 h study on continuous intravenous glucose (rate 2.4-2.7 mg/kg/min). The mean of the sum of maximal plasma glucagon decrements below the baseline up to 12 h was 282 +/- 36 and was similar to that seen in the previous group.     

Insulin-like growth factor I (somatomedin C) in premature infants on total parenteral nutrition. Relations with nutritional status and protein-energy intakes]

Insulin-like growth factor I (IGF I) is like prealbumin and transferrin a marker of nutritional status. Its level increases with gestational age. The levels of IGF I (96 times), transferrin (86 times) and prealbumin (69 times) were measured in blood samples from 26 premature infants aged 8 to 78 days (gestational age: 28 to 34 weeks, birth weight: 840 to 1,800 g). At the time of sampling, all the infants were on total parenteral nutrition (360 +/- 42 kJ/kg/day and 2.5 +/- 0.3 g of proteins/kg/day). The results were analysed with reference to anthropometric parameters (weight, height, head circumference, skinfolds and arm circumference). There was no correlation between plasma IGF I and anthropometric measurements. There were significant correlations between IGF I and transferrin (p less than 0.01), prealbumin (p less than 0.05), protein intake (p less than 0.01) an energy intake (p less than 0.05). Plasma IGF I increased at the end of the first week of parenteral nutrition in all the 5 infants having initial low values. The plasma IGF I was not correlated with the duration of parenteral nutrition in the 26 infants after the second week of nutrition. IGF I measurement is useful for evaluating the protein nutritional status of premature infants on total parenteral nutrition.