Metabolic events in infants of diabetic mothers during first 24 hours after birth. I. Changes in plasma glucose, insulin and glucagon

Changes in plasma glucose, nonantibody-bound insulin and glucagon concentrations were studied in 32 newborn infants of diabetic mothers (IDM) during the first 24 hours after birth. Ten infants were born to White class A mothers and 22 to class B-F mothers. The infants were kept fasting during the investigative period and blood was sampled from an umbilical artery catheter. At birth, plasma glucose and glucagon levels were similar in the class A and B-F infants, whereas nonantibody-bound insulin levels were approximately 15-fold higher in the class B-F infants than in the class A infants (p less than 0.001). After birth, plasma glucose fell in all infants, the nadir being reached at two hours (p less than 0.01). Plasma glucose fell by approximately 35% in the class A infants and 63% in the class B-F infants (p less than 0.01). Eight IDM had asymptomatic hypoglycemia (plasma glucose less than 1.9 mmol/l) and four of these infants had glucose levels below 1.7 mmol/l and were withdrawn from further study. In the remaining four hypoglycemic IDM, plasma glucose was about 1.6-fold higher (p less than 0.01) and insulin about 11-fold higher (p less than 0.001) at birth compared to the 24 normoglycemic IDM. The hypoglycemia was attended by unchanged insulin levels in the class A infants, whereas insulin fell in the class B-F infants (p less than 0.01). However, during the whole investigative period, plasma insulin of the class B-F infants was higher than that of the class A infants (p less than 0.01). After birth, plasma glucagon increased slowly in all IDM and peak values were reached after 12 hours in the class A infants (p less than 0.05) and 24 hours in the class B-F infants (p less than 0.01). Only those infants who became hypoglycemic after birth exhibited a significant increment in plasma glucagon from 0.2 hours (p less than 0.05). These results suggest that neonatal hypoglycemia of IDM results from high plasma levels of nonantibody-bound insulin together with a very retarded increment in plasma glucagon levels. The degree of neonatal hypoglycemia and hyperinsulinemia of an individual IDM seems to be positively correlated to the severity of the diabetes of the mother.     

METABOLIC EVENTS IN INFANTS OF DIABETIC MOTHERS DURING FIRST 24 HOURS AFTER BIRTH I.

ABSTRACT. Changes in plasma glucose, nonantibody-bound insulin and glucagon concentrations were studied in 32 newborn infants of diabetic mothers (IDM) during the first 24 hours after birth. Ten infants were born to White class A mothers and 22 to class B-F mothers. The infants were kept fasting during the investigative period and blood was sampled from an umbilical artery catheter. At birth, plasma glucose and glucagon levels were similar in the class A and B-F infants, whereas nonantibody-bound insulin levels were approximately 15-fold higher in the class B-F infants than in the class A infants (p<0.001). After birth, plasma glucose fell in all infants, the nadir being reached at two hours (p<0.01). Plasma glucose fell by approximately 35 % in the class A infants and 63 % in the class B-F infants (p<0.01). Eight IDM had asymptomatic hypoglycemia (plasma glucose <1.9 mmol/l) and four of these infants had glucose levels below 1.7 mmol/l and were withdrawn from further study. In the remaining four hypoglycemic IDM, plasma glucose was about 1.6-fold higher (p<0.01) and insulin about 11-fold higher (p<0.001) at birth compared to the 24 normoglycemic IDM. The hypoglycemia was attended by unchanged insulin levels in the class A infants, whereas insulin fell in the class B-F infant (p<0.01). However, during the whole investigative period, plasma insulin of the class B-F infants was higher than that of the class A infants (p<0.01). After birth, plasma glucagon increased slowly in all IDM and peak values were reached after 12 hours in the class A infants (p<0.05) and 24 hours in the class B-F infants (p<0.01). Only those infants who became hypoglycemic after birth exhibited a significant increment in plasma glucagon from 0-2 hours (p<0.05). These results suggest that neonatal hypoglycemia of IDM results from high plasma levels of nonantibody-bound insulin together with a very retarded increment in plasma glucagon levels. The degree of neonatal hypoglycemia and hyperinsulinemia of an individual IDM seems to be positively correlated to the severity of the diabetes of the mother.     

Course of the blood glucose level after cessation of a glucose infusion in the low-birth-weight infant

The evolution of plasma glucose concentration was investigated in 8 dysmature and 5 appropriate-for-gestational-age (AGA) preterm infants. Mean (+/- 1 SD) plasma glucose decreased from 3,3 +/- 0,8 to 2,3 +/- 1,2 mmol/l in 30 minutes (p less than 0,01) with two values below 1,8 mmol/l. It then increased to 2,7 +/- 0,7 mmol/l at 60 minutes with no values below 1,8 mmol. In 4 (AGA) preterm infants plasma glucose decreased from 2,73 +/- 0,76 to 2,04 +/- 1,6 mmol/l at 60 minutes. One preterm infant treated with theophylline showed an increase from 4,91 to 6,05 mmol/l at 60 minutes. A negative correlation was observed only in dysmature infants between the rate of glucose infusion and the maxima drop of plasma glucose (r = 0,77 ; p less than 0,01). In dysmature infants, a drop in plasma glucose appears in correlation to the previous infusion rate of glucose. However a counterregulation appears in all dysmature infants.     

Hypoglycemia in newborn infants: Features associated with adverse outcomes

The purpose of this review article is to document from the literature values of blood/plasma glucose concentration and associated clinical signs and conditions in newborn infants (both term and preterm) that indicate a reasonable clinical probability that hypoglycemia is a proximate cause of acute and/or sustained neurological injury and to review the physiological and pathophysiological responses to hypoglycemia that may influence the ultimate outcome of newborns with low blood glucose. Our overall conclusion is that there is inadequate information in the literature to define any one value of glucose below which irreparable hypoglycemic injury to the central nervous system occurs, at any one time or for any defined period of time, in a population of infants or in any given infant. Clinical signs of prolonged and severe neurological disturbance (coma, seizures), extremely and persistently low plasma/blood glucose concentrations (0 to <1.0 mmol/l [0 to <18-20 mg/dl] for more than 1-2 h), and the absence of other obvious central nervous system (CNS) pathology (hypoxia-ischemia, intracranial hemorrhage, infection, etc.) are important for the diagnosis of injury due to glucose deficiency. Specific conditions, such as persistent hyperinsulinemia with severe hypoglycemic episodes that include seizures, also contribute to the diagnosis of hypoglycemic injury. Such lack of definitive measures of injury specific to glucose deficiency indicates that clinicians should be on the alert for infants at risk of hypoglycemia and for clinical signs and conditions that might herald severe hypoglycemia; they should have a low threshold for investigating and diagnosing 'hypoglycemia' with frequent measurements of plasma/blood glucose concentration; and they should treat low glucose concentrations promptly and maintain them in a safe range. Because there is no conclusive evidence or consensus in the literature that defines an absolute value or duration of 'hypoglycemia' that must occur, with our without related clinical complications, to produce neurological injury, clinicians should consider the information currently available, determine a 'target' plasma or blood glucose concentration that is acceptable, and treat infants with glucose concentrations below this value accordingly. Our intent in this review article is to highlight the studies relevant to this issue and help clinicians formulate a safe and, hopefully, effective strategy for the diagnosis and treatment of hypoglycemia.     

Ketogenesis in hypoglycemic neonates. Carnitine and dicarboxylic acids in neonatal hypoglycemia

Since hypoglycemic neonates do not exhibit compensative ketosis, we investigated the possible involvement of carnitine deficiency or omega-oxidation in neonatal hypoglycemia. In a first group of 49 neonates, serum free fatty acid, acetoacetate and beta-hydroxybutyrate concentrations were similar in hypoglycemic and normoglycemic neonates. Serum free carnitine concentrations did not show any difference in the hypoglycemic small-for-date infants (median 40 mumol/l, range 16-92 mumol/l) compared to the normoglycemic small-for-date infants (median 30 mumol/l, range 8-64 mumol/l). In a second group of 45 neonates, urinary excretion of dicarboxylic acids (adipic, suberic, sebaric and succinic acids) was similar in hypoglycemic infants compared to normoglycemic neonates. Despite the limitations of interpretation of free carnitine determination, these data do not suggest an impaired beta-oxidation by carnitine depletion or an enzymatic defect in hypoglycemic neonates.     

Diagnostic evaluation of persistent neonatal hypoglycemia using the fasting test: behavior of glucoregulatory hormones and intermediary metabolites (1)

The effect of insulin induced hypoglycemia on glucoregulatory hormones and intermediary substrates was studied in four infants (three boys and one girl, ages 12-89 days) with persistent hyperinsulinism secondary to nesidioblastosis (two) or microadenoma of the pancreas (two). During the "fasting test" the following data expressed as mean basal plasma values +/- SEM vs. mean hypoglycemic values +/- SEM were obtained: insulin (57.3 +/- 17.9 vs. 27.5 +/- 10.6 microU/ml), C-peptide (4.9 +/- 1.1 vs. 3.5 +/- 0.9 ng/ml), free fatty acids (0.30 +/- 0.01 vs. 0.32 +/- 0.02 mmol/l), beta-hydroxybutyrate (less than 0.03 vs. 0.05 +/- 0.02 mmol/l), alanine (204.0 +/- 67.5 vs. 228.3 +/- 64.9 mumol/l), lactate (5.3 +/- 0.7 vs. 5.4 +/- 1.1 mg/dl), pyruvate (41.3 +/- 4.8 vs. 19.7 +/- 4.2 mg/dl). These data suggest "inappropriate" elevation of insulin and C-peptide levels, inhibition of lipolysis and lack of gluconeogenic substrates secondary to endogenous HI. An increase of cortisol (6.5 +/- 4.1 vs. 16.3 +/- 5.7 micrograms/dl), adrenaline (0.015 +/- 0.05 vs. 0.25 +/- 0.24 ng/ml) (3 out of 4) and noradrenaline (0.28 +/- 0.06 vs. 0.64 +/- 0.14 ng/ml) was noted, whereas only minute increase was found for glucagon (134.3 +/- 51.7 vs. 177.0 +/- 76.2 pg/ml) and HGH (5.7 +/- 1.1 vs. 7.1 +/- 1.1 ng/ml). Although some stimulation of neonatal glucoregulatory hormones was evident, this was not strong enough for counteracting endogenous HI.     

Influence of the maternal plasma glucose concentration at delivery on the risk of hypoglycaemia in infants of insulin-dependent diabetic mothers

Plasma glucose concentrations at birth and at two hours of age were measured in 53 infants of insulin-dependent mothers (IDMs). The plasma glucose concentrations at delivery were measured in the mothers of 17 IDMs and in the remaining 36 mothers, glucose was estimated by interpolation from concentrations achieved just before and after delivery. Clinical and laboratory data from the two groups were otherwise similar, so the groups were combined for further analyses. The maternal plasma glucose at delivery correlated positively with the glucose concentration of the IDMs at birth (rho = 0.82, p less than 0.001) and negatively with the glucose concentration at two hours of age (rho = -0.46, p less than 0.001). Maternal plasma glucose concentration was higher in mothers delivered by caesarean section than in vaginally delivered mothers (p less than 0.05). Eleven IDMs became hypoglycaemic at two hours of life (plasma glucose less than or equal to 1.7 mmol/l). These infants had higher cord plasma glucose concentrations at birth than those who remained normoglycaemic; the maternal glucose concentration was also higher. None of the IDMs became hypoglycaemic if the maternal glucose concentration at delivery was less than 7.1 mmol/l. In 28 IDMs the simultaneous plasma concentrations of non-antibody bound immunoreactive insulin (IRI) were recorded. Cord plasma IRI correlated with glucose and IRI at two hours of age (rho = -0.73, p less than 0.001 and rho = 0.77, p less than 0.001, respectively). Cord plasma IRI was higher in IDMs who became hypoglycaemic than in the remaining infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment with hypertonic dextrose and insulin in severe hyperkalaemia of immature infants

Over a three-year period, 12 infants received dextrose/insulin infusions for severe hyperkalaemia from a mean age of 24 h. The infants were born after 24 to 26 weeks of gestation and weighed 730 +/- 172 g (mean +/- SD) at birth. Serum potassium concentration ranged from 7.4 to 8.4 mmol/l (7.7 +/- 0.4 mmol/l; mean +/- SD). Four had cardiac arrhythmias. All infants showed an initial response, serum potassium concentration decreased below 6.5 mmol/l in 5 +/- 2 h. In two infants, rebound hyperkalaemia occurred and was resistant to treatment; both infants died, one during an exchange transfusion. In the other 10 infants, infusions were ceased at a mean postnatal age of 53 h. Hyperglycaemia was the major problem during infusion and was resistant to increases in insulin concentrations. Normoglycaemia was achieved in 10 infants. The hypertonic solution consisted of a dextrose/insulin ratio of 2.2 +/- 0.6 g/IU, which delivered glucose at a rate of 0.46 +/- 0.15 g/kg/h, in addition to the pre-existing stable maintenance glucose intake.     

Placental taurine and low birth weight infants

In order to determine whether the decrease in taurine concentration in the placenta during pregnancy could affect fetal development, as has been observed in animals, we measured the concentration of taurine in placentas obtained after vaginal expulsion. 31 placentas from women with normal pregnancies of over 37 weeks who have given birth to infants of normal weight (3,200 +/- 310 g) were included in the study. In addition, 26 placentas of infants considered to be hypotrophic were also included (gestation over 37 weeks, birth weight: 2,260 +/- 230 g). The taurine was assayed using gaz-liquid chromatography. The concentration of taurine in the placenta was 2.80 +/- 0.56 mumol/g for the placentas of normal birth weight infants and 2.40 +/- 0.64 mumol/g for the placentas of hypotrophic infants (p less than 0.02). There is no significant correlation in normal and hypotrophic newborns between the gestation period, the weight and height at birth, the weight of the placenta, and the taurine concentration in the placenta. The taurine concentration in placentas of hypotrophic born infants is significantly reduced compared to the placentas from normal infants.     

Pulmonary hemorrhages in newborn infants with inborn errors of the 1st 2 phases of the urea cycle

Two critically ill, male newborns developed pulmonary bleeding and died after four respectively three days. In both infants an inborn error in the urea cycle (carbamylphosphatsynthetase-deficiency and ornithintranscarbamylase-deficiency respectively) was demonstrable. It is suggested that hyperammonemia could be the reason for pulmonary bleeding. Plasma ammonia levels should be determined in newborns with pulmonary bleeding, especially in those with normal weight and good health at birth.     

The use of a continuous glucose monitoring system in hypoglycemic disorders

OBJECTIVE: To evaluate the use of a continuous glucose monitoring system (CGMS) in the evaluation and treatment of infants and children with hypoglycemic disorders. METHODS: Patients with hypoglycemic disorders wore the CGMS device in the Pediatric Clinic Research Center during their evaluation and treatment. Capillary blood glucose (CBG) values were obtained at least 3 times each day and entered into the device for calibration purposes. We evaluated the number of hypoglycemic episodes below 3.3 mmol/l (60 mg/dl) detected by CGMS compared to CBG values and characterized episodes by their duration and intensity. RESULTS: Five patients with hypoglycemic disorders were included in the study. There were a total of 13,369 sensor points, 343 paired sensor and CBG data points, and 57 days included. A total of 180 episodes of hypoglycemia occurred in these five patients, with an average duration of 55 +/- 13 minutes. Using a cut-off of 3.3 mmol/l (60 mg/dl) for hypoglycemia, the sensor had a sensitivity of 65.4%, specificity of 90.6%, and false positive rate of 42.9%. The positive and negative predictive values were 57.1% and 93.2%, respectively. CONCLUSION: CGMS is a useful adjunct in the diagnosis and evaluation of hypoglycemia, and for documentation of euglycemia in these patients following therapy.     

Intestinal absorption of vitamin E in low birth weight infants

Intestinal absorption of dl-alpha-tocopheryl acetate was studied in low birth weight infants. Vitamin E was given from the first day of life, either as a water-soluble (Ephynal) or as a lipid-soluble preparation (E-vitamin). Serum-alpha-tocopherol concentrations were determined before treatment and on days three and seven. Treatment with both vitamin E preparations increased serum-alpha-tocopherol on day three and seven. The mean serum-alpha-tocopherol +/- SD on day seven were 41.4 +/- 10.7 mumol/l for the Ephynal group and 26.7 +/- 12.5 mumol/l for the E-vitamin group, this difference being statistically significant (p less than 0.025). Oral feeding seems to influence the absorption of tocopherol from E-vitamin, as the infants with the highest serum-alpha-tocopherol concentrations were those with the highest oral/total feeding ratios. In infants with birth weight less than 1 000 g treatment with 25 mg Ephynal/day was found to increase serum-alpha-tocopherol on day seven to 46.9 +/- 12.3 mumol/l (mean +/- SD). This concentration is comparable to those reported by others using higher doses of oral vitamin E.     

Effect of oral lipid administration on glucose homeostasis in small-for-gestational-age infants

The metabolic effect of feeding with 1.3 g/kg bw lipids (67% medium chain triglycerides) was studied in 15 small-for-gestational age (SGA) term infants. It was compared to a control group of 7 SGA term infants, to 7 term infants with an appropriate birth weight (AGA) and to 7 AGA preterm infants. Plasma glucose concentration rose from (M +/- SE) 3.6 +/- 0.2 to 4.4 +/- 0.3 mmol/l at 30 min in SGA term infants (p less than 0.01). A similar increase was observed in AGA term and preterm infants. The lipid load produced no change in plasma glucagon concentration but a significant increase in insulin/glucagon molar ratio was observed in AGA term infants only. In term SGA infants, the disappearance rate of glucose in plasma after the lipid load was similar to the control: 1.24% per min. The evolution of blood pyruvate and lactate concentration was not modified by the lipid load. Despite lower concentrations of free fatty acids and ketone bodies (KB) in SGA infants than in AGA term infants, the lipid load induced a 120% increase of ketone bodies in SGA infants and a 40% increase only in AGA infants. These data show that these lipids produce a hyperglycemic response in SGA infants as in AGA infants without any change of the disappearance rate of glucose. They suggest that these lipids can stimulate gluconeogenesis and ketogenesis in SGA infants.     

Glycerol metabolism and triglyceride-fatty acid cycling in the human newborn: effect of maternal diabetes and intrauterine growth retardation.

Kinetics of glycerol metabolism and triglyceride/fatty acid cycling were quantified in 12 healthy, normal, appropriate-for-gestational-age (AGA) infants, eight small-for-gestational-age (SGA) infants, and five infants of insulin-dependent diabetic mothers (IDM) at less than 48 h of age. Stable isotope-labeled [2-13C]glycerol and [6,6-2H2]glucose in combination with indirect respiratory calorimetry were used. The tracers were used as constant rate infusion and steady state isotopic enrichment of glucose, glycerol, and bicarbonate was measured by mass spectrometric methods. After a 7- to 9-h fast, the plasma glucose, glycerol, and FFA concentrations were similar in the AGA and IDM groups. In the SGA group, the plasma glucose concentration was significantly lower than that in the AGA group throughout the study, but plasma FFA and glycerol concentrations were not different from those in the AGA infants. Plasma betahydroxybutyrate concentration was significantly elevated in the AGA group compared with IDM and SGA infants (AGA 0.59 +/- 0.39, SGA 0.35 +/- 0.09, IDM 0.33 +/- 0.21 mmol/L; mean +/- SD). The rate of appearance of glycerol was significantly elevated (p less than 0.05) in SGA infants (AGA 9.47 +/- 2.11, IDM 9.55 +/- 2.14, SGA 12.15 +/- 3.87 mumol/kg.min). Between 80 and 90% of glycerol turnover was converted to glucose, accounting for 20% of glucose turnover with no significant difference in the three groups. Approximately 35% of glycerol carbon was recovered in the bicarbonate (CO2) pool. Less than 5% of CO2 carbon was derived from glycerol. Estimation of triglyceride-fatty acid cycle revealed that the triglyceride energy mobilized was increased in SGA infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neonatal nutrition with enriched human milk. EOPROTIN 60 in comparison with human albumin]

The influence of feeding fresh human milk supplemented either with EOPROTIN (n = 13) or human albumin (n = 15) on biochemical parameters and growth were studied in preterm infants with gestational ages below 32 weeks p.m. up to the 42nd day of postnatal life. In both feeding groups the intakes of protein, energy and electrolytes were similar. The serum concentrations of bile acids, alpha-amino-nitrogen and prealbumin, the renal excretion of total nitrogen, alpha-amino-nitrogen, urea and ammonia as well as the growth in weight and length were studied in all infants. The supplementation of the fresh human milk with EOPROTIN results in significant lower serum concentrations of alpha-amino-nitrogen (1.56 +/- 0.21 vs 2.03 +/- 0.27 mmol/l; p less than 0.01), higher serum concentrations of prealbumin (89.8 +/- 20.3 vs 72.7 +/- 13.3 mg/l; p less than 0.02), and lower urinary excretion of total nitrogen (7.4 +/- 0.9 vs 8.9 +/- 1.1 mmol/kg/day); if compared to the results found in the infants fed human albumin supplemented human milk. The higher nitrogen retention in the EOPROTIN than in the human albumin fed infants was associated by a significant higher growth in weight (16.6 +/- 1.4 vs 13.7 +/- 1.9 g/kg/day; p less than 0.01) as well as in length (1.02 +/- 0.08 vs 0.87 +/- 0.1 cm/week; p less than 0.01). The results indicate that the bioavailability of EOPROTIN is higher than that of human albumin. The observed differences in the nutritional response between the two human milk supplements may be based on differences in the amino acids composition which is in EOPROTIN adapted to the nutritional available part of the protein in human milk.     

Postheparin plasma lipoprotein and hepatic lipase activities in hyperinsulinemic infants of diabetic mothers and in large-for-date infants at birth

To study postheparin plasma lipase activities in nonfed newborn infants immediately after birth and to investigate the possible influence of fetal hyperinsulinemia on lipoprotein lipase activity, we measured lipoprotein and hepatic lipase activities in 55 macrosomic newborn infants: group I consisted of 21 infants born to mothers with insulin-dependent diabetes. The infants were hyperinsulinemic at birth and had hypoglycemia and poor lipolysis at the age of 2 h. Group II consisted of 18 infants born to mothers with gestational diabetes. Group III consisted of 16 large-for-date infants born to nondiabetic mothers. The mean postheparin plasma lipoprotein lipase activities at 2 h of age were similar (mean 36 mumol free fatty acids/ml/h; SEM 15) in groups I-III. Lipoprotein lipase activity correlated negatively with cord-serum triglycerides (range 0.13-1.2 mmol/liter) but did not correlate with serum insulin (range 5.4-524 microU/ml) or C-peptide (range 0.6-21.0 micrograms/liter). Hepatic lipase activity was somewhat higher in group I (mean 68 mumol free fatty acids/ml/h; SEM 23) than in groups II and III (mean 55 mumol free fatty acids/ml/h; SEM 14). Hemoglobin Alc was the only important factor explaining the difference in hepatic lipase activities between groups. Lipoproteins and apolipoproteins A-I, A-II, and B were similar in all three groups. We conclude that in large-for-date infants lipoprotein lipase is active at birth without exogenous fat induction, and that these infants are capable of hydrolyzing fat, their main source of energy, immediately after birth. In addition, we conclude that postheparin plasma lipoprotein lipase activity is not affected by fetal hyperinsulinemia.     

Postheparin plasma lipoprotein and hepatic lipase activities in hyperinsulinemic infants of diabetic mothers and in large-for-date infants at birth

To study postheparin plasma lipase activities in nonfed newborn infants immediately after birth and to investigate the possible influence of fetal hyperinsulinemia on lipoprotein lipase activity, we measured lipoprotein and hepatic lipase activities in 55 macrosomic newborn infants: group I consisted of 21 infants born to mothers with insulin-dependent diabetes. The infants were hyperinsulinemic at birth and had hypoglycemia and poor lipolysis at the age of 2 h. Group II consisted of 18 infants born to mothers with gestational diabetes. Group III consisted of 16 large-for-date infants born to nondiabetic mothers. The mean postheparin plasma lipoprotein lipase activities at 2 h of age were similar (mean 36 mumol free fatty acids/ml/h; SEM 15) in groups I-III. Lipoprotein lipase activity correlated negatively with cord-serum triglycerides (range 0.13-1.2 mmol/liter) but did not correlate with serum insulin (range 5.4-524 microU/ml) or C-peptide (range 0.6-21.0 micrograms/liter). Hepatic lipase activity was somewhat higher in group I (mean 68 mumol free fatty acids/ml/h; SEM 23) than in groups II and III (mean 55 mumol free fatty acids/ml/h; SEM 14). Hemoglobin Alc was the only important factor explaining the difference in hepatic lipase activities between groups. Lipoproteins and apolipoproteins A-I, A-II, and B were similar in all three groups. We conclude that in large-for-date infants lipoprotein lipase is active at birth without exogenous fat induction, and that these infants are capable of hydrolyzing fat, their main source of energy, immediately after birth. In addition, we conclude that postheparin plasma lipoprotein lipase activity is not affected by fetal hyperinsulinemia.     

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.     

Cerebral blood flow and metabolism in fasting neonatal piglets

Cerebral blood flow and cerebral metabolism were studied in 8 fasting neonatal piglets. Cerebral blood flow was not significantly different (p greater than 0.1) at 24 h (75.0 +/- 30.7 ml/min/100 g) and 48 h (74.2 +/- 32.3 ml/min/100 g) of age. Blood glucose concentration was lower in 48-hour-old fasted piglets (1.27 +/- 0.60 mmol/l) in comparison with 24-hour-old fasted animals (2.90 +/- 0.52 mmol/l), and cerebral glucose utilisation rate was also reduced in the 48-hour-old piglets (17.6 +/- 6.0 mumol/min/100 g at 48 h, 34.2 +/- 12.2 mumol/min/100 g at 24 h). Blood lactate concentration and cerebral lactate utilisation rate were not significantly different at 24 and 48 h of age. Brain lactate utilisation accounted for approximately 10% of cerebral oxygen utilisation at 48 h in fasted piglets. Cerebral glucose and lactate utilisation at 48 h accounted for approximately 66% of cerebral oxygen uptake, indicating that other substrates make a major contribution to cerebral metabolic requirements in fasting neonatal piglets.     

Influence of the Maternal Plasma Glucose Concentration at Delivery on the Risk of Hypoglycaemia in Infants of Insulin-Dependent Diabetic Mothers

Plasma glucose concentrations at birth and at two hours of age were measured in 53 infants of insulin-dependent mothers (IDMs). The plasma glucose concentrations at delivery were measured in the mothers of 17 IDMs and in the remaining 36 mothers, glucose was estimated by interpolation from concentrations achieved just before and after delivery. Clinical and laboratory data from the two groups were otherwise similar, so the groups were combined for further analyses. The maternal plasma glucose at delivery correlated positively with the glucose concentration of the IDMs at birth (Q=0.82, p <0.001) and negatively with the glucose concentration at two hours of age (Q= -0.46, p <0.001). Maternal plasma glucose concentration was higher in mothers delivered by caesarean section than in vaginally delivered mothers ( p <0.05). Eleven IDMs became hypoglycaemic at two hours of life (plasma glucose ≥1.7 mmol/1). These infants had higher cord plasma glucose concentrations at birth than those who remained normoglycaemic; the maternal glucose concentration was also higher. None of the IDMs became hypoglycaemic if the maternal glucose concentration at delivery was less than 7.1 mmol/l. In 28 IDMs the simultaneous plasma concentrations of non-antibodybound immunoreactive insulin (IRI) were recorded. Cord plasma IRI correlated with glucose and IRI at two hours of age (Q=-0.73, p <0.001 and Q=0.77, p <0.001, respectively). Cord plasma IRI was higher in IDMs who became hypoglycaemic than in the remaining infants. The results suggest that among the factors which may be responsible for neonatal hypoglycaemia in IDMs a major factor may be the maternal plasma glucose concentration at the time of delivery.