John W. Reynolds

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.

Selenium and Vitamin E Sufficiency in Premature Infants Requiring Total Parenteral Nutrition

A randomized prospective study of LBW infants was undertaken to evaluate the effect of parenteral lipid infusions upon their antioxidant systems. Ten babies received a parenteral nutrition regimen with lipid emulsion, and ten received a regimen without lipid. Although the addition of lipid emulsion to the total parenteral nutrition regimen led to a rise in vitamin E levels, the selenium levels fell in both groups. Neither group showed evidence of deficient antioxidant systems by the peroxide hemolysis test or thiobarbituric acid test. There did not seem to be any adverse effect of the lipid infusion upon the clinical course of the infants except for hyperlipidemia. There was a better weight gain in infants receiving lipid.

Adrenal cortical function in the postmature fetus and newborn infant.

Summary: The umbilical venous blood concentrations of cortisol, dehydroepiandrosterone sulfate (DHAS), and unconjugated estriol were compared in 54 normal, 37 postterm, and 22 postmature newborns. Pre- and postadrenocorticotropic hormone (ACTH) stimulation levels of serum cort?sol and DHAS were compared in the first 2 to 4 days of life in 19 postterm and 15 postmature infants. Comparison was also made between vaginally and cesarean section delivered postterm and postmature newborns. There were significantly greater cord blood cortisol levels in the post-mature [260 ± 22 ng/ml (±S.E.)], than in the normal (193 ±11 ng/ml) (P ≤0.01) or postterm (193 ± 18 ng/ml) (0.01 ≤P ≤0.05) vaginally delivered infants. There were no significant differences in the mean cord blood DHAS levels in the three groups (normal, 2645 ± 130 ng/ml; postterm, 2323 ± 188 ng/ml; postmature, 2310 ± 224 ng/ml). Cortisol and DHAS responses to ACTH stimulation were the same in the postterm and postmature groups. There was a significantly lower mean umbilical venous unconjugated estriol level in the vaginally delivered postmature group (75 ±11 ng/ml) as compared to values in vaginally delivered postterm (120 ± 14 ng/ml (P = 0.01)] and normal [144 ± 10 ng/ml (P ≤0.002)] newborns. Stressed postmature infants delivered by cesarean section had higher unconjugated estriol levels (83 ± 12 ng/ml) than their unstressed, postterm cesarean section controls [40 ± 9 ng/ml (P ≤0.01)], but levels were still below those from vaginally delivered postterm infants. These findings substantiate normal adrenal function in the postmature fetus and newborn. Lowered umbilical venous unconjugated estriol levels in the postmature infants at birth appear to be a function of limited aromatizing activity of the placenta rather than due to low levels of fetal adrenal-derived neutral steroid substrate.Speculation: Early in the development of placental insufficiency, placental conversion of fetal-derived netural steroid estrogen precursors is the limiting factor in estrogen production in the feto-placemental unit. whether estrogen precursor production by the fetus also becomes an important factor in decreased feto-placemental unit. Whether estrogen precursor production by the fetus also becomes an important factor in estrogen production as placemental insufficiency progress has not been determined.

Relationship of Antioxidant Enzymes to Trace Metals in Premature Infants

Serum levels of the trace metals copper, zinc, and selenium were measured in premature infants. White blood cell glutathione peroxidase and superoxide dismutase levels were measured in conjunction with the trace metals. Three groups of infants were evaluated: group I was relatively healthy, group II were infants with stage 2 bronchopulmonary dysplasia (BPD) or less, group III were infants with stage 3 BPD or worse. Zinc and selenium levels declined in all groups during conventional parenteral nutrition (TPN) regimens, while copper remained stable. Copper did decline in groups I and II coincident with an acceleration in growth rate. An expected rise in antioxidant enzyme levels in infants with pulmonary oxygen toxicity was not seen. This study suggests that supplemental selenium as well as an increased zinc intake over current recommendations for premature infants receiving TPN may be indicated.

Serum Vitamin E Levels in Very Low-Birth Weight Infants Receiving Vitamin E in Parenteral Nutrition Solutions

Serum vitamin E levels were measured in 17 very low-birth weight infants in the first 2 wk of life, before and after the institution of intravenous vitamin E supplementation in a dosage of 4.5 mg/day, as a component of MVI Pediatric multivitamin preparation. Serum vitamin E levels were 0.22 +/- 0.16 (SD) mg/dl before supplementation, and rose to 2.55 +/- 0.65 (SD) mg/dl in nine infants more than 899 g birth weight, and rose to 3.68 +/- 0.70 (SD) mg/dl in six infants less than 900 g at birth. These postsupplementation serum vitamin E levels are in the range in which a reduction of incidence or severity of retinopathy of prematurity and intraventricular cerebral hemorrhage has been reported by others. No toxic effects of the preparation or of the increased vitamin E levels were found.

Nutritional balance studies in very-low-birth-weight infants: role of whey formula

Summary: Although the optimal type and amount of protein for feeding very-low-birth-weight (VLBW) infants is not well defined, a protein composition with a whey protein to casein ratio of 60/40 is generally considered desirable. This study used the metabolic balance technique to compare nitrogen retention rates in 19 VLBW (< 1,530 g) infants fed either an experimental whey protein-predominant formula (WPF) containing ultra filtered whey protein or a conventional casein-predominant formula (CPF) containing ∼20% more protein and more minerals. Blood chemistries and anthropometric measurements were assessed serially. Although infants fed CPF received and retained more protein than infants fed WPF, nitrogen retentions were 73.1 and 74.5% of intake, respectively, and not different between the two feeding groups. The data suggest that proteins from either WPF or CPF are adequately utilized by VLBW infants. Although WPF permitted nitrogen retention rates similar to fetal accretion rates, CPF more nearly met estimated nitrogen requirements of the low-birth-weight infant. Infants fed WPF showed a more favorable course with respect to their metabolic acid-base status, characterized by normal buffer base concentrations and less predisposition to metabolic acidosis. We conclude that whey-predominant protein is preferable to casein-predominant protein in the diet of VLBW neonates because it may lessen the risk of metabolic acidosis and its potential adverse effects.

Feto-Placental Steroid Metabolism in Growth Retarded Human Fetuses

ABSTRACT. The goal of the study was the determination of the relative roles of the placenta and the fetus in causing low serum estriol (E3) levels in women bearing fetuses with intrauterine growth retardation (IUGR). Umbilical venous levels of E3 and dehydroepiandrosterone sulfate (DHAS) were measured in 31 samples from fetuses with IUGR, 21 of whom were vaginally delivered and 10 who were delivered by cesarean section. In addition, estrone (E1) and estradiol (E2) were measured in 11 of the samples. The results were compared with 11 samples from cesarean section delivered control term infants and 54 samples from vaginally delivered control infants. The vaginally delivered IUGR group had a significantly lower mean umbilical venous DHAS level than did their control group (2128 ± 158 ng/ml SEM versus 2645 ± 130, p<0.05). Both the vaginally delivered and cesarean section delivered IUGR infants had umbilical venous E3 levels significantly lower than in their control groups (70 ± 10 ng/ml SEM versus 144 ± 10, p<0.001, and 46 ± 11 ng/ml SEM versus 136 ± 23, p<.01, respectively). Umbilical venous E1 and E2 levels were not different from the control values. E1, E2, E3, and DHAS were measured in eight maternal venous samples obtained from mothers bearing fetuses with IUGR. In comparison with 11 control mothers, only E3 was significantly different (10.7 ± 3.0 ng/ml SEM in mothers with IUGR fetuses versus 25.0 ± 4.9 in control mothers p< 0.01). The study provides evidence for reduced DHAS secretion in one group of the fetuses with IUGR, and no evidence for decreased placental conversion of DHAS to the estrogens E1 and E2. The significantly low E3 values in both umbilical and maternal samples are postulated to result not only from the reduced fetal adrenal DHAS secretion, but also underactive 16a-hydroxylase activity in fetal liver or low efficiency of 16a-OH-DHAS, relative to DHAS, as a substrate for placental conversion to an estrogen.

Fetoplacental steroid metabolism in prolonged pregnancies

The response to an intravenous load of 50 mg of dehydroepiandrosterone sulfate given to women with a pregnancy prolonged to more than 42 weeks was compared to the response in control pregnant women at 40 weeks. The half-life of dehydroepiandrosterone sulfate was longer in the prolonged pregnancy group than in the control group (mean +/- SEM, 3.64 +/- 0.24 hour versus 2.78 +/- 1.08 hour, p less than 0.05), and the rises of serum free estrone and free estradiol 4 hours after infusion were less in the prolonged pregnancy group than in the control group. Maternal venous and umbilical venous estrone, estradiol, free estriol, and dehydroepiandrosterone sulfate levels were compared in samples from control, postmature, and postterm groups. Umbilical estriol concentrations were significantly less in the postmature group (67.8 +/- 9.5 ng/ml, mean +/- SEM) than in the control group (136 +/- 22.8 ng/ml, mean +/- SEM, p less than 0.01), but there were no significant differences between dehydroepiandrosterone sulfate, estrone, and estradiol levels. Maternal venous estriol levels were lower in the postmature group (13.3 +/- 2.1, p less than 0.05) than in the control group (25.0 +/- 4.9). A reduction in overall placental estrogen production was indicated by the results of the dehydroepiandrosterone sulfate loads in the patients with prolonged pregnancy, yet the normal umbilical venous estrone and estradiol levels do not fit this conclusion. There is no explanation for the discrepancy at this time.

A scoring system for evaluating the condition of transported neonates

A scoring system for the evaluation of the clinical status of transported small premature infants was modified to make it applicable to the evaluation of both premature and term infants. Blood glucose concentration, systolic blood pressure, blood pH and PO2, and body temperature were assessed and given scores of 0, 1 or 2 for abnormal, borderline and normal values, respectively. The scoring system was used for quality assurance studies of changes in patient status during transport from community hospitals to the neonatal intensive care unit and proved useful in identifying inadequate attention to body-temperature maintenance. The scoring system showed an improvement in the criterion after changes in clinical monitoring and management of body temperature were instituted. An additional use of the scoring system was for the identification of specific problems in neonatal stabilization in referring community hospitals.

Serial Measurements of Thyroid Function in Verv Low Birth Weight Infants

To assess thyroid function in very low birth weight infants, serial free thyroxine (free T 4 ) determinations were made between age one week and 12 weeks using two radioimmunoassay (RIA) kits, Amersham and Clinical Assays, in 18 infants of 28-weeks gestation or less. TSH was normal in all infants. Both assays showed initial free T4 concentrations well below values in full term infants. The most severely ill babies had free T4 values which were significantly lower than the least ill babies in the first four weeks of life by the Amersham method only. By 6 weeks of age free T4 values increased to the range seen in normal term infants at 1-4 months of age. The increase in free T4 may be a result of maturation of an immature hypothalamic-pituitary-thyroid axis or resolution of the sick euthyroid syndrome. The Amersham kit showed significantly lower free T4 concentrations compared to the clinical assays kit up to age 6 weeks. Caution must be used in interpreting free T4 values in VLBW infants in the first month of life in light of the progression of free T4 into the normal range by 6 weeks of life and differences found between the two free T4 RIA kits.