Rosemary D. Leake

Measurement of “True” Glucose Production Rates in Infancy and Childhood with 6,6-Dideuteroglucose

“New” glucose production has been measured in 54 infants and children for the first time by continuous three-to-four-hour infusion of the safe, nonradioactive tracer 6,6-dideuterogiucose. The use of combined gas chromatography-mass spectrometry with monitoring of selected ions allowed deuterium enrichment in blood glucose to be measured on microliter samples with an error of less than 2 per cent. In the young child, glucose production increased in a slightly curvilinear manner from 1 kg. to 25 kg. body weight, when it reached 140 mg. per minute, almost the adult value of 173 mg. per minute (2.28 ± 0.23 mg./kg. ·min., mean ± S.E.). Normalized for weight, glucose production in premature infants was 5.46 ± 0.31 mg./kg. ·min., in term neonates averaged 6.07 ± 0.46 mg./kg. · min., in children below the age of six years was 7.1 ± 0.27 mg./kg.· min., and in late childhood averaged 5.4 ± 0.28 mg./ kg.· min. Relative to estimated brain weight, however, glucose production was essentially linear from the 1-kg. premature infant to the 80-kg. adult. These data, the first measurements of “new” glucose production in childhood, suggest that brain size may be a principal determinant of those factors that regulate hepatic glucose output throughout life.

Plasma catecholamine concentrations in infants at birth and during the first 48 hours of life

A radioenzymatic assay was used to measure plasma concentrations of the catecholamines, norepinephrine, and epinephrine in the perinatal period. Samples were obtained at birth from the umbilical artery and vein of infants born by vaginal and by cesarean section delivery; from peripheral venous samples of normal infants during the first 48 hours of life; and from peripheral venous samples of mothers prior to delivery. Concentrations of NE and E were elevated in umbilical samples, with umbilical artery levels exceeding umbilical venous concentrations. Umbilical plasma CAT concentrations were similar in vaginal and cesarean section delivered infants. Plasma concentrations of NE consistently predominated over E in all samples from neonates. Plasma CAT concentrations rapidly fell from cord levels within 15 minutes of delivery and remained at a lower plateau during the first three hours of life. By 12 hours of age plasma CAT concentrations fell to the levels of supine adult resting concentrations. Maternal plasma CAT concentration prior to delivery demonstrated a predominance of E over NE. These elevations of plasma CAT in the early neonatal period may play a rola in nonshivering heat production as well as in cardiovascular alterations associated with birth.

Glomerular filtration rate during the period of adaptation to extrauterine life.

Summary: Inulin clearance (Cin) was measured in 20 infants of 27–43 weeks of gestation during the First 24 hr of their extrauterine life. Cin ranged from 0.7–4.7 ml/min and correlated with gestational age (P < 0.05). In 18 infants of similar gestational ages studied after 2–3 days of extrauterine adaptation, the Cin ranged from 1.1–17.9 ml/min and also correlated with gestational age (P < 0.01). By day 2–3, the infants of near term gestational age achieved a greater increase in Cin than did the markedly preterm infants, as reflected by a significantly different slope of the regression line for Cin and gestational age for the infants studied at 1 vs. 2–3 days of age (P < 0.001).Speculation: Although gestational age does affect glomerular fitration rate (GFR) in the first day of life, additional factors influencing glomerular filtration rate during this period may be adjustments in extratenal hemodynamics, renal blood flow, and extracellular volume. We have shown previously that high rates of infusion of fluid result in an increase in glomerular filtration rate in the preterm infant. It is possible that the limitation noted in glomerular filtration rate during the first few days of life is partly related to decreasing extracellular fluid.

Increased Serum Gastrin Concentrations and Gastric Acid Hyposecretion in the Immediate Newborn Period

Thirty-two infants and their mothers were studied to determine the source of elevated serum gastrin concentrations in umbilical blood and to learn whether neonates hypersecreted acid in response to hypergastrinemia. Gastrin concentrations in the umbilical artery and vein were similar. Both were significantly higher than maternal gastrin concentrations. No significant amount of gastrin could be measured in placental extracts. These results suggest that the increased neonatal gastrin concentrations were fetal in origin. Continuous basal acid secretory studies done for 4 hr in 32 infants and for 8 hr in 9 infants demonstrated hyposecretion of gastric acid for the first 5 hr of life. Acid secretion from hour 6 to 8 was similar to that in older children. Increased gastrin levels were still present at hour 8 and were associated with normal gastric acid secretion.

Perinatal bacterial infection after prolonged rupture of amniotic membranes: An analysis of risk and management

Chi-square and logistic stepwise multiple regression analysis of perinatal determinants of infant bacterial infection following prolonged rupture of amniotic membranes for 24 hours or more prior to delivery was applied in 33 infected infants and 66 matched control infants from the NINCDS Collaborative Project. In order of statistical significance, the most important variables were placental inflammation (P = 0.002), gestational age less than 34 weeks (P = 0.008), gestational age 34 to 37 weeks (P = 0.013), male sex (P = 0.015), Apgar score less than 6 at 5 minutes (P = 0.023), and clinical amnionitis (maternal fever, fetal tachycardia, or amniotic or gastric fluid leukocytes or bacteria) (P = 0.044). Duration of labor during PROM, race, and maternal age and parity were insignificant. Using these predictive variables, identification of infected infants for either microbial surveillance (superficial and systemic cultures) or microbial surveillance and anticipatory antibiotic therapy (discontinued after 3 days of negative cultures) was highly significant (P = 0.0001). Incorporating these variables and derived coefficients from multivariate analysis, a mathematical model was used for evaluation and prediction of perinatal bacterial infection with a sensitivity of 82% and specificity of 70%. Analysis of 46 infants prior to and 310 infants after implementation of this process at Harbor-UCLA Medical Center indicated significant improvement in the appropriate management of these infants at risk (from 59% to 87% of the population, P less than 0.05). Inappropriate antibiotic therapy decreased from 35% to 10% (P less than 0.05). In the absence of a shift in the median days of hospitalization of non-PROM infants, determination of the grand median days of PROM infant hospital stay showed a decrease (P less than 0.01) after initiation of this evaluation and management scheme.

Inulin Clearance in the Newborn Infant: Relationship to Gestational and Postnatal Age

Extract: Thirty-eight healthy newborn infants with gestational ages ranging from 25 to 42 weeks were studied at 2 days to 9 weeks postnatal age to evaluate the rate of glomerular maturation after birth. Glomerular function was assessed by a constant infusion method for inulin clearance (Cin). Cin was nearly identical when measured by the traditional clearance method and by the constant infusion technique. The Cin of 22 infants 2-3 days old ranged from 0.6 to 17.9 ml/min and was directly related to gestational age (r = 0.81, P < 0.001). For 26 infants studied at 1-9 weeks of age, Cin was directly proportional to conceptual (gestational and postnatal) age (r = 0.89, P < 0.001), and approximated that of infants of similar gestational age studied at 2-3 days of age.Speculation: With the confirmation of the ease and accuracy with which Cin can be measured by the constant inulin infusion method, it should be possible to study glomerular filtration rate (GFR) under various clinical conditions, including very limited renal function. The lack of extrauterine acceleration of renal maturation which we have demonstrated may indicate an anatomic limitation in the first several months of life.

The effects of large volume intravenous fluid infusion on neonatal renal function

Twenty healthy infants weighing less than 2,000 gm were studied at low (3.6 ml/kg/hr) or high (10.3 ml/kg/hr) rates of intravenous infusion. Inulin clearance determined by the constant infusion method was greater at the high rate of infusion (p = less than 0.05). Inulin clearance in two groups of infants over 2,000 gm studies at the same low or high rates of infusion did not increase at the higher rate of infusion. Since the GFR in infants less than 2,000 gm depends partially on the rate of intravenous infusion, small, healthy preterm infants may benefit from a rate of fluid administration greater than the low rate. When studies at low and high rates of infusion were compared in the 20 infants less than 2,000 gm, the fractional urinary sodium excretion increased with the increased fluid load. Delivery of fluid from the proximal tubule (CH2O =Na per dl GFR) increased (p less than 0.005). Free-water clearance and the absolute volume of urine increased at the high rate of infusion. These data indicate that the healthy preterm infant less than 2,000 gm, like the adult, compensates by increasing free-water clearance and urine volume when challenged with a large fluid load. Although fluid changes of short duration are appropriately handled, the effect of continuous rapid infusion on water and sodium balance in infants of this size remains to be determined.

Possible mechanisms of high blood levels of vasopressinduring the neonatal period

who was old enough to be given the Bender-Gestalt test showed highly significant errors suggestive of perceptuomotor difficulties. No association could be found between IQ scores, respiratory distress syndrome, or hyperbilirubinemia. No inordinate delay in the placement of the venous catheter was observed in those with IQ < 90, nor was there any difference in the mean caloric intake of children with IQ < 90 when compared to the caloric intake of Group A as a whole. In Group B, the mean IQ of patients was 99.3, with their control children having a mean IQ of 99.1.

Fetal lung liquid regulation by neuropeptides

The fetal lung, filled with fluid during intrauterine life, is recognized as a site of fluid production, significantly contributing to amniotic fluid volume. To assess possible hormonal control of lung liquid production, we studied the effect of intravenous vasopressin or vasotocin on lung liquid production in chronically catheterized fetal sheep. Both vasopressin and vasotocin infusion resulted in a significant decrease in lung fluid production (38% and 40%, respectively) when compared to that in control animals receiving saline infusion. There was no significant change in lung fluid osmolality, sodium, or potassium. These findings suggest that lung liquid production in utero may be regulated by the fetus and that vasopressin or vasotocin may be of physiologic importance in lung fluid dynamics during the third trimester of ovine pregnancy and perhaps during parturition.

Oxytocin Concentrations during the Neonatal Period

Plasma oxytocin levels in the umbilical artery (UA) exceeded umbilical venous levels in newborn infants delivered by cesarean section (without maternal labor) (p less than 0.05) and following labor (NS). There was an initial rapid decrease in oxytocin concentration from UA levels to those in peripheral venous blood by 30 min of page. Plasma oxytocin levels for breast-fed and formula-fed infants remained elevated over adult basal levels (1.7 +/- 0.3 mu U/ml) throughout the 4-day study period. Mean oxytocin concentration measured in breast milk from 10 mothers 2-4 days following vaginal delivery was 10.0 +/- mu U/ml. The stimulus for fetal and neonatal oxytocin secretion remains obscure, but continues beyond the period of birth.