A. Aynsley-Green

METABOLIC AND ENDOCRINE RESPONSES TO A MILK FEED IN SIX‐DAY‐OLD TERM INFANTS: DIFFERENCES BETWEEN BREAST AND COW'S MILK FORMULA FEEDING

ABSTRACT. Lucas, A., Boyes, S., Aynsley‐Green, A. (Department of Paediatrics, John Radcliffe Hospital, Oxford) and Bloom, S. R. (Hammersmith Hospital, London, England). Metabolic and endocrine responses to a milk feed in six‐day‐old term infants: JMfferences between breast and cows milk formula feeding. Acta Paediatr Scand, 70:195, 1981. – There is little information on the metabolic and endocrine responses to milk feeding in the neonatal period particularly in relation to the mode of nutrition and composition of the milk. Plasma concentrations of insulin, glucagon and gastric inhibitory polypeptide (GIP) together with blood levels of glucose, ketone bodies, pyruvate, lactate and glycerol were measured pre‐ and post‐prandially in 79 healthy six‐day‐old term infants who had been either breast fed or fed on a modified cows milk formula (Cow and Gate Premium) from birth. Formula fed infants had a greater insulin and GIP response to feeding and their basal and postprandial blood ketones were considerably lower than in breast fed infants. In addition a significantly greater post feed rise in both lactate and pyruvate concentrations was observed with formula feeding. These results may have significant implications regarding infant feeding and postnatal metabolism.

METABOLIC AND ENDOCRINE CONSEQUENCES OF DEPRIVING PRETERM INFANTS OF ENTERAL NUTRITION

ABSTRACT. Plasma enteroglucagon, pancreatic polypeptide, gastrin, motilin, neurotensin, gastric inhibitory polypeptide, secretin, vasoactive intestinal peptide and blood glucose, alamine, ketone bodies, lactate and pyruvate were measured on the sixth postnatal day in (a) a group of 10 preterm infants who on account of hyaline membrane disease had not received enteral feeding since birth and (b) before and at 55, 90, and 120 minutes after feeding in a group of healthy preterm infants fed three‐hourly on human milk. Gut hormones were also measured in umbilical venous cord blood. The infants receiving regular boluses of milk from birth demonstrated postnatal surges in preprandial concentrations of gut hormones together with cyclical hormonal responses to feeding. None of these changes were seen in infants receiving intravenous fluids. The latter infants also had lower concentrations of blood alanine, glycerol and hydroxybutyrate and lacked the phasic changes in intermediary metabolites seen in the infants receiving enteral boluses of milk. Thus deprivation of enteral feeding results in a profound alteration of the metabolic and endocrine milieu which may have important effect on the process of adaptation to postnatal life.

FEEDING AND THE DEVELOPMENT OF ENTEROINSULAR HORMONE SECRETION IN THE PRETERM INFANT: EFFECTS OF CONTINUOUS GASTRIC INFUSIONS OF HUMAN MILK COMPARED WITH INTERMITTENT BOLUSES

ABSTRACT. Preterm infants receive gastric milk feeds as continuous infusions or intermittent boluses. It is not known whether these feeding methods have different effects on the development of digestive metabolism. We have measured plasma levels of insulin, pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), gastrin, motilin, enteroglucagon (EG) and neurotensin (NT) in 19 preterm infants (28‐34 weeks gestation) tolerating full enteral feeding from birth. 7 infants received human milk by continuous infusion, 12 infants were bolus fed. Hormones were measured in cord blood and at 6 and 13 days of age; samples were drawn preprandially in bolus fed infants. Both groups showed similar significant increases in plasma motilin, PP, NT and EG levels. At 13 days infusion fed infants had higher insulin. GIP and gastrin levels. No difference in rate of weight gain was seen in the two groups of infants. We conclude that both methods of feeding induce progressive changes in circulating enteroinsular hormone levels. However, the endocrine milieu is different in the two groups, particularly since bolus‐fed infants experience marked cyclical surges in hormones after boluses of milk by 13 days of age. These differences in hormone release may affect metabolic homeostasis.

Postnatal Surges in Plasma Gut Hormones in Term and Preterm Infants

Using sensitive radioimmunoassays we have measured and compared plasma concentrations of motilin, gastrin, enteroglucagon, neurotensin, gastric inhibitory polypeptide and pancreatic polypeptide in (a) 53 healthy, preterm infants at birth or preprandially at 2.5, 6, 13 or 24 days; (b) 45 normal, breast-fed, term infants at birth or preprandially at 6 or 16 days, and (c) 12 healthy fasting adults. Plasma concentrations of all six hormones rose during the neonatal period in both preterm and term infants, the first four of these hormones reaching levels which exceeded those seen in healthy fasting adults. The rate of increase and the magnitude of the changes were less in term infants than preterm infants. These changes in plasma hormone concentrations may be the result of enteral feeding. Gut hormones exert important effects on gut growth, secretion and motility and on intermediary metabolism, and the postnatal hormonal surges observed may play a key role in the postnatal adaptions to enteral feeding.

DEVELOPMENTAL ASPECTS OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) AND ITS POSSIBLE ROLE IN THE ENTEROINSULAR AXIS IN NEONATES

Abstract. Lucas, A., Sarson, D. L., Bloom, S. R. and Aynsley‐Green, A. (University Department of Paediatrics, John Radcliffe Hospital, Oxford and Hammersmith Hospital, London, England). Developmental aspects of gastric inhibitory polypeptide (GIP) and its possible role in the enteroinsular axis in neonates. Acta Paediatr Scand, 69: 321, 1980.—Little is known on the development of the release of gastric inhibitory polypeptide (GIP) in neonates or on its potential role in the enteroinsular axis. Using cross‐section data collection we studied: (a) 100 preterm neonates either at birth (cord blood), or before or after a feed on the sixth or 24th day and (b) 63 term neonates at birth or on the sixth day. Blood samples were assayed for GIP, insulin and glucose. At birth plasma GIP concentrations were low compared with fasting adults (p > 0.01). Basal plasma levels were significantly higher at six days in fed infants, but not in a group of sick preterm infants who had never been fed orally. On sixth day there was no GIP response to a feed, but by 24th day there was a marked postprandial elevation (p > 0.01). In preterm infants the insulin response was 68 % greater at 24 days than at six days in spite of a similar glycaemic response. We hypothesize that this increasing postnatal insulin response to enteral feeding may be due to the commencement of the postprandial release of GIP, thought to be an important effector in the enteroinsular axis.

GROWTH HORMONE RESPONSE TO FEEDING IN TERM AND PRETERM NEONATES

ABSTRACT. Plasma growth hormone concentrations were measured in 248 healthy term and preterm infants. At birth growth hormone concentrations in cord blood from both term and preterm babies were approximately 100‐fold higher than those in blood drawn from healthy adults. By the sixth postnatal day basal pre‐feed levels had fallen in term neonates by 65% and a marked postprandial rise was apparent; preterm infants did not show this initial fall in preprandial hormone levels nor was any response to feeding seen. However a fall in preprandial concentrations accompanied by the development of postprandial surges in growth hormone occurred during the next 2 weeks so that by 24 days the postprandial rise was similar to that of term neonates on the sixth day. We conclude that although the initial postnatal changes in plasma growth hormone concentrations are different in preterm and term infants, feeding is a major stimulus to growth hormone secretion in both groups of neonates. Further work is needed to define the precise role of this hormone in neonatal metabolic adaptation.

Plasma secretin in neonates.

Abstract. Lucas, A., Adrian, T. E., Bloom, S. R. and Aynsley‐Green, A. (University Department of Paediatrics, John Radcliffe Hospital, Oxford and Hammersmith Hospital, London). Plasma secretin in neonates. Acta Paediatr Scand, 69: 205, 1980.—Plasma secretin has been measured in 96 normal 6‐day‐old term infants and in 158 healthy preterm infants whose mean post‐partum ages were 2½, 6, 13 or 24‐days. At birth, plasma secretin levels in both term and preterm infants were high compared with those seen in healthy fasting adults (p > 0.001), but subsequently declined towards adult values. In contrast, preterm infants who had not been fed for the first 6 days of life, had presistently high basal plasma secretin values. In term infants at 6 days of age and in preterm infants up to 13 days, there was no se‐cretin response to a feed. However, by 24 days, preterm infants showed a marked post‐prandial secretin elevation (p > 0.02). No correlations were found between plasma secretin concentrations and either blood glucose or plasma insulin concentrations following a feed. Significant adjustments in plasma secretin levels occur in the early weeks of life which may be influenced by enteral feeding.

Feeding Premature Infants with Human Milk or Preterm Milk Formula

Results of a comprehensive longitudinal study comparing the effects of feeding healthy preterm infants with human milk or a specially adapted formula designed for the preterm infant are reported. 10 healthy infants were given human milk from birth, and 9 similar infants were given a formula which contained 80 kcal, 1.8 g protein, and 4.5 g fat per 100 ml. Anthropometric measurements were made weekly as were routine haematological and biochemical variables together with plasma amino acid and gastrointestinal regulatory peptide levels and metabolic fuel concentrations. Infants receiving the formula demonstrated a significantly greater growth velocity compared with infants receiving human milk. There were no significant differences between the two groups in routine haematological or biochemical variables measured nor in plasma insulin or blood glucose, lactate, pyruvate, or ketone body concentrations. Plasma amino acid profiles, however, did demonstrate some significant differences between the two groups with higher methionine and threonine levels in the formula-fed infants. Plasma motilin, enteroglucagon, neurotensin, cholecystokinin, gastric inhibiting polypeptide, and pancreatic polypeptide levels all demonstrated significant postnatal surges, with significant differences between the two groups in plasma gastric inhibiting polypeptide and pancreatic polypeptide concentrations.

The metabolic and endocrine milieu of the human fetus at 18-21 weeks of gestation. II. Blood glucose, lactate, pyruvate and ketone body concentrations.

Blood levels of glucose, lactate, pyruvate and total ketone bodies were measured in 16 conscious mothers and their minimally stressed fetuses at 18-21 weeks gestation. Blood samples were taken from the maternal antecubital vein and from the fetal umbilical vein and artery during fetoscopy prior to termination of pregnancy. The mean concentrations of blood glucose, lactate and pyruvate were similar in maternal and fetal venous blood; no significant difference was found between the fetal umbilical artery and vein concentrations. Maternal total blood ketone body levels were significantly higher than fetal levels with no detectable umbilical venous arterial concentration difference. There was a significant inverse relationship between the umbilical artery levels and the umbilical venous-arterial concentration differences for blood glucose and lactate.

Isolated glucocorticoid deficiency: metabolic and endocrine studies in a 5-year-old boy

A 5-year-old boy is described who presented with episodes of hypoglycaemia triggered by mild infections or fever. Subnormal glucocorticoid production was confirmed by demonstrating low urinary excretion of free cortisol, low plasma cortisol concentrations that did not rise after glucagon and ACTH stimulation, and by elevated plasma ACTH levels. The selective nature of the abnormality was confirmed by demonstrating normal plasma electrolyte concentrations and blood pressure on a salt-restricted diet. Plasma renin activity and plasma aldosterone levels were also normal and responded appropriately to salt restriction and to frusemide-induced diuresis. Starvation-induced hypoglycaemia was associated with raised levels of blood ketone bodies and low blood alanine concentrations. Catecholamine secretion during hypoglycaemia was reduced. Glucocorticoid replacement therapy was effective in restoring normal glucose homeostasis.