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.     

GASTRIC LIPOLYSIS OF HUMAN MILK LIPIDS IN INFANTS WITH PYLORIC STENOSIS

In gastric contents a potent lipase is present which hydrolyses the milk lipids to mainly diglycerides and free fatty acids. This hydrolysis hasearlier beendemonstratedinrats and now in human infants. The gastric lipo-lysis may facilitate the further digestian of the milk lipids by transformation of the fat droplets to a substrate that is more readily attacked by the pancreatic lipases.     

THE METABOLIC CONSEQUENCES OF HUMAN MILK AND FORMULA FEEDING IN PREMATURE INFANTS

Abstract. Schultz, K., Soltész, G. and Mestyán, J. (Department of Paediatrics, University Medical School, Pécs, Hungary). The metabolic consequences of human milk and formula feeding in premature infants. Acta Paediatr Scand, 69: 647, 1980.—Twenty premature low-birthweight infants were divided into two groups and assigned randomly to either a pooled human milk or to a cow's milk based infant formula feeding regimen. The protein intake was 2.0 g/kg/day in the human milk fed group and 4.4 g/kg/day in the formula fed group of infants. The concentrations of different metabolites were estimated at weekly intervals, and plasma amino acid analysis was performed biweekly on blood samples in the two groups of infants during the four-week study period. Formula milk fed infants had significantly lower fasting blood glucose levels and developed azotaemia, hyperaminoacidemia and metabolic acidosis in the early weeks of postnatal life. Blood lactate and plasma free fatty acid concentrations did not change significantly in the two groups during the study. No significant differences were found in the rate of weight gain between the two groups of infants, although formula fed infants regained their birthweight more slowly than human milk fed infants. High protein formula feeding causes potentially unfavorable metabolic and amino acid imbalances in preterm infants in the early postnatal life.     

IMMUNOLOGIC CONSEQUENCES OF FEEDING INFANTS WITH COW MILK AND SOY PRODUCTS

ABSTRACT. Various products and regimens proposed for feeding infants when the mother's milk is not available have been evaluated intensively for capacity to achieve optimal nutrition. The immunologic consequences of feeding the foreign proteins contained in the various products have received much less attention and no systematic investigations have been done for comparable immunologic evaluation. Sera obtained at intervals from normal infants fed cow milk and soybean products from birth in different regimens were analyzed for antibodies to five major milk proteins and a soy protein isolate. Antibody levels increased slowly during the first 4 months, reaching a peak about 6 months of age. In infants fed cow milk products or a soy product from birth to 112 days of age and then given various cow milk products the following antibody responses were observed: The level of serum antibodies attained was highest with pasteurized cow milk and lower with heat-treated cow milk or a milk base formula of lower protein content. Feeding a soy product from birth for 112 days did not prevent a brisk antibody response to cow milk introduced subsequently, comparable to or greater than the antibody response seen when cow milk products were fed from birth. Clinically no immunologic disorders were detected in association with antibody responses to the various products and regimens. The implications of the findings for infant feeding and immunologic disorders are discussed.     

THE OCCURRENCE AND ORIGIN OF DDT IN HUMAN MILK

Abstract. Gas chromatography has been applied for the analysis of organochlorine compounds of 49 samples of human milk. The average total DDT (2,2-bis(4-chlorophenyl)1,1,1-trichloroethane) content in human milk was found to be 0.058 mg/kg, ranging from 0.017-0.17 mg/kg (1.57 mg/kg milk fat, with a range of 0.50-4.00 mg/kg). Thirty-four cases contained traces of dieldrin, but the content of dieldrin reached 0.008 mg/kg in only one milk sample. The average content of PCB (polychlorinated biphenyls) was 0.024 mg/kg of human milk, with a range of 0.011-0.054 mg/kg (0.65 mg/kg of milk fat with a range of 0.33-1.10 mg/kg). The ratio of DDT metabolites/DDT varied from 1.1 to 7.8 (mean 2.8). Studies were also made of the effect of the weight, weight loss, diet, smoking habits and parity of the nursing mother upon the content of organochlorine compounds in human milk. A significant positive correlation was observed between the DDT content of human milk fat and cigarette smoking.
The average daily intake of total DDT for Finnish breastfed babies was calculated to be 0.0093 mg/kg, 1.9 times more than the daily intake of 0.005 mg/kg indicated by FAO/WHO as the acceptable value.     

EFFECT OF FEEDING AN INFANT FORMULA WITH HIGH ENERGY DENSITY ON GASTRIC EMPTYING IN INFANTS WITH CONGENITAL HEART DISEASE

ABSTRACT. Cavell, B. (Department of Paediatrics, University Hospital, Lund, Sweden). Effect of feeding an infant formula with high energy density on gastric emptying in infants with congenital heart disease. Acta Paediatr Scand, 70:513,.–Gastric emptying of meals of standard infant formula and formula fortified with a glucose polymer (Caloreen) were compared in 7 infants with severe congenital heart disease aged 9 days to 5 months. A marker dilution technique was used in estimating gastric emptying. Gastric half-emptying times were significantly longer for meals containing Caloreen than for meals of standard infant formula. Although significantly smaller amount of meal containing Caloreen had left the stomach after 2 hours, the net transfer of energy to the intestine was larger than after feeding a standard meal.     

THE EFFECT OF L-DOPA WITH AND WITHOUT DECARBOXYLASE INHIBITOR ON GROWTH HORMONE SECRETION IN CHILDREN WITH SHORT STATURE

Abstract The efficiency of L-dopa alone and L-dopa plus a dopa-decarboxylase inhibitor (carbidopa) in provoking growth hormone (GH) secretion was studied in 40 children with short stature. By preventing the extracerebral metabolism, carbidopa increases the availability of L-dopa to the brain. The study was designed as paired series of growth hormone stimulation tests in which the effect of L-dopa alone, in different dosage schedules, was compared with the same dose level of L-dopa plus carbidopa. When L-dopa was given in full dose (125–500 mg), there was no significant difference in the serum GH concentrations at any time of sampling. In the lower dose level, the stimulant effect of L-dopa alone tended to be exceeded by the combination of L-dopa and carbidopa. The serum GH responses to the different schedules indicate that an optimal hypothalamic dopamine concentration for GH release could be achieved with a considerably lower dose of L-dopa than those employed in previously reported studies. When L-dopa is combined with a dopa decarboxylase inhibitor, the children have the advantage of less side effects in the form of nausea and vomiting.     

THE EFFECTS OF GROWTH HORMONE THERAPY IN CHILDREN WITH RADIATION-INDUCED GROWTH HORMONE DEFICIENCY

Abstract. Shalet, S. M., Whitehead, E., Chapman, A. J. and Beard well, C. G. (Department of Endocrinology, Christie Hospital, Manchester, England). The effects of growth hormone therapy in children with radiation-induced growth hormone deficiency. Acta Paediatr Scand, 70:81, 1981.–The effects of growth hormone (GH) therapy were studied in 6 children, previously treated for brain tumours which did not directly involve the hypo-thalamic-pituitary axis, and who had received cranial irradiation between 2.1 and 10 years earlier. All 6 were short with a standing height standard deviation score (SDS) from -1.7 to -3.3. Impaired growth hormone responses to an insulin tolerance test (ITT) were observed in all 6 and to a Bovril stimulation test in 5 children. The remainder of pituitary function was essentially normal. All 6 were prepubertal and 5 had a retarded bone age. During the pre-treatment year the 6 children's grow lb rates varied from 2.0 to 5.1 cm. Subsequently all received human GH in a dose of 5 units 3 times weekly for 1 year. The growth rate in each was at least 2 cm greater during the treatment year than the pre-treatment year. Growth during the treatment year ranged from 6.0 to 10.1 cm. In 5 of the 6 the improvement in growth rate could be totally ascribed to the GH therapy. In the sixth there was significant pubertal maturation during the treatment year and only in this subject did the bone age advance at a significantly greater rate than the chronological age.     

STUDIES ON GROWTH HORMONE SECRETION IN A PATIENT WITH THE DIENCEPHALIC SYNDROME OF EMACIATION

A girl with a large optic glioma, and the typical features of diencephalic syndrome of emaciation (Russell) was followed up from ¹/₂ to 2 ¹/₂ years of age. She had very high levels of growth hormone (GH) in the plasma, which were not influenced by hyperglycaemia, by hypoglycaemia or by dexamethasone, reserpine or chlorpromazine. Interference by the glioma with GH releasing factor or more likely with GH inhibiting factor is suggested. In spite of the elevated plasma GH, linear growth was markedly retarded. Sulfation factor activity (Somatomedin) was low with no significant response to injections of HGH. The patho-genesis of the profound metabolic disturbances in this syndrome is not properly understood. The endogenous GH obviously exerts its full adipokinetic effect, whereas the synthesis of the sulfation factor (Somatomedin) must be defective. This case illustrates a type of retardation of linear growth, not seen in any other known syndrome.     

THE EFFECT OF L-DOPA ON THE BLOOD CONCENTRATIONS OF GROWTH HORMONE, THYROTROPHIN, GONADOTROPHINS, CORTISOL AND GLUCOSE IN CHILDREN WITH SHORT STATURE

ABSTRACT. Nilsson, K. O. and Thorell, J. I. (Department of Paediatrics, Endocrinology and Nuclear Medicine, University Clinics, Malmö General Hospital, Malmö, Sweden). The effect of L-dopa on the blood concentrations of growth hormone, thyro-trophin, gonadotrophins, cortisol and glucose in children with short stature. Acta Paediatr Scand, 63: 812, 1974.—Studies were performed in nine constitutionally short children to evaluate the diagnostic usefulness of oral L-dopa as compaired to insulin induced hypoglycemia as a provocative agent for the stimulation of growth hormone production. In addition the effect of L-dopa on the blood concentrations of thyro-trophin, gonadotrophins, cortisol and glucose was investigated. The mean growth hormone concentration was 4.8±1.6 (S.E.M.) ng/ml before L-dopa and 2.9±1.0 ng/ml before insulin. The mean peak growth hormone concentration was 20.7±2.6 ng/ml after L-dopa and 17.5±3.1 ng/ml during insulin induced hypoglycemia. AU children showed peak growth hormone concentrations at or above 8 ng/ml both after L-dopa and insulin, although in one patient this level was reached only after priming with testosterone. No significant changes in the blood concentrations of thyrotrophin, gonadotrophins, cortisol or glucose were observed. It is concluded that L-dopa is an effective stimulus for the release of growth hormone in young subjects.     

OSMOLALITY OF THE GASTRIC AND DUODENAL CONTENTS IN LOW BIRTH WEIGHT INFANTS FED HUMAN MILK OR VARIOUS FORMULAE1

ABSTRACT. The osmolality of gastric and duodenal contents were determined simultaneously during 30 test-meals at 0,45, 90, 135 and 180 min after feeding in 15 low birth weight infants, birthweight: 2 075 ± 330 g, gestational age: 35.4 ± 1.8 weeks and postnatal age: 8 ± 4 days. These infants were fed human milk or various formulae whose osmolalities ranged from 227 to 622 mosmol/kg. With human milk and isotonic formula, the osmolality in the stomach and duodenum remained close to 295 mosmol/kg throughout the test. With hypotonic formula (227), the osmolality in the stomach and duodenum rose during the first 45 min to a plateau of about 266 and 285 mosmol/kg, respectively. With the two most hypertonic diets (about 600) (10 g/dt glucose solution and an elemental formula), the osmolality in the stomach and duodenum remained high throughout the test, 470 ± 73 mosmol/kg at 45 min and 345 ± 55 mosmol/kg at 180 min. There was a significant positive linear correlation between the osmolality of the diet and the osmolality in the stomach and duodenum at each time of sampling but the slope of the regression lines decreased progressively during the 3 hours after feeding. On the pooled data, there was also a significant positive linear relationship between duodenal and gastric osmolalities. This study suggests that hyperosmolar feedings might be dangerous for the preterm infants and should be avoided if possible.     

THE CONCENTRATIONS OF COPPER AND ZINC IN HUMAN MILK A Longitudinal Study

Abstract. Vuori, E. and Kuitunen, P. (Department of Public Health Science and Children's Hospital, University of Helsinki, Helsinki, Finland). The concentrations of copper and zinc in human milk—a longitudinal study. Acta Pædiatr Scand, 68: 33, 1979.—Twenty-seven healthy Finnish mothers were followed during the course of their entire lactation period. A total of 229 individual milk samples, collected in the beginning and at the end of each feed during a 24-h period, were obtained from the 2nd week to the 9th month of lactation. The copper and zinc concentrations were determined by atomic absorption spectrophotometry. The concentrations of the trace-elements investigated were dependent on the stage of lactation. The median copper and zinc concentrations decreased during the course of lactation from about 0.60 mgyl and 4.0 mg/l to 0.25 mg/l and 0.5 mg/l, respectively. The importance of considering the stage of lactation in the evaluation of the trace-element nutrition value of breast milk should be emphasized. The calculated means of the concentrations of these trace-elements in mature human milk presented in the literature seem to overestimate the actual levels in prolonged lactation.     

PYRIDOXAL PHOSPHATE CONCENTRATION IN BLOOD IN NEWBORN INFANTS AND THEIR MOTHERS COMPARED WITH THE AMOUNT OF EXTRA PYRIDOXOL TAKEN DURING PREGNANCY AND BREAST FEEDING

Abstract. Ejderhamn, J. and Hamfelt, A. (Departments of Paediatrics and Clinical Chemistry, Sundsvalls Hospital, Sundsvall, Sweden.) Pyridoxal phosphate concentration in blood in newborn infants and their mothers compared with the amount of extra pyridoxol taken during pregnancy and breast feeding, Acta Paediatr Scand, 69:327, 1980.—The concentrations of pyridoxal phosphate have been estimated in cord blood and capillary blood samples taken at 3 hours, 2 days, 4 days, 7 days and 6 weeks of age, from eleven fullterm infants. Pyridoxal phosphate concentrations were also determined in venous blood samples taken from the mothers at delivery. A highly significant correlation between pyridoxal phosphate in cord whole blood and venous whole blood taken from the mothers at delivery was found. Infants whose mothers had taken extra pyridoxol during pregnancy had a higher concentration of pyridoxal phosphate at 3 hours of age compared with infants whose mothers had not taken extra pyridoxol. During the first week of life the concentration of pyridoxal phosphate in capillary blood decreases strikingly. At 6 weeks of age the concentration of pyridoxal phosphate is in the same range as that of normal adults. Findings are also discussed which indicates that: 1) Vitamin B₆ is transported in breast milk; 2) The giving of supplemental pyridoxol during pregnancy in ordinary doses (2–6 mg/day) does not have an antilactogenic effect. No correlation between the erythrocyte aspartate aminotransferase activation with pyridoxal phosphate in vitro and pyridoxal phosphate concentration in plasma was found during the first 6 weeks of life.     

GONADOTROPIN-RELEASING HORMONE (LH-RH) AND HUMAN CHORIONIC GONADOTROPIN IN THE TREATMENT OF TWO BOYS WITH HYPOGONADOTROPHIC HYPOGONADISM

Abstract. Two brothers, 16 and 14 years of age, with hypogonadotrophic hypogonadism and anosmia were treated with subcutaneous injections of 200μg gonadotropin-releasing hormone at 8-hour intervals for 4 weeks. Serum FSH increased to the range of normal adult men, but serum LH and serum testosterone showed little change and no clinical signs of pubertal development occurred. Thereafter the 2 patients were given HCG for 11 months and a combination of HCG and HMG for a further 3 months. In response to this treatment, the serum testosterone levels increased to the range of normal adult men and a marked development of the secondary sex characteristics was seen.     

N-ACETYL-BETA-GLUCOSAMINIDASE OF LYMPHOCYTES IN THE PREMATURE INFANT WITH SPECIAL REFERENCE TO THE FETAL DEVELOPMENT OF THE LYSOSOMAL APPARATUS

ABSTRACT. N-acetyl-beta-glucosaminidase activity was determined in peripheral blood lymphocytes by means of Hayashi's cytochemical method in 50 premature infants born between the 21st and 37th weeks of gestation. The lymphocytes exhibited three types of enzymatic cytochemical reaction, i.e. granular, diffuse and mixed (both granular and diffuse). The total count of enzyme-positive lymphocytes was significantly lower in the group of premature infants born between the 21st and 28th weeks of gestation as compared with those born later. This difference was due to the smaller numbers of enzyme-positive lymphocytes with granular reaction type in the group of more immature infants. The formation of enzyme-positive lysosomal granules within the lymphocyte cytoplasm during the last months of fetal development has been suggested and the relationship between the enzymatic equipment of lymphocyte lysosomes and immune response discussed.     

THE EFFECT OF DIGESTIVE ENZYMES ON THE BINDING AND BACTERIOSTATIC PROPERTIES OF LACTOFERRIN AND VITAMIN B12 BINDER IN HUMAN MILK

Abstract. Samson, R. R., Mirtle, C. and McClelland, D. B. L. (University Department of Therapeutics and Clinical Pharmacology, The Royal Infirmary, Edinburgh, Scotland). The effect of digestive enzymes on the binding and bacteriostatic properties of lactoferrin and vitamin B12 binder in human milk. Acta Paediatr Scand, 69:517, 1980.—Human milk contains unsaturated lactoferrin and vitamin B12 binding protein. It has been suggested that these proteins may exert antibacterial effects in the intestine of the breast fed infant, but the effect of the intestinal environment on the antibacterial effect of these proteins has not been described. In this study human milk was treated with pepsin and trypsin and the influence of digestion on iron and vitamin B12 binding capacity, bacterial uptake of iron and vitamin B12 from milk and bacteriostatic effect was studied. Pepsin digestion had no effect on vitamin B12 binding capacity, or the ability of bacteria to take up vitamin B12, or the growth inhibitory effect on a vitamin B12 dependant strain. In contrast, pepsin digestion (or low pH alone) released iron from milk and abolished its bacteriostatic effect. Trypsin digestion slightly reduced the molecular size of the vitamin B12 binding protein without releasing free vitamin B12; the bacteriostatic effect on a vitamin B12 dependant organism was, however, abolished. In contrast, trypsin digestion did not affect iron binding or bacteriostatic effects attributable to lactoferrin. The findings support an in vivo bacteriostatic role for lactoferrin in the breast fed neonate's intestine but do not support a similar role for the vitamin B12 binding protein.     

THE SYNERGISTIC EFFECT OF THROMBOPOIETIN IN ERYTHROPOIESIS WITH ERYTHROPOIETIN AND/OR IL-3 AND MYELOPOIESIS WITH G-CSF OR IL-3 FROM UMBILICAL CORD BLOOD CELLS OF PREMATURE NEONATES

The authors sought to determine whether recombinant human thrombopoietin (TPO) acts synergistically with other cytokine(s) on burst-forming unit-erythroid (BFU-E)-derived and colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colony formations from cord blood of premature neonates. Cord blood nonadherent mononuclear cells (MNC) from normal premature neonates were cultured in a methylcellulose system. When cultured with 1 &#50 10 4 MNC/mL, erythropoietin (EPO) 2 U/mL, interleukin-3 (IL-3) 50 ng/mL, and/or TPO 100 ng/mL, the addition of TPO to EPO gave rise to more BFU-E-derived colonies ( p = .000). The addition of TPO to EPO + IL-3 gave rise to more BFU-E-derived colonies ( p = .002) also. TPO synergizes erythropoiesis from cord blood of premature neonates. Likewise, the addition of TPO to G-CSF gave rise to more CFU-GM-derived colonies ( p = .000) also. TPO synergizes myelopoiesis from cord blood of premature neonates. Thus, TPO has synergistic effects on both erythropoiesis and myelopoiesis from cord blood of premature neonates.