D-PENICILLAMINE, A NON-BILIRUBIN-DISPLACING DRUG IN NEONATAL JAUNDICE

Abstract. Brodersen, R., Lakatos, L. and Karmazsin, L. (Institute of Medical Biochemistry, University of Aarhus, Denmark, and Pediatric Clinic, University Medical School, Debrecen, Hungary). D-penicillamine, a non-bilirubin-displacing drug in neonatal jaundice. Acta Paediatr Scand, 69:31, 1980.—D-penicillamine, a drug used clinically for the treatment of neonatal hyperbilirubinaemia, was tested for interference with the binding of bilirubin to human serum albumin by three methods: 1) The peroxidase technique, investigating the effect of D-penicillamine on the equilibrium concentration of unbound bilirubin in a solution containing a molar excess of albumin; 2) the MADDS method, measuring the concentration of vacant bilirubin binding site on albumin in a solution of pure albumin, or infant blood serum, with added D-penicillamine; and 3) injection of D-penicillamine into Gunn rats and determination of any decrease of plasma biiirubin which would be caused by displacement of the pigment. Results were negative in all cases. Quantitatively, the doses of D-penicillamine used clinically cannot displace bilirubin from its binding to albumin. The ameliorating effect on hyperbilirubinaemia in the newborn must be due to some other mechanism     

NASODUODENAL FEEDING IN HIGH RISK NEWBORNS

ABSTRACT. Rent reports indicate that nasoduodenal feeding is a suitable technique for high risk newborns, in particular those with a low birth weight. In the period between February 1975 and June 1976, 100 high risk newborns, divided into four cohorts on the basis of birth weight in 500 g divisions, were fed by nasoduodenal tube. The effect of nasoduodenal feeding has been measured in several ways, but particular consideration has been given to weight gain, its caloric cost, the mortality rates observed in the Unit before and after the introduction of this nutritional regime and complications. The use of nasoduodenal feeding abolished the physiological loss of weight which normally occurs during the first week of life and was associated with a subsequent rate of weight gain equal to or better than that observed in infants fed by other routes. The mean caloric intake was greater in smaller infants than in larger ones and it was accompanied by a steady decrease in weight gain per unit of caloric intake with increasing birth weight. In 1974 the overall mortality rate in the Unit was 18% and in 1975 following the introduction of nasoduodenal feeding fell to 11.4%. No serious complications were observed associated with nasoduodenal feeding. The conclusion is that this form of feeding is particularly suitable for infants with a birth weight of 1500 g or less.     

Neonatal Jaundice in Infants of Diabetic Mothers

Jährig, D., Jährig, K., Stiete, S., Beyersdorff, E., Poser, H. and Hopp, H. (Department of Paediatrics, the Data Centre of the Ernst Moritz Arndt University of Greifswald, Greifswald, and the'Gerhard Katsch'Central Research Institute for Diabetes, Karlsburg, G.D.R.). Neonatal jaundice in infants of diabetic mothers. Acta Paediatr Scand Suppl 360: 101, 1989.
357 IDMs and 20 healthy newborns of non-diabetic mothers were examined at term for body measurements, red blood cell count, serum bilirubin, cord blood insulin and blood glucose during the first postnatal week. The stage of maternal diabetes did not influence the course of neonatal bilirubin levels, but the IDMs had prolonged and higher bilirubinaemia compared with the controls. Hyperbilirubinaemia was found to be most prominent in newborns with an increased birthweightllength ratio and was not simply related to macrosomia (LGA). These infants had significantly lower blood glucose concentrations immediately after birth, whereas cord blood insulin was found to be identical between the IDM sub-groups. Bilirubinaemia in heavy for length infants was slightly correlated to haematocrit. For the pathogenesis of hyperbilirubinaemia in IDMs induction of heme oxygenase (due to a lack of energy provision following a phosphory lation disorder) is discussed. Nutritional support (early feeding, glucose infusions) does not affect the course of bilirubinaemia.     

GASTRIC EMPTYING IN NEWBORNS AND YOUNG INFANTS

ABSTRACT: Signer, E. and Fridrich, R. (University Children's Hospital and the Department of Nuclear Medicine, Kantonsspital, Basel, Switzerland). Gastric emptying in newborns and houng infants. Acta Paediatr Stand, 64:525, 1975.–The rate of gastric emptying was measured in newborns and young infants by a new radio-isotopic method. 28 control babies and 6 infants with projectile vomiting were given a 50 ml standard milk feeding containing 15µCi of Indium-113m-microcolloid. The radioactivity in the stomach was counted at regular intervals with a gamma-camera. The gastric emptying followed an exponential pattern with a "half-life" of 87±29 minutes in 24 out of 28 control babies. In 6 patients with projectile vomiting gastric emptying was impaired severely. Three of them with hypertrophic pyloric stenosis showed complete stasis of gastric contents. Gastric emptying returned to normal 8–16 days after pyloromyotomy. It is suggested that the radioisotopic technique is helpful in evaluating the severity of pyloric stenosis and that it is of value in studies of the action of pharmacological substances on gastric emptying.     

ENDOGENOUS CLEARANCE RATE AND SYNTHESIS OF ALPHAFOETOPROTEIN DURING AND AFTER BLOOD EXCHANGE TRANSFUSION IN HYPERBILIRUBINAEMIC NEWBORNS

Abstract. Teppo, A.-M. and Simell, O. (Department of Paediatrics, University of Helsinki, Helsinki, Finland). Endogenous clearance rate and synthesis of alphafoetoprotein during and after blood exchange transfusion in hyperbilirubinaemic newborns. Acta Paediatr Scand, 69: 491, 1980. —Plasma alphafoetoprotein (AFP) concentration was monitored in 22 hyperbilirubinaemic infants during blood exchange transfusion at the age of 0–4 days, in order to determine the endogenous clearance rate and demonstrate possible postnatal synthesis of AFP. The rapid fall in plasma AFP during the transfusion to 19±4% (mean ±1 S.D.) was followed by an increase to 81±15% of the initial concentration; only a 68% rise was expected after the establishment of a new equilibrium between the intra- and extravascular pools of AFP. Repeated transfusions in the same individuals gave similar findings. In two infants the total amount of AFP in these pools increased by 4.0–7.4 mg after the transfusions. The results could be accounted for by postnatal AFP synthesis. Because of the diffusion of AFP from the extravascular compartment to the intravascular pool the actual turnover rate of AFP could not be measured. The estimated magnitude of endogenous turnover rate of AFP, 0.02–0.09 min^-1, gave a mean half-life of about 20 min, which is distinctly shorter than that of AFP in plasma (3–5 days); this could be due to either continuous synthesis of AFP or transfer of presynthesized AFP from the liver cells to extracellular pool. We postulate that either the synthesis or the turnover rate of AFP is controlled by the plasma AFP concentration via a negative feedback mechanism.     

SERUM GAMMA-GLUTAMYL TRANSPEPTIDASE ACTIVITY AND URINARY D-GLUCARIC ACID EXCRETION IN NEWBORNS IN THE FIRST WEEK OF LIFE Effects of phenobarbital and nicethamide combination

Abstract. High serum γ-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of phenobarbital and nicethamide an increase of γ-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution.     

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.     

SERUM GAMMA-GLUTAMYL TRANSPEPTIDASE ACTIVITY AND URINARY D-GLUCARIC ACID EXCRETION IN NEWBORNS IN THE FIRST WEEK OF LIFE; Effects of phenobarbital and nicethamide combination

ABSTRACT. High serum γ-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of Phenobarbital and nicethamide an increase of γ-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution.     

SOMATOMEDIN IN NEWBORNS AND THE RELATIONSHIP TO HUMAN CHORIONIC SOMATOTROPIN AND FETAL GROWTH

ABSTRACT. The significance of somatomedin A (SM) and human chorionic somatomammotropin (HCS) in fetal growth was examined. SM, determined by chick embryo assay, was studied during the last trimester of pregnancy, in maternal serum and cord blood at term and in a group of normal newborns in the first week of life. Furthermore a group of newborns of diabetic mothers was studied in the first or second day of life. HCS was measured in maternal serum and in cord blood at term. In amniotic fluid inhibitory factors caused a low SM activity as measured by the bioassay. The following results were obtained: 1) Normal values of SM in the last trimester with a decline at term were found in 3 normal primigravidae. 2) The mean levels of SM in 22 mothers and their offspring were decreased. The difference between the two values was significant, but a positive correlation was found between the maternally related pairs of SM values. Moreover, a positive correlation was found between maternal SM, birth weight and length. HCS was not correlated to above-mentioned parameters, but there was positive correlation between placental weight and birth weight. 3) In 6 newborns during the first 5 days SM rose from very low values to normal values found in infants in their first year. 4) The mean value of SM in ten newborns of diabetic mothers was not significantly different from the mean value of control group. The results do not exclude the possibility of a transplacental transport of SM and the positive correlation between SM levels and birth weight found in this investigation supports the concept that SM plays an important role in fetal growth.     

EFFECT OF PHOTOTHERAPY AND EXCHANGE TRANSFUSION ON PRIMARY BILE ACIDS IN THE SERUM OF HYPERBILIRUBINAEMIC NEWBORNS

ABSTRACT. Serum primary bile acid (cholic (CA) and chenodeoxycholic (CDCA) acid) concentrations were measured in 14 preterm and 11 full-term hyperbilirubinaemic newborns at the beginning and end of, and 24 and 72 hours following phototherapy. Only in the preterm newborns with gestational ages of 35-38 weeks there was a significant decrease of mean serum bile acid concentrations which could be shown 72 hours after the beginning of phototherapy. It can be hypothesized that the decrease was a result of a direct effect of light on the excretory liver function. Serum CA and CDCA concentrations were also measured in 5 hyperbilirubinaemic newborns at the beginning and end, and 24, 48 and 72 hours after the end of exchange transfusion. Exchange transfusion caused a clear immediate decrease in the mean serum primary bile acid concentrations. However, on day 2 after exchange transfusion the mean serum concentration of CA was about 150% and that of CDCA about 110% of the initial values. The most hyperbilirubinaemic newborns had extremely high primary bile acid serum concentrations before therapy. As bile acids compete with bilirubin for albumin binding it should be considered whether high bile acids in the serum of hyperbilirubinaemic newborns presuppose exchange transfusions.     

ALBUMIN ADMINISTRATION COMBINED WITH PHOTOTHERAPY IN TREATMENT OF HYPERBILIRUBINAEMIA IN LOW-BIRTH-WEIGHT INFANTS

ABSTRACT. Ebbesen, F., and Brodersen, R. (Department of Neonatology, Rigshospitalet, Copenhagen and Institute of Medical Biochemistry, Aarhus, Denmark). Albumin administration combined with phototherapy in treatment of hyperbilirubinaemia in low-birth-weight infants. Acta Paediatr Scand, 70:649,.–Fifty-nine jaundiced light treated newborn infants with low birth weight were studied. At onset of phototherapy 30 infants received 1 g human serum albumin per kg body weight as a 9 % solution containing sodium caprylate and N-acetyltryptophan as stabilizers. 29 infants did not receive human serum albumin and served as controls. Blood samples were taken before initiation of the therapy and again 24 and 48 h thereafter, and the following determinations were made: Serum concentrations of unconjugated bilirubin, albumin, reserve albumin for binding of bilirubin by the [^l4C]-MADDS method, packed cell volume and pH. Before infusion of albumin it was found that the binding fraction of serum albumin, i.e. the sum of the serum concentrations of bilirubin-albumin and reserve albumin, constituted about half of the total serum albumin concentration. The other half was non-binding, in agreement with previous findings in neonates. The effect of albumin therapy was mainly an unexpected increase of the non-binding fraction of serum albumin, while the increase of the serum reserve albumin concentration was small and the concentration of bilirubin-albumin was not changed.     

IgE AND ATOPIC ALLERGY IN NEWBORNS AND INFANTS WITH A FAMILY HISTORY OF ATOPIC DISEASE

Abstract. Serum IgE levels were studied in 2 groups of children with a family history of atopic disease, 30 in whom the mother only and 38 in whom both parents had atopic disease. IgE antibodies were determined with Phadebas RAST® Test and serum IgE with Phadebas® IgE Test and Phadebas PRIST® at 0, 3, 9, 12 and 18 months of age. There was no correlation between the serum IgE levels in mothers and their newborns. RAST tests were frequently positive in maternal sera but no positive RAST test was found in the newborns. Obvious and probable atopic disease developed during the observation period in 42.1% of the children with a double family history of atopic disease. In 75% of these the serum IgE level was above the upper limit of normal on an average 6 months before the onset of atopic symptoms. An elevated IgE level without atopic symptoms during the observation period occurred in only one child. It is concluded that the serum IgE in newborns seems to be of foetal origin and that the determination of serum IgE in infants is of value in predicting atopic allergy.     

COMPARISON BETWEEN TWO PREPARATIONS OF HUMAN SERUM ALBUMIN IN TREATMENT OF NEONATAL HYPERBILIRUBINAEMIA

ABSTRACT. Thirty-six newborn infants with normal birth weights and with uncomplicated hyperbilirubinaemia, treated with light, were studied. At onset of phototherapy the infants received intravenously 1 g human serum albumin (HSA) per kg body weight as a 9 % solution. Two different preparations of HSA were used and compared. One of these, HSA_I, contained sodium caprylate and N-acetyltryptophan, 5 mmol/1 of each, as stabilizers. HSA_II contained only caprylate, 5 mmol/1. Nineteen infants received HSA_I and seventeen infants HSA_II. The reserve albumin for binding of bilirubin, measured by the [¹⁴C] MADDS method, was low in both preparations in vitro. During the infusion, the serum concentrations of albumin and reserve albumin increased and the serum unconjugated bilirubin concentration decreased, resulting in a fall in the index of plasma bilirubin toxicity in all infants. After completion of the infusion, the serum concentrations of albumin and reserve albumin declined, and a slight rise in index occurred. The increase in the serum reserve albumin concentration was markedly higher during infusion of HSA_II than of HSA_I. It is concluded that infusion of both HSA preparations during phototherapy provides an immediate protection against bilirubin encephalopathy. HSA_I is inferior to HSA_II, probably due to its content of N-acetyltryptophan.     

BREAST FEEDING TRENDS AND RECENT INFORMATION ACTIVITIES IN SWEDEN

Abstract. Hofvander, Y. and Sjölin, S. (Department of Paediatrics, University Hospital, Uppsala, Sweden). Breast feeding trends and recent information activities in Sweden. The breast feeding rate has been declining steadily in Sweden since the 1930's up to the early 1970's. It is suggested that this was linked to the changing role of women, the development towards the nuclear family, the changing way of living, the influence of strict routines at the maternities and many other factors. A Committee was appointed in 1973 by the National Board of Health and Welfare, which initiated a number of breast feeding promoting activities: the editing of a Manual for health personnel, and booklets for mothers, the systematic arranging of workshops for key personnel in each county, stimulation to more flexible and breast feeding favouring maternity routines, backing of working groups of La Leche League-type, etc. Coinciding with these activities and probably a result of changed breast feeding attitudes among mothers, the breast feeding rate has increased considerably—at 2 months from an all time low of 31 % in 1972 to 62% in 1976/77, and at 6 months from 6% to 20%.     

THE DECREASE IN THE SERUM BILIRUBIN LEVEL IN PREMATURE INFANTS BY OROTIC ACID

The influence of higher doses of orotic acid on the serum bilirubin level of premature infants was investigated following studies with a lower dose. 102 premature infants were treated with a daily dose of 300 mg of orotic acid from the 1st-6th day after birth. An equal number of children served as a control group. The serum level for the indirect bilirubin that was analysed from the 3rd-6th day of life could be statistical significantly decreased by the administration of orotic acid. Blood exchange transfusions were necessary only four times with the administration of orotic acid, whereas blood exchange transfusions were required in 30 premature infants of the control group. The question of eventual side effects and the supposed mode of action of the orotic acid are discussed.     

EFFECT OF LIGHT EXPOSURE ON GUT TRANSIT TIME IN JAUNDICED NEWBORNS

In order to elucidate the mechanism by which phototherapy induces loose stools in newborns, studies were performed on the speed of gut transit by performing the Carmine Red test on normal newborn, on jaundiced newborns before and after phototherapy. A statistically accelerated intestinal transit was observed in jaundiced newborns treated with phototherapy. The increased rate of intestinal transit produced by phototherapy is probably due to the action of the photo-decomposition derivatives of bilirubin, which are excreted during phototherapy.     

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 cow's 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 cow's 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.     

PLATELET AGGREGATION IN TERM AND PRETERM NEWBORNS

The platelets of newborns have a hyporeactive period. This period, during which the platelet count is normal but their functions are deficient, is called transient platelet hyporeactivity of newborns. The platelet functions and their normalizing process of term and preterm neonates are investigated. Twenty term and 20 preterm (gestational age <37 weeks) newborns were enrolled in the study. Twenty-eight healthy children aged 2 months to 3 years old participated in the study as the control group. Healthy newborns were followed for 15 days after birth longitudinally in 3 periods: period 1 (0–4 days), period 2 (5–9 days), period 3 (10–15 days). Aggregation studies were performed from whole blood samples. Whole blood aggregation was measured by the impedance method. Transient hyporeactivity of platelets was found in term and preterm groups, and there was no difference between term and preterms. Platelets of newborns gained their normal functions at postnatal 10–14 days. The results show that hyporeactivity of platelets during the first 9 days of life is physiological and transient.