BILIRUBIN, RESERVE ALBUMIN FOR BINDING OF BILIRUBIN AND pH IN PLASMA DURING PHOTOTHERAPY (ORDINARY AND DOUBLE LIGHT) OF TERM NEWBORN INFANTS

ABSTRACT. Ebbesen, F. (Department of Neonatology, Rigshospitalet, Copenhagen, Denmark). Bilirubin, reserve albumin for binding of bilirubin and pH in plasma during phototherapy (ordinary and double light) of term newborn infants. Acta Paediatr Scand, 70:223, 1981. –Forty-five term newborn infants with uncomplicated hyperbilirubinaemia were treated continuously with phototherapy for 24 hours. Twenty-eight infants received double light treatment and 17 infants ordinary phototherapy. During both treatments a significant decrease in the serum unconjugated bilirubin concentration, a significant increase in the serum reserve albumin concentration for binding of bilirubin determined by the [¹⁴C] MADDS method, and a significant decrease in the index of serum bilirubin toxicity occurred. The changes in these parameters were significantly greater during the double light treatment than during the ordinary phototherapy. During the treatment the fall in index was constant. No significant change in plasma pH was seen. Thus, the study gives further evidence that the risk of bilirubin encephalopathy is reduced by phototherapy and that double light treatment is in the respect superior to ordinary phototherapy. Prior to phototherapy the molar ratio in serum of unconjugated bilirubin plus reserved albumin for binding of bilirubin to albumin was only 0.60, on average, and during the treatment the increase in the serum reserve albumin concentration was less than the decrease in the serum bilirubin concentration. This can be explained either by the presence in infant serum of an unknown ligand interfering competitively or allosterically in the binding of MADDS and bilirubin to albumin, or by the existence of a foetal albumin with a lower affinity for MADDS than adult albumin.     

EFFECT OF EXCHANGE TRANSFUSION ON SERUM RESERVE ALBUMIN FOR BINDING OF BILIRUBIN AND INDEX OF SERUM BILIRUBIN TOXICITY

ABSTRACT. Ebbesen F. (Department of Neonatology, Rigshospitalet, Copenhagen, Denmark). Effect of exchange transfusion on serum reserve albumin for binding of bilirubin and index of serum bilirubin toxicity. Acta Paediatr Scand, 70:643,.–Seventeen newborn infants, who received their first exchange transfusion due to hyperbilirubinaemia and/or rhesus haemolytic disease, were studied. The exchange transfusions were performed with fresh, citrated blood. During the exchange transfusion a marked increase in the serum reserve albumin concentration for binding of bilirubin measured by the [^,4C]-MADDS method was observed, followed by a smaller decrease after the transfusion. Plasma pH increased both during and after the exchange transfusion. During the exchange transfusion a drastic fall in index of serum bilirubin toxicity was observed, followed by a smaller increase after the transfusion. Citrate was not found to interfere in the binding of bilirubin to albumin. The results are in agreement with the clinical finding that an exchange transfusion performed with fresh, citrated blood effectively reduces the risk of bilirubin encephalopathy. The ratio in serum of binding albumin, i.e. bilirubin plus reserve albumin, to total albumin failed to be increased by the exchange transfusion, and a decrease occurred after the transfusion. These findings indicate the presence in infant serum of non-binding albumin. Donor albumin with intact binding potential is partly transformed into the non-binding variety in the course of one hour after the transfusion. In the most severely rhesus sensitized infant a drastic decline of the serum albumin binding capacity was seen during the first day of life.     

LOW RESERVE ALBUMIN FOR BINDING OF BILIRUBIN IN NEONATES WITH DEFICIENCY OF BILIRUBIN EXCRETION AND BRONZE BABY SYNDROME

ABSTRACT. The plasma reserve albumin concentration for binding of bilirubin was found to be low in four newborn infants with deficiency of bilirubin excretion, of whom two had the bronze baby syndrome. Thus, the risk of bilirubin encephalopathy was increased. Also the ratio of binding fraction of albumin, i. e. unconjugated bilirubin plus reserve albumin, to total albumin was low. Possible causes of the low reserve albumin concentration and the ratio are discussed.     

RESERVE ALBUMIN AND BILIRUBIN TOXICITY INDEX IN INFANT SERUM

ABSTRACT. Reserve albumin concentration (the concentration of albumin available for binding of unconjugated bilirubin) was determined in 95 sera from 76 subjects by dialysis with ¹⁴C-monoacetyl diamino diphenyl sulfone (MADDS). An index, I of bilirubin toxicity in the plasma was calculated for each subject, based on the bilirubin and reserve albumin concentrations, the affinity of bilirubin for serum albumin, and the pH-dependent solubility of bilirubin in the plasma. The values of reserve albumin and of I varied significantly with gestational age, clinical condition (whether sick or well), and serum bilirubin level. The value of reserve albumin was decreased and I was increased in association with clinical factors (e. g., hyperbilirubinemia, hypoxia, acidosis, or sepsis) recognized as increasing the risk for bilirubin encephalopathy. The lowest values of reserve albumin and the highest values of I were found in the least mature and sickest infants.     

SERUM CONCENTRATIONS OF THYROXINE-BINDING GLOBULIN, PREALBUMIN AND ALBUMIN IN HEALTHY FULLTERM, SMALL-FOR-GESTATIONAL AGE AND PRETERM NEWBORN INFANTS

Abstract. Jacobsen, B. B., Peitersen, B., Andersen, H. J. and Hummer, L. (The University Clinic of Paediatrics, Children's Hospital Fuglebakken and the Departments of Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark). Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants. Acta Paediatr Scand, 68: 49, 1979.—Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels wer found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in full-term, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was evne lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.     

INCREASE IN BILIRUBIN BINDING TO ALBUMIN WITH CORRECTION OF NEONATAL ACIDOSIS

Abstract. Twenty-six serial measurements of free bilirubin concentration and apparent association constant of bilirubin for albumin (Ka) at a bilirubin: albumin molar ratio of 0.8 were performed and compared with baseline values in 11 newborn infants with acidosis before treatment and during recovery from acidosis. When arterial pH was corrected from 7.12±0.02 (Mean±S.E.M.) to 7.34±0.02, there was a significant decrease in serum free bilirubin concentration and a significant increase in the Ka at molar ratio 0.8. The data offer in vivo evidence that correction of acidosis in the neonate results in an improvement of the apparent bilirubin binding affinity of albumin.     

EFFECTS OF STABILIZERS IN PREPARATIONS OF HUMAN SERUM ALBUMIN ON THE SERUM BILIRUBIN IN GUNN RATS

ABSTRACT. Commercially available preparations of human serum albumin (HSA) containing stabilizers (i.e. 16 mmol/I Na caprylate plus 16 mmol/I Na N-acetyl- dl -tryptophan) were injected either s.c., i.p. or i.v. into homozygous infant Gunn rats. 30 min and 3 hours after s.c. injection, a serum bilirubin decline which surpassed dilution by the injected volume could be ascertained. It was mainly caused by N-acetyl- dl -tryptophan since s.c. injections of appropriate amounts of this substance alone or a mixture of both components of the stabilizer without HSA brought about similar results. HSA without these stabilizers had not such an effect. It is postulated that under these conditions Na N-acetyl- dl -tryptophanate displaced bilirubin from albumin bonds. It became obvious that after s.c. injection equilibration of HSA between skin and plasma was delayed, whereas Na N-acetyl- dl -tryptophan was rapidly transported to the blood. As for Na caprylate, a displacing effect of short duration could not be excluded by the experimental arrangement used, since the metabolism of the substance in the rat is very fast. When HSA and the stabilizers entered the plasma simultaneously (i.v. injection) no effect on serum bilirubin concentration could be proved 30 min and 3 hours later. All the bilirubin and the Na N-acetyl- dl -tryptophan present in the plasma at that time can be bound to the large amount of albumin which is directly given into the circulation of the animal. 30 min after i.p. injection of HSA preparations containing stabilizers a small decrease of serum bilirubin concentration could be recognized. It was less pronounced and less persisting than after s.c. injection. Probably equilibration of HSA between peritoneum and plasma went on faster than between skin and plasma. Only for a short period a lack of albumin binding sites in the plasma of the rat pointed to a surplus of Na N-acetyl- dl -tryptophan.     

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.     

RELATIONSHIP BETWEEN APNOEA AND BRADYCARDIA IN PRETERM INFANTS

Abstract. Vyas, H., Milner, A. D. and Hopkin. I. E. (Department of Child Health, Department of Neonatal Medicine and Surgery, City Hospital, Nottingham, England). Relationship between apnoea and bradycardia in preterm infants. Acta Paediatr Scand, 70: 785, 1981.-Nine studies were carried out on seven babies who were having repeated episodes of bradycardias without any clinically obvious apnoea. Their mean gestational age was 31.7 weeks (range 29 to 36 weeks) and the mean birth weight was 1.56 kg (range 1.08 kg to 2.16 kg). Investigations were carried out in a total body plethysmograph. Face mask with a pneumotachograph attached to it measured flow. Tidal volume was obtained by integrating these signals. An oesophageal balloon measured intrathoracic pressure changes and the heart rate was measured from ECG chest electrodes. A total of 172 episodes of apnoea were observed. In 50 % of these apnoeas, the airway was closed as determined by the absence of cardiac artefact on the flow signals. Apnoea was associated with bradycardia in just over 25 % of all apnoea. It tended to occur early (11 to 14 sec). Whether the apnoea was central or obstructive had no effect on the pattern provided the baby did not make any inspiratory efforts. Inspiration against a closed airway produced bradycardia in over 50 % of obstructive apnoea, the heart rate falling precipitously within 1 to 2 sec. These findings indicate that often bradycardias occur too early-in apnoea to be due to central hypoxia and must be due to a peripheral mechanism.     

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.     

早产儿血清白蛋白、前白蛋白、转铁蛋白水平的观察

本文通过对早产儿血清白蛋白(ALB)、前白蛋白(PA)和转铁蛋白(TF)的测定,来寻求评价早产儿营养状况的方法,用以指导临床.采集新生儿静脉血2ml,应用美国Backman公司CX-5型全自动化仪,白蛋白用溴甲酚绿比色法,前白蛋白用散射比浊法,转铁蛋白用免疫散射比浊法.结果显示,早产儿血清白蛋白、前白蛋白、转铁蛋白均明显低于正常对照组,其中两组白蛋白水平有显著性差异(P＜0.05),前白蛋白、转铁蛋白水平有非常显著性差异(P＜0.01),且三种蛋白随着胎龄及体重的减小而降低.因此,血清白蛋白、前白蛋白、转铁蛋白水平可以作为对早产儿营养状况评价的指标.     

THE EFFECT OF ANTIMICROBIAL AGENTS ON THE BINDING OF BILIRUBIN BY ALBUMIN

The effect of antibiotics, on the albumin binding capacity was studied by adding various concentrations of each drug in a standard solution of crystalline human serum albumin 4 g/ 100 ml, according to method of Porter & Waters (8). We found significant depression (above 25 %) of binding capacity of the albumin after addition of the following drugs in concentrations reaching therapeutical blood levels: Novobiocin and Sulfonamides (Elkosin, Sulfexin, Gantrisin). Moderate depression (11-25 %) was observed with the following drugs: Oxacillin, Ce-phalothin and Rifamycin. Little or no decrease of the albumin binding capacity was found after the addition of the following drugs: Penicillin, Penetracin, Methi-cillin (Staphcillin, Celbenin) Ampicillin, (Pen-trexyl, Penbritin), Cloxacillin, Lincomycin, Cephaloridin, Streptomycin, Colimycin, Chloramphenicol succinate, Erythromycin, Tetra-cyclin hydrochloride, Pyrolidynomethyl-tetra-cyclin and Oxytetracyclin.     

THE INFLUENCE OF OROTIC ACID ON THE SERUM BILIRUBIN LEVEL OF MATURE NEWBORN

Fifty-two mature newborn were treated with a daily dose of 200 mg of orotic acid from their 1st to their 5th day of life. An equally large number of untreated children served as a control group. Contrary to the premature infants, in the mature newborn no decrease in the serum bilirubin was achieved by administration of orotic acid. The question of the possible mode of action of the orotic acid is discussed.     

Risk of bilirubin acid precipitation in preterm infants with respiratory distress syndrome: considerations of blood/brain bilirubin transfer equilibrium

Twenty-six preterm infants with respiratory distress syndrome (RDS), were examined daily during the first 6 days of life. Twenty-six equally preterm but clinically well infants served as controls. In the RDS infants, plasma albumin concentration was low, hyperbilirubinemia was prolonged, plasma pH was decreased during the first two days, and the concentration of reserve albumin for binding of monoacetyldiaminodiphenylsulfone (MADDS), a deputy ligand for bilirubin, was decreased on the second throughout the sixth day, when compared with the controls. These factors concur in increasing the likelihood of bilirubin acid precipitation in RDS above the increased risk present in preterm infants. The plasma of the preterm controls was supersaturated with respect to crystalline bilirubin acid by an average factor 5 (index of plasma bilirubin toxicity = 0.7) on the first day of life, peaking at a factor 10 (index 1.0) on the third and fourth days while these factors were 10 and 20 (index 1.0 and 1.3), respectively, in the RDS infants. Two of the latter surpassed a level of 60 times supersaturation (index 1.8) where acute precipitation of amorphous bilirubin acid becomes possible.     

STUDIES ON THE EFFECT OF ORALLY ADMINISTERED AGAR ON THE SERUM BILIRUBIN LEVEL OF PREMATURE INFANTS and MATURE NEWBORNS

ABSTRACT: Windorfer, A. Jr, Kunzer, W., Bolze, H., Ascher, K., Wilcken, F. and Hoehne, K. (University Children's Hospital, Freiburg i. Brg., West Germany). Studies on the effect of orally administered agar on the serum bilirubin level of premature infants and mature newborns. Acta Paediatr Scand, 64:699, 1975.–The effect of orally administered agar on the serum concentration of bilirubin was tested in 366 premature and newborn infants. For this purpose two different concentrations of agar were added to the milk for 8–10 days. On none of the groups tested did the serum level of bilirubin show a significant decrease after administration of agar. Therefore the attempt to lower the level of serum bilirubin in premature and newborn infants by inhibiting enteric reabsorption by means of adsorbents must be considered a failure.     

PLASMA FERRITIN CONCENTRATIONS IN PRETERM INFANTS IN CORD BLOOD AND DURING THE EARLY ANAEMIA OF PREMATURITY

Abstract. Hågå, P. (Department of Paediatrics and Paediatric Research Institute, National Hospital of Norway, and Department of Paediatrics, Oslo City Hospital, Ullevål, Oslo, Norway). Plasma ferritin concentrations in preterm infants in cord blood and during the early anaemia of prematurity. Acta Paediatr Scand, 69: 637, 1980.—Ferritin concentrations in cord blood were determined in 22 normal term and 32 preterm infants (birth weights 600–2000 g). Eight of the preterms were SGA infants. AGA preterm infants had significantly lower concentrations than term infants, and the SGA preterm newborn had even lower levels. Plasma ferritin in cord blood of the term and AGA preterm infants correlated positively with plasma iron and transferrin saturations, but not with the transferrin level, while plasma iron and transferrin concentrations correlated positively. In a longitudinal study, 17 AGA preterm infants (birth wights 850–1500 g) were followed during the early anaemia of prematurity. Iron was supplemented from 4 weeks of age. Plasma ferritin rose rapidly during the first days after birth, peak levels being reached at 1–4 weeks. Thereafter linear falls (semilog) occurred with similar slopes in different infants. Transferrin concentrations showed a slow progressive increase from 0–8 weeks. Plasma ferritin, after reaching the peak value, correlated negatively with weight gain. No infant had low ferritin values indicating iron deficiency during the early anaemia.     

SEPARATION BY GEL FILTRATION AND MICRODETERMINATION OF UNBOUND BILIRUBIN

A gel filtration technique and a diazoreaction method for unbound bilirubin separation and determination, directly applicable to small blood volumes has been described. Precision of the microdetermination, reproducibility of the separation method and bilirubin recovery have been very satisfactory in our hands. The effects of pH and relative albumin concentration on the albumin-bilirubin binding were studied in sera and in commercial albumin-bilirubin mixtures.     

CERULOPLASMIN LEVELS AND ERYTHROCYTE SUPEROXIDE DISMUTASE ACTIVITY IN SMALL PRETERM INFANTS DURING THE EARLY ANEMIA OF PREMATURITY

Abstract. Hågå, P. (Paediatric Research Institute, National Hospital of Norway, and Department of Paediatrics, Ullevål Hospital, Oslo, Norway). Ceruloplasmin levels and erythrocyte superoxide dismutase activity in small preterm infants during the early anemia of prematurity. Acta Paediatr Scand, 70: 861, 1981.-Ceruloplasmin plasma levels and erythrocyte superoxide dismutase activity were studied in appropriate for gestational age preterm infants (birth weights ≤1500 g) during the first 10 weeks of life. Preterm infants had significantly lower ceruloplasmin concentrations in cord blood than term infants, the mean level in the preterm infants being 0.07 g/I. At 1 week of age ceruloplasmin levels had risen significantly, whereupon a fall occurred at 2 weeks of age. Ceruloplasmin concentrations increased slowly and progressively from 4 weeks of age. The low ceruloplasmin concentration during the early anemia of prematurity seems not to interfere with iron mobilization. The superoxide dismutase activity per gram hemoglobin in cord blood erythrocytes from normal term infants was significantly lower than that of red blood cells from adults. When the activity was expressed per erythrocyte no difference was found. The normochromic macrocytic red blood cells of the neonate most likely explain this discrepancy. The erythrocyte superoxide dismutase activity of the preterm infants did not change from birth until 10 weeks of age, and the levels seemed adequate judged from the levels found in red blood cells from adults and cord blood from term infants. Neither ceruloplasmin nor erythrocyte superoxide dismutase activity seem to play a role in the etiology of the early anemia of prematurity.