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.     

EXCRETION OF BILE ACIDS IN ERYTHROBLASTOSIS FOETALIS

The excretion pattern of intramuscularly injected cholic acid-24–¹⁴C was studied for 4 days after the injection in 10 cases of erythro-blastosis (EB). Seven patients with EB and raised serum conjugated bilirubin excreted 3643% of the injected isotope in the urine, whereas the amounts of isotope in the faeces varied greatly. In 3 cases without raised serum conjugated bilirubin less isotope was recovered in the urine and always more than 10% of injected isotope was recovered in the faeces. Cholic acid-24–¹⁴C was excreted essentially unchanged in all cases but in conjugated form. In all cases of EB the urine was found to contain bile acids, chiefly cholic acid. The infants with EB associated with cholestasis excreted 4.8–132.3 μmol of these acids per day; the corresponding values in the absence of cholestasis being 0.4–0.9 μmol per day. In the infants with physiological jaundice the excretion ranged from less than 0.01 to 0.7 μmol per day; the correspondign values in the 2 patients with hyperbilirubinaemia were about 0.2 μmol per day. The infants with EB associataed with cholestasis were found to excrete as large amounts of bile acids in the urine as the infants with intrahepatic cholestasis. These findings strongly suggest that increased serum conjugated bilirubin, irrespective of the patho-genesis of the liver damage, is associated with an impaired bile acid excretion to the intestine. EB without increased serum conjugated bilirubin did not seem to alter the bile acid metabolism, since the urinary excretion of cholic acid and chenodeoxycholic acid in these cases was practically the same as in jaundiced newborn infants.     

BILE ACID METABOLISM IN LOW BIRTHWEIGHT INFANTS

Strandvik, B. (Department of Paediatrics and Research Center, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden). Bile acid metabolism in low birth weight infants. Acta Paediatr Scand, Suppl. 296: 71, 1982.—The early synthesis of bile acids is described. From 28 weeks of gestation cholic acid is the predominating bile acid, but the bile acid pool is very small in preterm infants, leading to a low intraduodenal concentration of bile acids, especially during digestion of meals. Preliminary results indicate that preterm infants excrete less cholic and more 3β0H5-cholenoic acid in the urine than fullterm infants indicating a functional minor pathway in the synthesis of chenodeoxycholic acid. The tetrahydroxylated bile acids, which tend to dominate in the urine of newborn, have been shown to be products of the most common bile acid in cholestatic adults, and may thus be the result of a "physiological cholestasis" in the newborn.     

PLASMA CONJUGATED CHOLIC ACID IN PREMATURE AND TERM NEWBORNS AND YOUNG INFANTS

ABSTRACT. Tikanoja, T., Tikanoja, S. and Simell, O. (Children's Hospital, University of Helsinki, Helsinki, Finland). Plasma conjugated cholic acid in premature and term newborns and young infants. Acta Paediatr Scand, 70:491,.–Bile acid handling by neonates, both premature (Group 1, mean gestational age 34.3 weeks; Croup II, 36,6 weeks) and full-term (Group HI, 40.2 weeks) and by 3-month-old infants (Group IV) was assessed by measuring plasma concentrations of conjugated cholic acid (CCA) before and at successive intervals after feeds. The prefeeding CCA concentrations were highest in Group I (log mean 8.2; range 1.8–28.6 μmol/1) and lower in Groups II (7.5; 2.6–22.4 umol/1), III (5.1; 2.1–11.1 μ0mol/1), and IV (2.2; 0.5–6.1 μmol/1). The mean postprandial increments correlated with maturity: the rises for Groups I-IV were 3.7, 4.3, 1.0 and 0.7 μmol/1, respectively. Peak values were consistently reached at 30 min after the start of the feed, i.e., strikingly earlier than in older children and adults. After the peaks the return to prefeeding levels occurred rapidly in Groups II-IV but more slowly in the most premature infants (Group I). The rapid postprandial rise may be due to many factors, e.g., passive jejunal absorption, immature hepatic-clearing mechanisms, or rapid transit of bile acids to the ileum. Hence, measurements of postprandial plasma bile acids would appear ill-suited for detection of disturbed ileal function in young infants. The high concentrations in healthy newborns suggest that caution is necessary in interpreting plasma bile acid concentrations during the first few weeks of life, especially in premature infants.     

NUTRITION IN LOW-BIRTH-WEIGHT INFANTS

ABSTRACT: Olegård, R., Gustafson, A., Kjellmer, I. and Victorin, L. (Department of Paediatrics I, University of Göeborg, Göteborg, Sweden). Nutrition in low-birth-weight infants. III. Lipolysis and free fatty acid elimination after intravenous adminstration of fat emulsion. Acta Paediatr Scand, 64: 745, 1975.–Triglyceride linoleic acid in a fat emulsion for intravenous administration (Intralipid) was used as a marker in an evaluation of fat metabolism in newborn low-birth-weight (LBW) infants. Qualitative data on fatty acids as well as quantification of triglycerides and free fatty acids were obtained by gas-liquid chromatography. Influences on these parameters after a single and after repeated injections of Intralipid revealed differences between low-birth-weight infants appropriate-for-date (AFD) (n =8) and those light-for-date (LFD) (n =5). The LFD exhibited in comparison with the AFD infants an impaired lipolysis of injected triglycerides and a retarded elimination from plasma of released free fatty acids. In LFD, in general, this resulted in triglyceride accumulation and low free fatty acid levels. Heparin facilitated plasma triglyceride lipolysis and free fatty acid elimination from the blood stream.     

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.     

LIPIDS IN CORD SERUM AND FREE FATTY ACIDS IN PLASMA IN HEALTHY NEWBORN TERM INFANTS

ABSTRACT. Christensen, N. Chr. (Department of Obstetrics, Odense University Hospital, Odense, Denmark). Lipids in cord serum and free fatty acids in plasma in healthy newborn term infants. Acta Paediatr Scand, 63: 711, 1974.—Serum cholesterol, triglycerides, and glycerol in cord serum and plasma FFA in cord blood and at 1 1/2, 6, 12, 24 and 48 hours after birth were determined in 18 healthy term infants. Concentrations of lipids in cord blood were low; and there were no correlation between cord lipids and subsequent FFA values. A rapid increase in FFA level, with peak values at 12 hours, was seen. Significant, negative correlations were found between FFA concentration and rectal temperature at 1 1/2 hour and between total caloric intake and FFA concentration at 48 hours.     

EXCRETION OF BILE ACIDS IN EXTRAHEPATIC BILIARY ATRESIA AND INTRAHEPATIC CHOLESTASIS OF INFANCY

This series included 24 infants, 16 boys and 8 girls, who were admitted to hospital with the diagnosis of obstructive jaundice. Five of the infants were subsequently found to have extra-hepatic biliary atresia (BA) and the other 19 infants intrahepatic cholestasis of infancy (IHC). The infants were investigated given special attention to: the quantitative urinary excretion of cholic and chenodeoxycholic acids, the isotope excretion after intramuscular injection of cholic acid-24–¹⁴C, the nature of labelled urinary bile acids, the half-life and the pool size of cholic acid. At the first examination of the infants after admission the urinary excretion of cholic and chenodeoxycholic acids varied greatly between the patients. However, on comparing the values obtained in the two groups, it was found that there was virtually no difference between the mean daily values of cholic and chenodeoxycholic acids in urine, and the ratio cholic to chenodeoxycholic acid between the BA group and the IHC group. After the injection of isotopic cholic acid most of the isotope was recovered in the urine in all cases. In the infants with BA the faecal excretion of the isotope was low, being less than 3 per cent of the injected isotope. Out of the 19 infants with IHC the recovery of the injected isotope in faeces was also less than 3% in 11 infants. In 8 infants with IHC the faecal isotope excretion was significantly high to exclude extrahepatic biliary atresia. The first 24 hour urine specimen contained small amounts of unconjugated labelled cholic acid in all cases whereas in no case did the patients excrete unconjugated labelled cholic acid 48 hours after the injection of the isotope. No transformation of cholic acid was observed. There was no difference between the BA group and IHC group with regard to the percentage labelled glycine conjugates of total excreted urinary conjugates. Neither was there any difference between the two groups with regard to half-life and pool size of cholic acid. There was no difference with respect to the bile acid metabolism between infants with congenital CMV infection, decreased serum concentrations of alfal-antitrypsin and the other patients.     

URINARY MONOHYDROXY BILE ACIDS IN YOUNG INFANTS WITH OBSTRUCTIVE JAUNDICE

ABSTRACT. Using an aluminum oxide column, we fractionated and quantitatively determined urinary monohydroxy bile acids in young infants. For comparison purposes, monohydroxy bile acids were also measured in urine from older children and adults with obstructive jaundice. Lithocholic acid was not found in any specimens of the young infants examined, while 3β-hydroxy-5-cholenoic acid was detected in all. In the biliary atresia group, 3β-hydroxy-5-cholenoic acid excreted was 0.45 ± 0.28 μmol per day ( n = 7), and in the neonatal hepatitis group, 0.48 ± 0.44 μmol per day ( n = 9). The mean rate of 3β-hydroxy-5-cholenoic acid to total urinary bile acids in the biliary atresia group was 2.1%, and 1.3% in the neonatal hepatitis group. In the older children and adults with obstructive jaundice ( n =6), 3β-hydroxy-5-cholenoic acid was excreted at a mean rate of 3.9% of total urinary bile acids, ranging from 0.63 to 14.81 mol per day. The excretion rate of 3β-hydroxy-5-cholenoic acid was related to that of chenodeoxycholic acid ( p <0.05) in infants, while it was related to that of both chenodeoxycholic acid ( p <0.01) and cholic acid ( p <0.05) in older children and adults.     

AMINO ACIDS IN PARENTERAL NUTRITION OF PRETERM INFANTS

ABSTRACT. Parenteral feeding of preterm infants has been accepted as an alternative form of nutrition in those infants unable to accept oral feeding. The amount of amino acid nitrogen and the composition of the amino acid solution to be used, however, have not yet been defined. The amino acid intake and the plasma amino acid concentration of three groups of preterm infants were compared. Twenty-three infants were fed parenterally. Of these, 16 were studied during the first week of life (group I) and 7 during the second week (group II). A control group of 9 infants fed with oral formula was also studied in the second week (group III). In general, plasma amino acid concentrations in the parenterally fed groups were higher than in the orally fed group, in spite of a lower intake. Comparison of the amino acid intake of groups I and II relative to group III, with the plasma amino acid concentrations of groups I and II relative to group III, revealed a rather constant ratio with the exception of tyrosine and aspartic acid, where higher values were found. It is concluded that further increase in the amino acid nitrogen in parenteral feeding of preterm infants requires a more adapted preparation.     

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.     

EVIDENCE OF RIBOFLAVIN DEPLETION IN BREAST-FED NEWBORNS AND ITS FURTHER ACCELERATION DURING TREATMENT OF HYPERBILIRUBINEMIA BY PHOTOTHERAPY

Abstract. Phototherapy in the treatment of newborns with hyperbilirubinemia, resulting in degradation of bilirubin, also appears to have other photodynamic effects on metabolism. We studied flavin adenine dinucleotide (FAD) saturation of erythrocyte glutathione reductase, which should reflect riboflavin nutritional status, in 28 healthy newborns, and followed 37 newborns with hyperbilirubinemia prior to the start of and during phototherapy. The results indicate that healthy newborns on human milk feeding, relatively poor in riboflavin, have evidence of a transient riboflavin depletion soon after birth. This effect is made more pronounced by phototherapy and partially prevented by parenteral or oral administration of moderate amounts of riboflavin.     

EVIDENCE FOR A LARYNGEAL CHEMOREFLEX IN SOME HUMAN PRETERM INFANTS

ABSTRACT. Studies in animals have documented the presence of a laryngeal chemoreflex. This reflex reflex in apnea when water is placed in the laryngeal area. This study of ten premature infants presents data that would support the existence of a similar reflex response in some premature infants. All ten infants studied had apnea of unknown etiology.     

NUTRITION IN LOW-BIRTH-WEIGHT INFANTS: II. Repeated Intravenous Injections of Fat Emulsion

Abstract. Gustafson, A., Kjellmer, I., Olegård, R. and Victorin, L. (Department of Paediatrics, Children's Hospital, and of Medicine I, Sahlgren's Hospital, Goteborg, Sweden). Nutrition in low-birth-weight infants. II. Repeated intravenous injections of fat emulsion. Acta Paediat Scand, 63: 177, 1974.–The elimination of an exogenous fat emulsion from the blood stream after repeated intravenous injections was investigated in two groups of low-birth-weight infants: 11 appropriate-for-date (AFD) pre-term babies and 8 light-for-date (LFD) pre- and full-term infants. During a period with six injections hourly of 0.15 g fat/kg 'b.w. the total lipids of plasma increased only moderately in the AFD group, from 264 to 351 mg/100 ml, while in the LFD group a progressive rise of total lipids occurred from 244 to 466 mg/100 ml. The plasma turbidity increased correspondingly more in the LFD than in the AFD group. In 5 LFD babies, where a progressive accumulation of total lipids occurred with each injection of fat emulsion, heparin was given intravenously after eight fat injections. The plasma was rapidly cleared of fat although fat injections were continued. It is concluded that AFD infants are able to hydrolyse fat emulsions given at an hourly rate of 0.15 g/kg b.w., while this amount of fat to LFD babies will cause an accumulation of plasma lipds unless heparin is supplied simultaneously.     

BILE ACID EXCRETION AFTER DISAPPEARANCE OF JAUNDICE IN INTRAHEPATIC CHOLESTASIS OF INFANCY

In twelve cases of intrahepatic cholestasis of infancy the patients were re-examined 1–58 weeks after disappearance of jaundice. All infants were clinically healthy, but 4 infants showed raised serum transaminase. Cholic acid-24–¹⁴C was injected intramuscularly and the isotope excretion in the urine and faeces was investigated for 4 days after the injection. Most of the isotope was excreted in the faeces. In 5 of the 12 infants the urine contained 9–26% of the administered isotope whereas the other infants excreted less than 5%. No unconjugated labelled cholic acid was excreted. After solvolysis and hydrolysis the major labelled compound was identified as cholic acid. In 7 healthy infants used as controls no cholic and chenodeoxycholic acids were deteted in the urine. All the 12 patients excreted cholic and chenodeoxycholic acids in the urine at the time of the re-examination, the total daily urinary excretion ranging from 0.6 to 3.7 μmol. These results indicated that the bile acid excretion was still impaired after regression of jaundice in the infants who had had intrahepatic cholestasis.     

IRON RELEASE FROM THE STORES: A MECHANISM IN MAINTENANCE OF CONCENTRATION OF HEMOGLOBIN IN LOW-BIRTH-WEIGHT INFANTS

Abstract. Lundström, U. (Pediatric Hematology, Children's Hospital, University of Helsinki, Findland). Iron release from the stores: A mechanism in maintenance of concentration of hemoglobin in low-birth-weight infants. Acta Paediatr Scand, 69: 249, 1980.—After the resuming of the postnatal red cell production at two months of age infants are dependant on storage iron due to the great need for iron at a time when the iron content of the diet is low. This is even further accentuated in low-birth-weight infants. In this study the release of storage iron in the hemoglobin pool. During the two month period from two to four months of age at least 20 mg of iron per month was transferred from the storage sites for hemoglobin production. This amount represents 5 mg per kg of body weight and exceeds the rate iron was mobilized from storage sites in an adult male under experimental conditions. Rapid weight gain was associated with early depletion of iron stores. However, residual iron stores in infants with the slowest growth rate could not maintain the level of hemoglobin achieved in iron-supplemented low-birth-weight infants. These findings suggest that in rapidly growing low-birth-weight infants the need of iron for erythropoiesis is so great that iron deficient erythropoiesis may develop in the presence of iron stores if the diet is not supplemented with iron.