Effect of folic acid supplementation on small-for-gestational-age infants born at term

The effect of 250 g folic acid (FA)/day or placebo given to 21 small-for-gestational-age infants born at term was studied during the first 3 months of life. The design of the study was double blind with random allocation. No randomization was performed in respect of breast-feeding or formula-feeding with a folate content of 60–70 g/l. No significant differences were observed in haemoglobin concentration, haematocrit, weight and length between FA-supplemented and non-supplemented infants. A negative correlation was demonstrated between gestational age and erythrocyte folate (E-folate) concentration at 1 week. E-folate content was higher when no supplement was given in breast-fed than in formula-fed infants.     

Plasma folate levels in preterm infants,with and without a 1 mg daily folate supplement

One hundred and four preterm infants were studied during the first few months of life in the Special Care Baby Unit of Addenbrooke's Hospital, Cambridge, United Kingdom. Previously, it had been the daily practice within the Unit to give a 1 mg oral supplement of folate (in the form of pteroylglutamic acid), once the infants had commenced full enteral feeding. At least one blood sample was obtained from 70 infants before oral folate supplementation was started. In these, the plasma folate levels fell progressively from a median value of 45 g/l to a median of 12 g/l, by the 2nd–3rd week of life. Once started on the oral supplement, 83 of the infants provided at least one blood sample. The plasma folate level of these infants rose immediately to a median value of 300 g/l and a maximum of 1000 g/l. Within individuals, these plasma folate levels decreased progressively following the introduction of the supplement, despite continuing daily supplementation. In a typical baby this decrease appeared to be explained by an increase in body-size, i.e. dilution of the folate into a larger pool. The implications of this level of supplementation are discussed, and in the light of our observations we suggest that daily supplementation in the range, 0.05–0.2 mg folate may be preferable for well preterm infants.     

High folate intakes related to zinc status in preterm infants

The former practice of giving 1 mg (2.27 moles) oral folic acid daily to premature infants receiving enteral feeds was assessed with respect to zinc status in Cambridge, United Kingdom. A group of 60 preterm infants, 80% of whom were receiving 1 mg oral folic acid daily, were studied for up to the first 16 weeks of life. Plasma folate and plasma zinc were measured for each subject. A significant inverse relationship was found between the maximum attained serum folate level and the minimum attained serum zinc level, (t=5.0, 58 df, P<0.0001). This remained significant after corrections had been made for gestational age at birth, fetal growth retardation, birth weight, sex, diet, assisted ventilation and length of time to full enteral feeding. The hypothesis that very high folate intakes may adversely affect serum zinc levels and, by inference, zinc status in preterm infants could not be rejected. Caution is therefore advised when prescribing such very high folate doses daily for small preterm infants.     

Neutrophil chemotaxis in infants delivered by caesarean section

We evaluated polymorphonuclear leucocyte (PMN) chemotaxis and cortisol levels in cord blood from 15 healthy term infants delivered by caesarean section and from 15 healthy vaginally delivered term infants. Mean neutrophil chemotaxis was significantly higher in infants delivered by caesarean section (78.3±23.4m) than in vaginally delivered infants (57.8±16.6 m;P=0.01). Mean blood cortisol level was significantly lower in infants delivered by caesarean section (9.14±2.76 g/dl) than in infants born by vaginal delivery (20.71±6.98 g/dl;P=0.0001). No relationship was found between PMN chemotaxis and blood cortisol level. The higher neutrophil chemotactic activity observed in infants delivered by caesarean section could be related to general maternal anaesthesia.     

Serum iron,serum transferrin and transferrin saturation in healthy children without iron deficiency

Serum iron, serum transferrin and transferrin saturation were studied in 253 healthy, non-anaemic children 4, 8 and 13 years old, and in 60 healthy, non-anaemic adults having serum ferritin values 15 g/l. One hundred and ninety-six children had serum ferritin values 15 g/l (i.e. replete iron stores), 35 had intermediate ferritin values from 10–14 g/l and 22 had ferritin values <10 g/l (i.e. depleted iron stores). Iron replete children showed a gradual rise in serum iron and transferrin saturation values with age. Serum iron and transferrin saturation values were lower (P<0.001, P<0.0001) and transferrin values high (P<0.0001) in iron replete children compared to adults. Iron replete children had a 2.5 centile transferrin saturation value of 5%; 19.9% of these children had saturation values <15% and 8.2% had values <10%. In iron depleted children a transferrin saturation value <7% yielded the highest diagnostic efficiency as regards exhausted iron stores, although with a low predictive value of a positive test. The transferrin saturation is unsuitable as a single diagnostic criterion in the evaluation of iron deficiency in children and should always be combined with other indicators of iron status.     

Veränderungen von Produktion und Metabolismus des Cortisol bei gesunden Säuglingen nach dreitägiger Depot-ACTH-Gabe

Zusammenfassung Es wird über die Harnausscheidung von Pregnan-3-17-20-triol und Pregnan-3-20-diol nach einer dreitägigen Belastung mit Depot-ACTH bei gesunden Säuglingen berichtet.Die Basalmittelwerte liegen für Pregnantriol zwischen 33 und 37 g/d, für Pregnandiol zwischen 70 und 81 g/d. Nach ACTH kommt es zu einer Zunahme der Ausscheidungsgröße beider Substanzen, wobei sich das Verhältnis für Pregnantriol zu Pregnandiol gegenüber den Basalwerten umkehrt.Diese Umkehrung wird einerseits als Ausdruck einer intensiven Ausnutzung der für die beiden letzten Stufen der Cortisolsynthese maßgeblichen Hydroxylasen aufgefaßt, andererseits auf Grund der deutlichen Zunahme der Pregnantriolausscheidung eine funktionelle Limitierung der C-11-und C-21-Hydroxylase zur Diskussion gestellt.Die gegenüber der des Pregnantriol niedrige Pregnandiolausscheidung ergibt einen Hinweis, daß möglicherweise die Limitierung der enzymatischen Aktivität bei der Differenzierung der einzelnen Corticosteroide im Laufe der Umwandlungen in Richtung Endprodukt zunimmt.

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Summary In this paper we report about the urinary excretion of Pregnan-3-17-20-triol and Pregnan-3-20-diol in infants between 4 and 8 months after a three-day load-test with ACTH-depot.The basal mean-values are between 33 to 37 g/die of Pregnantriol and between 70 to 81 g/die of Pregnandiol. After ACTH-load there is an increase of the excretion of both substances whereas the ratio of Pregnantriol and Pregnandiol gets reciprocal. We consider this beeing a sign of an intensive utilization of the hydroxylating enzymes involved in the two last steps of cortisol synthesis. On the other hand it is possible that there is a functional limit in the activity of C-11-and C-21-hydroxylating enzymes regarding the clear increase of Pregnantriolexcretion.The relatively low values of Pregnandiol opposite to these of Pregnantriol may refer to the possibility that the limitation of the enzyme activities increases in way of performing the different corticosteroids.

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Die Arbeit wurde mit Unterstützung durch die Deutsche Forschungsgemeinschaft durchgeführt.     

Amine im menschlichen Stuhl

Zusammenfassung Die p- und m-Tyraminausscheidung wurde quantitativ im Stuhl von Neugeborenen, Säuglingen und Schulkindern unter verschiedenen Kostformen untersucht. Der p-Tyramingehalt von normalen Säuglingsstühlen (Naßgewicht) lag zwischen 0,030–0,460 Mol/g Stuhl, der normaler Stühle von Schulkindern zwischen 0,005 und 0,102 Mol/g Stuhl. m-Tyramin ließ sich in Säuglingsstühlen nicht nachweisen. Die Konzentration im Stuhl von Schulkindern überschritt sicher nicht 0,008 Mol/g Stuhl.

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Summary The excretion of para- and meta-tyramine in faeces was estimated in newborns, infants, and children during the application of various diets. The p-tyramine content of normal stools of infants (wet weight) amounted 0.030–0.460 moles per gr. faeces and that of children 0.005–0.102 moles per gr. m-Tyramine was not detected in the faeces of infants. If this substance is found at all in faeces of children it does not exceed 0.008 moles per gr. of faeces.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Serum creatinine and creatinine clearance in healthy neonates and prematures during the first 10 days of life

Normal serum creatinine (Scr) and creatinine clearance (Ccr) values during the first 10 days of life were obtained in 63 very premature (28–32 weeks of gestation), premature (33–37 weeks) and term infants (38–42 weeks). Scr fell, and Ccr rose less markedly in the very premature infants. Scr was 80 mol/l on the 1st day of life both in very premature and premature infants, and 77 mol/l in full-term neonates. After 10 days, Scr was 73, 53 and 35 mol/l respectively. There was an exponential correlation between Ccr and gestational age, indicating rapid maturation of glomerular function.Abbreviations Scr serum creatinine - Ccr creatinine clearance - GA gestational age - GFR glomerular filtration rate     

Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine

The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or IgA-antibodies on 3 mm blood spots collected from phenylketonuria [PKU cards (Guthrie cards)]. Toxoplasma-infected children received 3 months continuous treatment with 50–100 mg/kg per day sulfadiazine in two separate administrations and 1 mg/kg per day pyrimethamine after a 1-day loading dose of 2 mg/kg, and folinic acid 7.5 mg was administered twice weekly. Blood cell counts and body weight were recorded during follow-up. The plasma concentrations of pyrimethamine and sulfadiazine were analysed in a subgroup of seven children, using high performance liquid chromatography with ultraviolet and mass spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5×10⁹/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was 0.5×10⁹/l or lower in 4/29 (13.8%). None of the children had anaemia or thrombocytopenia. The drugs did not affect weight gain. Mean plasma drug concentrations varied between 1.3 g/ml and 2.2 g/ml for pyrimethamine and between 60 g/ml and 86 g/ml for sulfadiazine. Treatment efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits.     

The contribution of protein catabolism to metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria

Leucine and protein metabolism were studied using stable isotope techniques in 6-year-old twins with 3-hydroxy-3-methylglutaric aciduria during acute metabolic decompensation. The decompensation was preceded by prolonged fasting in twin 1 and by an upper respiratory infection in twin 2. Twin 2 was also studied when well (control study). During infection, leucine oxidation (36 mol/kg per hour), protein catabolism (6.0 g/kg per day) and urinary excretion of major leucine metabolites (104 mol/kg per hour) were all increased compared with the control study (16 mol/kg per hour, 4.7 g/kg per day and 28 mol/kg per hour respectively). During fasting, leucine oxidation (18 mol/kg per hour) was unchanged and protein catabolism (4.1 g/kg per day) was decreased despite substantially increased urinary metabolite excretion (87 mol/kg per hour) compared with the control study. These results indicate that protein mobilisation and leucine oxidation played important roles in metabolic decompensation during infection but not during fasting. It is likely that the increased metabolite excretion during fasting arose primarily from fatty acid catabolism, indicating the importance of this substrate in metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria.     

Late anaemia in infants with rhesus haemolytic disease treated with intensive phototherapy

The purpose of the present study was to determine the incidence of late anaemia in infants with rhesus haemolytic disease (RHD) who had received intensive phototherapy. Sixty infants with RHD and with strongly positive direct Coombs' tests who had received intensive phototherapy (blue double light) were followed as out-patients with regard to development of late anaemia. Fifteen (25%) infants developed moderate anaemia and 5 (8%) severe anaemia, one of the latter requiring a blood transfusion. The incidence of late anaemia was equal in non-exchanged infants and those who required exchange transfusion. The former developed anaemia significantly earlier than the latter, and in both groups the declining Hb level caused a marked reticulocyte response which was equal in both groups. This response may explain the low incidence of anaemia in both the non-exchanged and exchanged infants. From the present study and previous investigations it can be concluded that phototherapy, especially intensive phototherapy, is of great value in the treatment of rhesus haemolytic disease.     

Die p-Tyramin-Ausscheidung im Urin

Zusammenfassung Die Ausscheidung von freiem p-Tyramin im Urin wurde bei Kindern verschiedener Altersklassen fluorimetrisch nach der Methode von Oates bestimmt.Die Ausscheidung der Säuglinge betrug 1,97±0,75 g/mg Kreatinin, die der Kleinkinder 1,18±0,77 g/mg Kreatinin. Die p-Tyraminausscheidung von unreifen und reifen Neugeborenen schwankte stärker; ihre Ausscheidung lag aber in derselben Größnordnung, wenn keine Hypertyrosinämie vorlag.Bei Kindern mit Eiweißverwertungsstörungen des Darmes (Mucoviscidose und Cöliakie) war die Ausscheidung mit 3,16±1,98 g/mg Kreatinin signifikant erhöht. Keine Erhöhung der p-Tyraminausscheidung fand sich bei Säuglingen mit Toxikose auf dem Boden einer Enteritis.Die Ergebnisse werden im Rahmen der heutigen Kenntnisse über die Bildung und Ausscheidung von p-Tyramin diskutiert.

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Summary The urinary excretion of p-tyramine was fluorometrically estimated in children of different ages according to the method of Oates.The amount excreted was 1.97±0.77 g per mg. creatinine in infants and 1.18±0.77 g per mg. creatinine in children. If there is no hypertyrosinaemia in immature and mature newborns the excretion of p-tyramine fluctuates to a greater extent especially in the range of lower limits.Children with desturbed protein digestion (cystic fibrosis and coeliac disease) had a significantly increased excretion of p-tyramine (3.16±1.98 g per mg. creatinine). No elevation of p-tyramine excretory rates was in infants with severe enteritis. The results are discussed together with our present-day knowledge on synthesis and excretion of p-tyramine.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Fetal bile acids in congenital biliary atresia —production in the liver and clinical significance

The 1-hydroxy bile acids have been said to be fetal bile acids. These bile acids were evaluated in eight patients with congenital biliary atresia (CBA) using gas chromatography-mass spectrometry. At the time of operation 1,3,7,12-tetrahydroxy-5-cholan-24-oic acid (CA-1-ol) and 1,3,7-trihydroxy-5-cholan-24-oic acid (CDCA-1-ol) were 0.46 ± 34 g/ml and 0.72 ± 0.45 g/ml, respectively, which was significantly higher than in the control group. The percentage CA-1-ol of total bile acids showed a tendency to decrease as age advanced. The grade of hepatic fibrosis ranged from F₂ to F₃ and the values and percentages of CA-1-ol and CDCA-1-ol were relatively higher in F₂ than F₃ patients. The percentage of total bile acids gradually increased in patients without sufficient bile flow but fell sharply after Kasai's procedure in the patients with sufficient bile flow. It appears that fetal bile acids are produced in the livers of CBA patients in the same way as in fetal liver, and that production continues in patients without good bile secretion even after Kasai's procedure. These results suggest that these hydroxylases are reactivated in CBA patients.     

Pharmacodynamics and pharmacokinetics of esmolol,a short-acting β-blocking agent,in children

Summary Esmolol, a short-acting intravenous cardioselective -blocking agent, was evaluated for age-dependent pharmacodynamic and pharmacokinetic features in 17 young patients (6 months to 14 years). A loading dose (500 g/kg/min) alternating with a maintenance dose (25–200 g/kg/min, titrating by 25 g/kg/min every 4 min) was infused until the heart rate or mean arterial pressure decreased 10%. Cardiac index, left ventricular shortening fraction, and systemic vascular resistance were measured at baseline, peak esmolol effect, and recovery. Serum esmolol concentrations were obtained to determine the half-life and the elimination rate constant.Esmolol reduced the heart rate, blood pressure, shortening fraction, and cardiac index in all patients, but it did not change systemic vascular resistance. Maintenance esmolol dose was 118 ±49 g/kg/min, and the half-life was 2.88±2.67 min. Blood pressure and heart rate returned to normal within 2–16 min, but cardiac index and shortening fraction took longer to recover. There were no statistically significant age-dependent pharmacodynamic effects, but blood pressure decreased prior to heart rate and cardiac index took longer to recovery in patients who weighed15kg. The pharmacokinetic profile in young patients was similar to that of older patients, but the half-life was shorter. The only side effeect was transient nausea and vomiting in one patient. Esmolol is a safe and efficacious -blocking agent in young patients.     

Effect of selenium supplementation on the distribution of selenium among plasma proteins of a patient with maple syrup urine disease

Selenium (Se) status was studied in a patient with classical maple syrup urine disease (MSUD) receiving Se supplement. The basal plasma Se concentration was 0.06 mol/l increasing to 2.1 mol/l after 40 days of supplementation. When the plasma Se distribution was analysed by gel filtration, a major peak was seen close to the high molecular weight proteins with a second peak in the albumin region. When the Se dose was decreased in a stepwise manner from 50 g/day to 25 g/day and then to 17 g/day plasma Se decreased, but the proportion of plasma Se in the two protein peaks did not change. In a healthy girl not supplemented with Se, the proportion of plasma Se in the albumin region was somewhat lower. In the MSUD patient glutathione peroxidase activity was initially low, and increased ten-fold during Se supplementation. The study indicates that the Se requirement for plasma glutathione peroxidase activity was fulfilled at the lowest dose of Se used and that Se is incorporated into several plasma proteins after supplementation.Abbreviations MSUD maple syrup urine disease - Se selenium     

Excessive urinary oxalate excretion after combined renal and hepatic transplantation for correction of hyperoxaluria type 1

A 4.5-year-old boy received a combined liver and kidney transplant for correction of hyperoxaluria type 1. Both organs were from the same donor and functioned primarily. Three months after transplantation, urine oxalate excretion reached a maximum of 10500 mol/24 h and remained above 2300 mol/24 h for the next 2 months. Two months later, oxalate excretion decreased to about 565 mol/24 h, indicating exhaustion of a large oxalate pool. Six months after transplantation plasma oxalate is near normal (4.9 mol/l). With the exception of one episode of acute rejection of the renal transplant, both organs were tolerated well and continue to have a unimpaired function 9 months after transplantation. However, there is increased echogenity on renal ultrasound, indicating oxalate deposits in the grafted kidney. This case illustrates that successful combined transplantation of both liver and kidney can be performed in infants, resulting in cure of the metabolic defect. The prolonged or acute excretion of oxalate may lead to oxalate deposition in the grafted kidney without impaired graft function or early graft loss.     

Impact of different doses of ethinyl oestradiol on reduction of final height in constitutionally tall girls

Fifty-two tall girls were treated for constitutionally tall stature with different ethinyl oestradiol (EE) dosages. They were divided into three different treatment groups: group B (100 g EE/day;n=11); group C (300 g;n=25) and group D (500 g;n=16) and compared with an untreated group A (n=21) matched for age, height, bone age (BA) and height prediction. Using the height prediction method TW II, EE treatment reduced final height compared with the untreated girls in a weak dose-dependent manner, 2.3 cm (100 g/day), 3.0 cm (300 g/day), and 3.8 cm (500 g/day). Such a dose dependency was not found on applying the Bayley-Pineau height prediction method (100 g/day: 4.1 cm; 300 g/day: 4.2 cm; 500 g/day: 4.5 cm). However, there was a striking inverse correlation of the BA at the onset of treatment with the height reduction achieved using the TW II method (r: –0.43;P<0.001). Importantly, girls with a BA below 12 years at the onset of treatment experienced a height reduction of more than 6 cm.The EE dose used in the range of 100–500 g/day is not crucial for the amount of height reduction in tall girls. In general high dose EE treatment should be given restrictively, and especially so in girls with a BA (TW2 RUS-ZH) above 12.0 years.     

Vergleichende direkte und indirekte Blutdruckmessungen bei Neugeborenen in den ersten Lebensstunden

Ohne ZusammenfassungVorgetragen auf dem Symposion über Physiologische Besonderheiten im Säuglingsalter im Rahmen der 60. Tagung der Deutschen Gesellschaft für Kinderheilkunde in Heideberg.     

Serum zinc and copper levels in children with meningococcal disease

Mean serum zinc and copper levels were depressed in 94 children aged 1 month to 9 years who presented with meningococcal disease. The mean serum zinc level was 44 g/dl (reference value 78 g/dl, SD 18) and the mean serum copper level 157 g/dl (reference value 159 g/dl, SD 27). Nineteen patients had serum zinc levels less than 25 g/dl and ten patients had serum copper levels less than 101 g/dl.Serum zinc levels were significantly lower in patients who were septicaemic or in whom manifestations of severe disease such as shock, more than 20 petechiae, ecchymoses and evidence of disseminated intravascular coagulation occurred compared to those without these features.Serum copper concentrations were higher than reference levels in patients with meningitis and in less severely ill patients. Copper levels were significantly lower in patients with septicaemia, severe disease, shock, more than 20 petechiae, ecchymoses, disseminated intravascular coagulation, leucopenia and patients who died compared with patients without these features.Abbreviations DIC Disseminated intravascular coagulation - LEM leukocyte endogeneous mediator     

Adrenoceptors and the lung: their role in health and disease

- and -Adrenoceptors have each been divided into two subgroups (₁, ₂, ₁ and ₂). The basic mechanisms underlying the adrenoceptor/effector coupling are complex and vary for the -, but not for the -subpopulations. Adrenoceptors of the bronchi and the lung show a special pattern of distribution and response, ensuring that the airway system works as a functionary unit. Dysfunctions of adrenoceptormediated effects have been suggested to contribute to some important paediatric disorders such as hyaline membrane syndrome, wet lung, bronchial asthma, cystic fibrosis, and pertussis. Drugs which act on the adrenergic system influence some of these disorders directly. Further studies applying modern techniques to receptor research are needed in order to clarify the basic mechanisms involved in receptor-mediated lung disorders and the activity of drugs in lung tissue.Abbreviations AC adenylate cyclase - ADP adenosine diphosphate - -R -adrenoceptor - cAMP cyclic adenosine monophosphate - CF cystic fibrosis - GDP guanosine diphosphate - GTP guanosine triphosphate - IAP islet activating protein