P. H. Finne

Erythropoietin levels in cord blood as an indicator of intrauterine hypoxia.

The erythropoietin content in cord blood was determined from normal full term infants, fants, from infants born more than 2 weeks after term, from infants of preeclamptic, diabetic and Rh‐immunized mothers. The group of normal infants showed higher ergthropoietin levels than the premature group. Highly elevated erythropoietin levels were found in some infants in the preeclamptic, the postmature group and in the infants of diabetic mothers. The greatest frequency of increased erythropoietin levels were found in the preeclamptic group. The infants with the greatest rise in erythropoietin content often showed clinical signs of dysmaturity. Erythroblastotic infants seemed to show a rise in erythropoietin levels when capillary hemoglobin fell below 13‐11 g. The results indicate that both anemic and hypoxic hypoxia may give an increase in erythro‐poietin content, and that erythropoietin is a stimulating factor for red cell production in fetal life, at least in the last months.

Intermediate dose methotrexate (IDM) in childhood acute lymphocytic leukemia in Norway. Preliminary results of a national treatment program.

Abstract. Moe, P. J., Seip, M. and Finne, P. H. (Departments of Paediatrics, Universities of Trondheim and Tromsø, Department of Paediatrics, Rikshospitalet, Oslo and Department of Paediatrics, University of Bergen, Bergen, Norway). Intermediate dose methotrexate (IDM) in childhood acute lymphocytic leukemia in Norway. Acta Paediatr Scand, 70:73, 1981–Preliminary results of a national treatment program. The main objectives of this study were: 1. To determine whether early start of CNS prophylaxis with intrathecal methotrexate during induction treatment, followed by three courses of IDM plus intrathecal methotrexate after remission has been obtained, offers adequate protection against CNS‐leukemia. 2. To determine whether the use of IDM with leukovorin rescue as “sanctuary” therapy following remission reduced the incidence of sanctuary relapse and thereby also the incidence of hematological relapse. It has proved possible to institute this program on a national basis with good results, even in small departments treating 0–3 new cases of leukemia a year. Sixty‐six children (38 boys, 28 girls) with acute lymphocytic leukemia (ALL), diagnosed in the years 1976‐78, had received IDM while they were in complete primary remission. During the same period 13 additional cases of ALL were diagnosed in Norway, 4 (5% of 79 cases) of whom did not achieve complete remission, while 4 died early from infections, one received no treatment, and 4 were treated with other protocols. Life tables of patients in complete continuous remission (CCR) and survival tables are presented for standard risk patients and increased risk patients, respectively, and for all 66 together. Among these 66, 40 had been observed for 2½ years or more by January 1980. Of these 29 (72.5%) were still in CCR, and in 24 antileukemic treatment had been discontinued. So far there has been a total of 7 systemic, 2 CNS and 1 combined systemic and CNS relapses among the 66 cases diagnosed in the period 1976‐78. No testicular or other sanctuary relapses have been seen among these 66 cases, nor among the remaining 13 cases with the diagnosis of ALL in childhood in Norway during the years 1976‐78. The cessation rate of antileukemic treatment will probably be 70–75 % of all cases receiving IDM while in complete remission, and about 60 % of the total material diagnosed in 1976‐78 as ALL in childhood in Norway.

Males with Low Birthweight Examined at 18 Years of Age

ABSTRACT. An 18 years follow‐up study of 105 males born in 1962/63 with birthweight ≤ 2500 g was made at the military draft board examinations in 1981. The medical and psychological tests were compared to the tests of the total cohort of 35 728 Norwegian conscripts. The early neonatal mortality in the study was 15.2 %, and of those examined at 18 years of age was 6.7 % unfit for military service, compared to 6.2 % in the total cohort. Ten organ systems were analyzed, significantly increased frequency of unfitness being found only for the vision. Intelligence testing was done on 71 of the studied subjects, and the mean was the same as the national average. Children with weight‐for‐date centile < 10 at birth had the same general intelligence at 18 years as the national average. However, the weight and height at adult age were significantly correlated to the weight‐for‐date at birth. The study indicates that those low birthweight children who survived the neonatal period in the beginning of the nineteen‐sixties, were except for stature and minor defects of vision, indistinguishable from those of normal birthweight at the age of eighteen.

Erythropoietin Levels in the Amniotic Fluid, Particularly in Rh‐Immunized Pregnancies

The existence of a humoral erythropoietic regulatory mechanism is now generally accepted. Hypoxia, anemic or hypoxic, is the primary stimulus for the production of the humoral factor, erythropoietin (ESP), which again acts upon the bone marrow. The precise nature, site of production and physiological effect of the erythropoietic factor is not quite clear. Probably erythropoietin is mainly produced in the kidneys [5, 11, 181. The relationship of erythropoietin to anemia can be elucidated to some extent by measuring the erythropoietin content in plasma [S, 9, 14, 221. However, there is some difficulty in demonstrating normal or moderately increased crythropoietin levels with the assay methods used today, and not all anemic patients are found to have increased amounts of erythropoietin in their plasma [22]. The erythropoietin level and the corresponding anemia shows some difference between patients with various types of anemia [9]. Patients with a hypoplastic marrow tend to show a higher erythropoietin content than those with a hyperactive marrow, This has been taken in favor of the hypothesis that erythropoietin may be utilized by active

THE DIAGNOSIS OF IRON DEFICIENCY BY ERYTHROCYTE PROTOPORPHYRIN AND SERUM FERRITIN ANALYSES

ABSTRACT. Free erythrocyte protoporphyrin (FEP) and serum ferritin have been determined in 57 healthy children and in 25 children with varying degrees of iron deficiency. FEP was found to be inversely correlated to the concentration of hemoglobin (r=‐0.80) as well as to serum ferritin (r=‐0.64). Elevated FEP was found in children with hemoglobin less than 12.5 g/dl, or serum ferritin less than 8 μg/l. In a group of apparently hematologically normal children between the age of 10–14 years (hemoglobin≥ 12.5 g/dl), a 2‐month‐trial of iron medication resulted in an increase in hemoglobin and ferritin, and a decrease in FEP, indicating suboptimal supply of iron for hemoglobin synthesis before iron medication. In a patient with iron deficiency (FEP 15.3 μmole/l, hemoglobin 5.2 g/dl), iron therapy was followed by a rapid fall in FEP before any changes in hemoglobin, serum iron transferrin saturation and ferritin could be detected. The rapid fall in FEP during start of treatment in iron deficiency makes FEP a sensitive biochemical parameter on iron homeostasis in iron deficiency anemia.

CLINICAL ASSESSMENT OF GESTATIONAL AGE IN THE NEWBORN INFANT.: An Evaluation of Two Methods

ABSTRACT. Vogt, H., Haneberg, B., Finne, P. H. and Stensberg, A. (Department of Paediatrics, University of Bergen, and Department of Clinical Chemistry, Akershus Central Hospital, University of Oslo, Norway). Clinical assessment of gestational age in the newborn infant. An evaluation of two methods. Acta Paediatr Scand, 70:669,.–The scoring systems of Dubowitz et al. and Parkin et al. were evaluated in two selected materials of newborn infants referred to a neonatal unit. Our estimation of gestational age by Dubowitz scores tended to be too high for the extreme prematures. “Small‐for‐dates” were also overestimated, whilst “appropriate‐for‐dates” and infants with respiratory difficulties were underestimated. “Large‐for‐dates” fell close to the standard curve. Ninety‐five per cent confidence limits were up to ±5 weeks for Dubowitz scores and nearly ±6 weeks for Parkin scores. Further statistical analysis displayed some limitations in the use of linear regression formulas for scoring systems based on external and/or neurological characteristics. Thus, the results obtained with these methods must be used with caution in some selected newborn materials.

The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency

Abstract Native complement factors and complement activation products were measured in healthy neonates (n = 72) and in a group of infants with premature prolonged rupture of the membranes (PPROM) without sepsis (n = 10). Vitronectin concentration in normal cord blood was not correlated with gestational age, and the median value was 86.0% of adult values. This was markedly higher than other native complement factors studied (factor B: 35.9% , C4: 45.1% , C3: 56.2% ). The concentration of C9 showed a positive correlation with gestational age and was very low, 10.8% of normal adult values in cord blood and 8.3% in the patients. Fifteen percent of the neonates had C9 levels lower than 2% of adult values. The complement activation products Bb and SC5 b-9 were significantly elevated in the patients (159% and 130% of control values, respectively), indicating alternative and terminal pathway activation. In contrast, C4 bc and C3 bc levels were not increased. The maximum amount of SC5 b-9 which could be generated in the neonatal sera by cobra venom factor was highly correlated with C9 concentration (rs= 0.86, p = 0.0001) The profound C9 deficiency found in neonates is correlated with gestational age, limits the capacity to form bacteriolytic C5 b-9 (m) and may predispose for severe invasive bacterial infection. The plasma level of SC5 b-9 under normal conditions was very low, only 0.3% (0.1%–3.0 %) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels.

Rupture of the trachea: an unusual complication of delivery

We describe a neonate whose trachea ruptured during delivery. The baby developed respiratory symptoms shortly after delivery and became dramatically ill after 6 h. This particular birth trauma appears to be very unusual: there are few cases reported in the literature. Rupture of the trachea should be considered as a differential diagnosis in a neonate who develops pneumomediastinum after a complicated delivery.

ACUTE HEMOLYTIC ANEMIA RELATED TO DIPHTHERIA‐PERTUSSIS‐TETANUS VACCINATION

ABSTRACT. Three infants developed severe hemolytic anemia following the second or third diphtheria‐pertussistetanus vaccination. Direct antiglobulin tests were positive, and the infant most severely affected also had reduced serum complement levels, indicating an immunological mechanism for the hemolysis. The presence of IgM on the erythrocytes from 2 of the infants could be demonstrated by antiglobulin tests or immunization experiments. Heat eluates of the erythrocytes from one of the infants contained antibodies to tetanus and diphtheria toxoids, as well as to Bordetella pertussis, suggesting that these antibodies were antigenically bound to the erythrocytes. Virus antibodies or isoagglutinins, present in the serum, were not found in the eluate. No antibodies against the vaccine components could be demonstrated in eluates of erythrocytes from control subjects. In vitro experiments showed that tetanus and diphtheria toxoids were easily bound to human erythrocytes. This finding could help explain the pathogenesis of the autohemolysis.

Antenatal diagnosis of the anemia in Erythroblastosis. A comparison between spectrophotometry and erythropoietin determination in the amniotic fluid.

Spectrophotometry and erythropoietin determinations in the amniotic fluid have been used in the antenatal diagnosis of the anemia in erythroblastosis. An abrupt rise in the erythropoietin level was found when hemoglobin dropped below 11‐10 g. In cases with a milder degree of anemia only a slight or no elevation of erythropoietin levels, compared to normal amniotic fluid, were found. The height of the optical density peak at 450 mp calculated as described by Liley [11] shows a reasonably good correlation to the capillary hemoglobin level a t birth. It is concluded that for routine use spectrophotometric analysis of amniotic fluid is the method of choice.