Martti A. Siimes

Percentile curves for hemoglobin and red cellvolume in infnacy and childhood

Percentile curves were calculated for hemoglobin and mean corpuscular volume in children between 0.5 and 16 years of age. The curves were derived from several populations of non-indigent white children who lived near sea level. Subjects were excluded from the reference population if they had laboratory evidence of iron deficiency, thalassemia minor, and/or hemoglobinopathy. The final reference populations included 9,946 children for the derivation of the hemoglobin curves and 2,314 for the MCV curves. The percentile curves should be particularly applicable to the diagnosis and screening of iron deficiency and thalassemia minor.

Iron absorption in infants: High bioavailability ofbreast milk iron as indicated by the extrinsic tag method of iron absorption and by the concentration of serum ferritin†

Breast feeding is thought to result in a lower incidence of iron deficiency than does the use of unfortified cow milk forumalas, but there is scant documentation for this belief. The relationship of breast and cow milk feeding to absorption of iron and to iron status was investigated in a total of 45 term infants at about six months of age. Iron absorption was measured by total body counting. Laboratory assessment of iron status was based on the serum ferritin, hemoglobin, mean corpuscular volume, and transferrin saturation. The results indicated that infants fed breast milk during the entire first six to seven months of life attained greater iron stores than did those fed a cow milk formula. Breast-fed infants absorbed an average of 49% of a trace dose of extrinsic iron administered during a breast feeding in contrast to about 10% reported to be absorbed from cow milk under similar conditions. The data indicate that term infants who are breast fed may not require routine administration of supplemental iron.

Stimulation of polyamine synthesis in relation to nucleic acids in regenerating rat liver

Abstract The effect of partial hepatectomy on the liver polyamines and nucleic acids was studied in the rat. Partial hepatectomy causes an early stimulation of spermidine synthesis, as indicated by the marked increase in the incorporation of [14C]methionine into this polyamine, as early as 4–8 h after operation. At 16 h the specific activity of spermidine was about 10-fold that of the sham-operated controls. The total spermidine content of the liver was already significantly elevated at 16 h, and at 64 h it was 3.6-fold that of the controls. The specific activity of spermine, on the other hand, did not increase until 16–20 h and the total amount of spermine per liver not until 64 h post-operatively. The total amount of liver ribonucleic acid was significantly increased at 32 h and that of deoxyribonucleic acid at 64 h. The ratio polyamine nitrogen to RNA phosphate remained quite constant during liver regeneration. The present observations are discussed on the basis of the hypothesis that tissue polyamines may be essential as physiological stabilizers of nucleic acids, especially RNA.

At what age does iron supplementation become necessary in low-birth-weight infants?†

Prevention of iron deficiency in low-birth-weight infants requires iron supplementation before neonatal iron stores are exhausted. In order to accurately determine when this depletion occurs, we measured the hemoglobin, mean corpuscular volume, serum iron/iron-binding capacity, and serum ferritin in 117 low-birth-weight infants (1,000 to 2,000 gm) from 0.5 until 6 months of age. All infants received banked breast milk in the hospital and breast milk or cow milk formula later; those with odd birth dates received 2 mg iron as ferrous sulfate/kg/day starting at 0.5 months; those with even birth dates received no additional iron unless they developed anemia. The results indicate that low-birth-weight infants who receive no supplemental iron may develop iron deficiency by three months of age and that a dose of iron of 2 mg/kg/day started at two weeks of age prevents iron deficiency without providing excess.

A population-based study of 272 children with acute myeloid leukaemia treated on two consecutive protocols with different intensity: best outcome in girls, infants, and children with Down's syndrome.

From July 1984 the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) have registered all children with acute myeloid leukaemia (AML) and treated them on two consecutive protocols of different intensity (NOPHO‐84 and NOPHO‐88). We probably have information on every child with this diagnosis in our region. We found an annual incidence of AML of 0.7 new cases per 100 000 children <16 years of age. We observed a distinct peak of incidence in the first 2 years of life. Children with Down’s syndrome accounted for 13% of all cases.  Eighty of 105 cases treated on NOPHO‐84 achieved remission (78%). In NOPHO‐88, 100/118 patients entered remission (85%). The overall event‐free survival (p‐EFS) for the two studies was 0.32 for NOPHO‐84 and 0.42 for NOPHO‐88. The majority of relapses occurred within 2 years of diagnosis. When looking for prognostic factors the strongest significant adverse factor found was male sex. Children with Down’s syndrome (n=35) had a very favourable outcome if they received therapy according to protocol, and infants (n=26) had a superior outcome compared to children 1–2 years or <10 years of age at diagnosis.

Exclusively Breast-Fed Healthy Infants Grow Slower than Reference Infants

ABSTRACT: We have studied the nutritional adequacy of exclusive breast-feeding by following prospectively the growth and protein nutrition of healthy infants during the 1st yr of life. The number of exclusively breast-fed infants was 116 at the age of 6 months and 36 at 9 months. These infants had slower length velocity after age 3 months than a comparison group of 32 infants who were weaned early and given formula plus solids. As a group, the exclusively breast-fed infants lagged slightly, but progressively, behind in relative length. By 9 months, 45% of them versus 18% of the comparison group showed a > 1 SD decrease in relative length. No such decrease was found in relative weight. Skinfolds and weight for length2 index showed that they were heavier for their length than the comparison infants. At 6 and 9 months the calculated protein intake (0.9 g/kg/day) was much less than the recommended amount (2.0 g/kg/day). Serum prealbumin concentration was lower than in the comparison group but this was noted as early as 4 months. No relation was found between the parameters of growth and protein nutrition either individually or in general. Whether the slower growth of the exclusively breast-fed infants represents appropriate physiological growth or whether it indicates nutritional deficiency is not known but we did not find any evidence of protein deficiency. Six infants did, however, show subsequent catch-up growth which could indicate previous malnutrition.

Iron absorption from breast milk, cow's milk, and iron-supplemented formula: an opportunistic use of changes in total body iron determined by hemoglobin, ferritin, and body weight in 132 infants.

Summary: Iron absorption was measured by using changes in the calculated total body iron (TBI) in infants on three different milk regimens: breast milk (n = 86), home-prepared cows milk formula (n = 15), and proprietary iron-supplemented infant formula (n = 31) during the first 4 months of life. The TBI was determined as the sum of the hemoglobin iron (HbI) and the body storage iron (BSI). In the latter assessment, we found a close to linear correlation between the concentration of serum ferritin (SF) expressed as the logarithm and the BSI expressed as milligrams per unit of body weight. Accordingly, the BSI could be calculated from SF and body weight. Iron absorption from milk was estimated from the increment of TBI and from the estimated iron intake at different time intervals. From 2-4 months of age the monthly increment of TBI was 33.5 mg in the iron-supplemented formula group, 20 mg in the breast milk group, and 6.5 mg in the cows milk group. The differences were statistically highly significant (P < 0.001). The calculated percentage intake was about 70% for breast milk iron, about 30% for cows milk iron, and about 10% for the supplemental iron in infant formula. Our data emphasize the exceptionally high bioavailability of breast milk iron which markedly dropped after the introduction of solid foods at 4 months of age. These data suggest an inhibitory effect of the solid vegetable foods on iron absorption, especially from breast milk. Our findings indicate that exclusive breast feeding is an effective means in preventing iron deficiency in early infancy as an alternative to the use of iron-supplemented infant formulas.Speculation: Quantitative estimation of body iron stores by serum ferritin and body weight provides a way to calculate the amount of total body iron. This method provides a new way to study iron absorption without the use of radioactive isotopes, and indicates unusually high bioavailability of breast milk iron if the solid foods are introduced late.

A population-based study of childhood acute lymphoblastic leukemia diagnosed from July 1981 through June 1985 in the five Nordic countries. Incidence, patient characteristics and treatment results.

Six hundred and fifty‐six children with acute lymphoblastic leukemia (ALL) have been diagnosed in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) during the period from July 1981 through June 1985. Annual incidence of ALL was 3.6/100000 children aged < 15 years, with an incidence for males of 3.8 and for females of 3.4 respectively. Half of the children were younger than 5 years of age at diagnosis, with a peak incidence between 2–3 years of age. The leukemias were classified as Standard Risk (SR), Intermediate Risk (IR) or High Risk (HR) leukemia according to prognostic criteria at diagnosis. The remission rate was 95%. In children 1 year of age with non‐B‐cell ALL at diagnosis, the Event‐Free Survival (EFS) was 0.58; 0.65 for SR‐children, 0.51 for IR‐children and 0.52 for HR‐children. WBC count at diagnosis was the most important prognostic factor and a WBC count of 11‐20×109/l was associated with the worst prognosis of all WBC values (EFS=0.30), independent of other prognostic factors. Male sex was the second most important adverse prognostic criterion. The follow‐up in January 1986 (observation time 6–54 months), showed that 442 of the 656 children (67%) were in complete continuous remission. The total results indicate a possibility to improve the prognosis for most of the risk groups of ALL with a more intensive treatment.

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.

Developmental changes in red blood cell counts and indices of infants after exclusion of iron deficiency by laboratory criteria and continuous iron supplementation.

The developmental changes in red blood cell counts and indices were determined in infants after mild iron deficiency was excluded. The normal values were obtained from a selected group of healthy, term infants who were receiving continuous iron supplementation during a period of one year while normal values for transferrin saturation and serum ferritin were being maintained. The data indicated marked developmental changes in red blood cell counts and indices during the first year of life that are independent of iron intake. Serial analysis of individual infants values indicated that the red cell measurement at 4 months of age are, to some extent, predictive of the level of subsequent values within the normal range.