Vaccination associated thrombocytopenic purpura in children.

Patients who presented with purpura and blood platelets <30x10(9)/l within 1 month after vaccination were collected from a population based material of 506 consecutive pediatric patients with newly diagnosed ITP. Of the 35 such patients, 24 had thrombocytopenia after MMR vaccination giving an estimated ITP risk of approximately 1 in 30,000 MMR inoculations. Symptoms of the 35 patients were nearly always acute. Thrombocytopenia disappeared within a month in 74% of the study patients and lasted longer than 6 months in only 10%. Bleeding episodes were uncommon during the follow-up period. We conclude that the incidence of symptomatic thrombocytopenia after vaccinations is much lower than that after respective natural infections and that the outcome in most cases is excellent.

Chronic thrombocytopenia of childhood: use of non-invasive methods in clinical evaluation.

OBJECTIVES: An unselected group of 21 children with chronic thrombocytopenia was investigated to understand the patients' platelet abnormality better. METHODS: Platelet counts, mean platelet volumes (MPV), membrane glycoproteins and Fcgamma receptor type IIA (FcgammaRIIA) polymorphism H131R, reticulated platelets (% RP), antiplatelet antibodies and plasma thrombopoietin (TPO) were measured. RESULTS: Sixteen patients had idiopathic thrombocytopenic purpura (ITP) (group 1: platelets < 50 x 10(9)/L, n = 6; group 2: 50-99 x 10(9)/L, n = 4; group 3: 100-149 x 10(9)/L, n = 4; group 4: splenectomised patients with normal platelet counts, n = 2). Five patients had familial thrombocytopenia. Six healthy children were studied as a reference. In the 19 thrombocytopenic patients, the platelets were significantly larger and % RP and TPO levels were significantly higher than those in the controls. Increased megakaryocytosis at diagnosis was associated with larger MPV and higher % RP but not with platelet level or TPO. The % RP was remarkably high in all ITP patients of group 1 indicating a brisk production of platelets despite low peripheral count. In all patients with familial thrombocytopenia, TPO was increased suggesting that the syndrome was not because of defective TPO production. The distribution of FcgammaRIIA alleles in the patients was similar to that in the controls. CONCLUSIONS: A combined application of % RP and TPO could be helpful in classifying patients with chronic thrombocytopenia into different categories. The observations may be of value in the clinical evaluation of ITP patients and lead to avoidance of invasive examinations at least in some patients.

Long-term prognosis of children with Down's syndrome and leukaemia: a 34-year nation-wide experience.

BACKGROUND: Although the characteristics of leukaemia in patients with Down's syndrome (DS) have been well documented, little is known about the long-term results of treatment. METHOD: Retrospectively from 1968 to 1981 and prospectively from 1982 to 2002, the present authors collected data on every child with DS in Finland who had been diagnosed with leukaemia between 1968 and 1994. RESULTS: Forty-one children with DS had acute leukaemia: 28 had acute lymphoblastic leukaemia (ALL); and 13 had acute non-lymphoblastic leukaemia (ANLL). The median age of the subjects at diagnosis was 3.8 years (range = 0-15.9 years). Patients with ANLL were significantly younger (P = 0.001) and all patients under 2 years of age had ANLL. Out of the 28 patients with ALL, 23 (82%) entered primary remission, and of these 23 individuals, 10 remained alive and in continuous remission (CR) after a median of 11.6 years (range = 8.9-20.0 years). Out of the 13 patients with ANLL, five (38%) entered remission and four remained in CR after a median of 16.0 years (range = 9.1-19.2 years). Treatment -related toxicities were common: eight patients with ALL and two with ANLL died of septicaemia. Actuarial, event-free survival rates at 5 years were 53% and 43% for adequately treated subjects with ALL and ANLL, respectively. CONCLUSIONS: Standard leukaemia chemotherapy is effective in patients with DS. However, because toxicities are unacceptably frequent, specific anti-leukaemia regimens are needed for subjects with DS design.

Predicting neurological disorders in infants with extremely low birth weight using the movement assessment of infants.

PURPOSE: The aim of the study was to investigate the predictive value of the Movement Assessment of Infants (MAI) in early detection of neurological disorders in infants with extremely low birth weight (ELBW; <1000 g). METHOD: Thirty-three infants were examined and predictions regarding neurologic status were made at the corrected age of four months using the MAI. Follow-up examinations took place at the corrected age of 12 and 24 months by a pediatric neurologist and a physiotherapist. A neuropsychological assessment using the Bayley Scales of Infant Development was completed at the corrected age of two years. RESULTS: For predicting cerebral palsy (CP), the sensitivity was 64%; specificity 91%, and the positive and negative predictive values were 78% and 84%, respectively. For minor neurological disorders (MND), the value of sensitivity was 44%, specificity 71%, the positive predictive value was 50%, and the negative predictive value was 67%. CONCLUSION: The MAI assessment administered at the corrected age of four months is highly specific in predicting CP in the infants with ELBW.

Abnormal electroencephalogram at diagnosis of insulin-dependent diabetes mellitus may predict severe symptoms of hypoglycemia in children.

OBJECTIVES: To evaluate the predictive value of the electroencephalogram (EEG) at the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) for subsequent hypoglycemic coma and/or convulsion. To study whether such an episode causes long-term EEG abnormalities. STUDY DESIGN: An EEG was recorded in 36 patients with IDDM 2 to 3 weeks after diagnosis (median age, 7.5 years) and was then repeated after an episode of severe hypoglycemia associated with coma and/or convulsion (median age, 13.3 years). Paired EEGs were also recorded in 36 age-matched and IDDM duration-matched control patients who had never experienced severe hypoglycemia. A single EEG was recorded in 36 healthy children, matched with patients' ages at the time of IDDM diagnosis. RESULTS: Patients with severe hypoglycemia had an abnormal initial EEG recording more often than did control patients with IDDM (22.2% vs 2.8%, P =.03). Each of the healthy children had a normal EEG recording. The odds ratio for risk of subsequent coma and/or convulsion during hypoglycemia in patients with abnormal initial EEG recordings was 8 (95% CI, 1.1-354.7). After such an episode, the frequency of the abnormal EEG recordings was not elevated. CONCLUSIONS: EEG at the time of diagnosis of IDDM may be useful in identifying those patients at increased risk for coma and/or convulsion as a result of hypoglycemia. However, a single such episode did not appear to have a deleterious effect on the subsequent EEG.

Experience of severe hypoglycaemia may influence both patient's and physician's subsequent treatment policy of insulin-dependent diabetes mellitus.

UNLABELLED: Daily insulin doses and HbA1c were studied 0-3 months before and 2-6, 7-11, and 12-16 months after 48 consecutive episodes of severe hypoglycaemia (coma and/or convulsion) in children and adolescents with insulin-dependent diabetes mellitus. After 69% of the attacks, either physicians or patients or both decreased daily insulin doses (for the whole group, mean SD: 0-3 months before the episode 0.93 0.20 U/kg vs 2-6 months after 0.84 0.20 U/kg, P < 0.001), which may have worsened the subsequent glycaemic control as evidenced by a significant increase in HbA1c (8.3+/-1.5% vs 9.1+/-1.8%, P< 0.001, respectively). Physicians decreased the insulin dose even in 14 of the 33 patients with a preventable cause for their hypoglycaemia other than erroneous excess of insulin. CONCLUSION: Experience of severe hypoglycaemia may worsen the subsequent glycaemic control. This might in part be due to an excessive lowering of daily insulin doses by both physicians as well as patients and their families. Hypoglycaemia management must include intensive education about prevention without compromising diabetes control.

Severe hypoglycaemia in children and adolescents during multiple-dose insulin therapy.

Episodes of severe hypoglycaemia, resulting in coma and/or convulsions, were documented in an unselected, population-based group of 376 children and adolescents with Type 1 diabetes mellitus (Type 1 DM) treated at the Aurora Hospital, City of Helsinki. A prospective study in 1994-95 yielded 493 patient-years and a retrospective study in 1990-93, 904 patient-years of data. Of these patients, 77-85% received insulin in three or more daily doses. During 1990-95, 43 patients had a total of 48 severe hypoglycaemic episodes. For each episode (n = 48), one control Type 1 DM patient who had never experienced any severe hypoglycaemia, matched by age, diabetes duration and puberty, was sought from the study population. Incidence of severe hypoglycaemia was 3.1/100 patients years prospectively and 3.6/100 retrospectively. At the time of the episode, median age was 13.3 (range 2.2-21) years, and median diabetes duration 6.1 (0.5-14.6) years. Rates were similar in different age groups (< 6, 6-12.9 and > or = 13 years). A potential explanation for the hypoglycaemia was found in 79% of the episodes. Insulin dose was higher (p = 0.04) and HbA1c lower (p = 0.005) in patients with severe hypoglycaemia than in controls. In conclusion, multiple-dose insulin therapy in young patients with Type 1 DM can be associated with a low rate of severe hypoglycaemia. The majority of such episodes seem to be preventable.

Documented symptomatic hypoglycaemia in children and adolescents using multiple daily insulin injection therapy.

Symptomatic episodes of documented hypoglycaemia were characterized with the aid of a 3-month diary in a single-centre, unselected group of 161 children and adolescents with Type 1 diabetes mellitus, treated mainly (81%) with multiple-dose insulin therapy. Patients and families were asked to write in the diary all the symptomatic episodes in which blood glucose concentration proved to be < or =3 mmol l(-1) before treatment. Of the patients, 83 (52%) had a total of 287 hypoglycaemic episodes (0.6 attack per month per patient). The majority of the attacks, 221 (77%), were mild (patients > or =6 years able to treat themselves). Only two attacks were severe, resulting in coma and/or convulsion. The most common dominant symptoms were weakness (29%), tremor (20%), hunger (14%), and drowsiness (12%). Of all the dominant symptoms, 39% were classified as autonomic, 20% neuroglycopenic, and 41% non-specific. In children under 6 years, autonomic symptoms were less common than in adolescents 15 years or over (34% vs 57%, p = 0.01). In conclusion, the incidence of documented symptomatic hypoglycaemia was low. The symptoms were more often neuroglycopenic or non-specific than autonomic, especially in young children.

Granulocytopenia in Cohen syndrome.

Cohen syndrome is an autosomal recessive disorder characterized by mental retardation, microcephalia and typical craniofacial features, myopia and chorioretinal dystrophy. As some patients were reported to have leucopenia, we collected the haematological data of 26 Finnish Cohen patients. They all had experienced periods of isolated granulocytopenia from an early age. Granulocytopenia was mild to moderate, non-cyclic and never fatal. Most patients suffered from prolonged or repeated gingival or skin infections. We restudied 16 patients. Bone marrow examination revealed in all patients a normo- or hypercellular marrow, with a left-shifted granulopoiesis in 8/16 patients. The response to adrenaline stimulation was subnormal in 12/14 and to hydrocortisone in 8/16 patients, but administration of rhG-CSF caused granulocytosis in the three patients studied. No bone marrow malignancies were seen.

Peripheral blood cell counts in infants with Down's syndrome.

The current literature indicates that several abnormalities have been observed in the three hematopoietic cell lines of infants with Down's syndrome. This prospective, longitudinal study was designed to clarify the physiological variation in peripheral blood cell values of children with Down's syndrome by following 25 such infants during their first year of life. Apart from polycythemia in the first week of life, the hemoglobin concentration was, in general, the same as in normal term infants. At 9-12 months of age values for mean corpuscular hemoglobin and mean corpuscular volume tended to be elevated. Serum erythropoietin concentrations were low to normal. White blood cell counts were slightly lower in children with Down's syndrome than in normal children. The study infants had profound thrombocytosis from the age of 6 weeks to the end of follow-up at 1 year. This study, the first longitudinal follow-up of such subjects, indicates that infants with Down's syndrome often have evidence of polycythemia soon after birth and red blood cell macrocytosis and thrombocytosis later in infancy. In conclusion, we carried out peripheral blood cell counts in 25 infants with Down's syndrome, but with no actual hematological disturbance, during their first year of life, and compared them with values for normal term infants.

Tumor markers CA 125 and CA 19-9 in cord blood and during infancy: developmental changes and use in pediatric germ cell tumors.

Tumor markers CA 125 and CA 19-9 are elevated in a variety of malignancies in adult patients, but only little is known of their biology during gestation or infancy. We have addressed the developmental pattern of these carbohydrate antigens in pediatric patients by measuring their serum levels in 133 cord blood samples from the second through third trimester of gestation and in 39 infants aged less than 1.5 y. The serum concentrations of both markers revealed developmental changes, the levels being higher at earlier gestation (wk 24 through 37) than at term or during infancy. The clinical value of the markers was evaluated by monitoring 26 children with germ cell tumors; 14 benign and 2 immature teratomas, and 11 malignant germ cell tumors. Patients with immature sacrococcygeal teratomas showed constant and prolonged elevations of serum CA 125 and CA 19-9. In contrast, all but two children with mature teratomas had normal marker levels; these two patients with abnormally high serum CA 125 and CA 19-9 values for the first 4 postoperative weeks had a benign ovarian and ventricular teratoma, respectively. Of the 11 children with malignant germ cell tumors, serum CA 125 or CA 19-9 concentration was elevated in four patients at diagnosis and declined to normal within 2 wk after institution of therapy. Malignant recurrence in two patients was not associated with a reelevation of the CA 125 level. Taken together, our results demonstrate a developmentally regulated pattern of serum CA 125 and CA 19-9. The carbohydrate markers were usually inferior to alpha-fetoprotein in monitoring of germ cell tumors, but may be a useful adjunct in the follow-up of immature teratomas.

Transient incidental glucosuria in children.

A consecutive series of 78 children with transient asymptomatic glucosuria was studied and followed up for up to 7.3 years. The age at presentation was 0.9-17.6 (median 4.6) years. One third of the patients had random blood glucose levels of > 10.0 mmol/l (180 mg/dl). Five patients (6.4%) developed insulin-dependent diabetes mellitus within 2.1 years after the first incident of glucosuria. These patients presented with higher levels of glycaemia than others, and three out of five were positive for islet cell antibodies with a first-phase insulin response < 46 mU/l in all four studied. Of the remaining 73 children, 3 were positive for islet cell antibodies and 12/55 had a first-phase insulin response under 46 mU/l. The insulin response deteriorated in 3 but reverted to normal in 7 patients. CONCLUSION. For a child with transient glucosuria and with presence of islet cell antibodies and a subnormal first-phase insulin response, therapeutic attempts to prevent overt insulin-dependent diabetes mellitus should be considered.

Defective in-vitro colony formation of haematopoietic progenitors in patients with cartilage-hair hypoplasia and history of anaemia.

UNLABELLED: Cartilage-hair hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased. CONCLUSION: The present study shows defective in vitro colony formation in all myeloid lineages in patients with CHH, which is in accordance with the suggestion of a common cell proliferation defect in CHH.

Prolonged pure granulocytopenia in children.

In a prospective, population-based study, 31 patients with pure granulocytopenia lasting longer than six months were follow-up for up to 7.3 years after diagnosis. Their ages at diagnosis were 0.3-15.5 (median 0.9) years; 17 of the patients were less than 1 year of age. The lowest granulocyte count measured was 0.00-0.60 (median 0.03) x 10(9)/l. During the granulocytopenia, 12 patients suffered from repeated infections but none was life-threatening. In 21 patients, the granulocyte count normalized spontaneously within 0.5-5.5 (median 1.1) years: the other 10 remain granulocytopenic after follow-up for 2.5-7.3 (median 3.7) years. We conclude that selective granulocytopenia, if associated with unimpaired myelopoiesis, is a benign disorder in children and does not, even if prolonged, significantly increase the risk of severe infections.

Anaemia and macrocytosis--unrecognized features in cartilage-hair hypoplasia.

Cartilage-hair hypoplasia is an autosomal recessive osteo-chondrodysplasia which results in short stature, sparse hair and impaired cell-mediated immunity. In a study of 88 Finnish patients we found episodes of anaemia and/or macrocytosis during childhood in 86% of the patients. The reticulocyte index was always low in relation to anaemia. Bone marrow examination revealed decreased erythropoiesis in six of eight anaemic patients studied. Anaemia was most prevalent and severe during infancy. Spontaneous recovery occurred before adulthood in all patients except in three infants with fatal hypoplastic anaemia. Sixty-two percent of the patients had had lymphopenia and 24% neutropenia. Presence of anaemia significantly correlated to severity of immunodeficiency and growth failure and to presence of neutropenia. Disordered erythrogenesis is an integral feature of cartilage-hair hypoplasia and may, together with growth failure and immunodeficiency, reflect a generalized defect in cellular proliferation.