Dynamic changes in the trends in incidence of type 1 diabetes in children in Hungary (1978-98)

Abstract: Objective: To determine the recent trends in incidence, to analyze the age and geographic distribution, as well as the seasonal pattern of type 1 diabetes in Hungarian children aged 0–14 yr for the period from 1978 to 1998. Methods: Primary ascertainment of cases was by retrospective (1978–88) and by prospective (1989–98) registration using hospital notifications. The level of ascertainment was estimated by the capture–recapture method. The temporal trend was estimated by fitting Poisson regression models to the yearly incidence data. Roger's test was used to investigate possible seasonal variation in time of diagnosis. Heterogeneity between geographic areas was assessed by Poisson regression. Results: A total of 2616 patients (1214 in the first 11 yr, 1402 in the remaining 10 yr) were identified; the male:female ratio was 0.93. The overall standardized incidence rate was 7.87 (95% CI = 7.57–8.18) per 100 000 person‐yr, the lowest in the youngest (0–4 yr) and highest in the oldest (10–14 yr) age group. There was an increasing trend in incidence with a largest relative annual increase in the youngest age group. Seasonal and regional variations in incidence were also observed. Conclusion: Our 21‐yr study shows dynamic changes in incidence of childhood type 1 diabetes in Hungary, probably reflecting changes in the environment.     

Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children

Long-term survivors of acquired aplastic anemia (AA) have an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST). It is uncertain whether the increased survival time simply discloses the natural history of AA as a premalignant disease or whether secondary disease is related to the therapy itself. Between November 1992 and September 1997, 113 AA children with normal cytogenetics at diagnosis were treated with IST using antithymocyte globulin, cyclosporin, and danazol with or without granulocyte colony-stimulating factor (G-CSF). We assessed risk factors for developing MDS/AML by Cox proportional hazards models. Twelve of 113 patients developed MDS between 9 and 81 months following the time of diagnosis, giving a cumulative incidence of 13.7 +/- 3.9%. The following cytogenetic abnormalities were observed at the time of diagnosis of MDS: monosomy 7 (6 patients), monosomy7/trisomy21 (1 patient), trisomy 11 (1 patient), del (11) (9?:14) (1 patient), add (9q) (1 patient), add 7 (q 32) (1 patient), and trisomy 9 (1 patient). The number of days of G-CSF therapy and nonresponse to therapy at 6 months were statistically significant risk factors by multivariate analysis. The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST.     

Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

BACKGROUND: The objective of the current report was to compare the self-reported rates of special education (SE) and educational attainment among specific groups of childhood cancer survivors and a random sample of sibling controls. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort of individuals who were diagnosed with a cancer in childhood and survived at least 5 years postdiagnosis. This analysis includes 12,430 survivors and 3410 full siblings. Reported use of SE services and educational attainment were analyzed within subgroups defined by type of cancer, age at diagnosis, and type of treatment. RESULTS: The use of SE services was reported in 23% of survivors and 8% of siblings, with the greatest differences observed among survivors who were diagnosed before age 6 years, most notably survivors of central nervous system (CNS) tumors (odds ratio [OR], 18.8; 95% confidence interval [95%CI], 15.01-23.49), leukemia (OR, 4.4; 95%CI, 3.75-5.16), and Hodgkin disease (OR, 4.4; 95%CI, 2.64-7.24). It was found that intrathecal methotrexate (IT MTX) and cranial radiation (CRT), administered alone or in combination, significantly increased the likelihood that a survivor would use SE (IT MTX only: OR, 1.3; 95%CI, 1.09-1.78; CRT only: OR, 7.2; 95%CI, 6.14-8.39; IT MTX and CRT combined: OR, 2.6; 95%CI, 2.30-2.95). A positive dose response was identified between higher doses of CRT and use of SE. It was determined that survivors of leukemia (OR, 1.6; 95%CI, 1.23-2.16), CNS tumors (OR, 2.7; 95%CI, 1.92-3.81), non-Hodgkin lymphoma (OR, 1.8; 95%CI, 1.15-2.78), and neuroblastoma (OR, 1.7; 95%CI, 1.14-2.61) were significantly less likely to finish high school compared with siblings; however, when survivors received SE services, risk estimates approximated those of the sibling SE population. CONCLUSIONS: Children who are diagnosed with cancer should be followed closely during and after treatment to identify early signs of learning disabilities and to maximize intervention strategies for the successful completion of scholastic goals.     

Maternal employment and the initiation of breastfeeding

This study examines whether planning to be employed postpartum has an effect on initiation of breastfeeding. Data were collected from questionnaires completed by mothers who were subjects in the prospective, population-based, Avon Longitudinal Study of Pregnancy and Childhood. The mothers of 10,530 full-term singleton infants gave information during pregnancy on their postpartum employment plans and their initial infant feeding methods. Information was also given by 7642 of these mothers on the timing of their postpartum employment plans. Adjusted logistic regression was performed to identify associations between (a) "any" plans to work postpartum and the initiation of breastfeeding, and (b) the timing of the commencement of work postpartum, and the initiation of breastfeeding. A total of 8316 (79%) of the women initiated breastfeeding. The decision to breastfeed was not associated with "any" plans to work postpartum. However, women who planned to commence work prior to 6 wk postpartum were significantly less likely to initiate breastfeeding compared with those not intending to work postpartum. Older, more highly educated women, women who had or were planning to attend childbirth classes, women who were breastfed as infants, women who did not smoke and women who were giving birth to their first child were significantly more likely to initiate breastfeeding. Conclusion: Planning to return to employment prior to 6 wk postpartum reduces the likelihood of initiating breastfeeding. As increasing numbers of mothers are returning to work shortly after the birth of their child, this finding could have implications for maintaining the current level of breastfeeding.     

Stereoacuity at age 3.5 y in children born full-term is associated with prenatal and postnatal dietary factors: a report from a population-based cohort study

BACKGROUND: Observational studies suggested that breast-feeding benefits the visual development of preterm children, which has been attributed to the presence of docosahexaenoic acid (DHA) in breast milk but not most formula milks. Randomized studies showed that preterm children require a dietary supply of DHA in the first few weeks of life for optimal visual development, but it is unclear whether full-term children experience similar benefits from breast milk or DHA supplements. OBJECTIVE: The objective of this study was to compare stereoacuity at age 3.5 y in healthy, full-term children who were breast-fed and in similar children who had not been breast-fed after adjustment for socioeconomic status and maternal diet. DESIGN: Prospectively collected data on maternal diet during pregnancy (including intake of oily fish), the child's diet, and the socioeconomic status of the family were examined. Stereoacuity at age 3.5 y was assessed. RESULTS: Children who had been breast-fed for 4 mo were more likely to achieve high-grade stereopsis, or stereoscopic vision, than were children who had not been breast-fed (adjusted odds ratio: 2.77; 95% CI: 1.54, 4.97). The mother's antenatal blood DHA content was associated with her intake of oily fish (P < 0.0001). Children whose mothers ate oily fish during pregnancy were also more likely to achieve high-grade stereopsis than were children whose mothers did not eat oily fish (adjusted odds ratio: 1.57; 95% CI: 1.00, 2.45). CONCLUSIONS: The results of this study suggest that for full-term infants, breast-feeding is associated with enhanced stereopsis at age 3.5 y, as is a maternal DHA-rich antenatal diet, irrespective of later infant feeding practice.     

The burden of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema in children and adolescents in six New Zealand centres: ISAAC Phase One

AIM: To describe the burden of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema in children in six New Zealand centres. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One was undertaken in Auckland, Bay of Plenty, Hawke's Bay, Wellington, Nelson and Christchurch during 1992-1993. In each centre, approximately 3,000 six to seven year old children and 3,000 thirteen to fourteen year old adolescents were studied, a total of 37,592 participants. Both age groups answered written questionnaires and the adolescents a video questionnaire about asthma symptoms. RESULTS: The prevalences of symptoms were high, for asthma 25% and 30%, allergic rhinoconjunctivitis 10% and 19%, and atopic eczema 15% and 13% in each age group respectively. More than 40% of participants had symptoms in the last year of at least one condition, most commonly asthma. There were no significant differences among regions, except for six to seven year olds in Nelson who had significantly lower prevalences of some symptoms of asthma and allergic rhinoconjunctivitis. CONCLUSIONS: Asthma and allergies are common in New Zealand, with resultant morbidity and cost. However, there is little regional variation with the exception of lower rates in Nelson children. Explanations for these findings will be the subject of further studies.     

Food and nutrient intake in a cohort of 8-month-old infants in the south-west of England in 1993

OBJECTIVE: To investigate food and nutrient intakes in 8-month-old infants. DESIGN: Prospective study. SETTING: Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), south-west England. SUBJECTS: A total of 1131 singleton Caucasian infants (82% of those invited) from a 10% random sample of ALSPAC, known as Children in Focus (CIF). METHODS: Diet was assessed using a structured 3-day unweighed dietary record. Food and nutrient intakes were compared with intakes from the 6--9 month age group of a British infant feeding survey, which formed part of the National Diet and Nutrition Survey (NDNS). Nutrient intakes were compared with dietary reference values (DRV). RESULTS: Intakes of energy and most nutrients were very similar between CIF and NDNS. The main difference was in the type of fat eaten resulting in a higher polyunsaturated to saturated fatty acid ratio in CIF (0.34) compared with NDNS (0.21). Other differences included the much lower calcium and iodine intakes in CIF compared with the NDNS. Differences in the proportion of consumers of formula and cow's milk accounted for most of the nutrient differences. Energy intakes were similar to the estimated average requirements (EAR), however, breastfed infants were slightly below and non-breastfed were slightly above the EAR. Mean intakes of zinc and vitamin D were below the Reference Nutrient Intakes. CONCLUSIONS: The diets of 8-month-old infants in this study were adequate in most nutrients. Breastfed infants had slightly lower energy intakes than non-breastfed infants.     

Heterogeneity of lymphoblastic malignancies in children

Summary Lymphocyte surface markers show that lymphoblastic lymphomata in children are a heterogeneous but related group of diseases. Lymphoblastic lymphomas of T cell type fall into at least three subgroups: (1) HTLA positive, E rosette negative, TdT positive phenotype, with characteristically high levels of TdT and some associated expression of C-ALL antigen on a small proportion of cells. (2) E rosette positive lymphoblasts with intermediate range of TdT positivity, and which express antigens specific for thymic cortical lymphocytes. (3) E rosette positive and C3d positive T lymphoblasts with low levels of TdT enzyme.B lymphoblastic lymphomas show a major subgroup characterised by surface IgM expression, with or without detectable cytoplasmic IgM, and which may express ALL antigen. A minor subgroup of B lymphoblastic disease, of predominantly nodal presentation, expresses surface IgM with some expression of C3d receptors. Therefore at least 3 T cell, and 2 B cell subgroups of lymphoblastic lymphoma can be described.     

A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial

Data on 1711 patients, aged up to 55 years, in the MRC AML 10 trial were used to create a prognostic index for use in risk-directed therapy decision making for younger patients with acute myeloid leukaemia (AML). Two parameters, response after course 1 and cytogenetics, were strongly predictive of outcome. For patients with complete remission, partial remission and resistant disease, 5-year survival from the start of course 2 was 53%, 44% and 22% and relapse rates were 46%, 48% and 69% respectively, and for patients with favourable, intermediate and adverse karyotypic abnormalities, survival was 72%, 43% and 17% and relapse rates were 34%, 51% and 75% respectively (all P < 0.0001). Patients with FAB type M3 but no cytogenetic t(15;17) also had a low relapse rate (29%). These three factors were combined to give three risk groups: good (favourable karyotype or M3, irrespective of response status or presence of additional abnormalities), standard (neither good nor poor), poor (adverse karyotype or resistant disease, and no good-risk features). Survival for these three groups was 70%, 48% and 15% respectively and relapse rates were 33%. 50% and 78% (both P < 0.0001). The index is simple (based on just three parameters), robust (derived from 1711 patients), highly discriminatory (55% survival difference between good and poor risk) and validated, so can be applied in the clinical setting to assist with therapeutic decisions as in the current AML 12 trial.     

Recruitment of Participants in the Childhood Asthma Management Program (CAMP). I. Description of Methods

The Childhood Asthma Management Program (CAMP), a multicenter clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI), is the largest outcome study of mild to moderate asthma in children to be undertaken, with eight clinical centers in the United States and Canada participating. The initial recruitment goal was 960 children within an 18-month recruitment period. Recruitment was extended to 23 months, with 1041 children randomized from late December, 1993, to early September, 1995. In this time interval each of the eight centers met the recruitment goal of 120 using a variety of self-selected recruitment strategies. The goal for minority recruiting was 33%, or 320 of the planned 960 children to be recruited. CAMP achieved the overall goal for the number of minorities, with 330 patients. Three centers recruited at or above the expected rate from the beginning. The other five centers had significant delays in recruitment. Examination of the recruitment experiences of the centers with and without delays did not indicate any single recruitment strategy that was certain to be successful. The most commonly cited factors for success were a cohesive staff, endorsement of participation by the child's primary care provider, and ability of the staff to be flexible and honest in assessing progress and the value of recruiting methods being used.