Risk factors for childhood acute non-lymphocytic leukemia: an association with maternal alcohol consumption during pregnancy?

A population-based case-control study of acute non-lymphocytic leukemia (ANLL) was performed with 80 ANLL cases diagnosed between 1973 and 1979, who were derived from the nationwide register of the Dutch Childhood Leukemia Study Group. Cases were compared to three age- and sex-matched population controls and, in order to control for recall bias, to 517 cases with acute lymphocytic leukemia from the same study base. Information on a large number of exposures to putative risk factors was collected by a self-administered questionnaire mailed to the parents. No significant association of ANLL was observed with smoking habits of the mother during pregnancy, ultrasound examinations, prenatal exposure to x-rays, viral infections, or hydrocarbon exposure. When comparing ANLL cases to population controls, maternal use of alcohol during pregnancy was associated with a more than two-fold increased risk of ANLL (odds ratio = 2.6; 95% confidence interval = 1.4-4.6). A similar increase in risk was found when comparing ANLL cases to acute lymphocytic leukemia cases. There was no significant elevation in risk for ANLL found for parental use of alcohol 1 year before pregnancy. This study suggests that intrauterine exposure to alcohol may increase the risk for childhood ANLL.

Epidemiological and immunological characteristics of childhood leukaemia in The Netherlands: population-based data from a nationwide co-operative group of paediatricians.

In this review results are presented from several population-based epidemiological and immunological studies of children with leukaemia in The Netherlands, who were diagnosed between 1973 and 1982 through a nationwide co-operative group of paediatricians. From 1973 till 1980 annual incidence rates appeared to be 3.1 per 10(5) person-yr. No significant trend was observed in this period. However a preliminary analysis of patients in the 1980-1982 period showed an increase. Mortality rates are decreasing since 1973, as expected. Incidence rates and proportions of different morphological and immunological subtypes reflect the pattern of occurrence in populations with a high standard of living. A relatively high incidence rate of acute lymphocytic leukaemia (ALL) is observed with a peak at the age of 3-5. The proportion of patients with T-cell phenotype among ALL-patients, immunologically typed between 1979 and 1982, appeared to increase with age, while the proportion of common ALL decreased. Statistical analysis of the data of patients with ALL in the Western part of the country including areas with nuclear plants, gave no indication for the presence of clustering. Subclassification of childhood leukaemia (CL), notably ALL, may be necessary for obtaining more specific etiologic clues. In view of the incidence of CL and ALL large scale, immunological and epidemiological investigations of CL, and the related non-Hodgkin's lymphomas, preferably population-based, are necessary.

Are maternal fertility problems related to childhood leukaemia?

An explorative case-control study was conducted in The Netherlands. The cases were obtained from a complete nationwide register of childhood leukaemia (1973-1980). Controls were matched with the cases for year of birth, sex and place of residence. Information about exposures of the mother to potential risk factors in the year before pregnancy and during pregnancy was collected via mailed questionnaires. The analyses concerned data on 519 patients with acute lymphocytic leukaemia and 507 controls. An association between maternal subfertility and childhood leukaemia might be suggested by several findings. A history of two or more miscarriages (OR 1.6; 95% Cl 1.0-2.7) and fertility problems (OR 6.0; 95% Cl 0.9-38.2) were more frequently reported among mothers of cases. The use of oral contraceptives (OC) was significantly higher (OR 1.3; 95% Cl 1.0-1.8) and the duration between discontinuation of OC and the relevant pregnancy was significantly longer. The OR for threatened abortion during the relevant pregnancy was 1.6 (95% Cl 1.0-2.6) and the related use of 'drugs to maintain pregnancy' was 1.9; 95% Cl 1.0-3.5. Among known risk factors, an increased OR for diagnostic irradiation was confirmed (OR 2.2; 95% Cl 1.2-3.8). No association between childhood leukaemia and prenatal viral infections, smoking and alcohol was found.

Antipyretic efficacy of ibuprofen and acetaminophen in children with febrile seizures.

OBJECTIVE: To compare the antipyretic efficacy of ibuprofen syrup (5 mg/kg per dose) and acetaminophen syrup (10 mg/kg per dose) in children with a history of febrile seizures. DESIGN: Randomized, multiple-dose, double-blind, cross-over trial. SETTING: The outpatient department of a university-affiliated teaching hospital. PATIENTS: Seventy outpatients (mean age, 2.1 years; range, 10 months to 4 years) who had visited the hospital because of a febrile seizure were randomized to treatment at a temperature of 38.5 degrees C or higher. INTERVENTIONS: Study medication was given every 6 hours for 1 to 3 days. Rectal temperatures were recorded at 0, 2, 4, 6, 12, and 24 hours after the first dose. MAIN OUTCOME MEASURES: The temperature 4 hours after the first dose, the mean temperature during treatment, and the highest temperature during treatment were evaluated. Analysis of covariance corrected for the initial temperature, age, weight, and cause of the fever. RESULTS: Ibuprofen lowered the initial temperature from 39.1 degrees C to a mean temperature of 37.7 degrees C during treatment; acetaminophen lowered the initial temperature from 39.2 degrees C to 38.0 degrees C. Ibuprofen reduced fever 0.50 degree C more than did acetaminophen at 4 hours (95% confidence interval [CI], -0.98 to -0.02). The mean temperature was 0.26 degree C lower during ibuprofen treatment (95% CI, -0.59 to 0.07); the highest temperature was 0.30 degree C lower (95% CI, -0.73 to 0.13). In 22 patients, a second fever was treated with the opposite medication than the first. In the cross-over analysis, the respective differences were 0.66 degree C (95% CI, -1.29 to -0.06), 0.40 degree C (95% CI, -0.83 to 0.03), and 0.36 degree C (95% CI, -0.81 to 0.08) in favor of ibuprofen. CONCLUSIONS: Ibuprofen and acetaminophen are effective antipyretic agents in children with a history of febrile seizures. Ibuprofen yielded significantly greater fever reduction than did acetaminophen 4 hours after the first dose. Research is needed on the value of antipyretic agents for the prevention of febrile seizure recurrence.

Time space distribution of childhood leukaemia in the Netherlands.

In the western part of the Netherlands during 1973-80 leukaemia was diagnosed in 293 patients aged under 15 years. An overall incidence rate of 2.91 per 100000 person years was calculated. No seasonal influence on months of birth or months of diagnosis of these patients could be traced by the method of Edwards. Time space clustering was looked for by both methods of Mantel and Knox. No significant time space clustering of date and place of diagnosis of childhood leukaemia was found in all types of leukaemia, acute lymphocytic leukaemia (ALL), ALL in boys and girls, ALL in children under 6 years at diagnosis, and in acute non-lymphocytic leukaemia.

Bronchial carcinoid tumor in a 12-year-old child.

Symptoms (hemoptysis, recurrent pulmonary infections), diagnostic work-up (roentgenology, bronchoscopy with biopsy), and treatment (surgical resection of a bronchial carcinoid tumor in a 12 year old girl) are discussed. Special attention was paid to the tumor histochemistry, showing serotonin containing granules. Levels of circulating hormones and vasoactive agents, including serotonin, were within normal limits.

[Hypercalcemia in childhood. A boy with asymptomatic hypocalciuric hypercalcemia]. / Hypercalciëmie op de kinderleeftijd. Een jongen met asymptomatische hypocalciurische hypercalciëmie.

The diagnostic work-up of a patient with (familial) hypocalciuric hypercalcemia (FHH) is discussed. The patient showed no clinical signs of hypercalcemia. There were no indications of vitamin D intoxication. In the first degree family members no hypercalcemia was found. Physical examination was normal. In contrast to hyperparathyroidism, FHH is usually symptomless. Furthermore, FHH is characterized by a normal chloride/phosphate ratio, a normal, but relatively high, serum parathyroid hormone level, a relatively low urinary calcium excretion, a calcium-creatinine clearance ratio less than 0.01 and a normal cyclic AMP excretion.

[Epidemiology of leukemia in children]. / Epidemiologie van leukemie bij kinderen.

Epidemiological research of childhood leukaemia could provide clues for the aetiology. A review is given of time trend analysis of annual incidence rates, leukaemia incidences in different countries and time-space clustering. Aetiological factors as suggested in case-control studies on this subject are discussed.

Childhood leukemia and infectious diseases in the first year of life: a register-based case-control study.

In the Netherlands, a nationwide register of children with leukemia formed the basis for a case-control study (1973-1980). Population controls were matched with the cases for the year of birth, sex, and place of residence at the time of diagnosis. The information was collected by mailed questionnaires addressed to the parents. The analyses concerned infectious diseases in the first year of life of children with acute lymphocytic leukemia and their controls. Common colds, periods of fever, and primary childhood infections showed relative risks (RR) of 0.8, 0.9, and 0.8, respectively, after adjustment for birth order, family size, social class, and residential space. Furthermore, fewer cases reported infectious diseases which required hospitalization in their first year of life (RR = 0.6, 95% confidence interval (CI) = 0.4-1.0). The general infection risk profile of children with acute lymphocytic leukemia is compatible with these findings: there were more first-born children among the patients (RR = 1.8; 95% CI = 1.1-2.7), more children from one-child families (RR = 1.4; 95% CI = 0.8-2.3), more children of parents with higher education (RR = 1.2; 95% CI = 0.9-1.5), and more rooms in patient's houses (RR = 1.4; 95% CI = 0.6-2.6).

Childhood leukemia and parental occupation. A register-based case-control study.

To explore possible etiologic factors of childhood leukemia, a case-control study was performed in the Netherlands. Cases were selected from a complete nationwide register of cases of childhood leukemia which were diagnosed between 1973 and 1980. Controls were matched with cases for year of birth, sex, and place of residence at the time of diagnosis. Information about possible exposures was collected by a postal questionnaire addressed to the parents. This report concerns the results of the analysis of parental occupations and occupational exposures for 519 children with acute lymphocytic leukemia and 507 controls. During pregnancy, more mothers of patients were working in "hydrocarbon-related" occupations; relative risk (RR) = 2.5 (95% confidence interval (CI) = 0.7-9.4). Likewise, greater occupational exposure to chemicals (paint, petroleum products, and unspecified chemicals) during pregnancy was found for mothers of patients (RR = 2.4, 95% CI = 1.2-4.6). The kind of work being performed by the mothers one year before diagnosis did not differ between cases and controls. For the fathers, no relationship was found between a hydro-carbon-related occupation or occupational exposure to chemicals and leukemia in the offspring. Adjustment for birth order, social class, and degree of urbanization did not materially change the relative risks.

Risk factors for mechanical ventilation in respiratory syncytial virus infection.

In a prospective study, risk factors for mechanical ventilation were identified in 102 patients with respiratory syncytial virus (RSV) infection admitted to the Sophia Children's Hospital, Rotterdam. Age, weight on admission and prematurity were associated with the need for mechanical ventilation. Using multivariate analysis, only low weight was an independent risk factor for mechanical ventilation. For infants weighing less than 5 kg the relative risk for mechanical ventilation was 4.4 (95% confidential interval 1.3-13.9).

Incidence of childhood leukaemia in The Netherlands (1973-1980).

The childhood leukaemia incidence rate for the Netherlands was estimated at 3.11 per 100.000 children (aged 0-15 year) per year, based on a complete nation-wide childhood leukaemia registry comprising the period 1973-1980. Acute lymphocytic leukaemia (ALL) accounted for 82.4% of the patients, acute non-lymphocytic leukaemia for 13.6% and chronic myeloid leukaemia for 2.9%. ALL occurred more frequently in boys (sex ratio 1.2). The highest ALL rate was observed in the 3-4 year age group. These figures corresponded with the data of the Manchester Children's Tumour Registry. Neither the incidence rates according to year of diagnosis nor the incidence rates according to year of birth showed a significant trend with time. The total leukaemia incidence rate in urban areas was somewhat higher than in rural areas. While the direct comparison of the incidence rate between these areas is not significant, the trend over the three categories of urbanisation is significant.

Severity of respiratory syncytial virus infections and immunoglobulin concentrations.

In a prospective study in 86 children with respiratory syncytial virus infections, no relation was detected between the severity of infection (based on diagnosis, chest radiography findings, need for mechanical ventilation, and duration of hospitalisation) and serum concentrations of IgG, IgA, IgM, and IgG1-4 on admission.

Respiratory syncytial virus infections in children admitted to the intensive care unit.

During the winter of 1986-1987, 64 children with respiratory syncytial virus (RSV) infection were admitted to our hospital. The diagnosis was made by direct immunofluorescent antibody technique. Twenty-three children (36%) needed intensive care treatment. Nearly 11 (52%) had a preexisting disease state, identified as a risk factor i.e., prematurity (n = 8), bronchopulmonary dysplasia (n = 2), congenital heart disease (n = 1). Twelve patients (50%) were intubated and ventilated. Conditions for intubation and ventilation were repetitive apnea with or without bradycardia (n = 4), clinical deterioration (n = 3) or hypercarbia (n = 5). Seventy-five percent of the patients who needed intensive care management were under three months of age compared to 34% of the children who were admitted to the clinical ward. The mean age for ventilated patients was 7.9 weeks. The mean duration of ventilation was 5.5 days. Volume controlled ventilation was initially applied to all patients. Pulmonary complications (atelectasis, pneumonia, pneumothorax or adult respiratory distress syndrome) were present in 15 (65%) IC patients. Nine (39%) of them also had symptoms of inappropriate antidiuretic hormone secretion (IADHS). Only two patients had symptoms of IADHS and two others had convulsions. Three children (5%) died as a result of respiratory insufficiency. Two of these infants belonged to the risk group.

Excessive secretion of antidiuretic hormone in infections with respiratory syncytial virus.

The association between infections with respiratory syncytial virus and plasma concentrations of antidiuretic hormone was assessed in 48 patients who had been admitted to hospital. The mean (SEM) concentration of antidiuretic hormone was significantly raised in patients with bronchiolitis (9.3 (1.4) ng/l) compared with non-pulmonary respiratory syncytial virus infections that cause apnoea or upper respiratory tract symptoms (6.1 (1.7) ng/l). The highest concentrations of antidiuretic hormone were seen in patients receiving mechanical ventilation (18.0 (6.7) ng/l). There were no differences in mean serum sodium concentrations among the subgroups. Hypertranslucency on chest radiograph or an arterial carbon dioxide tension above 6.67 kPa were associated with a significantly higher concentration of antidiuretic hormone. Increased or normal maintenance fluid intake in children with pulmonary respiratory syncytial virus infections may cause the same symptoms of fluid overload as the syndrome of inappropriate secretion of antidiuretic hormone. Patients with pulmonary respiratory syncytial virus infection, hypertranslucency in chest radiograph, hypercapnia, or mechanical ventilation are at risk for raised concentrations of antidiuretic hormone. Restricted fluid intake and careful monitoring of fluid balance and plasma electrolyte concentrations are therefore necessary in these patients.

Outcome after febrile status epilepticus.

The neurological outcome after a first febrile status epilepticus (FSE) was retrospectively studied in 57 children. Patients were aged six to 57 months at first seizure and had had no previous seizures or neurological abnormalities. 12 children (24 percent: 2-year Kaplan-Meier estimate) had subsequent neurological sequelae varying from speech deficit (n = 9) to severe neurological sequelae and epilepsy (n = 3). Speech deficit was detected after a mean period of six months. The most important predictors for sequelae were the number of different drugs needed for seizure termination and the duration of the seizure. The authors recommend that children with FSE should be followed up for at least one year so that potential speech disorders can be detected and treated.

A predictive model to estimate the risk of serious bacterial infections in febrile infants.

UNLABELLED: Low risk criteria have been defined to identify febrile infants unlikely to have serious bacterial infection (SBI). Using these criteria approximately 40% of all febrile infants can be defined as being at low risk. Of the remaining infants (60%) only 10%-20% have an SBI. No adequate criteria exist to identify these infants. All infants aged 2 weeks-1 year, presenting during a 1-year-period with rectal temperature > or = 38.0 degrees C to the Sophia Children's Hospital were included in a prospective study. Infants with a history of prematurity, perinatal complications, known underlying disease, antibiotic treatment or vaccination during the preceding 48 h were excluded. Clinical and laboratory variables at presentation were evaluated by a multivariate logistic regression model using SBI as the dependent variable. By using likelihood ratios a predictive model was derived, providing a post test probability of SBI for every individual patient. Of the 138 infants included in the study, 33 (24%) had SBI. Logistic regression analysis defined C-reactive protein (CRP), duration of fever, standardized clinical impression score, a history of diarrhoea and focal signs of infection as independent predictors of SBI. CONCLUSION: CRP, duration of fever, the "standardized clinical impression score", a history of diarrhoea and focal signs of infection were the independent, most powerful predictors of SBI in febrile infants, identified by logistic regression analysis. Although the predictive model is not validated for direct clinical use, it illustrates the clinical potential of the used technique. This technique offers the advantage of assess the probability of SBI in every individual infant. This probability will form the best basis for well-founded decisions in the management of the individual febrile infant.

Relationship between clinical severity of respiratory syncytial virus infection and subtype.

The relationship between clinical severity of respiratory syncytial virus (RSV) infection and distribution of subtype A or B was investigated. The data of 232 children, who were admitted with RSV infection or diagnosed in the outpatient department of the Sophia Children's Hospital, Rotterdam between 1992 and 1995, were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence assay. Subtyping was performed by an indirect immunofluorescence assay using specific monoclonal antibodies. Gender, age at diagnosis, gestational age and birth weight, the presence of underlying diseases, feeding difficulties, the presence of wheezing and retractions, respiratory rate, temperature, clinical diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical ventilation were observed. Analysis was performed on data from all patients diagnosed with RSV infection in the period between 1992 and 1995 spanning three RSV seasons, and separately on the RSV season 1993-4. The outcome of the three year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and 24 (39.3%) subtype B isolates. None of the variables observed in the season 1993-4 differed significantly between RSV subtype A and B. Similar results were obtained from the analysis in the period 1992 until 1995, with the exception of PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more retractions were noted in patients with subtype A, p = 0.03). After correcting for possible confounders using regression analysis, these differences were not significant anymore. The data indicate that there is no relationship between clinical severity of RSV infection and subtype.