Prediction of febrile seizures in siblings: a practical approach.

UNLABELLED: To quantify the risk of febrile seizures (FS) in relatives of children with FS and to predict the risk of FS in siblings, we calculated cumulative risks of FS in first degree relatives of 129 children with FS. The study was conducted as a prospective follow up study of FS recurrences at the outpatient clinic of the Sophia Children's Hospital in Rotterdam. Thirteen parents and 12 siblings had experienced FS, accounting for a 6-year cumulative risk of 7%. The risk of FS was increased in relatives of children with recurrent FS (12%). The risk of FS in siblings (10%) in our study was more than twice the average risk in a similar population (4%). A positive FS history in a parent, young age at onset in the proband, and recurrences in the proband were selected in a multivariable prediction model. If two or more of these risk factors were present, the risk of West European siblings to develop FS was 46% (hazard ratio 5.4). CONCLUSION: The cumulative risk of FS in siblings of children with FS is increased. The age attained risk of FS can be estimated using a practical model incorporating three readily available risk factors.

Respiratory syncytial virus specific serum antibodies in infants under six months of age: limited serological response upon infection.

The decline of maternal respiratory syncytial virus (RSV) specific serum antibodies was studied in 45 children during the first 6 months of life, using a virus neutralization assay and competition ELISAs measuring fusion protein and glycoprotein specific antibodies. In all children RSV neutralizing antibodies were demonstrated at birth, with titers ranging from 33 to 1382. The calculated mean half life of these antibodies was 26 days. Furthermore, in a group of 38 children with suspected RSV infection, all younger than 6 months of age on admission, the diagnostic value of serological assays was evaluated. In 32 children RSV infection was confirmed by virus isolation, direct immune fluorescence and RT-PCR. In 7 patients of this group a significant titer rise in virus neutralization assay was demonstrated. Six additional RSV infected children could be identified by showing the presence of RSV-specific IgM or IgA serum antibodies or by showing an increase in fusion protein or glycoprotein specific antibodies. All serological tests together identified 13 (41%) of the 32 RSV infected patients. It is concluded that in children of this age group, which represent the majority of patients hospitalized with RSV infections, serological assays not only have a limited diagnostic value but are of limited value for sero-epidemiological studies.

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.

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.

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.

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.

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.

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.

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).

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.

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.

Childhood leukaemia in The Netherlands, 1973-1986: temporary variation of the incidence of acute lymphocytic leukaemia in young children.

The incidence of childhood leukaemia in The Netherlands in the period 1973-1986 was studied by means of the DCLSG nationwide register, which lists all patients according to bone marrow slides classified in the DCLSG central laboratory. Acute lymphocytic leukaemia (ALL) accounted for 81% of cases, acute non-lymphocytic leukaemia (ANLL) for 13%, chronic myelocytic leukaemia (CML) for 2.5%, and acute unclassifiable leukaemia (AUL) for 3%. The peak incidence of ALL was at age 3, common-ALL and pre B-ALL comprising about 95% of the immunophenotypes at this age. Incidence rates for ALL remained stable between 1973 and 1978 at 2.85 cases per 10(5) children per year, exhibited a temporary increase between 1979 and 1984 to 3.60 and dropped back to the lower, previous level in 1985 and 1986. This rise was seen mainly among children in the 1-4 year age group, especially at age 3, and those with common-ALL and an initial WBC less than 5.0 x 10(9) l-1. Cumulative incidence rates per year of birth were fairly homogeneous up to age 6, except for the 1978 birth cohort which exhibited higher rates. Incidence rates for ANLL, CML and AUL remained stable over time. Changes in ascertainment, declining birth rates and a 50% decrease in childhood mortality, e.g. from infectious diseases, could not explain this temporary variation. Moreover, incidence rates in this survey appeared to be similar to those reported in various developed countries for the same period. As far as the aetiology of childhood common-ALL is concerned, therefore, the Dutch data appear to support the hypothesis of 'random mutation' as well as that of a limited role of environmental factors.

Time-space distribution of extrahepatic biliary atresia in The Netherlands and West Germany.

Extrahepatic biliary atresia (EHBA) is an infrequent disease confined to early infancy. Its aetiology is not clear, but an infectious agent has been implicated. Demonstration of a time-space clustering would support this hypothesis. Therefore, we investigated the time-space distribution of all 89 cases of EHBA born in a 10-year period in the Netherlands. We carried out a similar study in West Germany and analysed 130 cases of EHBA, born between 1969 and 1986, from 4 paediatric surgical centres. Analysis of these cases did not reveal any evidence for clustering in specific years or in a specific period of the year. The places of birth of the patients also were randomly distributed over rural areas, villages and towns. Neither did a method to reveal time-space interaction give any support for clustering. This random distribution of patients with EHBA suggests that EHBA could be pathogenetically a heterogeneous disease.

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).

[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.

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.