Elisabeth E. Nibbelke

Prospective Validation of a Prognostic Model for Respiratory Syncytial Virus Bronchiolitis in Late Preterm Infants: A Multicenter Birth Cohort Study

Objectives This study aimed to update and validate a prediction rule for respiratory syncytial virus (RSV) hospitalization in preterm infants 33–35 weeks gestational age (WGA). Study Design The RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were assessed at birth among healthy preterm infants 33–35 WGA. All hospitalizations for respiratory tract infection were screened for proven RSV infection by immunofluorescence or polymerase chain reaction. Multivariate logistic regression analysis was used to update an existing prediction model in the derivation cohort (n = 1,227). In the validation cohort (n = 1,194), predicted versus actual RSV hospitalization rates were compared to determine validity of the model. Results RSV hospitalization risk in both cohorts was comparable (5.7% versus 4.9%). In the derivation cohort, a prediction rule to determine probability of RSV hospitalization was developed using 4 predictors: family atopy (OR 1.9; 95%CI, 1.1–3.2), birth period (OR 2.6; 1.6–4.2), breastfeeding (OR 1.7; 1.0–2.7) and siblings or daycare attendance (OR 4.7; 1.7–13.1). The model showed good discrimination (c-statistic 0.703; 0.64–0.76, 0.702 after bootstrapping). External validation showed good discrimination and calibration (c-statistic 0.678; 0.61–0.74). Conclusions Our prospectively validated prediction rule identifies infants at increased RSV hospitalization risk, who may benefit from targeted preventive interventions. This prediction rule can facilitate country-specific, cost-effective use of RSV prophylaxis in late preterm infants.

Immune reconstitution in children following chemotherapy for haematological malignancies: a long-term follow-up.

Modern intensive chemotherapy for childhood haematological malignancies has led to high cure rates, but has detrimental effects on the immune system. There is little knowledge concerning long‐term recovery of the adaptive immune system. Here we studied the long‐term reconstitution of the adaptive immune system in 31 children treated for haematological malignancies between July 2000 and October 2006. We performed detailed phenotypical and functional analyses of the various B and T cell subpopulations until 5 years after chemotherapy. We show that recovery of newly‐developed transitional B cells and naive B and T cells occurred rapidly, within months, whereas recovery of the different memory B and T cell subpopulations was slower and incomplete, even after 5 years post‐chemotherapy. The speed of B and T cell recovery was age‐independent, despite a significant contribution of the thymus to T cell recovery. Plasmablast B cell levels remained above normal and immunoglobulin levels normalised within 1 week. Functional T cell responses were normal, even within the first year post‐chemotherapy. This study shows that after intensive chemotherapy for haematological malignancies in children, numbers of several memory B and T cell subpopulations were decreased on the long term, while functional T cell responses were not compromised.

Respiratory syncytial virus prevention and asthma in healthy preterm infants: a randomised controlled trial

BACKGROUND Respiratory syncytial virus (RSV) infection is associated with subsequent wheeze and asthma. We previously reported on the causal relationship between prevention of RSV infection during infancy and reduced frequency of subsequent wheeze using a double-blind, randomised, placebo-controlled trial (MAKI). We continued follow-up and analysed the effect of RSV prevention during infancy on asthma and lung function at age 6 years. METHODS We studied 429 infants born at 32-35 weeks of gestation between 2008-10 who had randomly received either palivizumab for RSV immunoprophylaxis or placebo during the RSV season of their first year of life. After the first year of follow-up, single, assessor-blind follow-up of children continued until they were aged 6 years. Primary outcomes were parent-reported current asthma and forced expiratory volume in 0·5 s (FEV0·5). The trial is registered in the ISRCTN registry, number ISRCTN73641710. FINDINGS 395 (92%) of 429 participants completed this 6-year follow-up study. Parent-reported current asthma was reported in 28 (14·1%) of 199 children in the RSV prevention group and 47 (24·0%) of 196 children in the placebo group (absolute risk reduction [ARR] 9·9%, 95% CI 2·2 to 17·6). The difference in current asthma, which was a composite endpoint, was due to a difference in infrequent wheeze (one to three episodes in the past year; 12 [6·0%] of 199 vs 26 [13·4%] of 194, ARR 7·4%, 95% CI 1·5 to 13·2). FEV0·5 percentage predicted values were similar between the RSV prevention group (89·1% [SD 10·6]) and placebo group (90·1% [11·1]), with a mean difference of 1·0 (95% CI -1·3 to 3·3). The proportion of children with current physician-diagnosed asthma was similar between the RSV prevention group (19 [10·3%] of 185) and placebo group (18 [9·9%] of 182), with an ARR of -0·4 (95% CI -6·5 to 5·8). INTERPRETATION In otherwise healthy preterm infants, this single-blind, randomised, placebo-controlled trial showed that RSV prevention did not have a major effect on current asthma or lung function at age 6 years. Future research will inform on the effect of RSV prevention on asthma at school age in the general population. FUNDING AbbVie.

Impact of reduced chemotherapy treatment for good risk childhood acute lymphoblastic leukaemia on infectious morbidity

Reducing infectious morbidity is an important goal to improve childhood acute lymphoblastic leukaemia (ALL) survival. To explore the impact of chemotherapy reduction on infectious morbidity, we compared outpatient and inpatient infectious morbidity of reduced versus intensive (conventional) chemotherapy. One hundred and seventy‐one children newly diagnosed with ALL between 2004 and 2007 and treated according to the Dutch Childhood Oncology Group ALL 10 protocol were prospectively followed during the 2‐year treatment course. Stratified by minimal residual disease, 54 patients received reduced (standard risk; SR) and 117 patients received intensive (medium risk; MR) intensification/maintenance treatment. SR outpatients had a median of 1 febrile episode versus 4 in MR outpatients (P = 0·002). SR patients had fewer hospitalizations for fever. They were admitted a median of 0 times, with a median of 0 days of hospitalization, median 0 days of fever, median 0 times chemotherapy interruption and median 0 times intravenous antibiotics. MR patients were admitted for fever median 2 times (P < 0·001) with 10 days of hospitalization (P < 0·001), 2 days of fever (P < 0·001), one chemotherapy interruption (P < 0·001) and two intravenous antibiotics administration (P < 0·001). These data indicate that reduced intensification/maintenance compared to conventional intensive intensification/maintenance chemotherapy for good risk childhood ALL resulted in major decrease of infectious morbidity.

Cost-effectiveness of rule-based immunoprophylaxis against respiratory syncytial virus infections in preterm infants

AbstractThe objective of the paper is to assess the cost-effectiveness of targeted respiratory syncytial virus (RSV) prophylaxis based on a validated prediction rule with 1-year time horizon in moderately preterm infants compared to no prophylaxis. Data on health care consumption were derived from a randomised clinical trial on wheeze reduction following RSV prophylaxis and a large birth cohort study on risk prediction of RSV hospitalisation. We calculated the incremental cost-effectiveness ratio (ICER) of targeted RSV prophylaxis vs. no prophylaxis per quality-adjusted life year (QALYs) using a societal perspective, including medical and parental costs and effects. Costs and health outcomes were modelled in a decision tree analysis with sensitivity analyses. Targeted RSV prophylaxis in infants with a first-year RSV hospitalisation risk of > 10% resulted in a QALY gain of 0.02 (0.931 vs. 0.929) per patient against additional cost of €472 compared to no prophylaxis (ICER €214,748/QALY). The ICER falls below a threshold of €80,000 per QALY when RSV prophylaxis cost would be lowered from €928 (baseline) to €406 per unit. At a unit cost of €97, RSV prophylaxis would be cost saving. Conclusions: Targeted RSV prophylaxis is not cost-effective in reducing RSV burden of disease in moderately preterm infants, but it can become cost-effective if lower priced biosimilar palivizumab or a vaccine would be available.

Population-Attributable Risk of Risk Factors for Recurrent Wheezing in Moderate Preterm Infants During the First Year of Life

BACKGROUND Recurrent wheezing in young infants has a high prevalence, influences quality of life, and generates substantial health care costs. We previously showed that respiratory syncytial virus infection is an important mechanism of recurrent wheezing in moderate preterm infants. We aimed to provide population-attributable risks (PAR) of risk factors for recurrent wheezing during the first year of life in otherwise healthy moderate preterm infants. METHODS RISK is a multicentre prospective birth cohort study of 4424 moderate preterm infants born at 32-35 weeks gestation. We estimated PAR of risk factors for recurrent wheezing, which was defined as three or more parent-reported wheezing episodes during the first year of life. RESULTS We evaluated 3952 (89%) children at 1 year of age, of whom 705 infants (18%) developed recurrent wheezing. Fourteen variables were independently associated with recurrent wheezing. Hospitalisation for respiratory syncytial virus bronchiolitis had a strong relationship with recurrent wheezing (RR 2.6; 95% confidence interval, CI, 2.2, 3.1), but a relative modest PAR (8%; 95% CI 6, 11%) which can be explained by a low prevalence (13%). Day-care attendance showed a strong relationship with recurrent wheezing (RR 1.9; 95% CI 1.7, 2.2) and the highest PAR (32%; 95% CI 23, 37%) due to a high prevalence (67%). The combined adjusted PAR for the 14 risk factors associated with recurrent wheezing was 49% (95% CI 46, 52%). CONCLUSIONS In moderate preterm infants, day-care attendance has the largest PAR for recurrent wheezing. Trial evidence is needed to determine the potential benefit of delayed day-care attendance in this population.

Cesarean section and hospitalization for respiratory syncytial virus infection.

© 2015 Wolters Kluwer Health www.pidj.com | 227 by Ascaris lumbricoides (3.7%) and Entamoeba histolytica/dispar (3.7%). Prevalence of infection by Hymenolepis nana was significantly higher in children younger than 5, whereas prevalence of infection by Taenia spp., Trichuris trichura, A. lumbricoides, E. histolytica/dispar, and hookworms was significantly lower in the young children. Multiple parasitic infections were less common in children younger than 5 (2.8%) than in children between 5 and 14 years of age (4.3%) (P < 0.001). Our findings indicate that the prevalence of intestinal parasites in children younger than 5 was higher than that found in other studies. Differences in prevalence might be due to differences in hygiene practices, water supplies, latrine coverage, economic and educational status, and climatic conditions. G. intestinalis was the main intestinal parasitic infection, as demonstrated in other studies. Multiple intervention strategies could reduce the morbidity of acute diarrhea in young children such as health education, access to a safe water supply and improvement in hygiene.