Prevalence and clinical characteristics of perinatal chronic lung disease by infant gestational age.

BACKGROUND: Children with perinatal chronic lung disease (CLD) are at elevated risk for severe respiratory syncytial virus (RSV) disease in the first two years of life. The American Academy of Pediatrics policy does not recommend RSV immunoprophylaxis for infants with CLD born at ≥32 weeks' gestational age (wGA). The objective of this study was to describe the number and clinical characteristics of US infants in this population. METHODS: Birth hospitalization data from the Kids' Inpatient Database were utilized to estimate the prevalence of CLD (International Classification of Diseases, Ninth Revision [ICD-9] = 770.7) in 2003-2012 overall and by gestational age (ICD-9 = 765.21-765.29). CLD birth hospitalizations were evaluated by length of stay, costs, ventilatory support, and inpatient mortality. RESULTS: A total of 33,537 infants were diagnosed with CLD, representing 0.2% of US births; 79% had wGA coded in the database. Among infants with CLD with wGA, 3.5% were born at >32 wGA, representing 7 of every 100,000 US births, or approximately 300 infants annually. Across all wGA categories, birth hospitalization length of stay and costs were elevated, and mechanical ventilation use ranged from 73% to 97%. All-cause inpatient mortality was highest among those <27 wGA and >32 wGA. CONCLUSIONS: Approximately 300 infants born at >32 wGA are diagnosed with CLD annually in the United States. The all-cause perinatal mortality rate is high in this population. The rationale for excluding this small but high-risk group of infants from the recommendations for RSV immunoprophylaxis is unclear.

Standard methods based on last menstrual period dates misclassify and overestimate US preterm births.

OBJECTIVE: To compare number of US preterm births based on obstetric versus last menstrual period (LMP) estimates and evaluate their correlations with clinical risk indicators associated with prematurity. STUDY DESIGN: Preterm births were assessed from LMP, per standard practice, and, separately, from obstetric estimates using the 2012 Natality Public Use File. Percentages of infants with neonatal intensive care unit (NICU) admission and low birth weight (LBW) were calculated. RESULT: More births were <37 weeks gestational age (GA) by reported LMP (11.4%) versus obstetric estimates (9.5%). Among infants preterm by LMP, but born at 37-41 weeks by obstetric estimates, there were 5.7% NICU admission and 7.7% LBW rates versus 25.2% and 35.4%, respectively, of those preterm by obstetric estimates but born 37-41 weeks by LMP assessments. CONCLUSION: Obstetric estimates provide the most clinically relevant estimates of US preterm births. Assessments calculated from LMP alone may overestimate prematurity incidence by ~20%.

The healthcare and societal burden associated with influenza in vaccinated and unvaccinated European and Israeli children.

Few data exist regarding the healthcare and societal burden of culture-confirmed influenza illness in European and Israeli children. The current analysis describes this burden in vaccinated and unvaccinated children 2-17 years of age. Healthcare and societal burden outcomes were prospectively collected for culture-confirmed influenza illness in three previous randomized studies: a study of live attenuated influenza vaccine (LAIV) versus placebo in children aged <48 months attending day care (N = 846-973), and studies of LAIV versus inactivated influenza vaccine (IIV) in children aged <72 months with recurrent respiratory infections (N = 1,609) and in children aged 6-17 years with asthma (N = 2,211). The incidence of each endpoint among enrolled subjects and subjects with influenza was determined by treatment group and by country. Among subjects with influenza, 57-91% missed school or day care, 45-90% used non-antibiotic medications, 29-55% of parents missed work, 17-55% used antibiotics, 11-62% had additional provider visits, and 9-20% had acute otitis media. Where evaluated, rates of outcomes were generally similar between countries. Among all children enrolled, LAIV recipients missed 324-902 and 150 fewer days of day care per 1,000 children than those of placebo and IIV recipients, respectively; parents of LAIV recipients missed 197-340 and 76 fewer days of work per 1,000 children than those of placebo and IIV recipients, respectively. Influenza illness in European and Israeli children 2-17 years of age resulted in a considerable absenteeism and healthcare utilization that was similar across the countries studied. These data underscore the potential benefits of annual vaccination of children against influenza.

The test-negative design: validity, accuracy and precision of vaccine efficacy estimates compared to the gold standard of randomised placebo-controlled clinical trials.

The test-negative design (TND) is an efficient form of case-control study commonly applied to influenza vaccine effectiveness (VE) estimation. TND validity is predicated on the core assumption that the intervention (vaccine) has no effect on other non-targeted aetiologies resulting in similar illness/disease. Here we verify this core assumption and compare efficacy estimates derived by the TND versus classical per-protocol analysis of four datasets obtained from randomised placebo-controlled clinical trials (RCT) of the live attenuated influenza vaccine (LAIV) in children ≤7 years-old and the elderly ≥60 years-old. We further assess generalisability of the TND approach in two other RCT datasets to evaluate monoclonal antibody in the prevention of respiratory syncytial virus (RSV) hospitalisation. Efficacy estimates and their confidence intervals were virtually identical for per-protocol RCT versus TND analyses of LAIV and also for RSV monoclonal antibody. Neither LAIV nor monoclonal antibodies affected the risk of disease aetiologies that were not specifically targeted by the respective interventions (e.g. other respiratory viruses). This study validates the core assumption of the TND approach for influenza vaccine efficacy estimation and confirms the accuracy and precision of its estimates compared to the gold standard of classic per-protocol RCT analysis of the same data sets. The TND approach is generalisable for other conditions such as RSV for which the core assumption is also met. However, when used in observational studies, the TND, like all designs, still requires assessment for bias and confounding that may exist in the absence of randomised participation and blinded follow-up.

The safety and efficacy of live attenuated influenza vaccine in young children with asthma or prior wheezing.

In the European Union and Canada, an Ann Arbor strain live attenuated influenza vaccine (LAIV) is approved for use in children aged 2-17 years, including those with mild to moderate asthma or prior wheezing. The safety and efficacy of LAIV versus trivalent inactivated influenza vaccine (TIV) in children with asthma aged 6-17 years have been demonstrated. However, few data are available for children younger than 6 years of age with asthma or prior wheezing. Safety and efficacy data were collected for children aged 2-5 years with asthma or prior wheezing from two randomized, multinational trials of LAIV and TIV (N = 1,940). Wheezing, lower respiratory illness, and hospitalization were not significantly increased among children receiving LAIV compared with TIV. Increased upper respiratory symptoms and irritability were observed among LAIV recipients (p < 0.05). Relative efficacies were consistent with the results observed in the overall study populations, which demonstrated fewer cases of culture-confirmed influenza illness in LAIV compared with TIV recipients. Study results support the safety and efficacy of LAIV among children aged 2-17 years with mild to moderate asthma or a history of wheezing. Data regarding LAIV use are limited among individuals with severe asthma or active wheezing within the 7 days before vaccination.