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Word count: 3490At a Glance Commentary: Scientific Knowledge on the Subject: Ambient fine particulate matter (PM2.5) exposure in utero has been associated with the development of childhood asthma. However, little is known regarding the impact of ambient ultrafine particles (<0.1 μm) (UFPs) on childhood asthma development What this Study Adds to the Field: Our findings suggest that UFPs exposure during the second trimester of pregnancy was associated with an increased risk of developing asthma in children before age 6 independent of other air pollutants including NO2 and PM2.5. These findings highlight the need for further research on the effects of UFPs during the perinatal period on respiratory health in children. Online Data Supplement: This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournls.org 1 ABSTRACT Rationale: Little is known regarding the impact of ambient ultrafine particles (<0.1 μm) (UFPs) on childhood asthma development. Objective: To examine the association between prenatal and early postnatal life exposure to UFPs and development of childhood asthma. Methods: A total of 160,641 singleton live births occurring in the City of Toronto, Canada between April 1 st 2006and March 31 st 2012 were identified from a birth registry. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6) were estimated using random-effects Cox proportional hazards models, adjusting for personal-and neighborhood-level covariates. We investigated both single-and multi-pollutant models accounting for co-exposures to PM2.5 and NO2. Measurements and Main Results: We identified 27,062 children with incident asthma diagnosis during the follow-up. In adjusted models, second trimester exposure to UFPs (Hazard Ratio (HR) per interquartile (IQR) increase = 1.09, 95% CI: 1.06 -1.12) was associated with asthma incidence. In models additionally adjusted for PM2.5 and NO2, UFPs exposure during the second trimester of pregnancy remained positively associated with childhood asthma incidence (HR per IQR increase = 1.05, 95% CI: 1.01 -1.09). Conclusion: This is the first study to evaluate the association between perinatal exposure to UFPs and the incidence of childhood asthma. Exposure to UFPs during a critical period of lung development was linked to the onset of asthma in children, independent of PM2.5 and NO2. Abstract word count: 229

Objective To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood. Design Retrospective cohort study. Setting Population based birth registry linked with health administrative databases in the province of Ontario, Canada. Participants All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes. Main outcome measures Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding. Results Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups. Conclusions No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.

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