not-yet-known not-yet-known not-yet-known unknown Aim: To establish whether the initial positive effect of nusinersen (NUS) on respiratory outcomes in the first year of treatment was maintained in children with Spinal Muscular Atrophy (SMA) type 2 and to further define the effect on children with type 3 treated over 3 years. Methods: A prospective observational study of children with type 2 and 3 beginning NUS in Queensland, Australia between June 2018 – December 2020 was undertaken. Investigations conducted included age-appropriate lung function and polysomnography. Lung function data for two-years preceding NUS initiation was retrospectively collected. Change in lung function/polysomnography was assessed using mixed effects linear regression. Results: 24 of 30 children with type 2 and 3 SMA (14 males; 0.4-17.3 years) were included (type 2 n=12; type 3 n=12). No child had respiratory-related admissions during the period of study. For type 2, annual decline in FVC z-score pre-treatment was -0.75 (95% CI: -1.14, -0.39, p<0.001), and for the first 3 years on NUS was -0.20 ([95% CI: -0.33, -0.06, p=0.01] difference p=0.008). For type 3 minimal change was seen: pre-NUS and post FVC z-scores -0.20 (95% CI: -1.00, 0.61 p=0.05) and -0.46 (95% CI:-0.88, -0.04 p=0.40) respectively (difference p=0.46). Mean change in total apnoea-hypopnoea indices (total AHI) in type 2 tended to reduce -1.75 (95% CI: -4.95-0.9, p=0.24); type 3 appeared to remain stable (-0.39 [95% CI: -1.1-0.33, p=0.28). One child with type 2 ceased NIV due to normalisation of total AHI and gas exchange. Conclusion: Nusinersen lung function (FVC-z-scores) stability seen in the first year was maintained over 3 years and the total AHI tended to improve in type 2, but the long-term effects in type 3 are less clear.

Objective: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2-years of life, RSV-NA at 3-years, and respiratory health to age 5-years. Methods: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord-blood and at age 3-years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5-years and physician-diagnosed asthma at 5-years was collected by parent report. Results: In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio (aIRR) 0.63; 95% confidence interval (CI): 0.40–1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95%CI: 0.25–1.02) of RSV acute lower respiratory infections (ALRI) at 12–24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95%CI: 0.99–1.69), wheeze-associated ALRI (aIRR 1.75; 95%CI: 1.08–2.82) and severe ALRI (aIRR 2.76; 95%CI: 1.63–4.70) at age 6–<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3-years, or wheeze or asthma at 5-years. Conclusions: Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5-years of life. Additional strategies to control RSV-related illness in childhood are needed.