The shifting demographics of birth-related brachial plexus injury: The impact of socio-economic status and ethnic groups.

INTRODUCTION: Many of the risk factors for birth-related brachial plexus injury (BRBPI), such as maternal gestational diabetes and macrosomia, are known to vary between demographic groups. Socio-economic differences are known to influence access to healthcare, including elective caesarean section rates and access to consultant obstetricians, which could impact the rates of BRBPI. This study aims to explore whether BRBPI is affected by demographic factors. METHOD: This retrospective study compares cohorts of BRBPI patients referred to the Royal National Orthopaedic Hospital in 2004, 2014 and 2017. N = 67 in 2004, N = 61 in 2014 and N = 71 in 2017. RESULTS: The risk of BRBPI for Black patients was 6 times higher than for White patients, and 2.7 times higher for Asian patients as compared to White patients (p < 0.001). There was an unequal distribution of BRBPI occurring in patients from lower socio-economic groups based on the index of multiple deprivation, with the highest level seen in those from the second lowest quintile. Neither of these risk factors have changed within the three years that they were examined. CONCLUSION: In this sample, the risk of BRBPI varies with ethnic groups; patients from non-White backgrounds are at a higher risk overall and are disproportionately represented in the BRBPI cohort as compared to White groups. Similarly, there seems to be a trend towards greater risk for those from lower socio-economic groups. These changes are consistent each year, suggesting that these inconsistencies are yet to be addressed. Further studies are warranted to explore why these demographic factors are significantly affecting health outcomes.

Timing of proteasome inhibition as a pharmacologic strategy for prevention of muscle contractures in neonatal brachial plexus injury.

Neonatal brachial plexus injury (NBPI) causes disabling and incurable contractures, or limb stiffness, which result from proteasome-mediated protein degradation impairing the longitudinal growth of neonatally denervated muscles. We recently showed in a mouse model that the 20S proteasome inhibitor, bortezomib, prevents contractures after NBPI. Given that contractures uniquely follow neonatal denervation, the current study tests the hypothesis that proteasome inhibition during a finite window of neonatal development can prevent long-term contracture development. Following neonatal forelimb denervation in P5 mice, we first outlined the minimum period for proteasome inhibition to prevent contractures 4 weeks post-NBPI by treating mice with saline or bortezomib for varying durations between P8 and P32. We then compared the ability of varying durations of longer-term proteasome inhibition to prevent contractures at 8 and 12 weeks post-NBPI. Our findings revealed that proteasome inhibition can be delayed 3-4 days after denervation but is required throughout skeletal growth to prevent contractures long term. Furthermore, proteasome inhibition becomes less effective in preventing contractures beyond the neonatal period. These therapeutic effects are primarily associated with bortezomib-induced attenuation of 20S proteasome ß1 subunit activity. Our collective results, therefore, demonstrate that temporary neonatal proteasome inhibition is not a viable strategy for preventing contractures long term. Instead, neonatal denervation causes a permanent longitudinal growth deficiency that must be continuously ameliorated during skeletal growth. Additional mechanisms must be explored to minimize the necessary period of proteasome inhibition and reduce the risk of toxicity from long-term treatment.