The UK has the 4th highest rate of alcohol use in pregnancy worldwide. Alcohol exposure in pregnancy (prenatal alcohol exposure - PAE) can lead to a set of lifelong disabilities known as foetal alcohol spectrum disorder (FASD) - a neurodevelopmental disorder associated with over 400 comorbidities. In the UK, FASD affects an estimated 2–4% of schoolchildren, and 27% of children in care. FASD therefore presents a significant healthcare burden, estimated to be up to £152million. Young adults with FASD refer to it as a ‘whole body diagnosis’. However, with the exception of facial dysmorphia and growth deficiency, there is a paucity of evidence on the physical impacts of FASD, particularly beyond childhood.
Emerging evidence from small cross-sectional studies and non-representative surveys indicate indicate elevated rates of bone abnormalities and musculoskeletal conditions among young adults with PAE and FASD.. However, tTherefore, there is a critical need for longitudinal data to delineate the causal relationship between PAE and musculoskeletal health, including potential sexually dimorphic effects. This will offer important insights into mechanisms and potential opportunities for intervention, with. It is particularly important to examine any sex differences as these are currently under-researched in adults with PAE, and this could have important implications on for lifelong musculoskeletal health.
Using a mouse model, we recently found that PAE indeed has a sex-dependent effect on the skeleton. In adult males, PAE had a detrimental effect on bone volume and strength compared to controls. However female mice were protected. Moreover, these differences were not present in young mice, indicating the potential influence of environmental factors.
One such factor may be mechanical loading, which is known to exert beneficial effects on the skeleton through a process termed mechanoadaptation. This process is intimately linked to the bone vasculature, which we have shown to develop in a sex-dependent manner. Further, with PAE we found a reduction in the expression of genes related to blood vessel formation (e.g. VEGF) predominantly in male mice.
Therefore, it is currently unknown whether there are sex-differences in bone health in individuals with PAE, what the underlying mechanisms are, and what impacts these might have on physical functioning and health-service use.
Approach
Our proposal is at the interface of life and clinical sciences and, using ALSPAC data, will address the objective:

- Determine whether humans with PAE exhibit overall and sex-specific adverse impacts on musculoskeletal health and motor functioning and, if so, the extent to which this is mediated by bone composition

Benefits

This research will investigate the overall and sex-specific impacts of PAE on musculoskeletal health, aiming to inform targeted therapies and public health policies. By elucidating underlying mechanisms, it can improve FASD diagnosis and treatment, benefiting stakeholders including clinicians, researchers, policymakers, charities, and individuals with FASD.