A recent study published in the American Journal of Ophthalmology evaluated the impact of early life body size trajectories on the risk of developing primary open-angle glaucoma (POAG).
Give me some background.
Body mass index (BMI) has been proposed as a factor associated with POAG—though existing findings are complex and inconsistent.
- For example: Previous studies have demonstrated that a lower BMI is associated with an increased risk of POAG, a larger vertical cup-to-disc ratio, and more rapid progression of glaucomatous optic nerve damage and visual field loss.
However: Other studies have suggested that individuals with higher BMI are also at an elevated risk of developing POAG.
Anything else?
While numerous studies have explored the association between BMI and the risk of POAG, most have focused on BMI at a single time point, which may overlook the longitudinal BMI trajectory in early life.
Given the increasing global burden of POAG (as well as obesity), elucidating these associations holds significant public health implications for the development of targeted screening and prevention strategies.
Now talk about the study.
In this retrospective cohort study, investigators included 467,768 participants from the UK Biobank and organized them into nine distinct early life body size trajectories from childhood to adulthood:
- Low-low
- Low-average
- Low-high
- Average-low
- Average-average
- Average-high
- High-low
- High-average
- High-high
Note: Body size in childhood was determined via patient questionnaires and constructed in comparison with peers.
Go on …
As the majority of UK Biobank participants fell within the overweight category of BMI according to the World Health Organization (WHO) classification (BMI ≥ 25), using the WHO standard resulted in unbalanced group sizes and uneven distribution of health outcomes.
So: Adult body size was classified using a methodology from previous studies of sex-stratified regression models of BMI on age and age squared by sex.
Findings?
Individuals whose trajectories ended in low adult body size had an elevated POAG risk compared to the average-average trajectory (after adjusting for all covariates):
- Low-low (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.17-1.55, P < 0.001)
- Average-low (HR: 1.35, 95% CI: 1.18-1.53, P < 0.001)
- High-low (HR: 1.49, 95% CI: 1.17-1.91, P = 0.001)
And, interestingly …
Individuals with a low body size in adulthood consistently demonstrated an elevated risk of POAG compared to those with an average body size (HR: 1.30, 95% CI: 1.19-1.43, P < 0.001).
- Conversely: A high body size was associated with differing effects in childhood (HR: 1.14, 95% CI: 1.00-1.29, P = 0.046) and adulthood (HR: 0.86, 95% CI: 0.75-0.99, P = 0.037).
Anything else?
In the stratified analyses based on child body sizes, participants with a low child body size who attained an average (HR: 0.79, 95% CI: 0.68-0.93, P = 0.004) or high (HR: 0.58, 95% CI: 0.44-0.77, P < 0.001) weight in adulthood had reduced POAG risk.
Among individuals with high child body size, substantial weight loss to low body size in adulthood increased the risk of POAG (HR: 1.66, 95% CI: 1.19-2.32, P = 0.003), while moderate weight loss showed no significant risk.
Expert opinion?
The study authors noted that the results of this study hold substantial implications for clinical practice and public health strategies around POAG, including:
- For individuals with a low body size during childhood: Promoting appropriate weight gain to achieve an average or above-average body size in adulthood may contribute to a reduction in the risk of POAG.
- Nutritional interventions targeting underweight children exhibit potential long-term benefits for ocular health.
- Among individuals with an average body size during childhood: Maintaining weight stability throughout adulthood appears to be optimal.
- In individuals with high childhood body size: A moderate reduction to an average adult body size did not significantly increase the risk of POAG.
- In fact: Substantial weight loss resulting in a low adult body size markedly elevated this risk.
Limitations?
These included:
- Relying on retrospectively self-reported childhood body measurements introduces potential recall bias
- An absence of intermediate measurements between childhood and adulthood prevented them for capturing potentially significant body size fluctuations
- The study’s reliance on International Classification of Diseases (ICD) codes from the UK Biobank to identify POAG cases primarily captured severe instances, potentially overlooking milder POAG diagnoses.
- The UK Biobank cohort is subject to a “healthy volunteer” selection bias
Take home.
These findings demonstrate that low adult body size was consistently associated with an increased risk of POAG, emphasizing the importance of avoiding excessive weight loss in early life, which may be critical to reducing the burden of POAG.
As such: Personalized weight management strategies throughout early life and maintaining an adequate body size in adulthood are crucial to prevent the development of POAG.