Early indicators of child obesity to aid future clinical trials for lifecycle obesity prevention

Background

39M children worldwide are overweight or have obesity, accelerating risk for adult non-communicable diseases. Presently, interventions to prevent obesity have had limited success due to poor timing and lack of personalisation.

Objective

We aimed to identify early-life predictors of childhood obesity (ChOB) that could aid targeting specific population subsets for obesity prevention interventional studies.

Methods:

Data were from the Raine Study Gen2 participants (n=1494). Anthropometric and genetic predictors evaluated included birthweight (BW), early-life BMI (1-3 years), and three polygenic scores (PGS) [two BW-PGSs (BW-PGS ₂₀₁₆ and BW-PGS ₂₀₁₉ ) and a ChOB-PGS], developed from BW and ChOB genome-wide-association-studies, respectively. Multivariate analyses were performed to investigate associations between predictors and child-BMI (5-, 8- , 10-years).

Results:

BW-PGS ₂₀₁₉ associate with child-BMI at 5-years. BW-PGS ₂₀₁₆ was not associated with child-BMI. Remaining predictors positively associate with child-BMI at 5-, 8- and 10-years (p<0.001). Early-life BMI, ChOB-PGS and BW accounted for up to 38.7%, 5.8% and 3.4% of the variability in child-BMI, respectively.

Conclusions

Our data suggest early-life BMI is a better predictor of child-BMI than ChOB-PGS, and BW, accounting for up to ten-fold more variance in child-BMI. Future interventional studies to mitigate obesity could target early-life BMI as a marker to identify children at the highest risk.

Practitioner Points (up to 3 key points)

1. Birthweight is associated with later-life obesity, but it is a variable predictive marker. Polygenic scores (PGS) provide additional insight into obesity and overweight risk in adulthood. Little is known about other predictors that could provide insight into the risk of later-life obesity.

2. Early-life BMI (before 3-years of age) predicts childhood obesity better than genetic and birthweight markers, accounting for more variance. Interventions to prevent obesity could now be more appropriately targeted.

3. Early-life BMI is a better predictor of child BMI than birthweight or childhood obesity PGS, which could aid obesity risk-stratification and ensure interventions to prevent obesity are targeted to children who will most benefit.