Early Exposure to Nonnutritive Sweeteners and Long-term Metabolic Health: A Systematic Review

CONTEXT: Nonnutritive sweetener (NNS) consumption is increasing among children, yet its long-term health impact is unclear, particularly when exposure occurs during early life. OBJECTIVE: To synthesize evidence from prospective studies evaluating the association of early-life NNS exposure and long-term metabolic health. DATA SOURCES: Medline, Embase, and Cochrane Library (inception to July 2015). STUDY SELECTION: We aimed to include randomized controlled trials (RCTs) evaluating NNS-based interventions and prospective cohort studies reporting NNS exposure among pregnant women, infants, or children (<12 years of age), with a minimum study duration of 6 months. DATA EXTRACTION: The primary outcome was BMI; secondary outcomes included growth velocity, overweight/obesity, adiposity, and adverse metabolic effects. Study quality and risk of bias were evaluated using validated assessment tools. RESULTS: We identified 6 eligible cohort studies and 2 RCTs (n = 15 641 children). Half of the cohorts reported increasing weight gain or fat mass accumulation with increasing NNS intake, and pooled data from 2 cohorts showed a significant correlation with BMI gain (weighted mean correlation 0.023, 95% confidence interval 0.006 to 0.041). RCTs reported contradictory effects on weight change in children receiving NNSs. No eligible studies evaluated prenatal or infant NNS exposure. LIMITATIONS: Meta-analysis was limited because of the small number of eligible studies and heterogeneity of populations and outcomes. CONCLUSIONS: There is limited and inconsistent evidence of the long-term metabolic effects of NNS exposure during gestation, infancy, and childhood. Further research is needed to inform recommendations for the use of NNSs in this sensitive population.