Do non-nutritive sweeteners affect the metabolic health of infants and children? A systematic review of randomized controlled trials and prospective cohort studies
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Background: Non-nutritive sweeteners (NNS) have recently gained enormous popularity due to their perceived health benefits in weight loss and management; however, their long-term impact on human health is unknown, particularly when exposure occurs during early development. We conducted a systematic review of prospective cohort studies and randomized controlled trials (RCTs) to evaluate the association between NNS exposure in the prenatal period, infancy and childhood (age < 12 years) and metabolic health outcomes. Methods: A comprehensive peer-reviewed search strategy was used to search the Medline (OVID) database from inception to December 2014. Citations were screened in duplicate to identify RCTs and prospective cohort studies evaluating metabolic outcomes after NNS exposure during gestation or childhood. The primary outcomes were change in weight-for-length (WFL) z-score in infants and change in body mass index (BMI) z-score in children; secondary outcomes included growth velocity, birth weight, incidence of overweight/obesity, change in central and total adiposity, and incidence of adverse metabolic effects. Results: From 4591 citations reviewed, 12 studies met our inclusion criteria; 3 RCTs and 9 prospective cohort studies (total n = 83,426 participants). Studies were heterogeneous in the type and duration of NNS exposure and outcomes reported. Two of the nine prospective cohort studies identified significant associations between NNS exposure and increase in BMI or fat mass in children, yet six studies reported no association. Two RCTs evaluated NNS exposure in children and found significant but contradictory associations with weight gain. In two prenatal studies, NNS exposure was not associated with infant birth weight; however, no subsequent metabolic outcomes were evaluated. No studies reported on incidence of metabolic syndrome, insulin resistance, or type 2 diabetes mellitus. Conclusions: There is limited and inconsistent evidence for the metabolic effects of early-life NNS exposure. Further research is required to fully understand the impact of NNS exposure during gestation, infancy, and childhood.