title: Early Exposure to Nonnutritive Sweeteners and Long-term Metabolic Health: A Systematic Review.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Medline, Embase, and Cochrane Library (inception to July 2015).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Medicine.
authors.forename: Ashleigh E
authors.initials: AE
authors.lastname: Reid
authors.affiliation: George & Fay Yee Center for Healthcare Innovation, College of Pharmacy, Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada; and.
authors.forename: Bhupendrasinh F
authors.initials: BF
authors.lastname: Chauhan
authors.affiliation: George & Fay Yee Center for Healthcare Innovation.
authors.forename: Rasheda
authors.initials: R
authors.lastname: Rabbani
authors.affiliation: George & Fay Yee Center for Healthcare Innovation.
authors.forename: Justin
authors.initials: J
authors.lastname: Lys
authors.affiliation: George & Fay Yee Center for Healthcare Innovation.
authors.forename: Leslie
authors.initials: L
authors.lastname: Copstein
authors.affiliation: George & Fay Yee Center for Healthcare Innovation.
authors.forename: Amrinder
authors.initials: A
authors.lastname: Mann
authors.affiliation: George & Fay Yee Center for Healthcare Innovation.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abou-Setta
authors.affiliation: George & Fay Yee Center for Healthcare Innovation.
authors.forename: Michelle
authors.initials: M
authors.lastname: Fiander
authors.affiliation: Departments of Human Nutritional Sciences.
authors.forename: Dylan S
authors.initials: DS
authors.lastname: MacKay
authors.affiliation: Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada; and Pediatrics and Child Health, and Manitoba Developmental Origins of Chronic Diseases in Children Network.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McGavock
authors.affiliation: Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada; and Pediatrics and Child Health, and Manitoba Developmental Origins of Chronic Diseases in Children Network.
authors.forename: Brandy
authors.initials: B
authors.lastname: Wicklow
authors.affiliation: George & Fay Yee Center for Healthcare Innovation, Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;
authors.forename: Ryan
authors.initials: R
authors.lastname: Zarychanski
authors.affiliation: George & Fay Yee Center for Healthcare Innovation, Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada; and Pediatrics and Child Health, and Manitoba Developmental Origins of Chronic Diseases in Children Network meghan.azad@umanitoba.ca.
authors.forename: Meghan B
authors.initials: MB
authors.lastname: Azad
mesh_terms: D002648:Child; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D006304:Health Status; D006801:Humans; D015994:Incidence; D064306:Non-Nutritive Sweeteners / Q000009:adverse effects*; D009765:Obesity / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D064306:Non-Nutritive Sweeteners