No abstract

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 NNSbased 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.

No abstract

Nephronophthisis (NPHP) is a pediatric form of hereditary polycystic kidney disease (PKD), and is the leading cause of end stage renal disease in children. The pcy mouse is an orthologous model of human NPHP, with a mutation in the Nphp3 gene. Renal phospholipase A2, cyclooxygenase (COX) 1 and cyclic AMP are elevated in this model, suggesting that eicosanoid formation may be altered. In another type of PKD observed in the Han:SPRD-Cy rat, inhibition of eicosanoid production slows disease progression. If renal eicosanoids are similarly altered in NPHP, potential for pharmacologic intervention also may exist for this disorder. Therefore, renal fatty acids and eicosanoids were determined in pcy and normal mice at 15, 30 and 60 days of age by gas chromatography and HPLC-tandem mass spectrometry, respectively. Renal cysts in enlarged kidneys were observed in pcy mice by 15 days of age and increased over time. Renal phospholipid ARA levels were higher in pcy compared to normal mice at 15 and 30 days. Eicosanoid differences were observed starting at 30 days, when the COX products 6-keto-prostaglandin (PG) F1α, thromboxane B2 and PGE2 were higher in pcy compared to normal kidneys. Overall, total COX products were elevated at 30 and 60 days. In contrast, the levels of the lipoxygenase (LOX) products were not altered until 60 days of age and these were lower in pcy kidneys compared to normal. These findings suggest that altered eicosanoids play a role in NPHP, and that manipulating these levels with pharmacologic agents may have therapeutic potential.

No abstract

No abstract