Metabolic and behavioural effects of prenatal exposure to non-nutritive sweeteners: A systematic review and meta-analysis of rodent models.

Little is known about possible effects of maternal non-nutritive sweetener (NNS) consumption on the metabolic health of a child. Animal models of maternal NNS consumption during pregnancy or weaning have yielded widely varying results, and there appears to be no clear consensus on the consequences for offspring body weight, glycaemic control or sweet preference choices. Moreover, heterogeneity in study design has hampered a clear focus for future research relevant to human health. In an effort to bring clarity, we have conducted a systematic review and meta-analysis (protocol no: CRD42018109509) in animal models (rat or mouse) of maternal NNS feeding (compared to water or basal diet) during pre-gestation, pregnancy or lactation. Four databases were searched from inception to 15th September 2018: PubMed, EMBASE, SCOPUS and Web of Science. We present maternal and offspring data from 24 included studies, which have been quantitatively analysed after study quality assessment, to identify relationships between maternal diet and offspring body weight (BW), feeding behaviour and glycaemic control. In 11 data sets, exposure to NNS reduced maternal BW during pregnancy, with no effect on litter outcomes. Meta-analyses on offspring BW during weaning (1123 offspring) and adulthood (646 offspring) identified small decreases in BW for both sexes. Subgroup analyses revealed reductions in BW of rat, but not mouse models. High dosage appears to be a potential factor for reduced palatability that could influence BW results; however, a lack of reported data limited our ability to confirm. Despite this, and the fact many papers were predisposed to bias, the balance of evidence suggests a maternal NNS diet during pregnancy or lactation did not increase the body weight in offspring.