Effects of a non-nutritive sweetener restriction intervention during pregnancy and lactation on eating behavior, dietary intake, and growth from birth to 24 months - ABSTRACT A growing body of research indicates that weight gain is “programmed” during early development and conditions in utero, such as suboptimal maternal nutrition, contribute to development of obesity in infancy and childhood. One potential contributor to poor maternal nutrition is intake of non-nutritive sweeteners (NNS). Approximately 30% of pregnant women and 44% of lactating mothers in the United States report NNS intake on a given day, and infants are exposed to NNS in utero and during lactation. While effects of NNS intake during pregnancy and lactation on infants’ diet, weight, and health are not well understood, the available evidence suggests cause for concern. For example, NNS intake blunts satiety, increases appetite, increases sweet taste preference, increases energy intake, and promotes excess weight gain in rodents -- all of which increase the risk for obesity. Further, prospective cohort studies demonstrate NNS intake during pregnancy is associated with adverse infant outcomes such as macrosomia, large-for-gestational-age (LGA) status at birth, and higher body mass index (BMI z-scores) during infancy and childhood. However, effects of maternal NNS consumption on development of eating behaviors, sweet taste preferences, added sugar intake, and weight- for-length z-score (WLZ) during infancy have not been experimentally tested in humans, and continued reliance on observational data is a key challenge to advancing the rapidly evolving NNS field. We therefore propose to conduct the first randomized controlled trial (RCT) in humans to examine effects of NNS intake during pregnancy and lactation on the development eating of behaviors, sweet taste preferences, added sugar intake, and weight-for-length z-score from birth to 2 years. We will leverage “SweetPea” (R01HD107427, PI: Sylvetsky, 03/01/2024-02/28/2029), a three-arm randomized controlled trial (planned n=324) examining effects of NNS intake on maternal glucose tolerance during pregnancy and infant fat mass at 1 and 6 months of age. The proposed study (hereafter “SweetPea-Toddler”) will follow a subset of infants (n=220) in SweetPea until age 24 months to examine effects of maternal NNS intake during pregnancy and/or lactation on infants’ eating behaviors, sweet taste preferences, added sugar intake, and WLZ into early childhood. Our primary aims are to determine effects of maternal NNS intake during pregnancy and/or lactation on infants’: 1) eating in the absence of hunger (EAH) and the relative reinforcing value (RRV) of sweet food 2) sweet taste preferences and added sugar intake; and, 3) WLZ at ages 12 and 24 months. We hypothesize that NNS intake during pregnancy and/or lactation will increase EAH and the RRV of sweet food, increase sweet taste preference, increase added sugar intake, and increase WLZ at ages 12 and 24 months. This research will advance understanding of developmental programming of obesity and aligns with national priorities related to reversing the childhood chronic disease crisis and focus on additives in ultra-processed foods.