Effects of a non-nutritive sweetener reduction intervention in pregnancy and lactation on maternal and infant outcomes (the SWEETPEA trial) - ABSTRACT Increasing evidence demonstrates that suboptimal conditions in the womb, including poor maternal nutrition, contributes to obesity and cardiometabolic disease risk. One potential contributor to poor maternal nutrition is chronic consumption of non-nutritive sweeteners (NNS). Studies indicate that approximately 30% of pregnant women and 44% of lactating women in the United States regularly consume NNS. However, a growing body of evidence demonstrates that NNS consumption is paradoxically associated with obesity and metabolic risk factors. While effects of NNS consumption during pregnancy and lactation on maternal and infant metabolic health are not well understood, the available evidence suggests cause for concern. For example, NNS consumption during pregnancy increases maternal blood sugar and induces fetal hypoglycemia and growth restriction in mice – both of which are risk factors for offspring obesity. Further, three prospective cohort studies in humans have reported an association between maternal NNS consumption and childhood weight or adiposity, although another found no relationship. Our own pilot data indicate that NNS consumption during pregnancy increases infant fat mass and disrupts the infant gut microbiome at 1 month of age. However, the limited, contradictory, and observational nature of the human evidence collected to date has made it difficult to establish guidelines around NNS consumption during pregnancy. We therefore propose the first randomized controlled trial (RCT) to examine the effects of NNS during pregnancy and lactation. We will recruit 324 pregnant women who frequently consume NNS (≥7 servings/week) and examine the effects of NNS restriction on maternal and infant metabolic outcomes. Pregnant women will be randomly assigned to one of three groups: 1) no NNS restriction (control); 2) NNS restriction during lactation only; and 3) NNS restriction during pregnancy and lactation. The intervention will consist of monthly consultations with a dietitian to provide counseling on replacement of NNS consumption with unsweetened food and beverage alternatives and home delivery of such alternatives. Adherence will be assessed via 24-hour dietary recalls and by objectively measuring NNS concentrations in urine and breast milk. Our primary aims will be to determine the effects of NNS-restriction on: 1) infant body composition at 1 and 6 months of age; 2) maternal glucose tolerance at 24-28 weeks’ gestation; and, 3) infant gut microbiome and fecal metabolites at 1 and 6 months of age. We hypothesize that NNS restriction among pregnant women who habitually consume NNS during pregnancy and/or lactation will reduce infant fat mass (compared to a no NNS restriction (usual NNS intake) control group), via improvements to maternal glycemia and the infant gut microbiome and metabolome, with the greatest benefit in the pregnancy and lactation group. This research could shape recommendations around NNS consumption during pregnancy and lactation, thereby potentially reducing the global burden of obesity and cardiometabolic disease.
