Effects of a Non-nutritive Sweetener Reduction Intervention in Pregnancy and Lactation on Maternal and Infant Outcomes

Effects of a Non-nutritive Sweetener Reduction Intervention in Pregnancy and Lactation on Maternal and Infant Outcomes (the SweetPea Trial)

The effects of consuming non-nutritive sweeteners (NNS) during pregnancy and lactation on infant obesity and cardiometabolic disease risk are not well understood. In this project, pregnant women who frequently consume NNS will be randomly assigned to an NNS-restriction intervention (NNS restriction during pregnancy and lactation or during lactation only) or a control group (no NNS restriction) to determine whether NNS consumption during pregnancy and/or lactation affects infant body composition, maternal blood sugar during pregnancy, and the infants' gut microbiome and metabolome. The results of this study have the potential to shape recommendations around NNS consumption during pregnancy and lactation, thereby potentially improving maternal and infant metabolic health and reducing the global burden of obesity and cardiometabolic disease.

Study Overview

• Status: Recruiting
• Conditions: Gestational Diabetes Mellitus in Pregnancy; Glucose Intolerance During Pregnancy; Non-nutritive Sweeteners Consumption in Pregnancy and/or Lactation
• Intervention / Treatment: Behavioral: Control Intervention; Behavioral: NNS Restriction Intervention

• Study Type: Interventional
• Enrollment (Estimated): 324
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Allison C Sylvetsky, PhD; Phone Number: 202-994-5602; Email: asylvets@gwu.edu

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • Recruiting
      • The George Washington University
      • Contact: Allison C Sylvetsky, PhD; Phone Number: 202-994-5602; Email: asylvets@gwu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant
• ≤ 16 weeks gestation
• Singleton pregnancy
• Report frequent NNS beverage consumption (≥ 7 servings/week)
• 18-45 years of age
• Able to read English at a 5th grade level; and
• Intend to breastfeed for at least the first 6 months of life.
• For infants: The mother must be enrolled and provide assent for the infant to participate.

Exclusion Criteria:

• Physical or mental concerns preventing study participation;
• Medication (e.g., metformin; GLP-1 agonists) use that may affect body weight, body composition, insulin resistance, or lipid profiles;
• Tobacco or drug use during pregnancy;
• Alcohol consumption (>1 drink per week) during pregnancy;
• Pre-existing gastrointestinal, inflammatory, or malabsorptive disorders (e.g., - Crohn's disease, ulcerative colitis, inflammatory bowel disease) that may impact NNS absorption or gut microbiota;
• Known suspected/confirmed genetic fetal abnormalities or suspected or known congenital birth defects.
• History of prior gastric bypass surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control (Group 1); Participants in this arm will continue their usual consumption of NNS throughout pregnancy and lactation without any intervention. They will not receive any specific NNS-restriction intervention.	Behavioral: Control Intervention; Counsel about best practices for home safety and babyproofing. Provide a detailed booklet to take home, which will provide information about home safety and baby proofing. Educate about common causes of accidental infant and young child injuries or death. Automated text messages will also be sent to mothers once per week with reminders about home safety, infant safety, and baby proofing.
Active Comparator: NNS Restriction in Lactation (Group 2); Participants in this arm will maintain their usual NNS consumption during pregnancy but will receive an intervention to restrict NNS intake during lactation.	Behavioral: Control Intervention; Counsel about best practices for home safety and babyproofing. Provide a detailed booklet to take home, which will provide information about home safety and baby proofing. Educate about common causes of accidental infant and young child injuries or death. Automated text messages will also be sent to mothers once per week with reminders about home safety, infant safety, and baby proofing.; Behavioral: NNS Restriction Intervention; Discuss current scientific literature surrounding NNS consumption, obesity, and chronic disease and the emerging evidence that consumption in pregnancy/lactation may have unfavorable effects on infants' adiposity and health. Provide detailed handouts, which will include a list of specific foods and beverages containing NNS to avoid during the study and summarize current scientific evidence on the metabolic and health effects of NNS. Emphasize that sugar is not the best alternative to NNS, and that the participant should drink still water, sparkling water, flavored waters with no added sweeteners, or unsweetened tea instead. Bi-weekly shipments of unsweetened beverages of participant's choice to replace usual consumption of NNS containing beverages. Automated text messages will also be sent to mothers once per week with reminders that they should avoid NNS
Active Comparator: NNS Restriction in Pregnancy and Lactation (Group 3); Participants in this arm will receive an intervention to restrict NNS intake both during pregnancy and lactation.	Behavioral: NNS Restriction Intervention; Discuss current scientific literature surrounding NNS consumption, obesity, and chronic disease and the emerging evidence that consumption in pregnancy/lactation may have unfavorable effects on infants' adiposity and health. Provide detailed handouts, which will include a list of specific foods and beverages containing NNS to avoid during the study and summarize current scientific evidence on the metabolic and health effects of NNS. Emphasize that sugar is not the best alternative to NNS, and that the participant should drink still water, sparkling water, flavored waters with no added sweeteners, or unsweetened tea instead. Bi-weekly shipments of unsweetened beverages of participant's choice to replace usual consumption of NNS containing beverages. Automated text messages will also be sent to mothers once per week with reminders that they should avoid NNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infants' adiposity	Determine the impact of restricting usual consumption of non-nutritive sweeteners (NNS) during pregnancy and/or lactation influences infants' adiposity, which is known to be predictive of potential future obesity risk by assess infants' fat mass percent.	At 6 months of age
Mothers' incremental area under glucose response curves	Determine the impact of restricting usual consumption of non-nutritive sweeteners (NNS) during pregnancy on maternal glucose tolerance by assessing the incremental area under the 120 minute glucose response curves.	At 28 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infants' adiposity	Determine the impact of restricting usual consumption of non-nutritive sweeteners (NNS) during pregnancy and/or lactation influences infants' adiposity, which is known to be predictive of potential future obesity risk by assess infants' fat mass percent.	At 1 month of age
Mothers' fasting blood glucose concentration	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy on mothers' metabolic and inflammatory biomarkers by assessing fasting glucose concentrations.	At 28 weeks gestation
Mothers' fasting blood glucose concentration	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy on mothers' metabolic and inflammatory biomarkers by assessing fasting glucose concentrations.	At 1 month postpartum
Mothers' fasting blood glucose concentration	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy on mothers' metabolic and inflammatory biomarkers by assessing fasting glucose concentrations.	At 6 months postpartum
Mothers' 60 minute glucose concentration	Determine the impact of restricting usual consumption of non-nutritive sweeteners (NNS) during pregnancy on maternal glucose tolerance by assessing the blood glucose levels 60 minutes following ingestion of a standard glucose/water mixture	At 28 weeks gestation
Mothers' 120 minute glucose concentration	Determine the impact of restricting usual consumption of non-nutritive sweeteners (NNS) during pregnancy on maternal glucose tolerance by assessing the blood glucose levels 120 minutes following ingestion of a standard glucose/water mixture.	At 28 weeks gestation
Infants' gestational age	Determine gestational age at birth.	At birth
Infants' birthweight	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy and/or lactation on infants' growth by assessing birth weight.	At birth
Infants' birthweight based on gestational age	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy and/or lactation on infants' growth by assessing birth weight for gestational age.	At birth
Infants' age-sex specific percentile	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy and/or lactation on infants' height and weight for age by assessing age-sex specific percentile.	At 1 month of age
Infants' age-sex specific percentile	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy and/or lactation on infants' height and weight for age by assessing age-sex specific percentile.	At 6 months of age
Mothers' insulin sensitivity index	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy on maternal insulin sensitivity by assessing composite whole-body insulin sensitivity index (WBISI).	At 28 weeks gestation
Mothers' assessment of insulin resistance	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy on maternal insulin sensitivity by assessing homeostasis model assessment of insulin resistance (HOMA-IR).	At 28 weeks gestation
Mothers' energy intake	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during lactation on mothers' mean energy intake from dietary recalls during pregnancy.	At 28 weeks gestation
Mothers' energy intake	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during lactation on mothers' mean energy intake from dietary recalls during postpartum.	At 1 month postpartum
Mothers' energy intake	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during lactation on mothers' mean energy intake from dietary recalls during postpartum.	At 6 months postpartum

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infants' gut microbiome composition	Determine the effects of restricting usual consumption of non-nutritive sweeteners (NNS) during pregnancy and/or lactation on the composition of the infant gut microbiome as it changes dramatically over the first few years of life by evaluating relative abundance of Firmicutes, Akkermansia muciniphila, Bifidobacterium, Lactobacillus, Proteobacteria present in stool specimens.	At 1 month of age
Infants' gut microbiome composition	Determine the effects of restricting usual consumption of non-nutritive sweeteners (NNS) during pregnancy and/or lactation on the composition of the infant gut microbiome as it changes dramatically over the first few years of life by evaluating relative abundance of Firmicutes, Akkermansia muciniphila, Bifidobacterium, Lactobacillus, Proteobacteria present in stool specimens.	At 6 months of age
Mothers' gestational weight gain	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy on mothers' total weight gain during pregnancy by assessing maternal gestational weight gain (GWG).	At delivery
Mothers' waist circumference	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during lactation on mothers' adiposity by assessing waist circumference (WC).	At 1 month postpartum
Mothers' waist circumference	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during lactation on mothers' adiposity by assessing waist circumference (WC).	At 6 months postpartum
Mothers' body composition during pregnancy	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy on mothers' body composition by assessing percent body fat.	At 28 weeks gestation
Mothers' C-reactive protein (CRP) concentration	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy and postpartum on mothers' fasting concentration of C-reactive protein (CRP) concentrations.	At 28 weeks gestation
Mothers' C-reactive protein (CRP) concentration	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy and postpartum on mothers' fasting concentration of C-reactive protein (CRP) concentrations.	At 1 month postpartum
Mothers' C-reactive protein (CRP) concentration	Determine effects of restricting usual non-nutritive sweeteners (NNS) consumption during pregnancy and postpartum on mothers' fasting concentration of C-reactive protein (CRP) concentrations.	At 6 months postpartum

Collaborators and Investigators

• Sponsor: George Washington University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Children's National Research Institute; Children's Hospital Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pregnancy; Lactation; Glucose tolerance; Infant fat mass; PeaPod; Non-nutritive sweeteners (NNS); Gestational diabetes (GDM)
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Behavior; Nutritional and Metabolic Diseases; Feeding Behavior; Diabetes, Gestational; Breast Feeding
• Other Study ID Numbers: SweetPea; R01HD107427 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No