Impact of Perinatal Exposure to Non-caloric Sweeteners on Food Preferences and Weight Gain in the First Year of Life

Determination of Perinatal Exposure to Non-caloric Sweeteners. Implications for the Development of Preferences for Sweet Taste, and Weight Gain During the First Year of Life

During last years, non-caloric sweeteners (NCSs) have been increasingly incorporated into foodstuffs in replacement of sucrose in Chile. This situation has reached a point where it is currently difficult to find sugary foods without NCSs. As a result, the voluntary and involuntary consumption of these additives is growing significantly in the population, increasing the risk of exceeding the acceptable daily intake (ADI), especially for children. This situation is worrying as recent evidence suggests that NCSs are not inert in the body and can trigger adverse metabolic effects. For example, the consumption of beverages with NCSs has been shown to favor the development of obesity and type-2 diabetes in children and adults, and a recent study reported that the intake of NCSs during pregnancy was associated with a greater weight gain of the child at one year. It is likely that certain NCSs pass into the amniotic fluid and that the fetus is exposed to some of these compounds during pregnancy. This situation would persist in the infant through breast milk, as some studies detected sucralose and acesulfame-K in this fluid, even in mothers who claimed not to consume them. However, the real impact of NCS exposure during the neonatal period on the child health has been few studied. Therefore, the aim of this study is to determine the concentration of NCSs in samples of amniotic liquid and breastmilk and to correlate these data with the NCS intake by the mothers. Mothers/children will be classified in quintiles according to the results obtained. In the children from quintiles 1 and 5, we will also study whether neonatal exposure to NCSs may affect the sweet taste threshold and the preferences for this taste, the levels of salivary insulin and the weight gain in the first year. Breastmilk microbiota and child fecal microbiota will be also evaluated.

Study Overview

• Status: Unknown
• Conditions: Exposures Associated With Pregnancy, Delivery and Lactation

• Study Type: Observational
• Enrollment (Anticipated): 315

Contacts and Locations

• Study Contact: Name: Martin Gotteland, PhD; Phone Number: 56-229786977; Email: mgottela@med.uchile.cl
• Study Contact Backup: Name: Bielka Carvajal, RM, MaSc; Phone Number: 56-229786611; Email: bielka.carvajal@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

315 dyades mother/child recruited at the San Jose Hospital Maternity

Description

Inclusion Criteria:

• Women with at least 36 weeks of gestation
• Spanish-speaking
• Elective cesarean delivery

Exclusion Criteria:

• Multiple pregnancy
• Type-2 diabetes
• Intelectual disability
• Presence of infectious disease compatible with chorio-amnionitis or immunosupression
• Newborns with serious pathologies affecting their growth

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mothers with breastmilk NCSs	Proportion of mothers with detectable NCSs in their breastmilk	One month post-partum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mothers with amniotic liquid NCSs	Proportion of mothers with detectable NCSs in their amniotic liquid	At delivery
Consumption of NCSs by the mothers	Daily intake (mg/d) of sucralose, acesulfame-K, cyclamate, saccharin and stevia evaluated through a validated consumer trend survey	At recruitment (in the last month of pregnancy) and at 1 mont post-partum
Pregnancy complications	Percentages of mothers with preclampsia, hypertension, gestacional diabetes, infections, or preterm labor	At delivery
Breastmilk concentrations of NCSs	Concentrations of sucralose, acesulfame-K, cyclamate, saccharin, steviol in breastmilk samples	One month post-partum
Amniotic liquid concentrations of NCSs	Concentrations of sucralose, acesulfame-K, cyclamate, saccharin, steviol in amniotic liquid samples	At delivery
Sweet taste of breastmilk	Intensity (arbitrary units) of sweet taste in breast milk samples, as detected by e-tongue	One month post-partum
Sweet taste of amniotic liquid	Intensity (arbitrary units) of sweet taste in amniotic liquid samples, as detected by e-tongue	At delivery
Threshold of sweet taste in children	Determination of sweet taste threshold (lower concentration of sucrose detected) in children from quintiles 1 and 5 of classification according to the concentrations of NCS in breast milk that received	6 months
Food preferences in children	Food consumption in children from quintiles 1 and 5 of classification according to the concentrations of NCS in breast milk that receiveded,through a validated consumer trend survey	At 6 month of age
Salivary insulin in children	Salivary concentration of insulin (pg/ml) in children from quintiles 1 and 5 of classification according to the concentrations of NCS in breast milk that they received	6 months
Infant gain weight	Changes in weight (kg) during the first year of life	At 12 months
Breast milk microbiota diversity	Intraindividual diversity of the breastmilk microbiota evaluated by Shannon index in samples from quintiles 1 and 5 of classification according to their NCS concentrations	At one month post-partum
Breast milk microbiota composition	Relative abundancies of the different bacterial taxa from the breastmilk microbiota, detected by high throughput sequencing, in samples from quintiles 1 and 5 of classification according to their NCS concentrations	At one month post-partum
Fecal microbiota diversity in children	Intraindividual diversity of the fecal microbiota, evaluated by Shannon index, in children from quintiles 1 and 5 of classification according to the concentrations of NCS in breast milk that they received	At six months post-partum
Fecal microbiota composition in children	Relative abundancies of the different bacterial taxa from the fecal microbiota, detected by high throughput sequencing, in children from quintiles 1 and 5 of classification according to the concentrations of NCS in breast milk that they received	At six months post-partum
Polymorphism of sweet taste receptor in children	Proportions of children presenting the different polymorphisms on the sweet taste receptor gene.	At six months post-partum

Collaborators and Investigators

• Sponsor: University of Chile
• Collaborators: University of Concepcion, Chile; Comisión Nacional de Investigación Científica y Tecnológica
• Investigators: Principal Investigator: Veronica Sambra, MaSc, University of Chile; Principal Investigator: Sandra Lopez, PhD, University of Chile; Principal Investigator: Paola Caceres, MaSc, University of Chile; Principal Investigator: Francisco Perez, PhD, University of Chile; Principal Investigator: Edgar Pastene, PhD, University of Concepción

Publications and helpful links

General Publications

• Mennella JA. Ontogeny of taste preferences: basic biology and implications for health. Am J Clin Nutr. 2014 Mar;99(3):704S-11S. doi: 10.3945/ajcn.113.067694. Epub 2014 Jan 22.
• Brown RJ, de Banate MA, Rother KI. Artificial sweeteners: a systematic review of metabolic effects in youth. Int J Pediatr Obes. 2010 Aug;5(4):305-12. doi: 10.3109/17477160903497027.
• Popkin BM, Hawkes C. Sweetening of the global diet, particularly beverages: patterns, trends, and policy responses. Lancet Diabetes Endocrinol. 2016 Feb;4(2):174-86. doi: 10.1016/S2213-8587(15)00419-2. Epub 2015 Dec 2.
• Sylvetsky AC, Walter PJ, Garraffo HM, Robien K, Rother KI. Widespread sucralose exposure in a randomized clinical trial in healthy young adults. Am J Clin Nutr. 2017 Apr;105(4):820-823. doi: 10.3945/ajcn.116.144402. Epub 2017 Feb 22.
• Duran Aguero S, Angarita Davila L, Escobar Contreras MC, Rojas Gomez D, de Assis Costa J. Noncaloric Sweeteners in Children: A Controversial Theme. Biomed Res Int. 2018 Jan 8;2018:4806534. doi: 10.1155/2018/4806534. eCollection 2018.
• Sylvetsky A, Rother KI, Brown R. Artificial sweetener use among children: epidemiology, recommendations, metabolic outcomes, and future directions. Pediatr Clin North Am. 2011 Dec;58(6):1467-80, xi. doi: 10.1016/j.pcl.2011.09.007. Epub 2011 Oct 14.
• Ruanpeng D, Thongprayoon C, Cheungpasitporn W, Harindhanavudhi T. Sugar and artificially sweetened beverages linked to obesity: a systematic review and meta-analysis. QJM. 2017 Aug 1;110(8):513-520. doi: 10.1093/qjmed/hcx068.
• Burke MV, Small DM. Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism. Physiol Behav. 2015 Dec 1;152(Pt B):381-8. doi: 10.1016/j.physbeh.2015.05.036. Epub 2015 Jun 3.
• Halldorsson TI, Strom M, Petersen SB, Olsen SF. Intake of artificially sweetened soft drinks and risk of preterm delivery: a prospective cohort study in 59,334 Danish pregnant women. Am J Clin Nutr. 2010 Sep;92(3):626-33. doi: 10.3945/ajcn.2009.28968. Epub 2010 Jun 30.
• Rother KI, Sylvetsky AC, Schiffman SS. Non-nutritive sweeteners in breast milk: perspective on potential implications of recent findings. Arch Toxicol. 2015 Nov;89(11):2169-71. doi: 10.1007/s00204-015-1611-9. Epub 2015 Oct 14. No abstract available.
• Azad MB, Sharma AK, de Souza RJ, Dolinsky VW, Becker AB, Mandhane PJ, Turvey SE, Subbarao P, Lefebvre DL, Sears MR; Canadian Healthy Infant Longitudinal Development Study Investigators. Association Between Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index. JAMA Pediatr. 2016 Jul 1;170(7):662-70. doi: 10.1001/jamapediatrics.2016.0301.
• Joseph PV, Reed DR, Mennella JA. Individual Differences Among Children in Sucrose Detection Thresholds: Relationship With Age, Gender, and Bitter Taste Genotype. Nurs Res. 2016 Jan-Feb;65(1):3-12. doi: 10.1097/NNR.0000000000000138.

Helpful Links

• New food labelling law in Chile

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2019
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: May 31, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Salivary insulin; Breastmilk; non-caloric sweetener; Amniotic liquid; Infant gain weight; Sweet taste preferences; Taste receptor polymorphism; Breastmilk microbiota; Infant gut microbiota
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain
• Other Study ID Numbers: UChile-Fonis SA18I0062

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No