Today the majority of pregnant women in the United States are either overweight or obese at conception with their offspring having greater adiposity at birth, a 2-fold greater risk of later obesity, and neonatal insulin resistance. Breastfeeding ha many clear benefits that may include protection against obesity and its sequelae, and exclusive breast milk feeding is recommended as the ideal infant feeding strategy for the first six months. It was long thought that breast milk composition was fairly uniform among women, having been optimized through evolutionary time to provide adequate sole nutrition for the growing infant regardless of the environmental circumstances. However, recent evidence shows that breast milk is a highly complex fluid with significant inter-individual variation in hormonal and cytokine concentrations. Pervasive maternal obesity is an evolutionarily novel condition for the human species but little effort has yet been made to systematically examine how this novel condition is associated with breast milk adipose-tissue derived hormone and cytokine (adipocytokine) variation, or whether that variation relates to infant metabolic status. Our objective is to comprehensively assess the """"""""lactational programming"""""""" hypothesis, that is, whether or not recently documented variation in breast-milk composition is related to both maternal adiposity and to infant metabolic status. The central hypothesis is that a graded, dose-response relationship between maternal adiposity and adipocytokine concentrations in breast milk exists and that milk adipocytokine concentrations are associated with altered body composition in their exclusively breast-fed offspring. Guided by compelling preliminary data, and with consideration of potential confounders, this hypothesis will be tested by pursuing three Specific Aims: 1) Identify windows of exposure during the perinatal period (pre-pregnancy, pregnancy, post-partum) when elevated maternal weight and weight gain are associated with milk adipocytokine concentrations;2) Test novel relationships between breast-milk adipocytokine concentrations and infant body composition and insulin secretion;and 3) Further characterize the relationship of maternal adiposity to milk variation and infant outcomes, to augment Aims 1 and 2 using state-of-the-science maternal and infant body composition methods, comprehensive breast-milk sampling techniques, and metabolomic analysis. The proposed research is significant because it tackles an understudied, but potentially important pathway explaining the vicious cycle of maternal-child obesity transmission prevalent today. The results of the study will be used to design interventions to reduce maternal weight during pregnancy and lactation and to augment lactation education materials to focus on the needs of obese breast-feeding women. The ultimate goal is to support women and infants during this crucial period of developmental plasticity, for the prevention of obesity, diabetes and cardiovascular disease.

Public Health Relevance

The proposed research will provide information on optimal windows for intervention to enhance the benefits of breast-feeding for obese mothers and their offspring. PROJECT NARRATIVE Today an intergenerational cycle of obesity is being played out from mother to infant, but how this occurs is still only partially understood. Altered breast milk composition is one possible pathway that the proposed study aims to examine in detail. Results of the study will identify when interventions to reduce maternal weight and body fatness may slow the vicious cycle of obesity.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD080444-01A1
Application #
8712987
Study Section
Special Emphasis Panel (ZRG1-PSE-H (02))
Program Officer
Raiten, Daniel J
Project Start
2014-07-10
Project End
2019-05-31
Budget Start
2014-07-10
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$609,551
Indirect Cost
$125,090
Name
University of Minnesota Twin Cities
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Berger, Paige K; Fields, David A; Demerath, Ellen W et al. (2018) High-Fructose Corn-Syrup-Sweetened Beverage Intake Increases 5-Hour Breast Milk Fructose Concentrations in Lactating Women. Nutrients 10:
Rother, Kristina I; Sylvetsky, Allison C; Walter, Peter J et al. (2018) Pharmacokinetics of Sucralose and Acesulfame-Potassium in Breast Milk Following Ingestion of Diet Soda. J Pediatr Gastroenterol Nutr 66:466-470
Fields, D A; George, B; Williams, M et al. (2017) Associations between human breast milk hormones and adipocytokines and infant growth and body composition in the first 6?months of life. Pediatr Obes 12 Suppl 1:78-85
Whitaker, Kara M; Marino, Regina C; Haapala, Jacob L et al. (2017) Associations of Maternal Weight Status Before, During, and After Pregnancy with Inflammatory Markers in Breast Milk. Obesity (Silver Spring) 25:2092-2099
Fields, David A; Schneider, Camille R; Pavela, Gregory (2016) A narrative review of the associations between six bioactive components in breast milk and infant adiposity. Obesity (Silver Spring) 24:1213-21