Environmental and nutritional exposures in-utero and early postpartum exert profound influences on the developing metabolic profile of an infant, impacting future risk of obesity. Rapid and excessive weight gain in the first 4-6 months of life, regardless of feeding mode, places an infant at elevated risk of later obesity. Bioactive components of human milk (HM) that may influence weight and adiposity gain remain unknown to a large extent. Furthermore, how maternal metabolic disorders such as obesity and diabetes, may impact the bioactive composition of HM, and how, in turn, this may influence infant growth remains largely unknown. The rise in prevalence in Type 2 diabetes (T2D) among pregnant and breastfeeding women has outstripped current knowledge of the impact this disease has on HM composition. This study will address this gap in knowledge. Exclusive breastfeeding is universally recommended for the first 6 months of life. Considering this recommendation, and the alarming prevalence of pediatric obesity, understanding how maternal obesity, with or without insulin resistance, may impact HM composition, and secondarily infant adiposity gain is of critical importance to addressing early risk factors for obesity. The over-arching hypotheses driving this research is that maternal metabolic dysfunction that accompanies obesity and T2D will impact the bioactive components of HM, and that these components will correlate with the rate of weight gain and body fat accumulated by the infant over a critical window of growth. Study Design: To address these essential questions, we will undertake a longitudinal cohort study and follow 60 well-characterized mother/infant pairs over the first 4 months of life, collecting longitudinal measures of breast milk composition and infant growth and body composition. We will follow 20 mother/infant pairs in each of the following study groups: normal weight (NW), overweight/obese (OW/Ob), and T2D women. The normo-glycemic OW/Ob group will allow us to distinguish the effects of maternal obesity alone vs. the impact of the insulin resistance of T2D, on HM composition and secondarily on infant growth.
Aims : We will use the samples obtained to determine if maternal characteristics impact bioactive components of HM: inflammatory and oxidative """"""""load"""""""", adipokine, insulin, glucose, and caloric content of HM. We will also determine whether critical windows exist over these first 4 months of lactation when differences in HM between groups are more severe. Finally we will determine if these differences in HM composition are associated with the rate of infant weight and fat gain. Impact: Answers to these questions will have clinical implications for early post-natal feeding recommendations for high risk women and their infants. Identifying primary components of HM that associate with risky infant weight gain will provide an ideal avenue for intervention to optimize HM composition and minimize infant risk. Understanding the earliest post-natal risk factors that promote later obesity will identify opportunities to modify these influences, and thereby potentially interrupt the intergenerational transmission of obesity.

Public Health Relevance

This project will tell us how maternal obesity and type 2 diabetes impact a woman's breast milk and her infant's growth over the first few months of life, which is a critical period of growth. This new knowledge will help us to understand the earliest risk factors for childhood obesity and help us to improve the growth patterns of babies that have a high familial risk of becoming overweight.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD078068-01A1
Application #
8712817
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Raiten, Daniel J
Project Start
2014-06-01
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Aurora
State
CO
Country
United States
Zip Code
80045
Rudolph, M C; Young, B E; Lemas, D J et al. (2017) Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI. Int J Obes (Lond) 41:510-517
Young, B E; Farazandeh, S; Westra, K et al. (2016) Maternal Beliefs Surrounding Infant Feeding, but Not Maternal BMI or Hospital Experience, Predict Breastfeeding Exclusivity and Behavior. Austin J Pediatr 3:
Rudolph, Michael C; Young, Bridget E; Jackson, Kristina Harris et al. (2016) Human Milk Fatty Acid Composition: Comparison of Novel Dried Milk Spot Versus Standard Liquid Extraction Methods. J Mammary Gland Biol Neoplasia 21:131-138