R01HD109915

Mom2Child Study: Leveraging Systems Biology Toward Discoveries in Maternal Obesity, Milk, and Translation to Child Health - Project Summary

Breastfeeding is recommended by the U.S. Public Health Service and American Academy of Pediatrics to optimize infant nutrition and health. Breastfeeding initiation is approaching 85% of U.S. mothers, yet significant gaps remain regarding our understanding of human milk and lactation as a biologic system. These gaps undermine our ability to identify influences that may impair breastfeeding or reduce quality of milk.

Obesity is an ongoing public health epidemic that affects at least 29% of pregnant women and 19% of children and adolescents. Maternal obesity influences not only pregnancy but also reduces breastfeeding duration and exclusivity. In turn, reduced breastfeeding is associated with greater risk of childhood obesity in most studies, though concerns about residual confounding undermine confidence in these findings.

In addition, many small studies have reported that maternal obesity is associated with shifts in milk components (notably, leptin, inflammatory cytokines, fatty acids, oligosaccharides, and peptides) associated with child adiposity or obesity. Many of these shifts could be unhealthy and contribute to child adiposity by various means. To convincingly define the impact of maternal obesity and its associated inflammation and co-morbidities on human milk, lactation, and child health, a systems approach is needed, drawing on the power of next-generation technologies and large cohorts.

Here, we propose the Mom2Child Study, which leverages systems biology towards discoveries in maternal obesity, milk, and translation to child health. Mom2Child will use data and samples from the PREVAIL and IMPRINT birth cohorts, which are funded under cooperative agreements with CDC and NIAID, respectively. These cohorts enroll Cincinnati mothers in pregnancy and follow children to over 2 years. PREVAIL has completed follow-up of 245 mother-infant pairs. IMPRINT will complete enrollment of 1,370 mother-infant pairs by 2023. Both cohorts were designed and enacted by the same team, involve comprehensive questionnaire and health databases and sample collection, including milk and other samples. Standardized human milk collections from study mothers are undertaken at weeks 2 and 6. Neither cohort was originally funded to extensively characterize human milk components, but samples have been carefully collected and banked for that purpose.

Under Mom2Child, we will use the wealth of data and samples from PREVAIL and IMPRINT cohorts and apply metabolomics, fatty acid profiling, proteomics, glycomics, and microbiome analysis, supported by state-of-the-art statistical and machine learning, to:

1) Extensively characterize the impact of maternal obesity, inflammation, and metabolic dysregulation on milk composition using a systems biology approach;
2) Identify the impact of maternal obesity, inflammation, and metabolic dysregulation on lactation success; and
3) Determine the impact of breastfeeding and variation in human milk composition on child adiposity/obesity, inflammation, and metabolome to age 2.

Our team is well-qualified in the scientific domains needed to succeed in our aims, which align with the NICHD BEGIN Initiative and RFA-HD-22-020.

Cincinnati Univ Of

TO CONDUCT AND SUPPORT LABORATORY RESEARCH, CLINICAL TRIALS, AND STUDIES WITH PEOPLE THAT EXPLORE HEALTH PROCESSES. NICHD RESEARCHERS EXAMINE GROWTH AND DEVELOPMENT, BIOLOGIC AND REPRODUCTIVE FUNCTIONS, BEHAVIOR PATTERNS, AND POPULATION DYNAMICS TO PROTECT AND MAINTAIN THE HEALTH OF ALL PEOPLE. TO EXAMINE THE IMPACT OF DISABILITIES, DISEASES, AND DEFECTS ON THE LIVES OF INDIVIDUALS. WITH THIS INFORMATION, THE NICHD HOPES TO RESTORE, INCREASE, AND MAXIMIZE THE CAPABILITIES OF PEOPLE AFFECTED BY DISEASE AND INJURY. TO SPONSOR TRAINING PROGRAMS FOR SCIENTISTS, DOCTORS, AND RESEARCHERS TO ENSURE THAT NICHD RESEARCH CAN CONTINUE. BY TRAINING THESE PROFESSIONALS IN THE LATEST RESEARCH METHODS AND TECHNOLOGIES, THE NICHD WILL BE ABLE TO CONDUCT ITS RESEARCH AND MAKE HEALTH RESEARCH PROGRESS UNTIL ALL CHILDREN, ADULTS, FAMILIES, AND POPULATIONS ENJOY GOOD HEALTH. THE MISSION OF THE NICHD IS TO ENSURE THAT EVERY PERSON IS BORN HEALTHY AND WANTED, THAT WOMEN SUFFER NO HARMFUL EFFECTS FROM REPRODUCTIVE PROCESSES, AND THAT ALL CHILDREN HAVE THE CHANCE TO ACHIEVE THEIR FULL POTENTIAL FOR HEALTHY AND PRODUCTIVE LIVES, FREE FROM DISEASE OR DISABILITY, AND TO ENSURE THE HEALTH, PRODUCTIVITY, INDEPENDENCE, AND WELL-BEING OF ALL PEOPLE THROUGH OPTIMAL REHABILITATION.

93.865 - Child Health and Human Development Extramural Research

National Institute of Child Health and Human Development (NICHD) [HHS - NIH]

Cincinnati, Ohio 452670001 United States

Single Zip Code

Human Milk as a Biological System (R01 Clinical Trial Optional) (RFA-HD-22-020)

Amendment Since initial award the total obligations have increased 294% from $789,533 to $3,113,115.