4M study-maternal metabolism, breast milk composition, and infant outcomes
Ellen Demerath, PhD (School of Public Health)
Katherine Jacobs, DO (Department of Obstetrics, Gynecology, and Women's Health), Cheryl Gale, MD (Department of Pediatrics), Dan Knights, PhD (Department of Computer Science and Biotechnology Institute), Samantha Hoffman, MD (Department of Obstetrics, Gynecology, and Women's Health), Stephanie Mackenthun, MD (Department of Obstetrics, Gynecology, and Women's Health)
The 4M cohort adds mothers with gestational diabetes to expand upon the MILK Study cohort, considering the entire range of potential maternal factors impinging on breast milk composition in obese as compared to normal weight women. With the addition of the 4M cohort, we will learn how breastmilk composition differs among women with and without gestational diabetes and how hormones and microbiome affect infant body composition and infant microbiome.
A prospective, observational, single-center study of the effects of illness and nutrition on growth and cognition in AGA VLBW preterm infants
Sara Ramel, MD (Department of Pediatrics)
Ellen Demerath, PhD (Department of Epidemiology and Community Health), Michael Georgieff, MD (Department of Pediatrics), Bridget Davern (Department of Pediatrics), Neely Miller (Department of Pediatrics), Heather Gray (Department of Maternal Fetal Medicine)
The objectives of this study are: 1) to investigate the relationship between linear growth and fat-free body mass (FFM), and subsequent cognitive function, and 2) to identify modifiable nutritional and non-nutritional factors that influence FFM accretion (and potentially cognition) during and after initial hospitalization in very low birth weight (VLBW) preterm infants. This study will test the following novel hypotheses: 1) cognitive function in VLBW preterm infants is a function of linear growth and FFM accretion; 2) both modifiable nutritional and non-nutritional factors influence FFM accretion during and after initial hospitalization in VLBW preterm infants and that these factors affect cognitive status at 24 months of age corrected for the degree of prematurity (CA); and 3) alterations in the growth hormone axis and increased pro-inflammatory cytokines mediate the relationship of slower length growth and FFM accretion to cognitive outcomes.
Assessment of body composition in infants with cystic fibrosis
Elissa M. Downs, MD, MPH (Pediatric Gastroenterology, Hepatology, and Nutrition)
Sarah Jane Schwarzenberg, MD (Pediatric Gastroenterology, Hepatology, and Nutrition), Terri Laguna, MD (Pediatric Pulmonary Medicine), Sara Ramel, MD (Department of Neonatology)
In a patient with cystic fibrosis, malnutrition has been directly associated with a worse prognosis due to negative effects on activity, quality of life, and pulmonary function. Obtainment of adequate weight during childhood has been associated with decreased hospital days, fewer acute pulmonary exacerbations, and increased survival at 18 years of age. Better nutrition, along with normalized fat absorption, lead to improved pulmonary function and survival rates. Current consensus guidelines stress that early identification of deficiencies is paramount to improve overall health and allow for proper intervention; however these guidelines are based on an assessment of body weight, a number that includes both lean body mass and fat mass. At the time of cystic fibrosis diagnosis, many infants already have poor weight gain, as well as failure to thrive, and exocrine pancreatic insufficiency. In those infants with cystic fibrosis that appear well and have a normal body weight, malabsorption of fat soluble vitamins and decreased lean body mass may be present.
A decreased proportion of lean body mass with a normal weight, so called “hidden depletion,” is important to identify. Decreased lean body mass correlates with worse disease status in older children and adolescents, increases morbidity, and may not be detected with the use of body mass index alone. An increased proportion of lean body mass has been associated with improved pulmonary function. The overall goal of this research is to improve nutrition in infants with CF to slow deterioration of pulmonary function and improve survival. A more accurate determination of body composition in infants with cystic fibrosis may allow targeting of children at highest risk of nutritional compromise and suggest improved nutritional interventions.
Enhanced early nutrition for preterm infants to improve neurodevelopment and minimize metabolic risk
Sara Ramel, MD (Department of Pediatrics)
Ellen Demerath, Ph.D. (Department of Public Health)
Preterm infants undergo early growth failure while in the Neonatal Intensive Care Unit (NICU) that persists for years after discharge home. This growth failure is occurring at a time of rapid brain development, and has been associated with negative long-term neurodevelopmental outcomes. In addition, early growth failure is often followed by rapid catch-up growth in childhood, which is associated with later metabolic (obesity/diabetes/hypertension) risk. Enhanced early nutrition has been associated with improved weight gain and neurodevelopment in several small observational studies, but is not routinely provided due to hesitancy surrounding possible intolerance and concern that increased nutrition will lead to increased adiposity. Lack of randomized controlled trials on this question create concern that the observed benefit of enhanced early nutrition is actually the result of confounding, whereby healthier babies are from the start inadvertently more likely to receive better nutrition, and also exhibit faster growth and better health outcomes.The overall objective of the proposal is to demonstrate the feasibility of providing increased calories and protein in the first week of life to VLBW preterm infants, and to generate pilot data on the effects of this intervention on growth and neurodevelopmental outcomes.
Alicia Kunin-Batson, PdD, LP (Department of Pediatrics), Mike Troy, PhD, LP (Children's MN - Behavioral Health)
Jerica Berge, PhD, MPH, LMFT, CRLE (Family Medicine and Community Health), Rachel Hardemann, PhD, MPH (Health Policy and Management)
The experience of discrimination and harassment due to race/ethnicity is a common and significant problem, with past studies suggesting 40-70% of people of color report such experiences. Evidence is accumulating that racism is a cause of health disparities and poor health outcomes in the United States. Most previous studies have focused on the direct experience of racism at the level of the individual and associations with adult health (e.g., hypertension, all-cause mortality). However, research also suggests that racism-related stress can also be experienced indirectly, through exposure to the prejudice and discrimination experienced by others (e.g., parent to child) and the persistence of social structures which maintain racial discrimination by fostering inequitable systems (e.g., housing, employment). Few studies have examined the impact of parent-reported discrimination and harassment on children’s health and development and even fewer of these have included measures of exposure to structural racism at the community level.
There is an urgent need to learn more about avenues to disrupt the relationship between racism-related stressors and poor health outcomes. This is particularly true in the context of the current sociopolitical climate which many have argued has created a less accepting environment for immigrants and people of color, contributing to further discrimination and harassment and compounding structural inequality already present in many social systems. Drawing from previous empirical and conceptual studies, we propose that racism-related stressors will be related to important health, mental health, and cognitive developmental outcomes, and that children’s HPA-axis regulation is impacted through exposure to racism-related stress and associated with children’s health and wellness. Parenting behaviors and skills may also be impacted by exposure to racism-related stressors and provide potentially malleable intervention targets to impact children’s stress physiology as well as children’s health and development.
Impact of the intestinal microbiome on infant neurodevelopment
Ellen Demerath, Ph.D. (Department of Epidemiology and Community Health)
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. Animal models indicate that maternal obesity may have deleterious effects on brain development in offspring. Preliminary data from our laboratory suggest that infants born to mothers with high pre-gravid BMI have altered cognitive processing of visual and audio stimuli compared to infants born to mothers with normal BMIs. Maternal obesity can also cause changes in the intestinal microbiome of offspring, both pre- and postnatally. Intestinal microbial communities are thought to affect the development immunity, metabolism, and brain function, with effects that extend across an individual’s lifespan. Our main objective is to determine how variations in microbiome signatures early in life correlate with variations in hippocampal development as indexed by ERPs. The specific aims are to 1) Examine the variation in the infant biome at one month and six months of age; and 2) Determine whether these variations are associated with poorer hippocampal-based electrophysiology outcomes and behavior, and slower myelination-dependent speed of processing not only at in the neonatal period but six months later as well.
Maternal obesity, breast milk composition and infant growth
Ellen Demerath, Ph.D. (Department of Epidemiology and Community Health)
Today, the majority of pregnant women in the US are either overweight or obese. Their offspring have a greater adiposity at birth, a greater risk of later obesity and neonatal insulin resistance. Breast feeding has many clear benefits that many include protection against obesity (its long term effects and sequelae). Recent evidence shows that breast milk is a highly complex fluid with significant variation both between and within lactating women. Little effort has been made to examine breast milk composition in obese women and its impact on infant metabolic status. The objective of this research study is to access whether or not variation in breast milk composition is related to both maternal adiposity and infant metabolic status.
NET-Works 2 at the U
Alicia Kunin-Batson, PhD, LP (Department of Pediatrics)
Lauren Crain, PhD (Health Partners Institute), Simone French, PhD (School of Public Health), Megan Gunner, PhD (Institute of Child Development), Aaron Kelly, PhD (Department of Pediatrics), Elyse Kharbanda, MD, MPH (Health Partners Institute), Nancy Sherwood, PhD (School of Public Health)
Heart disease accounts for 1 in 4 deaths in the US with obesity as a leading risk factor. While prior studies have linked early environmental stressors such as socioeconomic disadvantage to childhood obesity and later cardiovascular disease risk some youth will be resilient and will not develop disease despite risk exposure. Developing optimal interventions requires understanding the protective factors that foster resilience, the pathways through which early environmental stressors contribute to emerging dysregulation in cardiometabolic processes, and the timing during childhood when impacts are observed. There is a significant gap in our knowledge; specifically, a relative dearth of information on the pathways, timing, and risk and protective factors that translate early environmental stressors into emerging cardiometabolic risk during childhood. Prior studies have been hampered by limited assessment of environmental stressors, lack of assessment of biologically plausible pathways (e.g., activity of the hypothalamic-pituitary-adrenocortical (HPA) axis) and a lack of use of sufficiently sensitive measures to detect important cardiometabolic domains in childhood. Most importantly, prior studies have not rigorously examined parenting and child behavioral factors as moderators of the relationship between psychosocial stressors and cardiometabolic risk and resilience. Identification of these potentially modifiable protective factors is crucial for optimizing interventions to prevent the development of cardiovascular and metabolic diseases. The NET-Works 2 at the U study will address this knowledge gap using a unique cohort of racially/ethnically diverse, low income children who participated in a two-arm randomized controlled obesity prevention trial.
The goal of this prospective study and the next logical step in our work is to characterize the emergence of dysregulation in cardiometabolic processes in this high-risk cohort of children at 7-10 years of age, and identify the malleable factors that mitigate the deleterious impact of early environmental stressors on later cardiometabolic risk.