Obesity in a young child can not only result in short-term social, psychological, and health effects but also increases the probability to obesity later n life with many possible accompanying chronic conditions such as cardiovascular disease, diabetes, and cancer. Both animal and human studies unequivocally show that perturbations during critical early periods of development can have a life-long, sometimes irreversible, adverse impact on markers of metabolic disease like adiposity and insulin resistance. Obesity's multi-factorial etiology along with developmental processes makes the links between early life factors and childhood obesity a complex system requiring a multi-disciplinary systems approach. Although the potential mechanism is not completely clear, epigenetic mechanisms may play an important role. Our work has shown considerable individual variability of DNA methylation patterns detectable at birth and dynamic in the first two years of life; and that maternal prepregnancy BMI is associated with offspring DNA methylation alterations at birth relevant to chronic disease. However, no study has traced pathways from early life factors through epigenetic changes at birth and early childhood to the development of childhood obesity and related phenotypes among urban low- income African American and Hispanic children who have been disproportionally affected by the obesity epidemic.
The first aim of this application is to identify early life risk and protective factors for obesity development. We will investigate a comprehensive array of prenatal and birth to 24-month factors in the development of obesity by leveraging the extensive existing databases and ongoing follow-up of 3,000 Boston Birth Cohort (BBC) children from birth to age 10 years. We will pay particular attention to those potentially important factors that require further study.
The second aim i s to explore the mediating effect of the epigenome between early life factors and childhood obesity, using existing genome-wide DNA methylation data measured at birth and age 2 years (discovery sample); and replicate important findings by pyrosequencing in an independent sample.
The third aim i s to develop a Virtual Birth Cohort (VBC) systems dynamics model to represent and help better understand the complex system connecting early life factors with subsequent childhood obesity and determine the key modifiable factors that will most impact the subsequent development of childhood obesity; and test the intervention effects if modifying these factors to different degrees under a variety of scenarios. This highly innovative and efficient approach integrates real data from the BBC and then incorporates into a computational simulation model to better understand early life determinants of childhood obesity and epigenetic mechanisms. The VBC also will allow us to explore how findings from the BBC may apply to other locations and circumstances, thus helping generalize our findings. The impact of this project lies in the potential to inform new and sustainable strategies to reduce the burden of childhood obesity during the most critical developmental windows and among the most vulnerable segments of the US population.

Public Health Relevance

In this project, we will iteratively integrate a large prospective Boston Birth Cohort with a Virtual Birth Cohort (computational simulation model) to better understand the complex system connecting early life factors with subsequent childhood obesity and identify modifiable factors that intervention strategies can target. We will also explore the epigenetic mechanisms underlining early life factors and childhood obesity. The impact of this project lies in the potential to inform new and sustainable strategies to reduce the burden of childhood obesity and its consequences in the US urban low income minorities.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD086013-01
Application #
9006422
Study Section
Psychosocial Risk and Disease Prevention Study Section (PRDP)
Program Officer
Esposito, Layla E
Project Start
2016-01-01
Project End
2020-12-31
Budget Start
2016-01-01
Budget End
2016-12-31
Support Year
1
Fiscal Year
2016
Total Cost
$696,505
Indirect Cost
$227,732
Name
Johns Hopkins University
Department
Miscellaneous
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Hong, Xiumei; Sherwood, Ben; Ladd-Acosta, Christine et al. (2018) Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples. Epigenetics 13:163-172
Ji, Yuelong; Hong, Xiumei; Wang, Guoying et al. (2018) A Prospective Birth Cohort Study on Early Childhood Lead Levels and Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences. J Pediatr 199:124-131.e8
Zheng, Zihe; Bennett, Wendy L; Mueller, Noel T et al. (2018) Gestational Weight Gain and Pregnancy Complications in a High-Risk, Racially and Ethnically Diverse Population. J Womens Health (Larchmt) :
Olapeju, Bolanle; Saifuddin, Ahmed; Wang, Guoying et al. (2018) Maternal postpartum plasma folate status and preterm birth in a high-risk US population. Public Health Nutr :1-11
Raghavan, Ramkripa; Zuckerman, Barry; Hong, Xiumei et al. (2018) Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort. Autism Res 11:1416-1431
Zhang, Boyang; Hong, Xiumei; Ji, Hongkai et al. (2018) Maternal smoking during pregnancy and cord blood DNA methylation: new insight on sex differences and effect modification by maternal folate levels. Epigenetics 13:505-518
Okano, Lauren; Ji, Yuelong; Riley, Anne W et al. (2018) Maternal psychosocial stress and children's ADHD diagnosis: a prospective birth cohort study. J Psychosom Obstet Gynaecol :1-9
Cheng, Tina L; Mistry, Kamila B; Wang, Guoying et al. (2018) Folate Nutrition Status in Mothers of the Boston Birth Cohort, Sample of a US Urban Low-Income Population. Am J Public Health 108:799-807
Raghavan, Ramkripa; Riley, Anne W; Volk, Heather et al. (2018) Maternal Multivitamin Intake, Plasma Folate and Vitamin B12 Levels and Autism Spectrum Disorder Risk in Offspring. Paediatr Perinat Epidemiol 32:100-111
Ji, Yuelong; Riley, Anne W; Lee, Li-Ching et al. (2018) Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder. Brain Sci 8:

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