Over the past several decades, researchers have shown that an array of conditions in pregnant women, such as anxiety, stress, and obesity, are associated with a large and common cluster of behavioral and physical health conditions in the child. Now, researchers at the University of Rochester Medical Center (URMC) are embarking on a seven-year mission to study one factor that may explain the link: prenatal inflammation.
The research, supported by a grant from the National Institutes of Health that could total more than $18 million, is the first detailed longitudinal investigation of how inflammation — part of the body’s immune response — during pregnancy can affect a child’s neurodevelopment as well as the metabolic systems for processing nutrients and energy. Should the study reach its seven-year maturity, it will be one of the largest grants in URMC history.
“Obesity, stress, anxiety, and a history of trauma have all been linked with elevated levels of pro-inflammatory cytokines, which are chemicals that are part of the body’s immune response. This seems to be generally the case in adults and, of particular concern to us, in pregnant women,” said Thomas O’Connor, Ph.D., Professor of Psychiatry and Director of the Wynne Center for Family Research at URMC. “Inflammation underlies a number of health conditions which may all be connected, and that makes it a very compelling target for developmental health research starting in the prenatal period.”
Past research seeking to explain how and why maternal psychological states and physiology may have a long-term impact on child health focused on stress physiology, and especially the stress hormone cortisol, as a likely explanation. But the implications for human health were only modest, underscoring the need for further research.
Clinical scientists have known for some time that proinflammatory cytokines can be measured in the blood at varying levels among individuals. If URMC researchers find that prenatal immune activation does alter child growth and development, then that would open up new targets for intervention.
“In addition to providing new basic knowledge, our study is also positioned to identify additional mechanisms that may guide clinical treatment and improve child health outcomes and ultimately population health,” said O’Connor, the study director.
The grant is part of $157 million in funding announced today by the National Institutes of Health as it launches its Environmental influences on Child Health Outcomes (ECHO) program. The ECHO program will investigate how exposure to a range of environmental factors in early development — from conception through early childhood — influences the health of children and adolescents.
Working with collaborators at the University of Pittsburgh Medical Center, researchers will follow 500 families from the first trimester of pregnancy through the child’s fourth birthday. Researchers will administer prenatal assessments to examine social and family factors, psychological symptoms such as depression and anxiety, and clinical measures such as diet and nutrition. Biological samples including blood, urine, and saliva will also be collected from the mothers in each trimester, and regularly from babies starting at birth.
At birth, cord blood and placenta samples will be collected through a process developed by co-investigator Richard K. Miller, Ph.D., Professor of Obstetrics and Gynecology, and colleagues at URMC. Then, throughout the first four years of life, the child will undergo behavioral and developmental assessments, brain imaging, and dual energy X-ray absorptiometry, a non-invasive scan that quantifies body composition. Children’s immune, endocrine, and metabolic system development will also be tracked from samples collected throughout the child’s first 4 years.
“Every baby should have the best opportunity to remain healthy and thrive throughout childhood,” said Francis S. Collins, M.D., Ph.D., National Institutes of Health Director. “ECHO will help us better understand the factors that contribute to optimal health in children.”
The study builds on previous URMC research and will involve a wide range of university specialists including experts from the Departments of Psychiatry, Neurology, Pediatrics, Obstetrics and Gynecology, and Biostatistics and Computational Biology. The study will capitalize on a range of medical research infrastructure already present at the university, including the Rochester Center for Brain Imaging, the Rochester Human Immunology Center, the UR Genomics Research Center, and the Ernest J. Del Monte Neuromedicine Institute.
In addition to O’Connor and Miller, the URMC team includes Sanjiv Amin, M.B.B.S., Richard Aslin, Ph.D., Emily Barrett, Ph.D., Mary Caserta, M.D., John Foxe, Ph.D., Philip Katzman, M.D., Jan Moynihan, Ph.D., Shawn Murphy, Ph.D., Eva Pressman, M.D., Kristin Scheible, M.D., Chris Stodgell, Ph.D., and Xin Tu, Ph.D. They are assisted by Carrie Salafia, M.D., of Placental Analytics, LLC. The team at the University of Pittsburgh and Magee’s Women’s Hospital is led by Hyagriv Simhan, M.D., with Pathik Wadhwa, M.D., Ph.D., and Claudia Buss Ph.D., of the University of California-Irvine; and Damien Fair, Ph.D., and Alice Graham, Ph.D., of Oregon Health and Science University.