Since most cases of asthma occur in the first few years of life, examining its pre- and early postnatal determinants is crucial. This application focuses on determinants of the developing immune system. The Th2 pattern, characterized by higher levels of IgE, increased production of proinflammatory cytokines such as interleukin-4 (IL-4) or IL-13, and decreased production of interferon-gamma (IFN-gamma), predominates prenatally. If it is not balanced by a Th1 pattern after birth, e.g., increased IFN-gamma production, risk of asthma likely increases. Early childhood immune mechanisms associated with risk of asthma may also involve non-IgE/Th2 pathways, with increased production of IL-6 or TNF-alpha. Preliminary studies have linked asthma at various ages with reduced ratio of n-3 to n-6 polyunsaturated fatty acids, increased birth weight, and overweight. Preliminary data have also linked these dietary and weight variables to systemic production of IgE and both Th2 and non-Th2 proinflammatory cytokines. Thus allergy and inflammation may be pathways through which pre- and early postnatal dietary factors influence development of asthma. However, there are virtually no prospective human data linking maternal diet or fetal/early childhood growth with the asthma-related immune response in childhood. In this application our goal is to examine associations of maternal gestational n-3 and n-6 fatty acid intake, fatty acid levels in umbilical cord blood, fetal growth, and early childhood overweight with markers of allergy and inflammation at the age of 3 years. These markers include allergy-specific and total plasma IgE levels and levels of proinflammatory cytokines from antigen- and mitogen-stimulated lymphocytes. This application takes advantage of the resources of Project Viva, an ongoing NIH-funded prospective cohort study of pregnant women and their offspring. Project Viva already includes detailed dietary data on mother and infant, maternal and cord blood samples, and data on anthropometric, social, environmental, demographic, economic, psychological, and lifestyle variables. This application would support several elements not otherwise funded, including adding measurement of immune outcomes at age 3 years in a subset of 370 cohort participants. Given the existing infrastructure of Project Viva, the proposed project provides a relatively economical way to address scientific questions of major public health importance. This work also brings together a multidisciplinary research team with a proven track record of collaboration and expertise in immunology, epidemiology, and biostatistics.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
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Noel, Patricia
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Harvard Pilgrim Health Care, Inc.
United States
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Chatzi, L; Rifas-Shiman, S L; Georgiou, V et al. (2017) Adherence to the Mediterranean diet during pregnancy and offspring adiposity and cardiometabolic traits in childhood. Pediatr Obes 12 Suppl 1:47-56
Gaillard, Romy; Rifas-Shiman, Sheryl L; Perng, Wei et al. (2016) Maternal inflammation during pregnancy and childhood adiposity. Obesity (Silver Spring) 24:1320-7
Stratakis, Nikos; Roumeliotaki, Theano; Oken, Emily et al. (2016) Fish Intake in Pregnancy and Child Growth: A Pooled Analysis of 15 European and US Birth Cohorts. JAMA Pediatr 170:381-90
Perng, Wei; Stuart, Jennifer; Rifas-Shiman, Sheryl L et al. (2015) Preterm birth and long-term maternal cardiovascular health. Ann Epidemiol 25:40-5
Sordillo, Joanne E; Scirica, Christina V; Rifas-Shiman, Sheryl L et al. (2015) Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children. J Allergy Clin Immunol 135:441-8
Regnault, Nolwenn; Kleinman, Ken P; Rifas-Shiman, Sheryl L et al. (2014) Components of height and blood pressure in childhood. Int J Epidemiol 43:149-59
Regnault, Nolwenn; Gillman, Matthew W; Rifas-Shiman, Sheryl L et al. (2013) Sex-specific associations of gestational glucose tolerance with childhood body composition. Diabetes Care 36:3045-53
Stuebe, Alison M; Mantzoros, Christos; Kleinman, Ken et al. (2011) Duration of lactation and maternal adipokines at 3 years postpartum. Diabetes 60:1277-85
Stuebe, Alison M; Mantzoros, Christos; Kleinman, Ken et al. (2011) Gestational glucose tolerance and maternal metabolic profile at 3 years postpartum. Obstet Gynecol 118:1065-73
Stuebe, Alison M; Kleinman, Ken; Gillman, Matthew W et al. (2010) Duration of lactation and maternal metabolism at 3 years postpartum. J Womens Health (Larchmt) 19:941-50

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