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Principal Investigator: PHILIPPE ADAM GRANDJEAN
Organization: UNIVERSITY OF RHODE ISLAND
Fiscal Year: 2024
Award: $369,926
Funding agency: National Institute of Environmental Health Sciences
PROJECT SUMMARY/ABSTRACT – PROJECT 2 CRITICAL EFFECTS
Metabolic diseases, including obesity and type 2 diabetes, are major public health problems of multifactorial
etiology, in which early-life exposures to environmental pollutants, such as per- and polyfluoroalkyl substances
(PFAS), appear to play a role. In parallel, a critical effect of PFAS exposure is immunotoxicity that paves the
way for immune dysfunction and infectious disease. STEEP Project 2 (P2–Critical Effects) will examine the
role of developmental exposure profiles for these high-priority environmental pollutants and determine
outcomes up to ages 5 and 14 years to allow identification of windows of susceptibility. We will rely on two birth
cohorts from the Faroe Islands (total N >1000) to prospectively explore the associations between exposure
profiles of PFAS and outcomes, including immune deficiencies (suboptimal antibody production after
vaccinations, and increased frequency of infectious disease) and metabolic abnormalities (excess adiposity,
hyperlipidaemia, low bone mineral content, and prediabetes). P2–Critical Effects will further evaluate the
possible usefulness of clinically relevant biomarkers in serum (such as cholesterol subfractions,
adipocytokines, insulin-like growth factor-1). Exposure data are already available from analyses of maternal
pregnancy, cord blood and postnatal serum at ages 18 months, 5 and 9 years from the oldest Cohort 5, and
clinical data, including DXA scans, are available for comparisons with age 14 years. The youngest Cohort 6 is
currently being formed, with blood samples and human milk being taken during infancy for PFAS analyses that
will allow determination of PFAS transfer from lactation. Multiple regression analyses with adjustment for other
environmental chemicals will be complemented by structural equation models and other advanced statistical
methods. Thus, the proposed study will aim at providing prevention potentials and new insights into the
pathogenesis of major public health problems that are associated with early-life exposures to high-priority
environmental pollutants.
Terms: <0-11 years old><14 year old><14 years of age><21+ years old><5 year old><5 years of age><9 year old><9 years of age><Ab response><Achievement><Achievement Attainment><Adaptive Immune System><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Adverse effects><Affect><Age><Age Months><Antibodies><Antibody Formation><Antibody Production><Antibody Response><Apo-C><ApoC><Apolipoproteins C><Biological Markers><Birth><Blood><Blood Reticuloendothelial System><Blood Sample><Blood Serum><Blood specimen><Bone Mineral Contents><Breast Feeding><Breast Milk><Breast fed><Breastfed><Breastfeeding><Breastmilk><COVID disease severity><COVID severity><COVID-19 disease severity><COVID-19 severity><COVID19 disease severity><COVID19 severity><Causality><Cells Placenta-Tissue><Cellular Immune Function><Child><Child Youth><Childhood><Children (0-21)><Cholesterol><Clinical><Clinical Data><Cohort Studies><Communicable Diseases><Concurrent Studies><Cord Blood><DEXA><DXA><Data><Dependence><Development><Dual-Energy X-Ray Absorptiometry><Dual-Energy Xray Absorptiometry><Endocrine><Endocrine disruption><Environmental Pollutants><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Equation><Etiology><Exposure to><Faeroe Islands><Faroe Islands><Frequencies><General Population><General Public><Genetic><Gestation><Goals><HPV Vaccine><Health><Human><Human Development><Human Milk><Human Mother's Milk><Human Papilloma Virus Vaccine><Human papillomavirus Vaccine><IGF-1><IGF-I><IGF-I-SmC><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune Markers><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune system><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunologic Markers><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Incidence><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Insulin-Like Growth Factor 1><Insulin-Like Growth Factor I><Insulin-Like Somatomedin Peptide I><Joints><Ketosis-Resistant Diabetes Mellitus><Lactation><Life><Link><Lipids><Lymphocyte Count><Lymphocyte Number><Mammary Gland Milk><Maturity-Onset Diabetes Mellitus><Measures><Metabolic><Metabolic Diseases><Metabolic Disorder><Modeling><Modern Man><Mother's Milk><NIDDM><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Normal Placentoma><Obesity><Osteoporosis><Outcome><PFAS><Parturition><Pathogenesis><Pathway interactions><Pattern><Placenta><Placenta Embryonic Tissue><Placentome><Poly-fluoroalkyl substances><Prediabetes><Prediabetes syndrome><Prediabetic State><Predisposition><Pregnancy><Prevention><Prospective Studies><Puberty><Public Health><Regression Analyses><Regression Analysis><Regression Diagnostics><Reporting><Research><Risk><Risk Assessment><Rodent><Rodentia><Rodents Mammals><Role><SARS-CoV-2 disease severity><SARS-CoV-2 severity><SRP><Sampling><Scanning><Serum><Serum Markers><Signal Recognition Particle><Skinfold Thickness><Slow-Onset Diabetes Mellitus><Somatomedin C><Source><Stable Diabetes Mellitus><Statistical Methods><Statistical Regression><Susceptibility><T2 DM><T2D><T2DM><Thesaurismosis><Time><Total Lymphocyte Count><Toxoids><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Umbilical Cord Blood><Vaccination><Vaccines><acquired immune system><adipocytokines><adipokines><adiposity><adult onset diabetes><adulthood><age 14 years><age 5 years><age 9 years><ages><antibody biosynthesis><bio-markers><biologic marker><biomarker><causation><clinical exam><clinical examination><clinical phenotype><clinical relevance><clinically relevant><cohort><coronavirus disease 2019 disease severity><coronavirus disease 2019 severity><coronavirus disease severity><corpulence><developmental><disease causation><early life exposure><endocrine disrupting><environmental chemical><environmental contaminant><epidemiologic investigation><epidemiology study><fetal cord blood><five year old><five years of age><fourteen year old><fourteen years of age><hypoimmunity><immune deficiency><immune function><immune system function><immune-based biomarkers><immunodeficiency><immunoglobulin biosynthesis><immunological biomarkers><immunological markers><immunotoxicity><improved><infancy><infantile><inflammation marker><inflammatory marker><insight><ketosis resistant diabetes><kids><lactating><lactational><maternal milk><maturity onset diabetes><metabolism disorder><next generation><nine year old><nine years of age><pathway><pediatric><perfluorinated alkyl substances><perfluoroalkyl substances><perfluoroalkylated substances><polyfluorinated alkyl substances><polyfluoroalkyl substances><postnatal><pre-diabetes><pre-diabetic><prediabetic><prenatal><prospective><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 severity><sex dimorphism><sexual dimorphism><sexually dimorphic><skin fold measurement><skin fold thickness><skinfold measurement><social role><statistic methods><toxic reaction in immunology><type 2 DM><type II DM><type two diabetes><unborn><vaccine antibodies><vaccine failure><vaccine induced antibodies><vaccine-induced antibodies><youngster>