Markers of Individual Susceptibility and Outcome Related to Fetal and Infant Growth and DevelopmentEPA Grant Number: R830827
Title: Markers of Individual Susceptibility and Outcome Related to Fetal and Infant Growth and Development
Investigators: Berkowitz, Gertrud S. , Canfield, Richard L , Wetmur, James G. , Wolff, Mary S. , Yehuda, Rachel
Current Investigators: Wolff, Mary S. , Berkowitz, Gertrud S. , Canfield, Richard L , Engel, Stephanie M. , Wetmur, James G. , Yehuda, Rachel
Institution: Mount Sinai School of Medicine
EPA Project Officer: Hahn, Intaek
Project Period: August 1, 2002 through July 31, 2005 (Extended to July 31, 2006)
Project Amount: $748,512
RFA: Biomarkers for the Assessment of Exposure and Toxicity in Children (2002) RFA Text | Recipients Lists
Research Category: Children's Health , Health Effects , Human Health , Health
Epidemiologic studies have linked poor fetal and infant growth and development to risk of disease and impaired mental function in later life. Interplay between environmental exposures and genetically derived differences in individual metabolism influences fetal growth and development. To assess gene-environment effects, we propose to investigate biomarkers of susceptibility (CYP1A, GSTT1, GSTM1, PON1 polymorphisms), a biomarker of stress (maternal and infant salivary cortisol), two indices of abnormal fetal growth, two sensitive indices of early cognitive development as well as global neurodevelopmental assessments. In addition, timing of exposures in utero windows of susceptibility will be considered. Exposures will be characterized using both PAH-DNA adducts and meticulously constructed historical assessments of particulates (PM) and volatile organic compounds (VOCs), including benzene.
We shall undertake this research within a newly established population of an estimated 300 pregnant women who experienced high exposures in the immediate aftermath of the World Trade Center (WTC) destruction in September 2001. Growth will be assessed by weight, height, and head circumference at birth, 9 months, and at 2 and 3 years of age and neurodevelopment will be assessed at 9 months, 2 and 3 years of age. Biomarkers of maternal exposure to PAH, PAH-related genes in mothers (CYP1A, GSTT1, GSTM1), a biomarker of maternal stress (cortisol) are available under a parent grant. Detailed environmental assessments are being reconstructed for WTC exposures. Funds are now requested to determine maternal genotypes of PON1, to obtain infant DNA from buccal samples and infant genotypes of CYP1A, GSTT1, PON1, to measure infant stress response (cortisol), to measure infant information processing with the Fagan Infantest and a relatively newly designed, sensitive test, the Visual Expectation Paradigm (VEXP), and to evaluate two indices of disproportionality in fetal growth. Using multiple regression models, we shall examine relationships among exposures (including stress), timing of exposures (by trimester), at-risk genotypes, and indices of growth and neurodevelopment.
Toxic emissions at the WTC constituted unique timing of exposure to fetuses, times that may correspond to windows of susceptibility for growth restriction and developmental delay. We expect that the particulate and PAH exposure, relatively unconfounded by tobacco smoke exposures, will constitute genotoxic effects on growth and development. We expect that mothers and infants with the at-risk genetic polymorphisms will be more susceptible to environmental exposures, possibly more in the first trimester of pregnancy. We expect that effects will be stronger for the more sensitive markers of outcome (the Fagan Infantest, VEXP and disproportional growth) than for the other markers we are using (Bayley Scales of Development, birth weight, length and head circumference). We expect that cortisol levels will be lower in mothers with PTSD; that maternal cortisol levels may differ according to the timing of the WTC attack in relation to trimester of pregnancy; and that infant cortisol levels will be elevated for those whose mothers have PTSD.