The competitive renewal is responsive to recent epidemiologic and experimental evidence indicating that certain phthalates modulate thyroid function and reduce circulating thyroid hormone levels. The phthalates implicated include those already being studied under the current RO1 (Prenatal Phthalates, Placental Function and Fetal Growth R01 ES013543, Robin Whyatt, PI): di(2-ethylhexyl) phthalate (DEHP), butylbenzyl phthalate (BBzP) and dibutyl phthalate (DBP). Exposures to these phthalates are substantial among cohort subjects. Our proposed renewal will determine whether these exposures are associated with perturbations in thyroid function in children followed from birth through age 10-11 years. The study will also determine whether the phthalates are associated with deficits in child neuropsychological function, including in domains that might be associated with phthalate-induced reductions in thyroid function (intelligence, attention, executive function and motor skills). In addition, given that the purported mechanism whereby phthalates affect thyroid levels is through modulation of the Sodium Iodide Symporter (NIS) mediated iodide uptake activity in the thyroid gland, we will also evaluate whether prenatal phthalate exposures modulate expression of the NIS in placental tissue. Such a finding could have important implications for fetal thyroid function, as the NIS is the transport gene responsible for the active transfer of iodide across the placenta. Thyroid hormones during pregnancy and early childhood are critical to brain development, and even modest reductions in hormone levels may have long-lasting effects on child mental, motor and neuropsychological function. However, while prior studies have assessed the relationship between phthalates and thyroid hormones in adults, no prior studies have assessed these relationships in children, or evaluated the effects of prenatal and early-life phthalates exposures on child neuropsychological function. In our preliminary analyses, we found a significant inverse association between maternal prenatal DEHP exposure and child mental development at age 3 years among cohort children. This proposed renewal will build on these preliminary findings to evaluate the role of prenatal and early childhood phthalate exposures on: (1) measures of thyroid function in children from birth through age 11 years;(2) child cognition (language, working memory, executive function, problem solving);(3) child behavior (attention and impulsivity );(4) child motor development (fine manual control, manual coordination, body coordination, strength and agility, motor speed and visual scanning) and (5) expression of the NIS in placental tissue.

Public Health Relevance

The competitive renewal is responsive to recent epidemiologic and experimental evidence indicating that certain phthalates modulate thyroid function and affect child cognitive development. The proposal will determine whether prenatal and early postnatal exposure to the phthalates are associated with perturbations in thyroid function and with deficits in child europsychological function (intelligence, attention, executive function and motor skills) in a cohort of 400 children followed from birth through age 10-11 years.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES013543-09
Application #
8651483
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Gray, Kimberly A
Project Start
2004-12-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
9
Fiscal Year
2014
Total Cost
$563,435
Indirect Cost
$213,475
Name
Columbia University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Whyatt, Robin M; Liu, Xinhua; Rauh, Virginia A et al. (2012) Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor, and behavioral development at 3 years of age. Environ Health Perspect 120:290-5
Reyes, Marilyn; Perzanowski, Matthew S; Whyatt, Robin M et al. (2011) Relationship between maternal demoralization, wheeze, and immunoglobulin E among inner-city children. Ann Allergy Asthma Immunol 107:42-49.e1
Van Vliet, E D S; Reitano, E M; Chhabra, J S et al. (2011) A review of alternatives to di (2-ethylhexyl) phthalate-containing medical devices in the neonatal intensive care unit. J Perinatol 31:551-60
Just, Allan C; Adibi, Jennifer J; Rundle, Andrew G et al. (2010) Urinary and air phthalate concentrations and self-reported use of personal care products among minority pregnant women in New York city. J Expo Sci Environ Epidemiol 20:625-33
Adibi, Jennifer J; Whyatt, Robin M; Hauser, Russ et al. (2010) Transcriptional biomarkers of steroidogenesis and trophoblast differentiation in the placenta in relation to prenatal phthalate exposure. Environ Health Perspect 118:291-6
Adibi, Jennifer J; Hauser, Russ; Williams, Paige L et al. (2009) Maternal urinary metabolites of Di-(2-Ethylhexyl) phthalate in relation to the timing of labor in a US multicenter pregnancy cohort study. Am J Epidemiol 169:1015-24
Whyatt, Robin M; Adibi, Jennifer J; Calafat, Antonia M et al. (2009) Prenatal di(2-ethylhexyl)phthalate exposure and length of gestation among an inner-city cohort. Pediatrics 124:e1213-20
Adibi, Jennifer J; Hauser, Russ; Williams, Paige L et al. (2009) Placental biomarkers of phthalate effects on mRNA transcription: application in epidemiologic research. Environ Health 8:20
Adibi, Jennifer J; Whyatt, Robin M; Williams, Paige L et al. (2008) Characterization of phthalate exposure among pregnant women assessed by repeat air and urine samples. Environ Health Perspect 116:467-73