Grantee Research Project Results

2012 Progress Report: Prenatal Exposure to BPA/Phthalates: Infant Physical and Behavioral Development

EPA Grant Number: R834593C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834593
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Water Innovation Network for Sustainable Small Systems
Center Director: Reckhow, David A.
Title: Prenatal Exposure to BPA/Phthalates: Infant Physical and Behavioral Development
Investigators: Schantz, Susan L. , Korrick, Susan A. , Baillargeon, Renee L. , Aguiar, Andrea , Flaws, Jodi , Gardiner, Joseph
Current Investigators: Schantz, Susan L.
Institution: University of Illinois Urbana-Champaign , Harvard University , Michigan State University
Current Institution: University of Illinois Urbana-Champaign
EPA Project Officer: Hahn, Intaek
Project Period: February 15, 2010 through February 14, 2014
Project Period Covered by this Report: February 15, 2012 through February 14,2013
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Project 1 was undertaken to develop novel methods to assess the impact of prenatal BPA or phthalate exposure on sexually dimorphic physical and behavioral endpoints during the first few months of life. An important goal is to identify reliable and valid measures of cognitive function in newborns and young infants that are sensitive to prenatal chemical exposure and predictive of lasting cognitive deficits. To complete the proposed work, a cohort of pregnant women was recruited from a local clinic. The pregnant women complete a 24-hour product use diary and provide urine samples for assessments of total BPA and 11 phthalate metabolites at 16-18 and 35-37 weeks of gestation. Key physical and cognitive outcomes are being assessed in the infants at birth, 4-5, 7-8 and 10-11 months of age. The relationship between measures of exposure and reported product use, and the relationship between maternal exposures and physical or cognitive outcomes in infants will be examined. This study will provide important pilot data about the nature of phthalate and BPA exposure in pregnant women and the risk of physical and neurodevelopmental abnormalities in their infants. The results will provide a strong basis for expansion of the pilot birth cohort into a larger prospective birth cohort with longitudinal follow-up of the children from birth through puberty.

Progress Summary:

Recruitment for the study was completed in April 2013. A total of 188 pregnant women were enrolled between 16-18 weeks of gestation, exceeding our goal of 180 women. Eligible women were 18-40 years of age, fluent in English, not carrying multiples, not taking prescription medication for a chronic condition; planned to stay in the hospital for 48 hrs after delivery, resided within a 45 mi radius of the clinic, and planned to stay in the area for at least 1 year after birth. Maternal first morning urine samples were collected at 16-18 and 35-37 weeks for analysis of phthalates and BPA. All participants had given birth as of October 31, 2012. During pregnancy three women withdrew from the study and 14 women became ineligible because they developed a chronic health condition, moved out of the area, or changed to a non-participating obstetrical clinic. At birth, 13 mother-infant pairs became ineligible because of premature birth or because the infant was admitted to the neonatal intensive care unit. One mother did not notify us of her birth. A total of 157 healthy full-term infants were assessed at birth, exceeding our original target of 150 infants. Physical measures assessed at birth included birth weight, body length, head circumference, anogenital distance (AGD) and second to fourth finger ratio. Visual attention and visual recognition memory also were assessed. A total of 143 of the 157 infants (91%) were successfully followed up at 4-5 months of age. Assessments included physical measures as well as a sexually dimorphic cognitive task that assessed the infants' ability to reason about the physical relationships between objects. The 4-5 month assessments were completed in March 2013. At this time, follow-up assessments of physical and cognitive development at 7-8 months and 10-11 months are still underway. Currently, 117 infants have completed the 7-8 month assessment and 100 infants have completed the 10-11 month assessment.

Preliminary analysis of demographic data conducted in June 2012, showed that the sample is mostly middle class, Caucasian, and well-educated. Two first morning urines collected from the first 69 women in the cohort at 16-18 and 35-37 weeks of gestation were analyzed for BPA and 11 phthalate metabolites at the CDC Division of Laboratory Sciences. BPA was detectable in 94% of samples and phthalate metabolites (except MEHP) were present in 99-100%. The creatinine corrected concentrations of total BPA and metabolites from the two most prevalent phthalates (DEP and DEHP) were: BPA 1.91 ng/mg Cr, MEP 42.4 ng/mg, MEHP 1.94 ng/mg, MECPP 17.02 ng/mg, MEHHP 10.24 ng/mg, and MEOHP 7.87 ng/mg.

In preliminary analyses of outcome data, birth weight, body length, and head circumference were not associated with either BPA or phthalate exposure. However, both phthalates and BPA were associated with AGD. The phthalate effect was consistent with previous human and rodent studies. Boys with higher exposure to anti-androgenic phthalates had shorter AGD. In contrast, girls with higher BPA exposure had longer AGD.

A visual attention task administered to newborns was modeled after a task used in a longitudinal study showing that information processing speed at birth correlated with intelligence test scores in childhood and adolescence. Infants were shown two black and white checkerboards on a computer screen and we assessed whether they were attending to and processing information about the stimuli including the number of looks per minute (fixations) and the shift rate (number of shifts in gaze between the two boards). A higher number of fixations indicated that infants were less attentive (looking away more frequently). A higher shift rate indicated that infants were attending to and comparing the stimuli. Phthalates and BPA were associated with lower shift rates and higher fixation, respectively, indicating that more highly exposed infants were less attentive.

A visual recognition memory task was administered at 7 months. Infants were familiarized to two identical faces, and then saw the familiar face paired with a novel one. In models adjusted for multiple covariates including maternal IQ, phthalate exposure was negatively associated with novelty preference although the association was not significant in this small sample. This finding, together with the association of phthalate exposure with shift rate at birth, suggests that prenatal phthalate exposure may be associated with deficits in basic cognitive abilities including attention and working memory.

These preliminary analyses suggest that several of the physical and cognitive measures we assessed in this cohort are sensitive to prenatal phthalate and/or BPA exposure. However, it will be very important to assess the reproducibility of these initial findings in the full cohort using comprehensive multivariable models before any firm conclusions are drawn.

Future Activities:

Planned activities include completion of all 7-8 and 10-11 month follow-up assessments of the infants. The 7-8 month assessments will be completed by June 30, 2013. The 10-11 month assessments will be completed by September 30, 2013. Additional goals are to complete data entry and data coding, including the abstraction of health data from medical records for the mothers during pregnancy and the infants during the first year. As data collection, entry and coding are completed, the focus will shift to data analysis and manuscript preparation.

Journal Articles:

No journal articles submitted with this report: View all 33 publications for this subproject

Supplemental Keywords:

BPA, phthalates, child development, cognition, sex differences, Health, RFA, Scientific Discipline, Health Risk Assessment, Risk Assessments, Environmental Chemistry, Children's Health, Biochemistry, biological markers

Relevant Websites:

Children's Environmental Health Research Center at Illinois Exit /

Progress and Final Reports:

Original Abstract

2010

2011

Final Report

Main Center Abstract and Reports:

R834593 Water Innovation Network for Sustainable Small Systems

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834593C001 Prenatal Exposure to BPA/Phthalates: Infant Physical and Behavioral Development
R834593C002 Adolescent Exposure to BPA/Phthalates Cognitive and Behavioral Development
R834593C003 Mechanisms of In Utero BPA Exposure on Fetal Gonad Development
R834593C004 Effects of Bisphenol A on the Developing Cortex

Top of Page

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.