Council on Environmental Health
Article Review

Prepared by: Joel A. Forman, MD
April 2010

TITLE
Prenatal Phthalate Exposure is Associated with Childhood Behavior and Executive Functioning

AUTHORS
Stephanie M. Engel, Amir Miodovnik, Richard L. Canfield, Chenbo Zhu, Manori J. Silva, Antonia M. Calafat, Mary S. Wolff
 
FIND IT AT
Environmental Health Perspectives
http://ehsehplp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1289%2Fehp.0901470#Ahead%20of%20Print%20(AOP)

THE PROBLEM
Phthalates are a group of chemicals used in many consumer products as plasticizers, solvents, antifoam agents, or alcohol denaturants. These chemicals can be grouped by molecular weight into high molecular weight (HMW) phthalates (e.g. DEHP), frequently found in tubing, vinyl flooring, and wall covering, and low molecular weight (HMW) phthalates (e.g. DEP) more commonly found in personal care products such as fragrances, shampoo, cosmetics and nail polish. Large scale reliable biomonitoring studies demonstrate nearly ubiquitous exposure to these chemical throughout the world. Animal and human studies suggesting anti-androgen effects on the male reproductive system have led to regulatory action in the US and Europe. Another toxic effect of phthalates, particular LMW phthalates, is antagonism of the thyroid system. This effect is concerning because of the central role of the thyroid system in behavior and neurodevelopment.

WHAT THEY DID
Researchers at Mount Sinai Children’s Environmental Health Center evaluated the relationship between prenatal phthalate exposure and subsequent neurobehavioral development during childhood as part of a prospective cohort study. This multiethnic prenatal cohort in New York City gathered between 1998 and 2002 includes 404 primiparous participants. The researchers were able to follow 177 mothers (in whom urine was available for phthalate measurement) and their children at three time points: 4.5-5.5 years, 6-6.5 years, and 7-9 years. Mothers completed parent-report forms of the Behavior Rating Inventory of Executive Functioning (BRIEF), and the Behavior Assessment System for Children (BASC-PRS) at 365 total visits across these three age points. Prenatal phthalate exposure was determined by measuring the concentrations of 10 phthalate metabolites in 3rd trimester spot urine samples from 177 mothers; analysis was performed by the CDC.

WHAT THEY FOUND
Higher LMW phthalate concentrations in 3rd trimester maternal urine samples were associated with poorer scores on the Aggression, Attention Problems, Conduct Problems, Depression, and Externalizing Problems scales, and for the overall Behavioral Symptoms Index on the BASC at ages 4 to 9 years old. Similarly, poorer executive functioning at the same ages was indicated by elevated scores on the Emotional Control scale and on the Global Executive Composite index of the BRIEF.  HMW Phthalates were only associated with poorer scores on the adaptability scale of the BASC. When outlying (possible less reliable) scores were excluded there was a suggestion of a greater effect in boys but the effect was still significant in boys and girls. Although few scores fell in the ‘at risk’ or ‘clinically significant’ range, a sensitivity analysis demonstrated a trend towards an association with LMW phthalate concentration above the median. Attention problems (n=27 surveys) reached clinical significance (RR = 2.66 CI 1.06, 6.66).

DISCUSSION
This is the first prospective evidence of an association between prenatal LMW phthalate exposure and neurobehavioral abnormalities. The relationship is fairly strong and consistent and the measures of both exposure and outcomes are done in reliable laboratories and using well validated exams. Although attrition was fairly large there were few significant differences between the cohort studied and those lost to follow up. This builds on evidence of prenatal effects on neonatal behavior (Engel et al. 2009) and cross sectional associations seen in school aged children (Kim et al. 2009). Although few of the behavioral questionnaires scored in the clinically significant range, the result profiles are similar to those seen in children with ADHD and ODD.  The proposed mechanism for this effect is disruption of the maternal thyroid system for which there is a growing body of supporting literature.
 
The study does have some weaknesses, however.  In particular, there are many variables that impact on psychosocial development that are not accounted for in the model including parental psychological issues (depression, ODD, ADD), level of family psychosocial stressors, other exposures (e.g. concurrent childhood phthalate levels or lead levels), and other birth factors such as birth weight and childhood illnesses.
 
Because of the ubiquitous exposure of the population to phthalates and the lack of substantial regulation of these chemicals in products used by adults there is widespread exposure to a vulnerable population. If subsequent studies replicate these findings, it may be prudent for pregnant women to reduce their exposures and to expand regulation of LMW phthalates.

RELATED ARTICLES

  • Engel SM, Zhu C, Berkowitz GS, Calafat AM, Silva MJ, Miodovnik A, et al. 2009. Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort. Neurotoxicology 30(4): 522-528.
  • Kim BN, Cho SC, Kim Y, Shin MS, Yoo HJ, Kim JW, et al. 2009. Phthalates exposure and attention- deficit/hyperactivity disorder in school-age children. Biol Psychiatry 66(10): 958-963.
  • Sheela Sathyanarayana, Catherine J. Karr, Paula Lozano, Elizabeth Brown, Antonia M. Calafat, Fan Liu, and Shanna H. Swan. Baby Care Products: Possible Sources of Infant Phthalate Exposure. Pediatrics 2008;121;e260-e268
  • Susan M. Duty, Robin M. Ackerman, Antonia M. Calafat, and Russ Hausaser. Personal Care Product Use Predicts Urinary Concentrations of Some Phthalate Monoesters. Environ Health Perspect 113:1530–1535 (2005)

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