Over 70% of all birth defects in humans affect the head and face. Cleft lip with or without cleft palate (CL?P) is one of the most common of these defects, occurring in approximately 1 per 1,000 live births. Children with CL?P suffer deficits in speech, hearing and cognition and have higher morbidity and mortality throughout life compared to their unaffected contemporaries. Despite its frequency and clinical importance, little is known about the etiology of CL?P , and there are currently no strategies for reducing its prevalence. Because of this, the identification of risk factors for CL?P is part of the National Institute of Dental and Craniofacial Research (NIDCR) Strategic Plan for 2009-2013. Suspected CL?P risk factors that have not been fully explored include environmental toxicants. An important group of toxicants, as defined by the U.S. Environmental Protection Agency (EPA), are hazardous air pollutants, or HAPs (e.g., benzene, diesel particulate matter). HAPs are important potential risk factors for several reasons, including: 1) they are known or suspected to cause a range of adverse health outcomes;2) the potential for exposure is increasing in many communities throughout the U.S.;and 3) there are currently no national air quality standards as there are for other air pollutants (e.g., ozone). Although there is evidence from occupational studies that maternal exposure to certain HAPs is associated with CL?P, the teratogenic potential of environmental concentrations of HAPs (which are lower than in occupational settings but a more common source of exposure) has not been assessed. It is important to examine the association between maternal exposure HAPs and CL?P risk, as all women, in varying degrees, are exposed to HAPs during pregnancy. Furthermore, the developing embryo appears to be particularly vulnerable to the effects of HAPs. The investigators will examine the role of on CL?P risk using a novel application of Bayesian hierarchical modeling, which accounts for census tract-level data, exposure assessment confidence and multiple pollutants. Data on study subjects will be obtained from the Texas Birth Defects Registry;one of the largest population-based, active surveillance systems of birth defects in the world. Exposure to HAPs will be determined using the U.S. EPA National-Scale Air Toxics Assessment. The proposed study builds on 1) the exceptional resources provided by the Texas Birth Defects Registry, which includes data on approximately 2,500 nonsyndromic, isolated CL?P cases, 2) a large comparison group including all unaffected births in Texas, 3) the extensive HAP exposure assessment conducted by the U.S. EPA, 4) the principal investigator's expertise in birth defects epidemiology and 5) a strong group of research collaborators. This study is expected to identify those HAPs that deserve further exploration in independent populations, while resulting in a novel method for assessing these and other environmental toxicants. Ultimately, the identification of CL?P risk factors will open the door to new strategies for lowering the prevalence of these significant conditions.

Public Health Relevance

Cleft lip with or without cleft palate ( CL?P ) is a significant public health problem in the U.S., and because of this, the National Institute of Dental and Craniofacial Research (NIDCR) has made the identification of risk factors part of its Strategic Plan for 2009-2013. Although the causes of CL?P are complex and poorly understood, questions arise regarding the association between these adverse outcomes and maternal exposure to environmental toxicants, such as hazardous air pollutants (HAPs), due to evidence from occupational and animal studies. This study will provide the first assessment of maternal exposure to environmental concentrations of HAPs and the risk of CL?P in offspring and will be critical in identifying previously unidentified risk factors for these serious and relatively common conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE021739-02
Application #
8540860
Study Section
Special Emphasis Panel (ZDE1-MH (20))
Program Officer
Harris, Emily L
Project Start
2012-09-11
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$147,090
Indirect Cost
$14,679
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Ramakrishnan, Anushuya; Lupo, Philip J; Agopian, A J et al. (2013) Evaluating the effects of maternal exposure to benzene, toluene, ethyl benzene, and xylene on oral clefts among offspring in Texas: 1999-2008. Birth Defects Res A Clin Mol Teratol 97:532-7