UCLA

Background: Autistic Disorder (AD) is a serious developmental condition with a wide range of symptoms and the prevalence has risen dramatically over the past two decades. The pathogenic mechanisms of autism have yet to be determined or are not well understood. Epidemiologic investigations support a prenatal or early postnatal origin of autism and it is likely that multiple genes interacting with one or more environmental factors cause some cases. However, high-quality population-based research addressing etiology is limited. There may be phenotypic differences in the presentation of autism in minority groups that may indicate etiologic heterogeneity, but it is unknown whether maternal race/ethnicity and nativity are risk factors for childhood autism in the U.S. Few studies to date have examined the impact of air pollution on brain development in general during pregnancy, although epidemiologic studies have associated air pollution exposure during the prenatal period to a variety of adverse birth outcomes. Few studies to date have examined the impact of air pollution on brain development in general during pregnancy, although epidemiologic studies have associated air pollution exposure during the prenatal period to a variety of adverse birth outcomes. Our first aim was to investigate the association between traffic related air pollution exposures during pregnancy and autism using: 1) ambient criteria air pollutant measurements, and 2) land-use regression (LUR) to model traffic related air pollution exposures, using a matched case-control design. The second and third aim was to determine whether the risk of autism and autistic phenotypes, i.e., comorbid mental retardation, expressive language, and emotional/behavioral deficits, differ by maternal race/ethnicity and nativity. Using U.S.-born white mothers as reference, we examined autism relative risks in Hispanics and black mothers born in or outside of the U.S of which mothers born in Mexico or Central/South America were specified. In addition, we examined the association between autism and maternal Asian race/ethnicity in women born in the U.S., China, Japan, Korea, Philippines, or Vietnam.

Methods: Children of mothers who gave birth in Los Angeles who were diagnosed with a primary AD diagnosis at ages 3-5 years during 1998-2009 were identified through the California Department of Developmental Services and linked to 1995-2006 California birth certificates. For 7,603 children with autism, in the first study we selected 10 controls per case matched by sex, birth year, and minimum gestational age, birth addresses were mapped and linked to the nearest air monitoring station and a LUR model. For the second study, 6,485 children with AD were selected from a cohort of 1,461,610 births from white, Hispanic, and black mothers; and for the final study 2,532 children with AD were selected from a cohort of 401,091 births from Asian and U.S.-born white mothers. We further identified a subgroup of children with AD and a secondary diagnosis of mental retardation (AD-MR). To appropriately investigate language and behavior heterogeneity, we restricted assessments to 5-year olds. We identified from DDS evaluation records two subgroups with either "impaired" or "less impaired" expressive language; and two subgroups with "severe" or "less severe" emotional outburst behavior.

Summary of findings: Per interquartile range (IQR) increase, we estimated a 12-15% relative increase in odds of autism for O3 (11.54ppb) and PM2.5 (4.68 μg/m3) when mutually adjusting for both pollutants. Furthermore, we estimated 3-9% relative increases in odds per IQR increase for LUR-based NO (9.4ppb) and NO2 (5.4ppb) exposure estimates. LUR-based associations were strongest for children of mothers with less than a high school education. We found increases in risk for AD and AD-MR for children of foreign-born (FB) black mothers and Hispanic mothers from Central/South America, as well as of mothers who immigrated from the Philippines and Vietnam compared to U.S.-born whites. We estimated a 52% and 53% relative increase in risk of having a child with AD-MR for both U.S.-born African American/black and Hispanic mothers, respectively. Compared to children with autism of U.S.-born white mothers, most other maternal subgroups, except for foreign-born Chinese or Japanese mothers, had children with a higher risk of impaired expressive language. Severity of emotional outbursts was higher in children of foreign-born black and Centra/South American mothers, as well as in U.S.-born Hispanics. However, severe emotional outbursts seem to co-occur with impaired language.