The spatial distribution of known predictors of autism spectrum disorders impacts geographic variability in prevalence in central North Carolina

Environmental Health (Impact Factor: 2.71). 10/2012; 11(1):80. DOI: 10.1186/1476-069X-11-80
Source: PubMed

ABSTRACT BACKGROUND: The causes of autism spectrum disorders (ASD) remain largely unknown and widely debated; however, evidence increasingly points to the importance of environmental exposures. A growing number of studies use geographic variability in ASD prevalence or exposure patterns to investigate the association between environmental factors and ASD. However, differences in the geographic distribution of established risk and predictive factors for ASD, such as maternal education or age, can interfere with investigations of ASD etiology. We evaluated geographic variability in the prevalence of ASD in central North Carolina and the impact of spatial confounding by known risk and predictive factors. METHODS: Children meeting a standardized case definition for ASD at 8 years of age were identified through records-based surveillance for 8 counties biennially from 2002 to 2008 (n=532). Vital records were used to identify the underlying cohort (15% random sample of children born in the same years as children with an ASD, n=11,034), and to obtain birth addresses. We used generalized additive models (GAMs) to estimate the prevalence of ASD across the region by smoothing latitude and longitude. GAMs, unlike methods used in previous spatial analyses of ASD, allow for extensive adjustment of individual-level risk factors (e.g. maternal age and education) when evaluating spatial variability of disease prevalence. RESULTS: Unadjusted maps revealed geographic variation in surveillance-recognized ASD. Children born in certain regions of the study area were up to 1.27 times as likely to be recognized as having ASD compared to children born in the study area as a whole (prevalence ratio (PR) range across the study area 0.57-1.27; global P=0.003). However, geographic gradients of ASD prevalence were attenuated after adjusting for spatial confounders (adjusted PR range 0.72-1.12 across the study area; global P=0.052). CONCLUSIONS: In these data, spatial variation of ASD in central NC can be explained largely by factors impacting diagnosis, such as maternal education, emphasizing the importance of adjusting for differences in the geographic distribution of known individual-level predictors in spatial analyses of ASD. These results underscore the critical importance of accounting for such factors in studies of environmental exposures that vary across regions.

Download full-text


Available from: Kate Hoffman, Feb 12, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heightened areas of spatial relative risk for autism spectrum disorders (ASD), or ASD hotspots, in Utah were identified using adaptive kernel density functions. Children ages four, six, and eight with ASD from multiple birth cohorts were identified by the Utah Registry of Autism and Developmental Disabilities. Each ASD case was gender-matched to 20 birth cohort controls. Demographic and socioeconomic characteristics of children born inside versus outside ASD hotspots were compared. ASD hotspots were found in the surveillance area for all but one birth cohort and age group sample; maximum relative risk in these hotspots ranged from 1.8 to 3.0. Associations were found between higher socioeconomic status and birth residence in an ASD hotspot in five out of six birth cohort and age group samples.
    Journal of Autism and Developmental Disorders 09/2014; 45(4). DOI:10.1007/s10803-014-2253-0 · 3.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tremor is one of the most common neurological signs, yet its etiology is poorly understood. Case-control studies suggest an association between blood lead and essential tremor, and that this association is modified by polymorphisms in the δ-amino-levulinic acid dehydrogenase (ALAD) gene. To examine the relationship between lead and tremor, including modification by ALAD, in a prospective cohort study, using both blood lead and bone lead-a biomarker of cumulative lead exposure. We measured tibia (n=670) and patella (n=672) bone lead and blood lead (n=807) among older men (age range: 50-98 years) in the VA Normative Aging Study cohort. A tremor score was created based on an approach using hand-drawing samples. ALAD genotype was dichotomized as ALAD-2 carriers or not. We used linear regression adjusted for age, education, smoking, and alcohol intake to estimate the associations between lead biomarkers and tremor score. In unadjusted analyses, there was a marginal association between quintiles of all lead biomarkers and tremor scores (p values <0.13), that did not persist in adjusted models. Age was the strongest predictor of tremor. Among those younger than the median age (68.9), tremor increased significantly with blood lead (p=0.03), but this pattern was not apparent for bone lead. We did not see modification by ALAD or an association between bone lead and change in tremor score over time. Our results do not strongly support an association between lead exposure and tremor, and suggest no association with cumulative lead biomarkers, although there is some suggestion that blood lead may be associated with tremor among the younger men in our cohort.
    Environmental Health Perspectives 01/2015; DOI:10.1289/ehp.1408535 · 7.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We analyzed data from the Israeli National Insurance Institute (NII). Autism Spectrum Disorder (ASD) incidence was calculated for all children born in Israel 1992-2009, and by population groups. Overall, 9,109 ASD cases among 2,431,649 children were identified. ASD cumulative incidence by age 8 years increased 10-fold during 2000-2011, from 0.49 % to 0.49 %, while other child disabilities in NII increased only 1.65-fold. There was a consistent increase in ASD incidence with advancing birth cohorts born 1992-2004, stabilizing among those born 2005-2009. ASD rates among Israeli Arabs were substantially lower, and increased about 10 years later than the general population. The findings suggest a role for ASD awareness, accessing of the government benefit, or the way the concept of ASD is perceived.
    Journal of Autism and Developmental Disorders 10/2014; 45(4). DOI:10.1007/s10803-014-2262-z · 3.34 Impact Factor