To examine temporal specificity of any associations between PM and ASD, we considered the association with PM2.5 exposure during the 9 months before pregnancy, the pregnancy period, and the 9 months after birth. These examinations were restricted to nonmovers with complete data for all exposure periods, and each time period was considered independently, and then also in a single model that included all three time periods simultaneously. Because of differences in ASD rates by sex and prior suggestions that air pollution effects may be specific to boys, we a priori decided to also examine associations stratified by sex of the child. For simplicity, we did this only among the children whose mothers did not move during pregnancy. We used SAS version 9.3 (SAS Institute Inc., Cary, NC) for data extraction, and R version 3.0.1 () for Linux-gnu for analyses. All analyses were conducted at the 0.05 alpha level.
In 2005, NHS II participants were asked whether any of their children had been diagnosed with autism, Asperger’s syndrome, or “other autism spectrum,” and 839 women replied affirmatively. In 2007, we initiated a pilot follow-up study, shortly followed by a full-scale follow-up as described previously (). The follow-up questionnaire included questions about the pregnancy and birth, child’s sex, and diagnosis. NHS II protocol allows re-contacting only the nurses who responded to the most recent biennial questionnaire. Thus, this follow-up was attempted with the 756 mothers of ASD cases for whom this was the case. Mothers who reported having more than one child with ASD were directed to report about the youngest one. Controls were selected from among parous women not reporting a child with ASD in 2005. For each case mother, controls were randomly selected from among those women who gave birth to a child in a matching birth year, to yield a total of 3,000 controls. Six hundred thirty-six (84%) mothers of cases and 2,747 (92%) mothers of controls responded; 164 women (including 51 case mothers) declined to participate.
ASD cases were more likely to be male, to have been exposed to maternal preeclampsia or maternal smoking during gestation, and to be missing data on premature birth compared with controls (). The median (25th–75th percentile) year of birth for cases and controls was the same: 1993 (1991–1996). As expected given time trends in air pollution, control children born in earlier years were more likely to be in higher PM2.5 quartiles. Census income and parental age also decreased slightly, but generally steadily by exposure, whereas there was little clear pattern of difference by exposure for other variables ().
Our goal was to explore the association between ASD and exposure to PM during defined time periods before, during, and after pregnancy, within the Nurses’ Health Study II (NHS II), a large, well-defined cohort with detailed residential history. This nested case–control study includes participants from across the continental United States, and exposure was linked to monthly data on two size fractions of PM.
In our nested case–control study of nurses from across the continental United States, ambient PM2.5 concentrations during pregnancy were significantly associated with having a child diagnosed with ASD. Importantly, the association we found appeared specific to PM2.5 during pregnancy; PM2.5 exposure before or after pregnancy showed weaker associations with ASD, and PM10–2.5 during pregnancy showed little association with ASD. In a model mutually adjusted for all three exposure periods, only the pregnancy period was associated with ASD. The change in the ORs with mutual adjustment did not appear to be an artifact of collinearity because the precision of the mutually adjusted model was not substantially lower than the single exposure model (e.g., CI widths for an IQR change in PM2.5 during pregnancy of 2.3 vs. 1.7, respectively). The 95% CIs were not notably larger in this analysis, suggesting that collinearity was not a significant problem. Moreover, during pregnancy we found the association to be specifically with the third-trimester exposure in models that included exposure in all trimesters together. The specificity of the association to the prenatal period is in line with several other lines of evidence that suggest a prenatal origin of ASD, including data on differences in brain cytoarchitecture in brains of children with ASD (; ) and associations between maternal exposure to teratogens during pregnancy and ASD (). Our results also suggest an association predominantly in boys, but this finding should be interpreted with caution, given the small number of girls with ASD in our sample.
These results generally agree with previous studies. A report from the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study among 304 ASD cases and 259 controls, in several areas in California, used residential address history reported by parents to calculate distance to roads as a proxy for traffic-related air pollution exposure and found increased risk for ASD among women who lived in proximity to a freeway (). Further analysis of the CHARGE study group in a subset of 279 cases and 245 controls using data from the U.S. EPA Air Quality System suggested positive associations of ASD with traffic-related air pollution during pregnancy, and specifically with PM2.5 (). ASD was also associated with pregnancy exposure to PM10, and—in contrast to our results—the association with traffic-related air pollution exposure during the first year of life was higher than that found for the exposure during pregnancy. In the CHARGE study, associations were also seen with exposures in the year after birth that were about as strong as exposures during pregnancy. Our findings suggested a weaker association with postpregnancy exposure that was essentially null in models that included exposure during all time periods. In the CHARGE study, however, the pregnancy and postpregnancy exposure periods were not included together in the same regression model.
Lung cancer is a lethal malignancy, however, no serum marker is routinely recommended till now. Prospectively two groups of patients included: Group I: Patients with advanced lung cancer. Group II: patients with benign lung disease as control. Serum Tissue Polypeptide Antigen (TPA) levels were measured by ELISA technique before the first line chemotherapy. The TPA cutoff taken was 1800 pg./ml. End points were comparison of high TPA in cases and controls and correlation between high TPA and disease progression (PD), progression free survival (PFS) and overall survival (OS). 30 patients with advanced lung cancer (16 non-small and 14 small cell lung cancer) and 15 patients with benign lung disease were included and followed up during the period from October 2008 to October 2011 with median follow-up of 1.5 years. High TPA was found in 50% of lung cancer cases compared to 26% in controls (p = 0.014). High TPA was found in 64% of cases showing PD versus 36% normal TPA (p = 0.08). 1 year PFS in high TPA was 32% versus 39% in normal TPA, (p = 0.2). 1 year OS in high TPA was 46% versus 73% in normal TPA (p = 0.6). Serum TPA is a potential marker for advanced lung cancer.
Citation: Raz R, Roberts AL, Lyall K, Hart JE, Just AC, Laden F, Weisskopf MG. 2015. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case–control analysis within the Nurses’ Health Study II cohort. Environ Health Perspect 123:264–270;
Another study, from Los Angeles (LA) County, used birth certificate address and ASD cases identified from the Department of Developmental Services in California (). Using exposure data from the nearest monitoring stations and from a land use regression model (), they found a positive association between PM2.5 exposure and autism (OR per 4.68 μg/m3 PM2.5 = 1.15; 95% CI: 1.06, 1.24 in a model of exposure over the entire pregnancy and also adjusted for ozone levels). There was not a consistent association with PM10. The LA study included many more ASD cases than any of the other studies, so the effect estimate could represent a more stable estimate of the true effects of PM. Alternatively, differences in the composition of PM in the LA area could result in smaller effects. Other differences in study design could also have led to smaller effect sizes in the LA study. The case definition was a primary diagnosis of autistic disorder, the most severe among ASD diagnoses, and the association with PM could be preferentially with milder forms of ASD. Slightly more measurement error from using a nearest monitor exposure assignment approach or addresses from the birth certificate could have biased results toward the null. Smaller associations in that study could also have occurred if there was under-ascertainment of cases among children of more highly exposed mothers. Lower socioeconomic status has been associated with under-ascertainment in ASD registries such as that used in the LA study (). Although estimates were not much different when the sample was stratified by education level, if residual socioeconomic differences were associated with PM2.5 exposures (lower socioeconomic status with higher PM2.5) this could lead to bias toward the null because the controls included all birth certificates in the region. The importance of the environment in the development of ASD was recently implicated in a comparison of concordance rates between monozygotic and dizygotic twins that found that the shared environment accounted for 58% (95% CI: 30, 80%) of the broader autism phenotype (). In line with these findings, a comparison of sibling ASD recurrence risk in a different population revealed a much higher rate of ASD recurrence in half-siblings with the same mother (2.4; 95% CI: 1.4, 4.1) compared with half-siblings with the same father (1.5; 95% CI: 0.7, 3.4) (). This finding may be attributed either to maternal factors affecting the in utero environment or to common mitochondrial DNA.
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