In utero pyrethroid pesticide exposure in relation to autism spectrum disorder (ASD) and other neurodevelopmental outcomes at 3 years in the MARBLES longitudinal cohort.

BACKGROUND: We assessed the relationships between prenatal pyrethroid pesticide exposure and autism spectrum disorders (ASD) or non-typical development (non-TD) at 3 years. METHODS: Participants were mother-child pairs (n = 201) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Because familial recurrence risk is high, MARBLES enrolls pregnant women with a family history of ASD. Children from these pregnancies were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, typically developing (TD), or non-TD (neither TD or ASD). Repeated maternal second and third trimester urine samples were analyzed for pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). Multinomial logistic regression was used to obtain relative risk ratios (RRR) linking 3-PBA concentrations averaged across each trimester and over pregnancy with child's outcome: ASD or non-TD vs. TD. Models were adjusted for specific gravity, maternal pre-pregnancy BMI, prenatal vitamin use, birth year, home-ownership, and pregnancy concentrations of TCPy (3,5,6-trichloro-2-pyridinol, a metabolite of chlorpyrifos). RESULTS: The median specific gravity corrected 3-PBA concentration of all samples was 1.46 ng/mL. Greater second trimester 3-PBA concentrations were associated with a relative risk ratio (RRR) for ASD of (RRR: 1.50 (95% CI 0.89 to 2.51), p = 0.12). There were no differences between non-TD and TD. CONCLUSIONS: This study found no evidence for differences in 3-PBA comparing non-TD with TD. A modestly elevated RRR was found comparing second trimester urinary 3-PBA concentrations for ASD versus TD; however, the confidence interval was wide and hence, these findings cannot be considered definitive.

Variability of urinary pesticide metabolite concentrations during pregnancy in the MARBLES Study.

BACKGROUND: Variability of short-lived urinary pesticide metabolites during pregnancy raises challenges for exposure assessment. OBJECTIVES: For urinary metabolite concentrations 3-phenoxybenzoic acid (3-PBA) and 3,5,6-trichloro-2-pyridinol (TCPy), we assessed: (1) temporal variability; (2) variation of two urine specimens within a trimester; (3) reliability for pesticide concentrations from a single urine specimen to classify participants into exposure tertiles; and (4) seasonal or year variations. METHODS: Pregnant mothers (N = 166) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) Study provided urine specimens (n = 528). First morning void (FMV), pooled, and 24-h specimens were analyzed for 3-PBA and TCPy. For 9 mothers (n = 88 specimens), each urine specimen was analyzed separately (not pooled) to estimate within- and between-person variance components expressed as intraclass correlation coefficients (ICC). Pesticide concentrations from two specimens within a trimester were also assessed using ICC's. Agreement for exposure classifications was assessed with weighted Cohen's kappa statistics. Longitudinal mixed effect models were used to assess seasonal or year variations. RESULTS: Urinary pesticide metabolites were detected in ≥ 93% of specimens analyzed. The highest ICC from repeated individual specimens was from specific gravity-corrected FMV specimens for 3-PBA (ICC=0.13). Despite high within-person variability, the median concentrations did not differ across trimesters. Concentrations from pooled specimens had substantial agreement predicting exposure categories for TCPy (K = 0.67, 95% CI (0.59, 0.76)) and moderate agreement for 3-PBA (K = 0.59, 95% CI (0.49, 0.69)). TCPy concentrations significantly decreased from 2007 to 2014. CONCLUSIONS: Pooled specimens may improve exposure classification and reduce laboratory costs for compounds with short biological half-lives in epidemiological studies.

Extensively drug-resistant tuberculosis in california, 1993-2006.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a global public health emergency. We investigated the characteristics and extent of XDR TB in California to inform public health interventions. METHODS: XDR TB was defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre-XDR TB was defined as TB with resistance to isoniazid and rifampin and either a fluoroquinolone or second-line injectable agent but not both. We analyzed TB case reports submitted to the state TB registry for the period 1993-2006. Local health departments and the state TB laboratory were queried to ensure complete drug susceptibility reporting. RESULTS: Among 424 multidrug-resistant (MDR) TB cases with complete drug susceptibility reporting, 18 (4.2%) were extensively drug resistant, and 77 (18%) were pre-extensively drug resistant. The proportion of pre-XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 (P = .02)). Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were diagnosed in patients within 6 months after arrival in the United States. Mexico was the most common country of origin. Five cases (29%) of XDR TB were acquired during therapy in California. All patients with XDR TB had pulmonary disease, and most had prolonged infectious periods; the median time for conversion of sputum culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%) completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to receive treatment. CONCLUSIONS: XDR TB and pre-XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting.

Maternal metabolic profile predicts high or low risk of an autism pregnancy outcome.

BACKGROUND: Currently there is no test for pregnant mothers that can predict the probability of having a child that will be diagnosed with autism spectrum disorder (ASD). Recent estimates indicate that if a mother has previously had a child with ASD, the risk of having a second child with ASD is ~18.7% (High Risk) whereas the risk of ASD in the general population is ~1.7% (Low Risk). METHODS: In this study, metabolites of the folate-dependent transmethylation and transsulfuration biochemical pathways of pregnant mothers were measured to determine whether or not the risk of having a child with autism could be predicted by her metabolic profile. Pregnant mothers who have had a child with autism before were separated into two groups based on the diagnosis of their child whether the child had autism (ASD) or not (TD). Then these mothers were compared to a group of control mothers who have not had a child with autism before. A total of 107 mothers were in the High Risk category and 25 mothers in the Low Risk category. The High Risk category was further separated into 29 mothers in the ASD group and 78 mothers in the TD group. RESULTS: The metabolic results indicated that among High Risk mothers, it was not possible to predict an autism pregnancy outcome. However, the metabolic profile was able to predict with approximately 90% sensitivity and specificity whether a mother fell into the High Risk group (18.7% risk) or Low Risk group (1.7% risk). CONCLUSIONS: Based upon these measurements it is not possible to determine during a pregnancy if a child will be diagnosed with ASD by age 3. However, differences in the folate-dependent transmethylation and transsulfuration metabolites are indicative of the risk level (High Risk of 18.7% vs. Low Risk of 1.7%) of the mother for having a child with ASD.

Matching AIDS and tuberculosis registry data to identify AIDS/tuberculosis comorbidity cases in California.

The purpose of this study was to evaluate the sensitivity and positive predictive value (PPV) of a registry data linkage procedure used in the California AIDS and Tuberculosis (TB) Registry Data Linkage Study to identify AIDS/TB comorbidity cases in California. The California AIDS registry data from 1981 to 2006 were linked to the California TB registry data from 1996 to 2006 using LinkPlus, a probabilistic record linkage program developed by the Centers for Disease Control and Prevention, and matched results were manually reviewed to determine true or false matches. We estimated the sensitivity of this procedure to range from 98.0 per cent (95% confidence interval, CI: 97.3%, 98.7%) to 98.8 per cent (95% CI: 98.1%, 99.2%), and the PPV to be 100 per cent (95% CI: 96.8%, 100.0%). Our study demonstrated the feasibility of using this linkage procedure to match AIDS and TB registry data with a very high degree of accuracy.