An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk: The Early Markers for Autism Study.

Background: The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes.

Methods: Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform.

Differences in Prenatal Tobacco Exposure Patterns among 13 Race/Ethnic Groups in California.

Prenatal tobacco exposure is a significant, preventable cause of childhood morbidity, yet little is known about exposure risks for many race/ethnic subpopulations. We studied active smoking and environmental tobacco smoke (ETS) exposure in a population-based cohort of 13 racially/ethnically diverse pregnant women: white, African American, Hispanic, Native American, including nine Asian/Pacific Islander subgroups: Chinese, Japanese, Korean, Filipino, Cambodian, Vietnamese, Laotian, Samoan, and Asian Indians (N = 3329). Using the major nicotine metabolite, cotinine, as an objective biomarker, we analyzed mid-pregnancy serum from prenatal screening banked in 1999⁻2002 from Southern California in an effort to understand differences in tobacco exposure patterns by race/ethnicity, as well as provide a baseline for future work to assess secular changes and longer-term health outcomes.

Recurrence after hospitalization for acute coronary syndrome among HIV-infected and HIV-uninfected individuals.

Objectives: We evaluated the association of HIV infection and immunodeficiency with acute coronary syndrome (ACS) recurrence, and with all-cause mortality as a secondary outcome, after hospitalization for ACS among HIV-infected and HIV-uninfected individuals.

Methods: We conducted a retrospective cohort study within Kaiser Permanente Northern California of HIV-infected and HIV-uninfected adults discharged after ACS hospitalization [types: ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina] during 1996-2010. We compared the outcomes of ACS recurrence and all-cause mortality within 3 years, both overall by HIV status and stratified by recent CD4 count, with HIV-uninfected individuals as the reference group.

Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.

Background: The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control.

Prenatal Serum Concentrations of Brominated Flame Retardants and Autism Spectrum Disorder and Intellectual Disability in the Early Markers of Autism Study: A Population-Based Case-Control Study in California.

Background: Prior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders.

Objectives: Our aim was to determine whether prenatal exposure to brominated flame retardants (BFRs) is associated with autism spectrum disorder (ASD) or intellectual disability without autism (ID).

Methods: We conducted a population-based case-control study including children with ASD (n=545) and ID (n=181) identified from the California Department of Developmental Services and general population (GP) controls (n=418) from state birth certificates.

Maternal perchlorate exposure in pregnancy and altered birth outcomes.

Background: At high medicinal doses perchlorate is known to decrease the production of thyroid hormone, a critical factor for fetal development. In a large and uniquely exposed cohort of pregnant women, we recently identified associations between environmental perchlorate exposures and decreased maternal thyroid hormone during pregnancy. Here, we investigate whether perchlorate might be associated with birthweight or preterm birth in the offspring of these women.

Independent Maternal and Fetal Genetic Effects on Midgestational Circulating Levels of Environmental Pollutants.

Maternal exposure to environmental pollutants could affect fetal brain development and increase autism spectrum disorder (ASD) risk in conjunction with differential genetic susceptibility. Organohalogen congeners measured in maternal midpregnancy blood samples have recently shown significant, but negative associations with offspring ASD outcome. We report the first large-scale maternal and fetal genetic study of the midpregnancy serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children collected in California by the Early Markers for Autism (EMA) Project.

Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation.

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology.

Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study.

Maternal pregnancy levels of the inflammatory marker C-reactive protein (CRP) has been previously associated with autism spectrum disorder (ASD) in the offspring. We conducted a population-based nested case-control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP) controls to further investigate whether elevated CRP during pregnancy increases the risk of ASD. Maternal CRP concentration was measured in archived serum collected during 15-19 weeks of pregnancy and genome-wide single-nucleotide polymorphism (SNP) data were generated.

Racial-ethnic differences in midtrimester maternal serum levels of angiogenic and antiangiogenic factors.

Background: Little is known about racial-ethnic differences in the distribution of maternal serum levels of angiogenic and antiangiogenic factors and their associations with early-onset preeclampsia.

Objective: We sought to investigate the distribution of midtrimester maternal serum levels of placental growth factor, soluble endoglin, and soluble vascular endothelial growth factor receptor 1 and their associations with early-onset preeclampsia in whites, Hispanics, and blacks.

Study Design: A population-based nested case-control design was used to identify cases and controls of white, Hispanic, and black origin from a 2000 through 2007 live-birth cohort in 5 southern California counties.

Thyroid Hormones and Moderate Exposure to Perchlorate during Pregnancy in Women in Southern California.

Background: Findings from national surveys suggest that everyone in the United States is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring.

Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population.

Background: Staphylococcus aureus can cause life-threatening infections. Human susceptibility to S. aureus infection may be influenced by host genetic variation.

Increased female autosomal burden of rare copy number variants in human populations and in autism families.

Autosomal genetic variation is presumed equivalent in males and females and makes a major contribution to disease risk. We set out to identify whether maternal copy number variants (CNVs) contribute to autism spectrum disorders (ASDs). Surprisingly, we observed a higher autosomal burden of large, rare CNVs in females in the population, reflected in, but not unique to, ASD families.

Cost of Care for HIV-Infected Patients with Co-Occurring Substance Use Disorder or Psychiatric Disease: Report from a Large, Integrated Health Plan.

Background. The costs of providing care to HIV-infected (HIV+) patients with co-occurring diagnoses of substance use (SU) disorder or psychiatric disease (PD) are not well documented. It is our objective to evaluate costs in these HIV+ patients receiving care in a large health plan.

Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders.

Background: Prenatal and early-life exposures to mercury have been hypothesized to be associated with increased risk of autism spectrum disorders (ASDs).

Objectives: This study investigated the association between ASDs and levels of total mercury measured in maternal serum from mid-pregnancy and infant blood shortly after birth.

Methods: The study sample was drawn from the Early Markers for Autism (EMA) Study.

Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study.

Background: Biologic markers of infection and inflammation have been associated with Autism Spectrum Disorders (ASD) but prior studies have largely relied on specimens taken after clinical diagnosis. Research on potential biologic markers early in neurodevelopment is required to evaluate possible causal pathways and screening profiles.

Objective: To investigate levels of cytokines and chemokines in newborn blood specimens as possible early biologic markers for autism.

A genome-wide survey of transgenerational genetic effects in autism.

Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction.

Levels of cotinine in dried blood specimens from newborns as a biomarker of maternal smoking close to the time of delivery.

The precise quantitation of smoking during pregnancy is difficult in retrospective studies. Routinely collected blood specimens from newborns, stored as dried blood spots, may provide a low-cost method to objectively measure maternal smoking close to the time of delivery. This article compares cotinine levels in dried blood spots to those in umbilical cord blood to assess cotinine in dried blood spots as a biomarker of maternal smoking close to the time of delivery.

Factors associated with treatment initiation for psychiatric and substance use disorders among persons with HIV.

Objective: Prior studies of individuals with HIV infection have found that accessing psychiatric and substance abuse treatment when needed can improve health and prolong life, yet little is known about factors associated with treatment initiation.

Methods: In a retrospective cohort design including individuals with HIV infection (≥14 years old) in an integrated health care system in Northern California, this study included 822 patients with a major psychiatric diagnosis and 1,624 with a substance use disorder diagnosis. Data were extracted from a regional HIV registry and computerized databases.

Trends in annual incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in HIV-infected and HIV-uninfected patients.

We describe trends in incidence rates of methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected and HIV-uninfected patients enrolled in a large northern California Health Plan, and the ratio of MRSA to methicillin-susceptible S. aureus (MSSA) case counts. Between 1995 and 2010, 1549 MRSA infections were diagnosed in 14060 HIV-infected patients (11·0%) compared to 89546 MRSA infections in 6597396 HIV-uninfected patients (1·4%) (P = 0·00).

California Very Preterm Birth Study: design and characteristics of the population- and biospecimen bank-based nested case-control study.

Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and racial disparity in the US. The underlying causes of VPTB are multiple and poorly understood. The California Very Preterm Birth Study was conducted to discover maternal and infant genetic and environmental factors associated with VPTB.

Association between second-generation antipsychotics and newly diagnosed treated diabetes mellitus: does the effect differ by dose?

Background: The benefits of some second-generation antipsychotics (SGAs) must be weighed against the increased risk for diabetes mellitus. This study examines whether the association between SGAs and diabetes differs by dose.

Methods: Patients were ≥18 years of age from three US healthcare systems and exposed to an SGA for ≥45 days between November 1, 2002 and March 31, 2005.

Excess mortality among HIV-infected patients diagnosed with substance use dependence or abuse receiving care in a fully integrated medical care program.

Background: We examined the association between substance use (SU) disorder and mortality among HIV-infected patients in a large, private medical care program.

Methods: In a retrospective cohort design, HIV-infected patients (≥14 years old) from a large health plan (Northern California) were studied to examine mortality associated with diagnosis of SU dependence or abuse over an 11-year period.

Results: At study entry or during follow-up, 2,279 (25%) of 9,178 HIV-infected patients had received a diagnosis of SU disorder.

Mortality after diagnosis of psychiatric disorders and co-occurring substance use disorders among HIV-infected patients.

We examined the associations between psychiatric diagnoses, substance use disorders, health services, and mortality among 9751 HIV-infected patients (≥14 years old) in a large, private medical care program, in a retrospective cohort design over a 12-year period. All study data were extracted from computerized clinical and administrative databases. Results showed that 25.