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.

BackgroundPrior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders.ObjectivesOur 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).MethodsWe 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. ASD cases were matched to controls by sex, birth month, and birth year. Concentrations of 10 BFRs were measured in maternal second trimester serum samples stored from routine screening. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses.ResultsGeometric mean concentrations of five of the six congeners with ≥55% of samples above the limit of detection were lower in mothers of children with ASD or ID than in controls. In adjusted analyses, inverse associations with several congeners were found for ASD relative to GP (e.g., quartile 4 vs. 1, BDE-153: AOR=0.56, 95% CI: 0.38, 0.84). When stratified by child sex (including 99 females with ASD, 77 with ID, and 73 with GP), estimates were consistent with overall analyses in boys, but in the opposite direction among girls, particularly for BDE-28 and -47 (AOR=2.58, 95% CI: 0.86, 7.79 and AOR=2.64, 95% CI: 0.97, 7.19, respectively). Similar patterns overall and by sex were observed for ID.ConclusionsContrary to expectation, higher PBDE concentrations were associated with decreased odds of ASD and ID, though not in girls. These findings require confirmation but suggest potential sexual dimorphism in associations with prenatal exposure to BFRs. https://doi.org/10.1289/EHP1079

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. Prevalence of active smoking (based on age- and race-specific cotinine cutpoints) was highest among African American, Samoan, Native Americans and whites (6.8⁻14.1%); and lowest among Filipinos, Chinese, Vietnamese and Asian Indians (0.3⁻1.0%). ETS exposure among non-smokers was highest among African Americans and Samoans, followed by Cambodians, Native Americans, Vietnamese and Koreans, and lowest among Filipinos, Japanese, whites, and Chinese. At least 75% of women had detectable cotinine. While for most groups, levels of active smoking corresponded with levels of ETS, divergent patterns were also found. For example, smoking prevalence among white women was among the highest, but the group's ETS exposure was low among non-smokers; while Vietnamese women were unlikely to be active smokers, they experienced relatively high ETS exposure. Knowledge of race/ethnic differences may be useful in assessing disparities in health outcomes and creating successful tobacco interventions

HLA-G 14bp Polymorphism in Autism

Autism Spectrum Disorder (ASD) is a neurodevelopment disorder characterized by deficits in communicative and social behaviors (Meltzer, 2017) . As of 2012 the CDC reported that 1 of 68 children born in the U.S. have ASD (Christensen, 2016). The immune systems of mother and child can be important in ASD. A signaling molecule, HLA-G, helps regulate maternal natural killer cell interaction with the fetus. A defect in HLA-G could increase NK cell activity, leading to abnormal neurodevelopment in the fetus (Carosella, 2008). Our study focuses on a 14 base pair insertion/deletion found in the HLA-G gene of autistic subjects and their mothers, previously examined in an Italian population by Guerini (2014). We are also expanding to look at HLA-G and intellectual disability (ID) in ASD. HLA-DRB1, another gene in the HLA region of chromosome 6, has been linked to ASD and impaired ID (IQ\u3c80, Wang, 2013)

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. METHODS:This is the first genetic study of > 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. RESULTS:We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. CONCLUSIONS:Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders

Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs

In November 2003, CDC and the Cystic Fibrosis Foundation cosponsored a workshop to review the benefits and risks associated with newborn screening for cystic fibrosis (CF). This report describes new research findings and outlines the recommendations of the workshop. The peer-reviewed evidence presented at the workshop supports the clinical utility of newborn screening for CF. Demonstrated long-term benefits from early nutritional treatment as a result of newborn screening for CF include improved growth and, in one study, cognitive development. Other benefits might include reduced hospitalizations and improved survival. Mixed evidence has been reported for pulmonary outcomes. Newborn screening in the United States is associated with diagnosis of CF a median of 1 year earlier than symptomatic detection, which might reduce the expense and anxiety associated with workup for failure to thrive or other symptoms. Certain psychosocial risks for carrier children and their families (e.g., anxiety and misunderstanding) are associated with newborn screening. Exposure of young children to infectious agents through person-to-person transmission in clinical settings, although not an inherent risk of newborn screening, is a potential cause of harm from early detection. Involving specialists in CF care and infection control, genetic counseling, and communication can minimize these potential harms. Although screening decisions depend on a state\u27s individual resources and priorities, on the basis of evidence of moderate benefits and low risk of harm, CDC believes that newborn screening for CF is justified. States should consider the magnitude of benefits and costs and the need to minimize risks through careful planning and implementation, including ongoing collection and evaluation of outcome data

Redundancy, Diversity, and Modularity in Network Resilience : Applications for International Trade and Implications for Public Policy

Sustainability is increasingly concerned with the complex interactions between nature and society, and we need to seek solutions towards the challenges that threaten humanity's collective wellbeing. Towards this end, it is critical to advance the application of research examining the dynamic interactions of the components of complex social-ecological systems and their emerging properties. A key research area is on advancing tools and strategies relevant to the evaluation and strengthening of resilience. Redundancy, diversity, and modularity are important characteristics of resilience with a high potential for application in various critical social-ecological systems. This paper provides a critical overview of the theoretical underpinnings of modularity and redundancy and their application in measuring resilience of trade networks with implications for public policy and institutional design

Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study

<p>Abstract</p> <p>Background</p> <p>Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders.</p> <p>Methods</p> <p>Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (<it>n </it>= 84), (2) a developmental delay (DD) but not autism (<it>n </it>= 49) or (3) no known developmental disability (general population (GP); <it>n </it>= 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis.</p> <p>Results</p> <p>Elevated concentrations of IFN-γ, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism.</p> <p>Conclusion</p> <p>The profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.</p

The Association Between Pre-pregnancy BMI and Preterm Delivery in a Diverse Southern California Population of Working Women

Whereas preterm birth has consistently been associated with low maternal pre-pregnancy weight, the relationship with high pre-pregnancy weight has been inconsistent. We quantified the pre-pregnancy BMI—preterm delivery (PTD) relationship using traditional BMI categories (underweight, normal weight, overweight and obese) as well as continuous BMI. Eligible women participated in California’s statewide prenatal screening program, worked during pregnancy, and delivered a live singleton birth in Southern California in 2002–2003. The final analytic sample included 354 cases delivering at <37 weeks, as identified by clinical estimate of gestational age from screening records, and 710 term normal-birthweight controls. Multivariable logistic regression models using categorical BMI levels and continuous BMI were compared. In categorical analyses, PTD was significantly associated with pre-pregnancy underweight only. Nonparametric local regression revealed a V-shaped relationship between continuous BMI and PTD, with minimum risk at the high end of normal, around 24 kg/m2. The odds ratio (OR) for PTD associated with low BMI within the normal range (19 kg/m2) was 2.84 (95%CI = 1.61–5.01); ORs for higher BMI in the overweight (29 kg/m2) and obese (34 kg/m2) ranges were 1.42 (95%CI = 1.10–1.84) and 2.01 (95% CI = 1.20–3.39) respectively, relative to 24 kg/m2). BMI categories obscured the preterm delivery risk associated with low-normal, overweight, and obese BMI. We found that higher BMI up to around 24 kg/m2 is increasingly protective of preterm delivery, beyond which a higher body mass index becomes detrimental. Current NHLBI/WHO BMI categories may be inadequate for identifying women at higher risk for PTD