Trends in the Prevalence of Autism Spectrum Disorder in California: Disparities by Sociodemographic Factors and Region Between 1990-2018.

Autism Spectrum Disorders (ASD) prevalence has risen globally, with regional variation and sociodemographic disparities affecting diagnosis and intervention. This study examines ASD trends from 1990 to 2018 in California (CA), focusing on sociodemographic factors that may inform policy/interventions. Using CA Department of Public Health birth records (1990-2018) and Developmental Services ASD cases (1994-2022), we analyzed diagnosis incidence by age 4 or 8, stratified by sociodemographic and regional factors. From 1990 to 2018, for each birth year the cumulative incidence of ASD by 4 and 8 years of age in CA increased while the diagnosis age decreased. Distinct patterns emerged over these three decades. Children born to White and Asian and Pacific Islander (API) mothers, or to mothers with higher education or living in high socioeconomic status (SES) neighborhoods exhibited higher ASD cumulative incidences throughout the 1990s and early 2000s. However, in the mid-2000s, ASD incidence in children born to Black or Hispanic mothers, with low education, or living in low SES neighborhoods surpassed that of White/API children or those living in high SES neighborhoods. Black or Hispanic children now have the highest ASD cumulative incidence, even though age at first diagnosis remains lowest in high SES regions, for the highly educated, and for White/API children. ASD cumulative incidence in CA from 1990 to 2018 exhibited demographic reversals with higher rates in children born to Black or Hispanic mothers or lower SES neighborhoods. Black and Hispanic children still have delayed age at diagnosis compared to White/API children.

News media coverage of LGBT identities over 10 years in a 400-million-word corpus.

BACKGROUND: This study is the first to analyze LGBT portrayals in a news media dataset over a decade (2010-2020). We selected Singapore as a country of interest, emblematic of a nation grappling with state-encouraged heteronormativity and a remnant colonial law against homosexuality (377A), fraught with calls for its repeal that was only enacted in 2022. Our study is interested in this period bookended by challenge and change, particularly in newspaper portrayals of LGBT narratives. Newspapers are an important source of current information and have the power to shape societal perceptions. We lay the groundwork and provide a framework to analyze news media narratives of other Commonwealth nations with colonial pasts and inherited laws criminalizing LGBT communities. OBJECTIVES: This study analyzes LGBT portrayals in a 400-million-word news media dataset over a decade (2010-2020). First, we aimed to track the volume of LGBT media coverage over time and elucidate differences in coverage of different identity markers. Second, we aimed to track sentiments on LGBT portrayals. Third, we aimed to track salient narratives circulated about LGBT stories. METHODS: The study leveraged a 400-million-word corpus from news media in Singapore, identifying the following target keywords: LGBT, Lesbian, Gay, Bisexual, Transgender, Pink Dot (a local Pride event), 377A. First, coverage volume was tracked using annual changes in keyword mentions per million, elucidating differences in coverage of different sub-groups. Second, sentiment analysis on a valence scale was conducted on LGBT collocates. Third, we distilled salient narratives about LGBT identities using thematic labelling of top-frequency collocates. RESULTS: First, overall coverage of LGBT steadily increased over the decade, though Gay identities evidenced asymmetrical coverage-outstripping 'Bisexual' keywords by seven times, 'Lesbian' by four, 'Transgender' by two. Second, sentiment scores for Pink Dot (a local pride event) were most positive; Lesbian, Gay, LGBT, Transgender were neutral; Bisexual and 377A dipped slightly negative. Third, topics differed across the four identities: uniquely, 'Lesbian' collocates related to sensationalized cinema; 'Gay' about hate crimes; 'Bisexual' about population surveys; 'Transgender' about challenges (transitioning, alienation, suicide). CONCLUSIONS: Practically, we presented a decade-long barometer of LGBT sentiments and themes on a national level, providing a framework to analyze media for more effective communication strategies-applicable to Commonwealth countries with similar inherited colonial laws. Salient repetition through media association may unwittingly frame certain issues negatively; caution is prudent in representing each sub-group adequately, rather than portraying the LGBT identity as monolithic.

Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study.

BACKGROUND: Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring. OBJECTIVE: This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery. METHODS: This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery. RESULTS: Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset. CONCLUSIONS: Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.

Exposure to gestational diabetes mellitus in utero impacts hippocampal functional connectivity in response to food cues in children.

Objectives: Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affects hippocampal functional connectivity during exposure to food cues using functional magnetic resonance imaging. Methods: Participants were 90 children age 7-11 years (53 females) who underwent an fMRI-based visual food cue task in the fasted state. Hippocampal functional connectivity (FC) was examined using generalized psychophysiological interaction in response to high-calorie food versus non-food cues. Food-cue induced hippocampal FC was compared between children with and without GDM exposure, while controlling for possible confounding effects of age, sex and waist-to-hip ratio. Results: Children with GDM exposure exhibited stronger hippocampal FC to the insula and striatum (i.e., putamen, pallidum and nucleus accumbens) compared to unexposed children, while viewing high caloric food cues. Conclusions: Intrauterine exposure to GDM was associated with higher food-cue induced hippocampal FC to reward processing regions. Future studies with longitudinal measurements are needed to clarify whether increased hippocampal FC to reward processing regions may raise the risk of the development of metabolic diseases later in life.

Associations between brake and tire wear-related PM2.5 metal components, particulate oxidative stress potential, and autism spectrum disorder in Southern California.

BACKGROUND: Air pollution is a global health concern, with fine particulate matter (PM2.5) constituents posing potential risks to human health, including children's neurodevelopment. Here we investigated associations between exposure during pregnancy and infancy to specific traffic-related PM2.5 components with Autism Spectrum Disorder (ASD) diagnosis. METHODS: For exposure assessment, we estimated PM2.5 components related to traffic exposure (Barium [Ba] as a marker of brake dust and Zinc [Zn] as a tire wear marker, Black Carbon [BC]) and oxidative stress potential (OSP) markers (Hydroxyl Radical [OPOH] formation, Dithiothreitol activity [OPDTT], reactive oxygen species [ROS]) modeled with land use regression with co-kriging based on an intensive air monitoring campaign. We assigned exposures to a cohort of 444,651 children born in Southern California between 2016 and 2019, among whom 11,466 ASD cases were diagnosed between 2018 and 2022, Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained with logistic regression for single pollutant and PM2.5 mass co-adjusted models, also adjusting for sociodemographic characteristics. RESULTS: Among PM2.5 components, we found the strongest positive association with ASD for our brake wear marker Ba (ORper IQR = 1.29, 95 % CI: 1.24, 1.34). This was followed by an increased risk for all PM2.5 oxidative stress potential markers; the strongest association was with ROS formation (ORper IQR = 1.22, 95 % CI: 1.18, 1.25). PM2.5 mass was linked to ASD in Hispanic and Black children, but not White children, while traffic-related PM2.5 and OSP markers increased ASD risk across all groups. In neighborhoods with the lowest socioeconomic status (SES), associations with ASD were stronger for all examined pollutants compared to higher SES areas. CONCLUSIONS: Our findings suggest that brake wear-related PM2.5 and PM2.5 OSP are associated with ASD diagnosis in Southern California. These results suggest that strategies aimed at reducing the public health impacts of PM2.5 need to consider specific sources.

Powerful tool or too powerful? Early public discourse about ChatGPT across 4 million tweets.

BACKGROUND: This paper investigates initial exuberance and emotions surrounding ChatGPT's first three months of launch (1 December 2022-1 March 2023). The impetus for studying active discussions surrounding its implications, fears, and opinions is motivated by its nascent popularity and potential to disrupt existing professions; compounded by its significance as a crucial inflexion point in history. Capturing the public zeitgeist on new innovations-much like the advent of the printing press, radio, newspapers, or the internet-provides a retrospective overview of public sentiments, common themes, and issues. OBJECTIVES: Since launch, few big data studies delved into initial public discourse surrounding the chatbot. This report firstly identifies highest-engagement issues and themes that generated the most interaction; secondly, identifies the highest-engaged keywords on both sides of the sentiment valence scale (positive and negative) associated with ChatGPT. METHODS: We interrogate a large twitter corpus (n = 4,251,662) of all publicly available English-language tweets containing the ChatGPT keyword. Our first research aim utilizes a prominent peaks model (upper-quartile significance threshold of prominence>20,000). Our second research aim utilized sentiment analysis to identify, week-on-week, highest-frequency negative, and positive keywords and emojis. RESULTS: Six prominent peaks were identified with the following themes: 'hype and hesitance', 'utility and misuse in professional and academic settings', 'demographic bias', 'philosophical thought experiments on morality' and 'artificial intelligence as a mirror of human knowledge'. Of high-frequency valence, negativity included credibility concerns, implicit bias, environmental ethics, employment rights of data annotators and programmers, the ethicality of neural network datasets. Positivity included excitement over application, especially in coding, as a creative tool, education, and personal productivity. CONCLUSIONS: Overall, sentiments and themes were double-edged, expressing excitement over this powerful new tool and wariness toward its potential for misuse.

Maternal obesity and diabetes during pregnancy and early autism screening score at well-child visits in standard clinical practice.

LAY ABSTRACT: Early intervention and treatment can help reduce disability in children diagnosed with autism spectrum disorder. Screening for autism spectrum disorder in young children identifies those at increased likelihood of diagnosis who may need further support. Previous research has reported that exposure to maternal obesity and diabetes during pregnancy is associated with higher likelihood of autism spectrum disorder diagnosis in children. However, little is known about whether these maternal conditions are associated with how very young children score on autism spectrum disorder screening tools. This study examined associations between exposure to maternal obesity and diabetes during pregnancy and offspring scores on the Quantitative Checklist for Autism in Toddlers, an autism spectrum disorder screening questionnaire administered between 18-24 months at well-child visits. A higher score on the Quantitative Checklist for Autism in Toddlers suggests a higher likelihood of autism spectrum disorder; children with scores 3 or greater are referred to developmental pediatricians for evaluation. Our study found that children of mothers with obesity or diabetes during pregnancy had higher scores than children whose mothers did not have these conditions. Associations with maternal obesity and gestational diabetes diagnosed at or before 26 weeks of pregnancy were also present in children who did not have later autism spectrum disorder diagnoses, suggesting that exposure to these conditions during early pregnancy may be associated with a broad range of social and behavioral abilities. Identifying associations between maternal health conditions and early Quantitative Checklist for Autism in Toddlers screening scores could influence future screening and provision of support for children of mothers with these conditions.

Neighborhood Disadvantage and Autism Spectrum Disorder in a Population With Health Insurance.

Importance: Family socioeconomic status has been associated with autism spectrum disorder (ASD) diagnoses. Less is known regarding the role of neighborhood disadvantage in the United States, particularly when children have similar access to health insurance. Objective: To evaluate the association between neighborhood disadvantage and the diagnosis of ASD and potential effect modification by maternal and child demographic characteristics. Design, Setting, and Participants: This cohort study examined a retrospective birth cohort from Kaiser Permanente Southern California (KPSC), an integrated health care system. Children born in 2001 to 2014 at KPSC were followed up through KPSC membership records. Electronic medical records were used to obtain an ASD diagnosis up to December 31, 2019, or the last follow-up. Data were analyzed from February 2022 to September 2023. Exposure: Socioeconomic disadvantage at the neighborhood level, an index derived from 7 US census tract characteristics using principal component analysis. Main Outcomes and Measures: Clinical ASD diagnosis based on electronic medical records. Associations between neighborhood disadvantage and ASD diagnosis were determined by hazard ratios (HRs) from Cox regression models adjusted for birth year, child sex, maternal age at delivery, parity, severe prepregnancy health conditions, maternal race and ethnicity, and maternal education. Effect modification by maternal race and ethnicity, maternal education, and child sex was assessed. Results: Among 318 372 mothers with singleton deliveries during the study period, 6357 children had ASD diagnoses during follow-up; their median age at diagnosis was 3.53 years (IQR, 2.57-5.34 years). Neighborhood disadvantage was associated with a higher likelihood of ASD diagnosis (HR, 1.07; 95% CI, 1.02-1.11, per IQR = 2.70 increase). Children of mothers from minoritized racial and ethnic groups (African American or Black, Asian or Pacific Islander, Hispanic or Latinx groups) had increased likelihood of ASD diagnosis compared with children of White mothers. There was an interaction between maternal race and ethnicity and neighborhood disadvantage (difference in log-likelihood = 21.88; P < .001 for interaction under χ24); neighborhood disadvantage was only associated with ASD among children of White mothers (HR, 1.17; 95% CI, 1.09-1.26, per IQR = 2.00 increase). Maternal education and child sex did not significantly modify the neighborhood-ASD association. Conclusions and Relevance: In this study, children residing in more disadvantaged neighborhoods at birth had higher likelihood of ASD diagnosis among a population with health insurance. Future research is warranted to investigate the mechanisms behind the neighborhood-related disparities in ASD diagnosis, alongside efforts to provide resources for early intervention and family support in communities with a higher likelihood of ASD.

Types of diabetes during pregnancy and risk of depression and anxiety in offspring from childhood to young adulthood.

AIMS: To assess maternal pre-existing type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM) during pregnancy and risk of depression and anxiety from childhood to young adulthood in offspring. MATERIALS AND METHODS: This birth cohort included singletons born during 1995-2015, followed using electronic medical records through 2020. Cox regression was used to estimate hazard ratio (HR) of depression or anxiety diagnosis during follow-up associated with in-utero exposure to maternal diabetes. RESULTS: Among 439 590 offspring, 29 891 (6.8%) had depression and 51 918 (11.8%) had anxiety. T1D, followed by T2D and GDM requiring antidiabetes medication were associated with risk of depression and anxiety in offspring. Compared with no diabetes during pregnancy, the adjusted HRs (95% confidence interval) of depression in offspring associated with T1D, T2D or GDM requiring medications were 1.44 (1.09-1.91), 1.30 (1.15-1.47) and 1.18 (1.11-1.26) respectively; conversely, HRs were 0.97 (0.82-1.15) for T2D and 0.99 (0.94-1.04) for GDM without medications. The associations with anxiety followed similar patterns. The significant associations were observed for offspring ages 5-12 and >12-18 years and attenuated for 18-25 years. CONCLUSION: These data suggest that the severity of diabetes (T1D vs. T2D requiring medications vs. GDM requiring medications) during pregnancy may increase the vulnerability of offspring for depression or anxiety.

Prenatal Exposure to Gestational Diabetes Mellitus is Associated with Mental Health Outcomes and Physical Activity has a Modifying Role.

Background: Studies suggest a link between prenatal gestational diabetes mellitus (GDM) exposure and poor mental health outcomes. We examined associations between prenatal GDM exposure and depressive and anxiety symptoms in children and assessed physical activity as a potential modifier of these associations. Method: Seventy children (AgeM(SD): 12(2.0), 56% GDM, 59% female) and their parents completed surveys: Center for Epidemiological Studies Depression Scale for Children (CES-DC), State-Trait Anxiety Inventory for Children (STAIC), Child Behavior Checklist (CBCL), and 3-day physical activity recall (3DPAR). Associations between mental health measures with GDM exposure and interactions between GDM exposure and child moderate-to-vigorous physical activity (MVPA) were assessed using regression. Results: GDM-exposed children had higher anxiety (p = 0.03) and internalizing symptoms (CBCL) (p = 0.04) than unexposed children. There was an interaction between GDM exposure and child MVPA on anxiety (p = 0.02), internalizing (p = 0.04) and externalizing symptoms (p = 0.004). In the low MVPA group, GDM exposed children had more depressive (p = 0.03), anxiety (p = 0.003), and internalizing symptoms (p = 0.03) than unexposed children. In the high MVPA group, there were no group differences except with externalizing symptoms (p = 0.04). Conclusion: Prenatal GDM is associated with higher anxiety and internalizing symptoms in children. Child MVPA modified the relationship between GDM exposure and mental health outcomes suggesting that physical activity during childhood could mitigate the negative mental health outcomes associated with prenatal GDM exposure.

Prenatal air pollution, maternal immune activation, and autism spectrum disorder.

BACKGROUND: Autism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter < 2.5 µm (PM2.5) and maternal immune activation (MIA) conditions. Because these exposures may share common biological effect pathways, we hypothesized that synergistic associations of prenatal air pollution and MIA-related conditions would increase ASD risk in children. OBJECTIVES: This study examined interactions between MIA-related conditions and prenatal PM2.5 or major PM2.5 components on ASD risk. METHODS: In a population-based pregnancy cohort of children born between 2001 and 2014 in Southern California, 318,751 mother-child pairs were followed through electronic medical records (EMR); 4,559 children were diagnosed with ASD before age 5. Four broad categories of MIA-related conditions were classified, including infection, hypertension, maternal asthma, and autoimmune conditions. Average exposures to PM2.5 and four PM2.5 components, black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-), were estimated at maternal residential addresses during pregnancy. We estimated the ASD risk associated with MIA-related conditions, air pollution, and their interactions, using Cox regression models to adjust for covariates. RESULTS: ASD risk was associated with MIA-related conditions [infection (hazard ratio 1.11; 95% confidence interval 1.05-1.18), hypertension (1.30; 1.19-1.42), maternal asthma (1.22; 1.08-1.38), autoimmune disease (1.19; 1.09-1.30)], with higher pregnancy PM2.5 [1.07; 1.03-1.12 per interquartile (3.73 µg/m3) increase] and with all four PM2.5 components. However, there were no interactions of each category of MIA-related conditions with PM2.5 or its components on either multiplicative or additive scales. CONCLUSIONS: MIA-related conditions and pregnancy PM2.5 were independently associations with ASD risk. There were no statistically significant interactions of MIA conditions and prenatal PM2.5 exposure with ASD risk.

Association of Labor Epidural Analgesia, Oxytocin Exposure, and Risk of Autism Spectrum Disorders in Children.

Importance: Maternal labor epidural analgesia (LEA) and oxytocin use for labor and delivery have been reported to be associated with child autism spectrum disorders (ASD). However, it remains unclear whether these 2 common medications used during labor and delivery have synergistic associations with ASD risk in children. Objective: To assess the independent associations of LEA and oxytocin during labor and delivery with ASD, as well as outcome modification associated with the concurrent use of both interventions. Design, Setting, and Participants: Data for this cohort study included 205 994 singleton births with vaginal deliveries in a single integrated health care system in Southern California from calendar years 2008 to 2017. Children were followed up to December 31, 2021. Data on use of LEA and oxytocin, covariates, and ASD outcome in children were obtained from electronic medical records. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) adjusting for covariates. Exposures: Labor epidural analgesia and/or oxytocin use during labor and delivery. Main Outcomes and Measures: A child's clinical diagnosis of ASD during follow-up and at age of diagnosis. Results: Among the cohort, 153 880 children (74.7%) were exposed to maternal LEA and 117 808 children (57.2%) were exposed to oxytocin during labor and delivery. The population of children was approximately half boys and half girls. The median (IQR) age of the mothers was 30.8 (26.8-34.5) years for those not exposed to LEA, 30.0 (25.9-33.8) years for those exposed to LEA, 30.4 (26.5-34.1) years for those unexposed to oxytocin, and 30.0 (25.9-33.9) years for those exposed to oxytocin during labor and delivery. A total of 5146 children (2.5%) had ASD diagnosed during follow-up. Oxytocin exposure was higher among LEA-exposed (67.7%) than -unexposed (26.1%) children. The ASD risk associated with LEA was independent of oxytocin exposure (HR, 1.28; 95% CI, 1.18-1.38); however, the ASD risk associated with oxytocin was not significant after adjusting for LEA exposure (HR, 1.05; 95% CI, 0.99-1.12). A significant interaction of LEA and oxytocin on child ASD risk was found (P = .02 for interaction). Compared with no exposure, HRs were 1.20 (95% CI, 1.09-1.32) for LEA alone, 1.30 (95% CI, 1.20-1.42) for both LEA and oxytocin, and 0.90 (95% CI, 0.78-1.04) for oxytocin alone. Conclusions and Relevance: The findings of this cohort study suggest an association between maternal LEA and ASD risk in children, and the risk appeared to be further increased if oxytocin was also administered. Oxytocin exposure without LEA exposure was not associated with ASD risk in children. These findings must be interpreted with caution. Further studies are needed to replicate or refute the study results and examine biological plausibility.

Maternal exposure to aircraft emitted ultrafine particles during pregnancy and likelihood of ASD in children.

BACKGROUND: There is increasing evidence for adverse health effects associated with aircraft-emitted particulate matter (PM) exposures, which are largely in the ultrafine (PM0.1) size fraction, but no previous study has examined neurodevelopmental outcomes. OBJECTIVE: To assess associations between maternal exposure to aircraft ultrafine particles (UFP) during pregnancy and offspring autism spectrum disorder (ASD) diagnosis. METHODS: This large, representative cohort study included 370,723 singletons born in a single healthcare system. Demographic data, maternal health information, and child's ASD diagnosis by age 5 were extracted from electronic medical records. Aircraft exposure estimates for PM0.1 were generated by the University of California Davis/California Institute of Technology Source Oriented Chemical Transport model. Cox proportional hazard models were used to assess associations between maternal exposure to aircraft PM0·1 in pregnancy and ASD diagnosis, controlling for covariates. RESULTS: Over the course of follow-up, 4,554 children (1.4 %) were diagnosed with ASD. Increased risk of ASD was associated with maternal exposure to aircraft PM0.1 [hazard ratio, HR: 1.02, (95 % confidence interval (CI): 1.01-1.03) per IQR = 0.02 µg/m3 increase during pregnancy. Associations were robust to adjustment for total PM0.1 and fine particulate matter (PM2.5), near-roadway air pollution, and other covariates. Noise adjustment modestly attenuated estimates of UFP effects, which remained statistically significant. DISCUSSION: The results strengthen the emerging evidence that maternal particulate matter exposure during pregnancy is associated with offspring ASD diagnosis and identify aircraft-derived PM0.1 as novel targets for further study and potential regulation.

Prenatal exposure to tailpipe and non-tailpipe tracers of particulate matter pollution and autism spectrum disorders.

BACKGROUND: Traffic-related air pollution exposure is associated with increased risk of autism spectrum disorder (ASD). It is unknown whether carbonaceous material from vehicular tailpipe emissions or redox-active non-tailpipe metals, eg. from tire and brake wear, are responsible. We assessed ASD associations with fine particulate matter (PM2.5) tracers of tailpipe (elemental carbon [EC] and organic carbon [OC]) and non-tailpipe (copper [Cu]; iron [Fe] and manganese [Mn]) sources during pregnancy in a large cohort. METHODS: This retrospective cohort study included 318,750 children born in Kaiser Permanente Southern California (KPSC) hospitals during 2001-2014, followed until age 5. ASD cases were identified by ICD codes. Monthly estimates of PM2.5 and PM2.5 constituents EC, OC, Cu, Fe, and Mn with 4 km spatial resolution were obtained from a source-oriented chemical transport model. These exposures and NO2 were assigned to each maternal address during pregnancy, and associations with ASD were assessed using Cox regression models adjusted for covariates. PM constituent effect estimates were adjusted for PM2.5 and NO2 to assess independent effects. To distinguish ASD risk associated with non-tailpipe from tailpipe sources, the associations with Cu, Fe, and Mn were adjusted for EC and OC, and vice versa. RESULTS: There were 4559 children diagnosed with ASD. In single-pollutant models, increased ASD risk was associated with gestational exposures to tracers of both tailpipe and non-tailpipe emissions. The ASD hazard ratios (HRs) per inter-quartile increment of exposure) for EC, OC, Cu, Fe, and Mn were 1.11 (95% CI: 1.06-1.16), 1.09 (95% CI: 1.04-1.15), 1.09 (95% CI: 1.04-1.13), 1.14 (95% CI: 1.09-1.20), and 1.17 (95% CI: 1.12-1.22), respectively. Estimated effects of Cu, Fe, and Mn (reflecting non-tailpipe sources) were largely unchanged in two-pollutant models adjusting for PM2.5, NO2, EC or OC. In contrast, ASD associations with EC and OC were markedly attenuated by adjustment for non-tailpipe sources. CONCLUSION: Results suggest that non-tailpipe emissions may contribute to ASD. Implications are that reducing tailpipe emissions, especially from vehicles with internal combustion engines, may not eliminate ASD associations with traffic-related air pollution.

Associations of Autism Spectrum Disorder with PM2.5 Components: A Comparative Study Using Two Different Exposure Models.

This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM2.5) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up (N = 4559) were identified by ICD codes. Prenatal exposures to PM2.5, elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM2.5, EC/BC, OM, and SO42- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO3-. EC/BC, OM, and SO42- were generally robust to adjustment for other components and for PM2.5. EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO42- in the third trimester. Future PM2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.

Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring.

LAY ABSTRACT: Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.

Associations Between Sleep and Metabolic Outcomes in Preadolescent Children.

Context: Growing evidence suggests an important role for sleep for the metabolic health of children. Objective: We aimed to determine how sleep is related to insulin sensitivity, insulin secretion, beta-cell function, and adiposity (BMI z-scores, body fat %, waist to height ratio) using objectively measured sleep and oral glucose tolerance test (OGTT)-derived measures. Methods: Sixty-two children aged 7-11 years, born at Kaiser Permanente Southern California, wore wrist accelerometers for 7 days to objectively measure sleep, completed an OGTT, and had anthropometric measures (height [cm], weight [kg], waist [cm], body fat [%]) collected. Using linear regression, associations between Matsuda insulin sensitivity index (ISI), insulinogenic index (IGI), disposition index (DI), BMI z-score, waist to height ratio, and body fat % with sleep parameters [total sleep time (TST; min), sleep efficiency (SE; %), time in bed (TIB; min), wake after sleep onset (WASO; min), and sleep latency (SL; min)] were assessed. Body fat % was tested as a mediator of the relationship between TST and ISI. Results: Longer TST was associated with better insulin sensitivity (P = 0.02), but not after adjusting for body fat %. Sleep parameters were not associated with IGI or DI. Longer TST was associated with lower % body fat (P = 0.01) and lower waist-to-height-ratios (P = 0.05). Body fat % explained 62% (P = 0.01) of the relationship between TST and ISI. Longer TIB was associated with lower adiposity measures (P < 0.05). There were no associations between SE, WASO, or SL and metabolic outcomes. Conclusion: Objectively measured sleep duration was associated with lower adiposity, and the relationship between sleep duration and ISI appeared partly through adiposity levels in preadolescent children. Longer sleep duration may be important for metabolic health.

Exposure to Gestational Diabetes Mellitus Prior to 26 Weeks Is Related to the Presence of Mediobasal Hypothalamic Gliosis in Children.

Intrauterine exposure to metabolic dysfunction leads to offspring metabolic dysfunction in human and rodent models, but underlying mechanisms are unclear. The mediobasal hypothalamus (MBH) is involved in energy homeostasis and weight regulation, and MBH gliosis is associated with obesity and insulin resistance. We tested the hypothesis that offspring exposed to gestational diabetes mellitus (GDM) in utero versus those unexposed would show evidence of MBH gliosis. Participants in the BrainChild Study (age 7-11 years with confirmed GDM exposure or no GDM exposure) underwent brain MRI to acquire T2-weighted images. By using the amygdala (AMY) and white matter (WM) as reference regions, MBH:AMY and MBH:WM T2 signal ratios were calculated as a radiologic measure of MBH gliosis. Linear regressions were used to examine associations between GDM exposure (GDM overall) and by timing of GDM exposure (≤26 weeks or >26 weeks) and MBH gliosis. Associations between prepregnancy BMI and child MBH gliosis were examined in secondary analyses. There were no differences in T2 signal ratios in children exposed versus not exposed to GDM overall, but children exposed to early GDM (≤26 weeks of gestation) had higher MBH:WM signal ratios than those not exposed (ß = 0.147; SE 0.06; P = 0.03), adjusting for child's age, sex, and BMI z score and maternal prepregnancy BMI, whereas no associations were seen for the control ratio (AMY:WM). Prepregnancy BMI was not associated with evidence of MBH gliosis. Early exposure to GDM was associated with radiologic evidence of MBH gliosis in children. These data provide mechanistic insight into brain pathways by which exposure to GDM may increase risk for metabolic dysfunction.

A Multicenter Cohort Study on the Adverse Effects Evaluation After Messenger RNA COVID-19 Vaccination Among Pregnant Healthcare Employees in Penang General Hospitals.

Introduction: The year 2020 saw the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which became a great threat to public health worldwide. The exponential spread of the disease with millions of lives lost worldwide saw the emergence of an accelerated vaccine development with emergency approval from well-known regulatory bodies such as the US Food and Drug Administration, followed by widespread vaccine deployment despite a paucity in safety profile data. This issue becomes even more pronounced when it involves expectant mothers considering the possible undesirable effect toward the unborn child. Method: This was a retrospective cohort study which was conducted at six general hospitals in the state of Penang, Malaysia. All the pregnant employees who have consented to take the mRNA COVID-19 vaccine and participate in this study were monitored from the time of their first vaccination and up to 28 days after they delivered their babies. Results: All the participants had adequate maximum vertical pocket (MVP) and no obvious anomalies or detection of intrauterine growth restriction (IUGR) were detected during the second trimester. However, one subject was reported to have miscarried during the second trimester. The reported mean neonate birth weight was 3.0 kg with the mean Apgar score of 8.8 and 9.8 at 1 and 5 min, respectively. Approximately seven (5.8%) neonates were reported to be small for their gestational age. Another three (2.5%) neonates were reported to have anomalies. Conclusion: As a whole, the inference that can be made from this study is that mRNA COVID-19 vaccine appears to be safe in pregnant women regardless of the trimester as the findings did not show obvious safety warning signs.