A Comparative Analysis of the Full and Short Versions of the Social Responsiveness Scale in Estimating an Established Autism Risk Factor Association in ECHO: Do we Get the Same Estimates?

PURPOSE: Prior work developed a shortened 16-item version of the Social Responsiveness Scale (SRS), a quantitative measure of social communication and autism spectrum disorder (ASD)-related traits. However, its properties for use in risk factor estimation have not been fully tested compared to the full SRS. We compared the associations between gestational age (previously established risk factor for ASD) and the 65-item "full" and 16-item "short" versions of the SRS to test the shortened version's ability to capture associations in epidemiologic analyses of ASD risk factors. METHODS: We used data from participants in the Environmental influences on Child Health Outcomes (ECHO) Program (n = 2,760). SRS scores were collected via maternal/caregiver report when children were aged 2.5-18 years. We compared estimates of associations between gestational age and preterm birth between the full and short SRS using multivariable linear regression, quantile regression, and prediction methods. RESULTS: Overall, associations based on full and short SRS scores were highly comparable. For example, we observed positive associations between preterm birth with both full ([Formula: see text]=2.8; 95% CI [1.7, 4.0]) and short ([Formula: see text]=2.9; 95% CI [1.6, 4.3]) SRS scores. Quantile regression analyses indicated similar direction and magnitude of associations across the distribution of SRS scores between gestational age with both short and full SRS scores. CONCLUSION: The comparability in estimates obtained for full and short SRS scores with an "established" ASD risk factor suggests ability of the shortened SRS in assessing associations with potential ASD-related risk factors and has implications for large-scale research studies seeking to reduce participant burden.

Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. OBJECTIVES: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. RESULTS: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of ß=-0.15 [95% confidence interval (CI): -0.27, -0.03], ß=-0.14 (95% CI: -0.28, -0.002), ß=-0.22 (95% CI: -0.23, -0.10), ß=-0.06 (95% CI: -0.18, 0.06), and ß=-0.25 (95% CI: -0.37, -0.14), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: ORPFNA=0.56 (95% CI: 0.38, 0.83), ORPFDA=0.52 (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [-0.28; 95% highest posterior density (HPD): -0.44, -0.14] and decreased odds of large-for-gestational-age (OR=0.49; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. DISCUSSION: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.

Cardiometabolic Pregnancy Complications in Association With Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO.

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (ß = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (ß = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts.

Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72-1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02-2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73-4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. LAY SUMMARY: Evidence on the association between maternal prenatal smoking and the child's risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results.

Enforcement agencies and smoke-free policy compliance: An observational study in Qingdao, China.

INTRODUCTION: In recent years, tobacco control policy initiatives have emerged at the subnational level in China. In 2013, for example, Qingdao enacted a 100% smoke-free policy that gave regulatory authority to multiple enforcement agencies. Given that little is known about the extent of smoke-free policy compliance in smaller Chinese cities, this study assessed compliance with Qingdao's Tobacco Control Regulation and whether compliance differed by enforcement agency. METHODS: A cross-sectional observational study was undertaken between October and November 2018. Venues were selected based on enforcement agency and included restaurants, retail stores, schools, government buildings, hospitals, business offices, and other hospitality venues. Comprehensive lists of venues were identified where they existed, and a random sample of venues were subsequently selected. For venue categories for which there were no comprehensive lists, a walking protocol was used. Observational data included evidence of smoking, the presence of no-smoking signage, and designated smoking areas (DSAs). Descriptive statistics were obtained. Subsequently, logistic regression models were used to determine the association between enforcement agency and policy compliance. RESULTS: A total of 694 venues were observed. For all venue types, 64.7% were compliant with the composite indicator 'evidence of smoking'. Findings also showed that smoke-free compliance varied by enforcement agency (p<0.001). Venues with evidence of smoking and not posting of no-smoking signs at the main entrance were lowest among venues that fall under Public Security Bureau. Compliance with posting no-smoking signs inside was lowest in venues that fall under the Industry and Commercial Administration (I&C). While Qingdao's smoke-free policy prohibits DSAs, our findings showed that 2% of venues that fall under the jurisdiction of I&C had DSAs. CONCLUSIONS: An effective coordination mechanism that can ensure a consistent and standardized approach is urgently needed in Qingdao. With such a concerted effort, it will be possible to achieve the target of 100% smoke-free indoor places in Qingdao.

Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research.

Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item "short" to 65-item "full" SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores.

Diabetes, its duration, and the long-term risk of abdominal aortic aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND AND AIMS: We aimed at comprehensively evaluate the independent association of diabetes and its duration with incident abdominal aortic aneurysm (AAA) and aortic diameter. METHODS AND RESULTS: We prospectively studied incident AAA according to baseline glycemic status (diabetes, prediabetes, normal glycemia) in 13,116 ARIC participants (1990-1992) and the time-varying exposure of duration post incident diabetes in 11,675 participants (1987-1989) using Cox models. Additionally, we cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4710 participants (2011-2013) using linear regression models. Over ~20 years of follow-up, diabetes (vs. normal glycemia) at baseline was independently associated with lower AAA risk (489 cases) (hazard ratio: 0.71 [95%CI 0.51-0.99]), especially after 10 years (hazard ratio: 0.58 [0.38-0.87]). Prediabetes did not demonstrate an independent association. The inverse association was more evident with longer duration of diabetes (p for trend = 0.045), with 30-50% lower risk in eight years after diabetes diagnosis. The cross-sectional analysis demonstrated smaller aortic diameters with longer duration of diabetes (e.g., -0.76 mm [-1.24, -0.28] in diabetes with 8-12 years) compared to non-diabetes, whereas prediabetes consistently showed nominally greater diameter. CONCLUSIONS: Diabetes, especially with longer duration, but not prediabetes, was independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that long lasting clinical hyperglycemia plays an important role in the reduced AAA risk, and the reduced aortic diameter may be a structural mechanism behind this paradoxical association.

Association of Sleep Duration with Weight Gain and General and Central Obesity Risk in Chinese Adults: A Prospective Study.

OBJECTIVE: Evidence on the association between sleep duration and obesity among adults is inconsistent. Prospective studies investigating the association in Chinese adults have been limited. This study aims to prospectively evaluate sleep duration in relation to subsequent weight gain and general and central obesity risk among Chinese adults. METHODS: A total of 21,958 participants aged 30 to 79 years reported their daily sleep duration. Obesity indicators were objectively measured; then significant weight gain (≥ 5 kg) and general and central obesity were modeled as the outcome. Logistic regression models were used to estimate odds ratios and 95% CIs. RESULTS: Average sleep duration was 7.5 hours at baseline. During 8.0 ± 0.8 years of follow-up, participants who reported sleeping ≤ 6 hours had higher risk for significant weight gain than those who slept 7 hours (multivariable-adjusted odds ratio: 1.13; 95% CI: 1.02-1.29). The association was stronger among those who were physically inactive at baseline (P = 0.04 for interaction). Short sleep duration was also associated with subsequent incident central obesity, with odds ratio of 1.13 (95% CI: 1.00-1.28), but not with incident general obesity (P = 0.31). CONCLUSIONS: Compared with those who slept 7 hours per day, short sleepers had an increased risk of significant weight gain and central obesity.

Demonstrating the impact of POLST forms on hospital care requires information not contained in state registries.

BACKGROUND: Physician Orders for Life-Sustaining Treatment (POLST) programs have expanded rapidly, but evaluating their impact on hospital care is challenging. OBJECTIVES: To demonstrate how careful study design can reveal POLST's impact at hospital admission and why analyses of state registry data are unlikely to capture POLST's effects. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Adult in-patients with Do Not Intubate and/or Do Not Resuscitate (DNR/I) orders in the electronic medical record at the time of discharge from Johns Hopkins Hospital over 18 months. For patients with unplanned readmissions within 30 days, records were reviewed to determine if a Maryland Medical Order for Life-Sustaining Treatment (MOLST) form was presented and for the time from readmission to a DNR/I order in the EMR. Analyses were stratified by whether patients could communicate or were accompanied by a proxy at readmission. RESULTS: Among 1,507 patients with DNR/I orders at discharge, 124 (8%) had unplanned readmissions, 112 (90%) could communicate or were accompanied by a proxy at readmission, and 12 (10%) could not communicate and were unaccompanied. For patients who were unaccompanied and could not communicate, MOLST significantly decreased the median time from readmission to DNR/I order (1.2 vs 27.1 hours, P = .001), but this association was greatly attenuated among patients who could communicate or were accompanied by a proxy (16.4 vs 25.4 hours P = .10). CONCLUSION: Among patients who wanted to avoid intubation and/or CPR, MOLST forms were protective when the patient was unaccompanied by a healthcare proxy at admission and could not communicate. Fewer than 10% of patients met these criteria during unplanned readmissions, and state registry data does not allow this sub-population to be identified.