Dataset Information

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

ABSTRACT: 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 (β = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (β = 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.

SUBMITTER: Lyall K

PROVIDER: S-EPMC9614927 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Lyall Kristen K Ning Xuejuan X Aschner Judy L JL Avalos Lyndsay A LA Bennett Deborah H DH Bilder Deborah A DA Bush Nicole R NR Carroll Kecia N KN Chu Su H SH Croen Lisa A LA Dabelea Dana D Daniels Julie L JL Duarte Christiane C Elliott Amy J AJ Fallin M Daniele MD Ferrara Assiamira A Hertz-Picciotto Irva I Hipwell Alison E AE Jensen Elizabeth T ET Johnson Susan L SL Joseph Robert M RM Karagas Margaret M Kelly Rachel S RS Lester Barry M BM Margolis Amy A McEvoy Cindy T CT Messinger Daniel D Neiderhiser Jenae M JM O'Connor Thomas G TG Oken Emily E Sathyanarayana Sheela S Schmidt Rebecca J RJ Sheinkopf Stephen J SJ Talge Nicole M NM Turi Kedir N KN Wright Rosalind J RJ Zhao Qi Q Newschaffer Craig C Volk Heather E HE Ladd-Acosta Christine C Environmental Influences On Child Health Outcomes On Behalf Of Program Collaborators For OBOPCF

American journal of epidemiology 20220701 8

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 i ...[more]

PMID: 35362025

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Project description:BackgroundAutism Spectrum Disorders (ASD) are phenotypically heterogeneous, characterized by impairments in the development of communication and social behaviour and the presence of repetitive behaviour and restricted interests. Dissecting the genetic complexity of ASD may require phenotypic data reflecting more detail than is offered by a categorical clinical diagnosis. Such data are available from the Social Responsiveness Scale (SRS) which is a continuous, quantitative measure of social ability giving scores that range from significant impairment to above average ability.MethodsWe present genome-wide results for 64 multiplex and extended families ranging from two to nine generations. SRS scores were available from 518 genotyped pedigree subjects, including affected and unaffected relatives. Genotypes from the Illumina 6 k single nucleotide polymorphism panel were provided by the Center for Inherited Disease Research. Quantitative and qualitative analyses were done using MCLINK, a software package that uses Markov chain Monte Carlo (MCMC) methods to perform multilocus linkage analysis on large extended pedigrees.ResultsWhen analysed as a qualitative trait, linkage occurred in the same locations as in our previous affected-only genome scan of these families, with findings on chromosomes 7q31.1-q32.3 [heterogeneity logarithm of the odds (HLOD) = 2.91], 15q13.3 (HLOD = 3.64), and 13q12.3 (HLOD = 2.23). Additional positive qualitative results were seen on chromosomes 6 and 10 in regions that may be of interest for other neuropsychiatric disorders. When analysed as a quantitative trait, results replicated a peak found in an independent sample using quantitative SRS scores on chromosome 11p15.1-p15.4 (HLOD = 2.77). Additional positive quantitative results were seen on chromosomes 7, 9, and 19.ConclusionsThe SRS linkage peaks reported here substantially overlap with peaks found in our previous affected-only genome scan of clinical diagnosis. In addition, we replicated a previous SRS peak in an independent sample. These results suggest the SRS is a robust and useful phenotype measure for genetic linkage studies of ASD. Finally, analyses of SRS scores revealed linkage peaks overlapping with evidence from other studies of neuropsychiatric diseases. The information available from the SRS itself may, therefore, reveal locations for autism susceptibility genes that would not otherwise be detected.

Project description:The Social Responsiveness Scale (SRS) has been validated in high-income countries but not yet in low- and middle-income countries. We aimed to assess the reliability of the SRS in a community sample and its validity to discriminate between children with and without autism spectrum disorder (ASD) in Vietnam. We used a three-phase study: piloting the translated SRS, reliability testing, and validation of the SRS in 158 Vietnamese caretakers and their children (ages 4-9 years). We examined reliability, validity and sensitivity, and specificity to ASD diagnosis. We applied receiver operator characteristic (ROC) analysis to determine optimal cutoff scores discriminating the children with ASD from those without ASD. We also assessed the performance of the SRS short form. We found that reliability was good with high internal consistency (0.88-0.89), test-retest reliability (0.82-0.83), sensitivity (93%), and specificity (98%) for identification of children with ASD. The ROC curves were similar for total raw score and total T-score, with the area under the curve (AUC) values reaching 0.98 and the optimal cutoff of 62 for raw scores and 60 for T-scores. The SRS short form also performed well in distinguishing children with ASD from children without ASD, with high AUC (0.98), sensitivity (90%), and specificity (98%) when using a raw score of 15 as a cutoff. In conclusion, the translated and culturally adapted SRS shows good reliability, validity, and sensitivity for identification of children with ASD in Vietnam. Both SRS long and short forms performed adequately to discriminate between children with and without ASD. Autism Res 2019, 00: 1-13. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Middle-income countries often lack validated tools to evaluate autism symptoms. The Social Responsiveness Scale (SRS) translated to Vietnamese was reliable and performed well to distinguish between children with and without autism spectrum disorder in Vietnam. The Vietnamese SRS, and translations of the tool to other languages with this methodology, may be useful in pediatric practice, potentially allowing providers to make more appropriate referrals for diagnostic evaluations and identify children for intervention to help them fulfill their developmental potential.

Project description:ImportanceWomen are recommended to limit caffeine consumption to less than 200 mg per day based on risks to fetal health. Impacts of caffeine on maternal health remain unclear.ObjectiveTo determine whether caffeinated-beverage intake and plasma caffeine and paraxanthine are associated with cardiometabolic complications in pregnancy (ie, gestational diabetes [GDM], preeclampsia, and gestational hypertension [GH]).Design, setting, and participantsThis cohort study used data from a longitudinal pregnancy cohort study from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons (2009-2013). This post hoc secondary analysis of 2802 pregnant women without major chronic conditions enrolled at 12 US clinical sites was completed in 2021. The final sample for caffeinated beverage analyses included 2583 women. After excluding women who did not consent to have their biospecimens stored for future research (n = 54), plasma caffeine analyses included 2529 women. Analyses of caffeine consumption and fasting cardiometabolic profiles included 319 women.ExposuresDaily total caffeine intake was estimated at 10 to 13 gestational weeks and 16 to 22 gestational weeks based on self-reported past week intake of caffeinated coffee, tea, soda, and energy drinks. Plasma caffeine and paraxanthine were measured in specimens collected at 10 to 13 weeks.Main outcomes and measuresClinical diagnoses of GDM, preeclampsia, GH, glucose concentrations from GDM screening, and blood pressure were extracted from medical records.ResultsParticipants had a mean (SD) age of 28.1 (5.5) years and 422 participants (16.3%) were Asian/Pacific Islander women, 741 (28.9%) were Hispanic women, 717 (27.8%) were non-Hispanic Black women, and 703 (27.2%) were non-Hispanic White women. At 10 to 13 weeks, 1073 women (41.5%) reported consuming no caffeinated beverages, 1317 (51.0%) reported consuming 1 mg/d to 100 mg/d, 173 (6.7%) reported consuming 101 mg/d to 200 mg/d, and 20 (0.8%) reported consuming more than 200 mg/d. At 16 to 22 weeks, 599 women (23.6%) reported consuming no caffeinated beverages, 1734 (68.3%) reported consuming 1 mg/d to 100 mg/d, 186 (7.3%) reported consuming 101 mg/d to 200 mg/d, and 20 (0.8%) reported consuming more than 200 mg/d caffeinated beverages. Intake at 16 to 22 weeks was associated with lower GDM risk and lower glucose concentrations (1 mg/d to 100 mg/d vs none: relative risk, 0.53 [95% CI, 0.35 to 0.80]; β, -2.7 mg/dL [95% CI, -5.4 mg/dL to 0 mg/dL]) and lower C-reactive protein and C-peptide concentrations and favorable lipid profiles. Total plasma caffeine and paraxanthine at 10 to 13 weeks was inversely associated with glucose (quartile 4 vs quartile 1: β = -3.8 mg/dL [95% CI, -7.0 mg/dL to -0.5 mg/dL]; trend of P = .01). No associations were observed with preeclampsia or GH.Conclusions and relevanceIn this cohort study, second trimester caffeinated beverage intake within current recommendations was associated with lower GDM risk, but not preeclampsia or GH. These findings may be reassuring for women with moderate caffeine intake.

Project description: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.

Project description:BackgroundThe influence of multiple maternal and pregnancy characteristics on offspring cardiometabolic traits at birth is not well understood and was evaluated in this study.Methods and findingsThe Family Atherosclerosis Monitoring In earLY life (FAMILY) Study prospectively evaluated 11 cardiometabolic traits in 901 babies born to 857 mothers. The influence of maternal age, health (pre-pregnancy weight, blood pressure, glycemic status, lipids), health behaviors (diet, activity, smoking) and pregnancy characteristics (gestational age at birth, gestational weight gain and placental-fetal ratio) were examined. Greater gestational age influenced multiple newborn cardiometabolic traits including cord blood lipids, glucose and insulin, body fat and blood pressure. In a subset of 442 singleton mother/infant pairs, principal component analysis grouped 11 newborn cardiometabolic traits into 5 components (anthropometry/insulin, 2 lipid components, blood pressure and glycemia), accounting for 74% of the variance of the 11 outcome variables. Determinants of these components, corrected for sex and gestational age, were examined. Baby anthropometry/insulin was independently predicted by higher maternal pre-pregnancy weight (standardized estimate 0.30) and gestational weight gain (0.30; both p<0.0001) and was inversely related to smoking during pregnancy (-0.144; p?=?0.01) and maternal polyunsaturated to saturated fat intake (-0.135;p?=?0.01). Component 2 (HDL-C/Apo Apolipoprotein1) was inversely associated with maternal age. Component 3 (blood pressure) was not clustered with any other newborn cardiometabolic trait and no associations with maternal pregnancy characteristics were identified. Component 4 (triglycerides) was positively associated with maternal hypertension and triglycerides, and inversely associated with maternal HDL and age. Component 5 (glycemia) was inversely associated with placental/fetal ratio (-0.141; p?=?0.005). LDL-C was a bridging variable between the lipid factors and glycemia.ConclusionsMaternal health, health behaviours and placenta to fetal weight ratio are associated with newborn cardiometabolic traits over and above gestational age. Future investigations are needed to determine if these factors remain important determinants of cardiometabolic health throughout childhood.

Dataset Information

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

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

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