We examined the relationship between maternal intake of established dietary patterns and child autism-related outcomes in two prospective cohorts in the United States. Participants were drawn from ...the Early Autism Risk Longitudinal Investigation (EARLI, n = 154) and the Nurses’ Health Study II (NHSII, n = 727). Dietary information was collected via food frequency questionnaires (FFQs) and used to calculate the empirical dietary inflammatory pattern (EDIP), Alternative Healthy Eating Index (AHEI), Western and Prudent dietary patterns, and the alternative Mediterranean Diet (aMED) score. Primary analyses examined associations with continuous autism-related traits as measured by the Social Responsiveness Scale (SRS), and secondary analyses with autism spectrum disorder (ASD) diagnosis. We used crude and multivariable quantile regression fixed at the 50th percentile to examine associations between quartiles of dietary patterns and SRS scores, and logistic regression to examine associations with ASD diagnosis. There was suggestion of a positive association with the Western diet (Q4 vs. Q1, ß = 11.19, 95% CI: 3.30, 19.90) in EARLI, though the association was attenuated with adjustment for total energy intake, and no clear associations were observed with other dietary patterns and ASD diagnosis or SRS scores. Further work is needed to better understand the role of maternal dietary patterns in ASD and related outcomes.
Using a cross-sectional survey of 673 multidisciplinary autism spectrum disorder providers recruited from five different sites in the United States, we examined the frequency with which ...community-based providers inquire about, screen, and treat trauma-related symptoms in their patients/students and assessed their perceptions regarding the need for and barriers to providing these services. Univariate and bivariate frequencies of self-reported trauma service provision, training needs, and barriers were estimated. Multivariable logistic regressions identified provider and patient-related factors associated with trauma-related symptoms screening and treatment. Over 50% of providers reported some screening and treatment of trauma-related symptoms in youth with autism spectrum disorder. Over 70% informally inquired about trauma-related symptoms; only 10% universally screened. Screening and treatment varied by provider discipline, setting, amount of interaction, and years of experience with autism spectrum disorder, as well as by patient/student sex, ethnicity, and socioeconomic status. Most providers agreed that trauma screening is a needed service impeded by inadequate provider training in trauma identification and treatment. The findings indicate that community providers in the United States of varied disciplines are assessing and treating trauma-related symptoms in youth with autism spectrum disorder, and that evidence-based approaches are needed to inform and maximize these efforts.
Children with autism spectrum disorder (ASD) have a greater prevalence of gastrointestinal (GI) symptoms than children without ASD. We tested whether polygenic scores for each of three GI disorders ...(ulcerative colitis, inflammatory bowel disease, and Crohn's disease) were related to GI symptoms in children with and without ASD. Using genotyping data (564 ASD cases and 715 controls) and external genome‐wide association study summary statistics, we computed GI polygenic scores for ulcerative colitis (UC‐PGS), inflammatory bowel disease (IDB‐PGS), and Crohn's disease (CD‐PGS). Multivariable logistic regression models, adjusted for genetic ancestry, were used to estimate associations between each GI‐PGS and (1) ASD case–control status, and (2) specific GI symptoms in neurotypical children and separately in ASD children. In children without ASD, polygenic scores for ulcerative colitis were significantly associated with experiencing any GI symptom (adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI) = 1.03–1.81, p = 0.03) and diarrhea specifically (aOR = 5.35, 95% CI = 1.77–26.20, p = 0.01). Among children without ASD, IBD‐PGS, and Crohn's PGS were significantly associated with diarrhea (aOR = 3.55, 95% CI = 1.25–12.34, p = 0.02) and loose stools alternating with constipation (aOR = 2.57, 95% CI = 1.13–6.55, p = 0.03), respectively. However, the three PGS were not associated with GI symptoms in the ASD case group. Furthermore, polygenic scores for ulcerative colitis significantly interacted with ASD status on presentation of any GI symptom within a European ancestry subset (aOR = 0.42, 95% CI = 0.19–0.88, p = 0.02). Genetic risk factors for some GI symptoms differ between children with and without ASD. Furthermore, our finding that increased genetic risks for GI inflammatory disorders are associated with GI symptoms in children without ASD informs future work on the early detection of GI disorders.
Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well understood. In this population‐based cohort study, we examined ...the familial risk and heritability of ASD with and without co‐occurring intellectual disability (ID). We estimated odds ratios and heritability of ASD with ID (ASD+ID) and ASD without ID (ASD−ID) using register‐based diagnosis data of 567,436 index persons born in 1984–2009 in Stockholm County, Sweden, and their parents, siblings, cousins, aunts, and uncles. The familial risk profile exhibited differences between ASD−ID and ASD+ID, most notably for index persons with affected parents. For example, for an index person who had at least one parent with ASD, the child's odds of ASD−ID and ASD+ID (95% confidence interval (CI)) increased by 16.2 (14.2–18.6) and 7.4 (5.5–10.0) folds, respectively. The more closely related a family member with ASD was, the greater the observed risk was of ASD in the index person, especially for ASD−ID. The broad‐sense heritability (95% CI) for ASD − ID and ASD+ID were 64.6% (46.0–100.0%) and 33.4% (14.4–58.4%), respectively. Familial risk and heritability of ASD may vary by intellectual ability, which implies that risk factors between these ASD phenotypes may differ. Our findings from the heritability analysis and familial risk analysis suggest that ASD−ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies.
Lay Summary
Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well‐understood. In a population‐based cohort study on families of 567,436 index persons using Swedish registers data, we found that the familial risk profile differed between ASD with and without intellectual disability. Our findings from the heritability analysis and familial risk analysis suggest that ASD−ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies.
Familial aggregation of mental and neurological disorders is often observed in autism spectrum disorders (ASD), but reports have generally focused on single disorders and are limited to first-degree ...relatives.
To examine family history of mental and neurological disorders among first- to fourth-degree relatives and risk of ASD with and without intellectual disability (ID) in index persons.
In this population-based cohort study, 567 436 index persons were identified from the Stockholm Youth Cohort, an ongoing longitudinal register-linkage cohort study of the total population aged 0 to 17 years residing in Stockholm County, Sweden. Index persons were nonadopted singleton births born between 1984 and 2009 who were at least 2 years of age at the end of follow-up on December 31, 2011, had resided in Stockholm County for at least 2 years since birth, and could be linked to both biological parents. Data analysis was conducted from May 2017 to December 2018.
Mental and neurological diagnoses of relatives of the index persons.
Diagnosis of ASD, with or without co-occurring ID, in the index persons.
The cohort included 567 436 index persons (291 191 51.3% male; mean SD age at the end of follow-up, 14.3 7.5 years). The prevalence of ASD with and without ID was 0.4% and 1.5%, respectively. Positive family history of mental and neurological disorders was associated with higher odds of ASD in index persons; 6895 (63.1%) of index persons with ASD had a parent with history of mental and/or neurological disorders, compared with 252 454 (45.4%) of index persons without ASD. Family history of multiple disorders was associated with higher odds of ASD in index persons, including history of ASD (odds ratio among first-degree relatives for ASD with and without ID: 14.2, 9.0), intellectual disability (7.6, 2.3), attention-deficit/hyperactivity disorder (3.3, 4.7), obsessive compulsive disorder (1.9, 2.1), schizophrenia and other nonaffective psychotic disorders (2.1, 1.8), depression (1.4, 2.0), bipolar disorder (1.4, 2.2), personality disorder (2.1, 2.6), cerebral palsy (2.2, 1.5), and epilepsy (2.0, 1.3). The more closely related the affected family member was, the higher the odds was of ASD for the index person. ASD without intellectual disability was associated with more disorders compared to ASD with intellectual disability. ASD with intellectual disability exhibited a weaker familial association with other mental disorder diagnoses but a stronger familial association with some neurological diagnoses as compared to ASD without intellectual disability.
This study suggests that family history of mental and neurological disorders is associated with increased risk of ASD. The familial component of ASD etiology may differ by presence or absence of co-occurring ID.
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•Tooth dentin extracts were profiled with untargeted chemical analysis.•390 metabolites and exogenous exposures were annotated in tooth extracts.•Over 250 metabolite features ...discriminated the prenatal and postnatal tooth fractions.•Unique metabolite features were found in the prenatal tooth fraction.•Tooth exposome provides retrospective measurements of fetal and early life exposures.
Teeth have unique histology that make this biomatrix a time-capsule for retrospective exposure analysis of fetal and early life. However, most analytic methods require pulverizing the whole tooth, which eliminates exposure timing information. Further, the range of chemicals and endogenous exposures that can be measured in teeth has yet to be fully characterized.
We performed untargeted metabolomics on micro-dissected layers from naturally shed deciduous teeth. Using four liquid-chromatography high-resolution mass spectrometry analytical modes, we profiled small molecules (<1000 Da) from prenatal and postnatal tooth fractions. In addition, we employed linear regression on the tooth fraction pairs from 31 children to identify metabolites that discriminate between prenatal and postnatal exposures.
Of over 10,000 features measured in teeth dentin, 390 unique compounds were annotated from 62 chemical classes. The class with the largest number of compounds was carboxylic acids and their derivatives (36%). Of the annotated exogenous metabolites (phthalates, parabens, perfluoroalkyl compounds, and cotinine) and endogenous metabolites (fatty acids, steroids, carnitines, amino acids, and others), 91 are linked to 256 health conditions through published literature. Differential analysis revealed 267 metabolites significantly different between the prenatal and the postnatal tooth fractions (adj. p-value < 0.05, Bonferroni correction), and 21 metabolites exclusive to the prenatal fraction.
The prenatal and early postnatal exposome revealed from dental biomarkers represents a broad range of endogenous and exogenous metabolites for a comprehensive characterization in environmental health research. Most importantly, this technology provides a direct window into fetal exposures that is not possible by maternal biomarkers. Indeed, we identified several metabolites exclusively in the prenatal fraction, suggesting unique fetal exposures that are markedly different to postnatal exposures. Expansion of databases that include tooth matrix metabolites will strengthen biological interpretation and shed light on exposures during gestation and early life that may be causally linked with later health conditions.
While many studies of motor control in autism have focused on specific motor signs, there has been a lack of research examining the complete range of subtle neuromotor signs. This study compared ...performance on a neurologic examination standardized for children (PANESS, Physical and Neurological Exam for Subtle Signs, Denckla "1974 Developmental Medicine and Child Neurology, 16(6)", 729-741) between a group of 40 boys aged 6-17 with autism and average range IQs and a group of 55 typically developing boys. The Autism group was shown to have significant impairment on several measures of motor control compared to the Control group. Regression analyses revealed that a model including four PANESS variables offered a high level of discrimination in distinguishing boys with high-functioning autism from controls.
The purpose of this study was to investigate associations between use of β-2-adrenergic receptor (B2AR) agonist drugs during pregnancy and risk for autism spectrum disorders (ASD).
A case-control ...study was conducted by using Denmark's health and population registers. Among children born between 1997 and 2006, 5200 cases with ASD admission diagnoses and 52 000 controls without ASD were identified and individually matched on month and year of birth. Conditional logistic regression models were used to estimate odds ratios (OR) and confidence intervals (CI) for any B2AR agonist exposure during pregnancy, preconception, and by trimester.
In total, 3.7% of cases and 2.9% of controls were exposed to B2ARs during pregnancy. Use of B2ARs during pregnancy was associated with increased risk of ASD, even after adjustment for maternal asthma and other covariates (OR: 1.3, 95% CI: 1.1-1.5). The elevated risk was observed with use of B2AR during preconception (OR: 1.3, 95% CI: 1.0-1.6), first trimester (OR: 1.3, 95% CI: 1.1-1.5), second trimester (OR: 1.5, 95% CI: 1.1-1.7), and the third trimester (OR: 1.4, 95% CI: 1.1-1.7). There was some evidence that longer B2AR within-pregnancy use was associated with the increased risk.
B2AR agonist exposure during pregnancy may be associated with an increased risk for ASD. If the effect is real, any intervention must be balanced against benefits of indicated medication use by pregnant women.
We examined the association between prenatal fish intake and child autism-related traits according to Social Responsiveness Scale (SRS) and cognitive development scores in two US prospective ...pregnancy cohorts. In adjusted linear regression analyses, higher maternal fish intake in the second half of pregnancy was associated with increased child autism traits (higher raw SRS scores; ß = 5.60, 95%CI 1.76, 12.97). Differences by fish type were suggested; shellfish and large fish species were associated with increases, and salmon with decreases, in child SRS scores. Clear patterns with cognitive scores in the two cohorts were not observed. Future work should further evaluate potential critical windows of prenatal fish intake, and the role of different fish types in association with child autism-related outcomes.
We examined maternal prenatal vitamin use or supplemental folic acid intake during month one of pregnancy for association with autism spectrum disorder (ASD) in the Early Autism Risk Longitudinal ...Investigation, an enriched-risk pregnancy cohort. Total folic acid intake was calculated from monthly prenatal vitamins, multivitamins, and other supplement reports. Clinical assessments through age 3 years classified children as ASD (n = 38) or non-ASD (n = 153). In pregnancy month one, prenatal vitamin use (59.7%) was not significantly associated with odds of ASD (OR = 0.70, 95%CI 0.32, 1.53). Sample size was limited and residual confounding was possible. Given the estimated effect sizes in this and previous work, prenatal vitamin intake during early pregnancy could be a clinically useful preventative measure for ASD.
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