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In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95 149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The hazard risk ratio for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

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., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n = 672), with other developmental delays (DD)/(n = 938), and children in the general population (POP)/(n = 851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Maternal prepregnancy BMI and gestational weight gain (GWG) are examined in relation to autism spectrum disorder (ASD) and other developmental disorders (DD) in offspring in a multisite case-control study., Methods: Maternal prepregnancy BMI, obtained from medical records or self-report, was categorized as underweight, normal weight, overweight, obesity Class 1, or obesity Class 2/3. GWG was standardized for gestational age (GWG z score), and the rate (pounds/week) was categorized per adherence with clinical recommendations. Logistic regression models, adjusting for demographic factors, were used to assess associations with ASD (n = 1,159) and DD (n = 1,617), versus control children (n = 1,633)., Results: Maternal obesity Class 2/3 was associated with ASD (adjusted odds ratio [AOR] = 1.87, 95% CI: 1.40-2.51) and DD (AOR = 1.61, 95% CI: 1.22-2.13). GWG z score was not associated with DD (AOR = 1.14, 95% CI: 0.95-1.36), but the GWG z score highest tertile was associated with higher odds of ASD, particularly among male children (AOR = 1.47, 95% CI: 1.15-1.88)., Conclusions: Results indicate that maternal prepregnancy severe obesity increases risk of ASD and DD in children and suggest high gestational-age-adjusted GWG is a risk factor for ASD in male children. Because maternal BMI and GWG are routinely measured and potentially modifiable, these findings could inform early interventions for high-risk mother-child dyads., (© 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objectives: The developmental disabilities questions in the 2014 National Health Interview Survey (NHIS) were changed from previous years, including question reordering and a new approach to asking about autism spectrum disorder (ASD). This report examines survey-based estimates of the lifetime prevalence of ASD, intellectual disability (ID), and any other developmental delay (other DD) following the inclusion of a standalone ASD question, the inclusion of specific diagnoses in the ASD question, and the ASD question preceding the other DD question, and compares them with estimates from previous years., Methods: In NHIS, one child is randomly selected from each family to be the subject of detailed questions on health conditions, functional limitations, and health care utilization. Parents are asked if a doctor or health professional had ever told them that their child had each of a series of developmental disabilities. Prevalence estimates of ASD, ID, and other DD for children aged 3–17 years were calculated using data collected in 2011–2014., Results: The estimated prevalence of ASD based on 2014 data was 2.24%, a significant increase from the estimated annualized prevalence of 1.25% based on 2011–2013 data. In contrast, the prevalence of other DD declined significantly from 4.84% based on 2011–2013 data to 3.57% based on 2014 data. The prevalence of ID did not significantly change from 2011–2013 (1.27%) to 2014 (1.10%). The prevalence of having any of the three conditions was constant across survey years., Conclusions: The revised question ordering and new approach to asking about developmental disabilities in the 2014 NHIS likely affected the prevalence estimates of these conditions. In previous years, it is likely that some parents of children diagnosed with ASD reported this developmental disability as other DD instead of, or in addition to, ASD. Following these changes, the 2014 ASD estimate was more similar to ASD prevalence estimates from other sources., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Previous studies report associations between conception with assisted reproductive technology (ART) and autism. Whether these associations reflect an ascertainment or biologic effect is undetermined. We assessed diagnosis age and initial autism symptom severity among >30,000 children with autism from a linkage study of California Department of Developmental Services records, birth records, and the National ART Surveillance System. Median diagnosis age and symptom severity levels were significantly lower for ART-conceived than non-ART-conceived children. After adjustment for differences in the socio-demographic profiles of the two groups, the diagnosis age differentials were greatly attenuated and there were no differences in autism symptomatology. Thus, ascertainment issues related to SES, not ART per se, are likely the driving influence of the differences we initially observed.

Objectives: We assessed the association between assisted reproductive technology (ART) and diagnosed autistic disorder in a population-based sample of California births., Methods: We performed an observational cohort study using linked records from the California Birth Master Files for 1997 through 2007, the California Department of Developmental Services autism caseload for 1997 through 2011, and the Centers for Disease Control and Prevention's National ART Surveillance System for live births in 1997 through 2007. Participants were all 5 926 251 live births, including 48 865 ART-originated infants and 32 922 cases of autism diagnosed by the Department of Developmental Services. We compared births originated using ART with births originated without ART for incidence of autism., Results: In the full population, the incidence of diagnosed autism was twice as high for ART as non-ART births. The association was diminished by excluding mothers unlikely to use ART; adjustment for demographic and adverse prenatal and perinatal outcomes reduced the association substantially, although statistical significance persisted for mothers aged 20 to 34 years., Conclusions: The association between ART and autism is primarily explained by adverse prenatal and perinatal outcomes and multiple births.

We estimated the prevalence of obesity, overweight, and underweight among US adolescents with and without autism and other learning and behavioral developmental disabilities (DDs) and assessed the health consequences of obesity among adolescents with DDs. From the 2008 to 2010 National Health Interview Survey, we selected 9,619 adolescents ages 12-17 years. Parent respondents reported weight, height, presence of DDs and health conditions. We calculated body mass index (BMI) and defined obesity, overweight, and underweight as ≥95th, ≥85th to <95th, and <5th percentiles, respectively, using established criteria. We created mutually-exclusive DD subgroups using the following order of precedence: autism; intellectual disability; attention-deficit-hyperactivity-disorder; learning disorder/other developmental delay. We compared BMI outcomes among adolescents in each DD group versus adolescents without DDs using multivariable logistic regression. Socio-demographic factors and birthweight were included as confounders. Estimates were weighted to reflect the US population. Both obesity and underweight prevalences were higher among adolescents with than without DDs [adjusted prevalence ratios (aPR) 1.5 (1.25-1.75) and 1.5 (1.01-2.20), respectively]. Obesity was elevated among adolescents with all DD types, and was highest among the autism subgroup [aPR 2.1 (1.44-3.16)]. Adolescents with either a DD or obesity had higher prevalences of common respiratory, gastrointestinal, dermatological and neurological conditions/symptoms than nonobese adolescents without DDs. Adolescents with both DDs and obesity had the highest estimates for most conditions. Obesity is high among adolescents with autism and other DDs and poses added chronic health risks. Obesity prevention and management approaches for this vulnerable population subgroup need further consideration.

The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case-control design with population-based ascertainment of children aged 2-5 years with an autism spectrum disorder (ASD) and children in two control groups-one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes.

Background: A 57% increase in the U.S. prevalence of autism spectrum disorders (ASD) for 8-year-old children born in 1994 versus 1998 was recently reported., Methods: To quantify the possible contributions of given risk/predictive factors on the recent ASD prevalence increase, we formulated a mathematical model based on the baseline risk factor prevalence (RFP), the proportionate change in RFP (cRFP), and the magnitude of the association between the risk factor and ASD [estimated relative risk (RR)]. We applied this model to several pregnancy-related factors (preterm, very preterm, low and very low birth weight, multiple birth, cesarean delivery, breech presentation, and assisted reproductive technology use). RFP and cRFP estimates for each factor were obtained from U.S. population-based surveillance datasets. Estimated RRs were obtained from a series of systematic literature reviews., Results: We estimate that each risk factor examined, alone or in various combinations, accounted for a very small proportion (<1%) of the ASD increase. Additionally, hypothetical scenarios indicate RFP, cRFP, and RR all need to be sizable for a risk factor to appreciably influence ASD prevalence., Conclusions: Thus, although various pregnancy factors have been found to be associated with ASDs, the contribution of many of these factors to the recently observed ASD increase is likely minimal., (Published by Elsevier Inc.)

This study evaluated independent effects of maternal and paternal age on risk of autism spectrum disorder. A case-cohort design was implemented using data from 10 US study sites participating in the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network. The 1994 birth cohort included 253,347 study-site births with complete parental age information. Cases included 1,251 children aged 8 years with complete parental age information from the same birth cohort and identified as having an autism spectrum disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. After adjustment for the other parent's age, birth order, maternal education, and other covariates, both maternal and paternal age were independently associated with autism (adjusted odds ratio for maternal age > or =35 vs. 25-29 years = 1.3, 95% confidence interval: 1.1, 1.6; adjusted odds ratio for paternal age > or =40 years vs. 25-29 years = 1.4, 95% confidence interval: 1.1, 1.8). Firstborn offspring of 2 older parents were 3 times more likely to develop autism than were third- or later-born offspring of mothers aged 20-34 years and fathers aged <40 years (odds ratio = 3.1, 95% confidence interval: 2.0, 4.7). The increase in autism risk with both maternal and paternal age has potential implications for public health planning and investigations of autism etiology.

Objective: We assessed associations between parenting a child with autism and stress indicators., Methods: In the 2003 National Survey of Children's Health, parents or other knowledgeable adult respondents for children aged 4 to 17 years reported their recent feelings about their life sacrifices to care for their child, difficulty caring for their child, frustration with their child's actions, and anger toward their child. Responses were compiled in the Aggravation in Parenting Scale. Parents of children reported to have autism (N = 459) were compared with parents of: (1) children with special health care needs including emotional, developmental, or behavioral problems other than autism that necessitated treatment (children with other developmental problems [N = 4545]); (2) children with special health care needs without developmental problems (N = 11475); and (3) children without special health care needs (N = 61826). Weighted estimates are presented., Results: Parents of children with autism were more likely to score in the high aggravation range (55%) than parents of children with developmental problems other than autism (44%), parents of children with special health care needs without developmental problems (12%), and parents of children without special health care needs (11%). However, within the autism group, the proportion of parents with high aggravation was 66% for those whose child recently needed special services and 28% for those whose child did not. The parents of children with autism and recent special service needs were substantially more likely to have high aggravation than parents of children with recent special service needs in each of the 3 comparison groups. Conversely, parents of children with autism but without recent special service needs were not more likely to have high aggravation than parents of children with other developmental problems., Conclusions: Parenting a child with autism with recent special service needs seems to be associated with unique stresses.