References:
Autism Prevalence
US Dept. of health & Human Services (2025) ‘Autism Epidemic Runs Rampant,’ New Data Shows 1 in 31 Children Afflicted | HHS.gov
Zhu et al. (2025) Global and Regional Trends in Autism Burden from 1990 to 2021 “Our findings indicated an increasing global trend in the incidence, prevalence, and DALYs associated with ASD.”
Cakir et al. (2020) The lifetime social cost of autism: 1990–2029
Pearson (2025) Autism is on the rise: what’s really behind the increase?
Bougeard et al. (2021) Prevalence of Autism Spectrum Disorder and Co-morbidities in Children and Adolescents: A Systematic Literature Review “Overall, current evidence is supportive of a global increase in ASD over the past years, while suggesting that the augmentation is not specific to a particular region or healthcare system, but is observed at a broader level.”
Harris (2023) Autism Prevalence Has Been on the Rise in the US for Decades—And That’s Progress
Santomauro et al. (2021) The global epidemiology and health burden of the autism spectrum: findings from the Global Burden of Disease Study 2021 - The Lancet Psychiatry “With epidemiological data only available for a limited number of global regions and countries, we urge researchers to initiate more inclusive population representative diagnostic surveys with active case finding to enhance geographical coverage.”
CDC MMWR Vol. 4, No. 2 Prevalence and Early Identification of Autism Spectrum Disorder Among Children Aged 4 and 8 Years
Brain Differences in Autism
Matuskey et al. (2024) 11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults | Molecular Psychiatry)
Ha et al. (2015) Characteristics of Brains in Autism Spectrum Disorder: Structure, Function and Connectivity across the Lifespan
Berto et al. (2022) Association between resting-state functional brain connectivity and gene expression is altered in autism spectrum disorder
Sachdeva et al. (2024) Resolving autism spectrum disorder (ASD) through brain topologies using fMRI dataset with multi-layer perceptron (MLP) “ASD is characterized by reduced functional connectivity throughout the cortical language systems.”
Mapelli et al. (2022) The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models “The cerebellum is the brain structure most constantly found abnormal in ASD, and an increased risk for ASD is dependently associated with cerebellar damage”
Ma et al. (2023) Editorial: A multi-talented butterfly: the role of the cerebellum in social cognition, emotion, and language “Going beyond the traditional understanding of the cerebellum as a motor controller, there is a growing awareness that the cerebellum also plays a critical role in non-motor domains; from basic cognitive functions to complex social functions....With this in mind, it is surprising that neuroscientists have only relatively recently become interested in cerebellar involvement in social, emotional and linguistic processes”
Autism History
Czech (2018) Hans Asperger, National Socialism, and “race hygiene” in Na zi-era Vienna
Falk (2020) Non-complicit: Revisiting Hans Asperger’s Career in Nazi-era Vienna
Simmonds (2020) The first account of the syndrome Asperger described? Part 2: the girls
Pozzi et al. (2024) Revisiting the history of autism before Kanner and Asperger: a tribute to Grunya Sukhareva
Horne (2022) From the archives: Rare photos of Grunya Sukhareva | The Transmitter: Neuroscience News and Perspectives
Herman (2019) Autism in the DSM – The Autism History Project
Miller et al. (2015) Autism Spectrum Disorder Reclassified: A Second Look at the 1980s Utah/UCLA Autism Epidemiologic Study
Sarris (2017) A Lost Generation: Growing Up With Autism Before The "Epidemic" | Kennedy Krieger Institute
Sex Differences in Autism Diagnoses
Loomes et al. (2017) What is the Male-to-Female Ratio in Autism Spectrum Disorder? A Systematic Review and Meta-Analysis
O'Nions et al. (2023) Autism in England: assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data - The Lancet Regional Health “Although this approaches the c. 3:1 ratio reported in a meta-analysis of community case-finding studies,28 a study suggested that girls with equivalent autism characteristics to boys require additional behavioural challenges to receive a diagnosis.29 There is also regional variation in the male to female ratio across local authority districts, indicating that in certain areas, females may be particularly likely to miss out on a diagnosis.8 Therefore, there could be even more undiagnosed autistic females than we have estimated.”
Harrop et al. (2024) Are the diagnostic rates of autistic females increasing? An examination of state-wide trends
Saure et al. (2022) Intellectual disabilities moderate sex/gender differences in autism spectrum disorder: a systematic review and meta‐analysis “Such phenotypic differences could be a potential cause of underrecognition of girls/women with ASD, and it is also possible that observed phenotypic differences may reflect underdiagnosing of girls/women with ASD.”
Berry et al. (2024) A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk | Nature Communications “These results provide a framework for understanding the relationship between X and Y chromosome dosage on ASD, which may inform future research investigating genomic contributors to the observed sex difference.”
Genetic Components of Autism
Rylaarsdam & Guemez-Gamboa (2019) Genetic Causes and Modifiers of Autism Spectrum Disorder
Castelbaum et al. (2020) On the Nature of Monozygotic Twin Concordance and Discordance for Autistic Trait Severity: A Quantitative Analysis | Behavior Genetics
Folstein & Rutter (1977) Infantile Autism: A Genetic Study Of 21 Twin Pairs
Frazier et al. (2015) A Twin Study of Heritable and Shared Environmental Contributions to Autism
Tick et al. (2015) Heritability of autism spectrum disorders: a meta‐analysis of twin studies
Genovese & Butler (2023) The Autism Spectrum: Behavioral, Psychiatric and Genetic Associations
Havdahl et al. (2021) Genetic contributions to autism spectrum disorder
Starnawska & Janecka (2023) Epigenomic contributions to autism spectrum disorders
Wamsley et al. (2024) Molecular cascades and cell type–specific signatures in ASD revealed by single-cell genomics
Franklin et al. (2025) Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex
Paulsen et al. (2022) Autism genes converge on asynchronous development of shared neuron classes | Nature
Stoner et al. (2014) Patches of Disorganization in the Neocortex of Children with Autism
Courchesne et al. (2020) Prenatal origins of asd: the when, what and how of asd development
Courchesne et al. (2024) Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms
Zhou et al. (2022) Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes
Yoon et al. (2021) Rates of contributory de novo mutation in high and low-risk autism families
Cirnigliaroa et al. (2023) The contributions of rare inherited and polygenic risk to ASD in multiplex families
Goin-Kochel et al. (2018) Gene Disrupting Mutations Associated with Regression in Autism Spectrum Disorder
Goin-Kochel et al. (2017) Gene Disrupting Mutations Associated with Regression in Autism Spectrum Disorder
Parental Age - Association with Autism
Shelton et al. (2014) Independent and Dependent Contributions of Advanced Maternal and Paternal Ages to Autism Risk "Children with autism are more likely than controls to be male (males: females = 4.6:1), to have older parents … The median age of mothers at the time of delivery was 30 for cases and 27 for controls. The median age of fathers was 32 among cases and 29 among controls."
Lyall et al. (2020) The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism
Maternal Metabolic Status - Association with Autism
Insulin action in the brain: cell types, circuits, and diseases “The brain is an insulin-sensitive tissue. Insulin signaling plays a key role in different brain cell types.”
Sanchez et al. (2017) Maternal pre‐pregnancy obesity and child neurodevelopmental outcomes: a meta‐analysis “Findings indicated that compared with children of normal weight mothers, children whose mothers were overweight or obese prior to pregnancy were at increased risk for compromised neurodevelopmental outcomes (overweight: OR = 1.17, 95% CI [1.11, 1.24], I2 = 65.51; obese: OR = 1.51; 95% CI [1.35, 1.69], I2 = 79.63). Pre-pregnancy obesity increased the risk of…autism spectrum disorder (OR = 1.36; 95% CI [1.08, 1.70], I2 = 60.52)”
Duko et al. (2024) Associations between maternal preconception and pregnancy adiposity and neuropsychiatric and behavioral outcomes in the offspring: A systematic review and meta-analysis “In our meta-analyses of 42 epidemiological studies involving 3,680,937 mother-offspring pairs, we found increased risks of…autism spectrum disorder [OR=1.42, 95 % CI: 1.22-1.65]”
Fieldhouse (2025) Gestational diabetes linked to autism in study: what scientists say
Allan et al. (2025) Pre-Conception Maternal Obesity Confers Autism Spectrum Disorder-like Behaviors in Mice Offspring Through Neuroepigenetic Dysregulation “Our study demonstrates that maternal obesity prior to conception can lead to lasting epigenetic alterations in the oocyte that subsequently influence transcriptional regulation in the developing brain of first-generation offspring.”
Li et al. (2016) The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities “When examined in combination, only mothers with obesity and PGDM (hazard ratio 3.91, 95% confidence interval 1.76–8.68) and those with obesity and gestational diabetes (hazard ratio 3.04, 95% confidence interval 1.21–7.63) had a significantly increased risk of offspring ASD.”
Ye et al. (2025) Association between maternal diabetes and neurodevelopmental outcomes in children: a systematic review and meta-analysis of 202 observational studies comprising 56.1 million pregnancies “In studies adjusting for multiple confounders (n=98, 49%), children exposed to maternal diabetes had an increased risk of…autism spectrum disorder (1·25; 1·20–1·31)”
Xiang et al. (2015) Association of Maternal Diabetes With Autism in Offspring | Pregnancy | JAMA “In this large, multiethnic clinical cohort of singleton children born at 28 to 44 weeks’ gestation, exposure to maternal GDM diagnosed by 26 weeks’ gestation was associated with risk of ASD in offspring.”
Xu et al. (2014) Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis “In conclusion, maternal diabetes was significantly associated with a greater risk of ASD in the offspring.”
Infant Mortality Rates in the US - Trends Over Time
Shapiro-Mendoza et al. (2016) CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth “Declines in infant mortality (53%) since the 1980s have been largely attributed to increasing preterm survival, owing to improvements in neonatal intensive care and treatments for lung immaturity.”
National Infant Mortality Surveillance (NIMS) 1980 “In 1980, there were 3,542,995 single-delivery and 69,912 multiple-delivery infants born in the United States. In 1980-1981, there were 43,217 deaths among these infants, for a total IMR of 12.0/1,000 live births”
Vital Statistics Rapid Release - Infant Mortality Quarterly Provisional Estimates
Pre-term Birth & Birth Complications - Association with Autism
Ellouk et al. (2025) The association between preterm delivery and autism spectrum disorder in childhood: A retrospective cohort study “This retrospective cohort study found no significant association between PTB and childhood ASD diagnosis.”
Brami et al. (2024) 125 Adverse labor events and childhood autism- is there a link? - American Journal of Obstetrics & Gynecology “Adverse labor events, although concerning in terms of immediate neonatal health, do not appear to contribute to a higher risk of ASD in children as they grow older.”
Getahun et al. (2017) Association of Perinatal Risk Factors with Autism Spectrum Disorder “Exposure to antepartum or intrapartum complications increases the risk of ASD in the offspring. Therefore, pregnancy complications may help identify children who could benefit from early screening and intervention for this common neurodevelopmental condition.”
D'Onofrio et al. (2013) Preterm birth and mortality and morbidity: a population-based quasi-experimental study “For example, extreme preterm birth (23-27 weeks of gestation) was associated with…autism (hazard ratio [HR], 3.2; 95% CI, 2.6-4.0)”
Crump et al. (2023) Preterm or early term birth and risk of autism - pmc
Air Pollution - Association with Autism
Imbriani et al. (2021) Early-Life Exposure to Environmental Air Pollution and Autism Spectrum Disorder: A Review of Available Evidence “Several studies have identified in recent years a positive association between exposure to different environmental pollutants—such as atmospheric particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3)—and the onset of neurodevelopmental diseases, including ASD. The neurotoxicity mechanisms of these pollutants have not been fully understood. However, inflammation and oxidative stress processes seem to play a crucial role in the structural and functional changes affecting the central nervous system (CNS) that may cause mental disorders, possibly mediated by epigenetics modifications of the genes involved in these processes.”
Ojha & Amal (2024) Air pollution: an emerging risk factor for autism spectrum disorder
Pelch et al. (2019) Environmental Chemicals and Autism: A Scoping Review of the Human and Animal Research
Lu et al. (2022) Rethinking autism: the impact of maternal risk factors on autism development
Khachadourian et al. (2025) Familial confounding in the associations between maternal health and autism
Pesticides - Association with Autism
Shelton et al. (2014) Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study “Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4).”
He et al. (2022) The relationship between pesticide exposure during critical neurodevelopment and autism spectrum disorder: A narrative review “Recent studies have shown that low-level agricultural pesticide exposure during the critical period of neurodevelopment (pregnancy and lactation) is closely related to autism spectrum disorder (ASD).”
Biosca-Brull et al. (2021) Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models “It is difficult to draw solid conclusions as there are a wide variety of studies that differ in many aspects such as route, age, or source of exposure”
von Ehrenstein et al. (2019) Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study
Frequently Asked Questions about the Current Status of Chlorpyrifos and Anticipated Path Forward
Heavy Metals - Association with Autism
Dou et al. (2024) Exposure to heavy metals in utero and autism spectrum disorder at age 3: A meta-analysis of two longitudinal cohorts of siblings of children with autism
Campbell et al. (2021) Prenatal exposure to metals and autism spectrum disorder: Current status and future directions
A systematic literature review on the association between exposures to toxic elements and an autism spectrum disorder “Toxic metal content significantly differed between individuals with ASD and HC in the current meta-analysis. The results assist in clarifying the significance of toxic metals as environmental factors in the development of ASD”
Folic Acid Supplementation - Association with Autism
Levine et al. (2018) Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring “Maternal exposure to folic acid and multivitamin supplements before and during pregnancy is associated with a reduced risk of ASD in the offspring compared with the offspring of mothers without such exposure.”
Brieger et al. (2021) The Association of Prenatal Vitamins and Folic Acid Supplement Intake with Odds of Autism Spectrum Disorder in a High-Risk Sibling Cohort, the Early Autism Risk Longitudinal Investigation (EARLI) “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.”
Compañ Gabucio et al. (2021) The Use of Lower or Higher Than Recommended Doses of Folic Acid Supplements during Pregnancy Is Associated with Child Attentional Dysfunction at 4–5 Years of Age in the INMA Project “In conclusion, this prospective mother–child cohort study shows that the periconceptional non-recommended FAs doses (<400 µg/day or ≥1000 µg/day) compared to the FAs use of 400–999 µg/day may have negative effects on attentional function development in children at 4–5 years of age”
Fardous & Heydari (2023) Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review “Moderate prenatal FA supplementation of at least 400 µg from the diet and supplements was associated with a decreased ASD risk in children, while excess FA corresponded with lower cognitive development and increased ASD risk. This suggests a U-shaped relationship, where both inadequate and high FA exposure could increase the ASD risk.”
Valproate - Association with Autism
Zarate-Lopez et al. (2023) Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder “In recent decades, clinical studies have shown that in-utero exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug, is an environmental factor associated with an increased risk of ASD.”
Andrade et al. (2025) Gestational Exposure to Valproate and Autism Spectrum Disorder or Attention‐Deficit/Hyperactivity Disorder in Offspring: Systematic Review and Meta‐Analysis “Gestational exposure to valproate was associated with an increased risk of ASD and ADHD; the risks for ASD were greater at doses ≥ 1000 mg/day. These findings add to the literature that strongly discourages the use of valproate by women of childbearing age, especially during pregnancy.”
Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism “Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy.”
Emerging mechanisms of valproic acid-induced neurotoxic events in autism and its implications for pharmacological treatment “However, the mechanism of VPA exposure-induced ASD remains unclear. Several factors are involved in the pathological phase of ASD, including aberrant excitation/inhibition of synaptic transmission, neuroinflammation, diminished neurogenesis, oxidative stress, etc.”
Acetaminophen - Association with Autism
Prada et al. (2025) Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology “Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs.”
Ahlqvist et al. (2024) Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability “Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism”
Li et al. (2018) Use of nonsteroidal antiinflammatory drugs during pregnancy and the risk of miscarriage
Bisson et al. (2018) Antenatal and Postnatal Analgesia - BJOG: An International Journal of Obstetrics & Gynaecology
ACOG Response to Consensus Statement on Paracetamol Use During Pregnancy “ACOG and obstetrician-gynecologists across the country have always identified acetaminophen as one of the only safe pain relievers for pregnant individuals during pregnancy. This consensus statement, and studies that have been conducted in the past, show no clear evidence that proves a direct relationship between the prudent use of acetaminophen during any trimester and fetal developmental issues.”
Infection/Fever - Association with Autism
Egloff et al. (2020) Causes and consequences of fever during pregnancy: A retrospective study in a gynaecological emergency department
Waller et al. (2017) Maternal report of fever from cold or flu during early pregnancy and the risk for noncardiac birth defects, National Birth Defects Prevention Study, 1997–2011 ”We observed that report of a cold or flu accompanied by fever during early pregnancy was associated with 8 of the 30 categories of birth defects that we studied.
PrabhuDas (2021) Immune Regulation, Maternal Infection, Vaccination, and Pregnancy Outcome | Journal of Women's Health “The inflammatory process induced by these infectious insults, as well as some noninfectious insults, occurring during pregnancy can disrupt this carefully achieved balance and, in turn, lead to a state of rampant inflammation, immune activation, and dysregulation with deleterious health outcomes for the mother and fetus.”
Madjunkov (2022) Risk of Autism Spectrum Disorder in Offspring Following Exposure to Maternal Fever during Pregnancy: A Systematic Review and Meta-Analysis “Prenatal exposure to maternal fever was found to be associated with fetal neurotoxicity during critical windows of CNS development and increased risk for ASD. An association of prenatal fever with ASD in genetically predisposed women may aid in early diagnosis, prevention, and management.”
Antoun et al. (2021) Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis “Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12–1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13–95% CI: 1.02–1.26].”
al-Haddad et al. (2019) Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero | Depressive Disorders | JAMA Psychiatry “Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42).”
SSRIs - Association with Autism
Lee et al. (2024) Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring | European Child & Adolescent Psychiatry “These results imply that the association between prenatal antidepressant exposure and ASD and ADHD is not contributed to by an intrauterine medication effect but more likely to be accounted for by maternal depression, genetic, and potential environmental factors.”
Kim et al. (2019) Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence
Vaccines - Association with Autism
Taylor et al. (1999) Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association - PubMed
Deer (2011) How the case against the MMR vaccine was fixed
Taylor et al. (2014) Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies
Hviid et al. (2019) Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study: Annals of Internal Medicine
Pietrantonj et al. (2021) Vaccines for measles, mumps, rubella, and varicella in children
Mohammed et al. (2022) Does Vaccination Increase the Risk of Autism Spectrum Disorder?
Mawson & Croft (2019) Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism
SCN1A - Association with Autism
Ding et al. (2021) SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis - PMC
Gut Microbiome - Association with Autism
Peralta-Marzal et al. (2024) A robust microbiome signature for autism spectrum disorder across different studies using machine learning
Holingue (2024) Overview of Connections between the Gut, Autism, and Mental health
Madra et al. (2021) Gastrointestinal issues and Autism Spectrum Disorder
Hung & Margolis (2024) Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance | Nature Reviews Gastroenterology & Hepatology
Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review “Compared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.”
Misc.
Maternal Alcohol Consumption During Pregnancy and the Risk of Autism Spectrum Disorders in Offspring: A Retrospective Analysis of the Millennium Cohort Study “Alcohol consumption during pregnancy was not associated with the risk of developing ASD in this study cohort.”
The co-occurrence of epilepsy and autism: A systematic review - ScienceDirect “The median overall period prevalence of epilepsy in people with autism was 12.1%”...”In 2010, the prevalence of ASD in the general population was estimated at 0.76% and responsible for 7.7 million disability adjusted life years (DALYs) across the globe [6]. Similarly, the active prevalence of epilepsy in the general population is 0.6% [7], and it was the fourth most burdensome (DALY) neurological disorder worldwide in 2015.”
Autism - The World Health Organization Factsheet