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Clinical and Practical Psychopharmacology April 14, 2025

Autism Spectrum Disorder, 1: Genetic and Environmental Risk Factors

J Clin Psychiatry 2025;86(2):25f15878

Abstract

The global prevalence of autism spectrum disorder (ASD) has quadrupled during the past 3 decades; the reasons for this are many and include broadening of the diagnostic concept, increased awareness of the disorder, increased screening (including of adults and of girl children), and, possibly, increased exposure to environmental risk factors. This article examines genetic and especially environmental risk factors for ASD. Unsurprisingly, hundreds of potential genes have been identified, many of which overlap between ASD, schizophrenia, depression, and cardiometabolic disorders. Likewise, over a hundred environmental exposures have been associated with ASD risk. These include exposure to parental and family characteristics, exposure to maternal disorders arising during pregnancy, exposure to chronic maternal disorders present during pregnancy, exposure to fetal and other pregnancy-related problems/events, exposure to neonatal problems/events, exposure to maternal nutritional deficiencies during pregnancy, maternal exposure to substances during pregnancy, maternal exposure to pharmacological agents during pregnancy, in utero exposure to toxic substances, and early life exposure to toxic substances. Some of the risk factors identified may be causal, some may be markers of intermediary mechanisms, and some may be unrelated markers. About 40 of these risk factors have been confirmed in meta-analysis for association with ASD. Nearly 70 maternal diagnoses have also been associated with ASD, but, after correcting for false discovery error and shared risk, only 30 remain; and, of these 30, almost all may be explained by genetic and environmental risk factors shared between mother and child, judging from findings in discordant sibling pair and paternal negative control analyses. Caveats and nuances in the interpretation of risks are briefly discussed.

J Clin Psychiatry 2025;86(2):25f15878

Author affiliations are listed at the end of this article.

The prevalence of autism and autism spectrum disorder (ASD) has increased sharply during the past 50 years. In 1978, the population prevalence of infantile autism, diagnosed using the Rutter criteria, was 0.02% among children in the city of Gothenburg, Sweden.1 In contrast, in 2021–2022, the weighted population prevalence of ASD, diagnosed using DSM-5 criteria, was 170 times higher (at 3.42%) among children and adolescents in the US.2 A systematic review and meta-analysis found that the global pooled point prevalence of ASD rose from 0.25% in 1994–1999 to 0.99% in 2015–2019.3

The prevalence of ASD has varied widely across studies. There are many possible explanations for this, including for the increase in prevalence across time4–8; a nonexhaustive list is provided in Table 1.

ASD is considered to be multifactorial in origin, with contributions from both genes and environment. This article considers genetic and environmental risk factors for ASD, with especial focus on environmental risk factors. The interpretation of risks is briefly discussed.

Genetic Risk Factors for Autism Spectrum Disorder

There is little doubt that ASD is a highly heritable, polygenic disorder. At least 12 single nucleotide polymorphisms on 5 candidate genes have been identified in meta-analyses.9 However, hundreds of genes are also likely to be associated with the disorder10,11; in fact, more than a hundred genes are suggested to be shared between ASD and congenital heart disease, alone.12 Furthermore, many of the genetic risk factors associated with ASD are also associated with other neuropsychiatric disorders, including schizophrenia and depression13; this is important because pharmacological agents used in the treatment of these disorders during pregnancy may be associated with (or blamed for) ASD in offspring when the shared genes drive the risk for both maternal mental illness and offspring ASD.14

Environmental Risk Factors for Autism Spectrum Disorder

Many sociodemographic, clinical, gestational, and other environmental risk factors have been associated with an increased risk of ASD; these are at least 50 in number, and total to 100 or more, depending on how one defines the concept of risk; whether one interprets a significant finding to represent a causal variable, a marker variable, or a mediator variable; and how one counts risk factors that tend to go together. For convenience, these will all be listed separately and referred to, generically, as risk factors.

Many risk factors have consistently been associated with increased risk of ASD, where consistent association is operationalized as statistically significant findings obtained from systematic review and meta-analysis (Table 2). These risk factors include parental and family characteristics such as greater maternal age15,16 and greater paternal age15,16; exposure to maternal disorders arising during pregnancy, including hyperemesis gravidarum,17 immune activation with altered levels of inflammatory markers,18 infection,19 fever,20 preeclampsia,21 and excessive weight gain22; exposure to chronic maternal disorders during pregnancy, including (prepregnancy) obesity,23 polycystic ovarian disease,24,25 type 1 diabetes, type 2 diabetes, and gestational diabetes,26 hypothyroidism,27 and epilepsy not on treatment28; exposure to labor epidural anesthesia but not other anesthesia during delivery29; exposure to cesarean section30; pregnancy-related fetal adversities, including preterm birth, low birth weight, and small for gestational age31; possible maternal nutritional deficiencies during pregnancy, including low levels of vitamin D32 and no folic acid supplementation33; exposure to substances such as tobacco34 and cannabis35; exposure to pharmacological agents during pregnancy, including acetaminophen (paracetamol),36 antibiotics,37 antidepressants,38 valproate,39 and topiramate,40 but not antipsychotics41 or benzodiazepines42; in utero exposure to mercury,43 air pollution,44 pesticides,45 heavy metals,46 bisphenol A,47 and phthalates48; and early life exposure to air pollution49 and low or high levels of trace elements.50

Many recent studies have identified increased risks for which data from meta-analysis are unavailable. These risks (Table 3) include maternal and paternal depression, regardless of time of pregnancy,51 maternal and paternal asthma,52 gestational exposure to ultrasound with deeper penetration,53 gestational exposure to systematic glucocorticoids used to treat autoimmune disorders, inflammatory disorders, or risk of preterm birth,54 gestational exposure to ritodrine used for tocolysis55 and beta-2 adrenoceptor agonists used to treat asthma,56 gestational exposure to maternal anemia,57 lower maternal levels of estradiol and cortisol,58 inadequate weight gain during pregnancy,59 low maternal fish intake during pregnancy,60 maternal exposure to lithium in drinking water,61 maternal alcohol use and fetal alcohol syndrome,62 (surprisingly) higher maternal levels of vitamin B12,63 and indices of neonatal immune activation.64 This is a nonexhaustive list.

Other Risk Factors: Meta-Analyses

Two meta-analyses merit special attention. The first study65 was a meta-analysis of 50 prenatal risk factors extracted from 40 eligible studies. Among these, risk factors significantly associated with offspring ASD were non-native mother, older maternal and paternal age, earlier birth order, and gestational exposure to medications, diabetes, and bleeding during pregnancy. Many of these risk factors were validated in later meta analyses, referenced in a previous section in this article. The other study66 was a meta-analysis of 60 perinatal and neonatal risk factors extracted from the same 40 eligible studies. Among these, risk factors significantly associated with offspring ASD were summer birth, multiple birth, blood group incompatibilities, fetal distress, abnormal presentation, cord complications, birth injury or trauma, maternal hemorrhage, low birth weight, small for gestational age, congenital malformations, low Apgar score at 5 minutes, meconium aspiration, hyperbilirubinemia, neonatal anemia, and feeding difficulties.

These 2 meta-analyses examined data extracted from the same set of studies. One concern with these meta analyses is that many of the risk factors examined (both within and between the 2 meta-analyses) may have been simultaneously present in the same pregnancy; that is, they may not have been independent risk factors. Another concern is that, despite the very large number of risk factors tested (110 in all), no corrections were applied to protect against false positive errors.

Other Risk Factors: an Omnibus Cohort Study

An extraordinary Danish nationwide cohort study67 examined the association of 236 maternal ICD-10 level 3 diagnosis codes (exposures) with ASD in offspring (outcome); the analysis was conducted in several steps and included sibling studies, discordant sibling pair analysis, and paternal negative control analyses.

The sample comprised 648,901 women with 1,131,899 children born in Denmark during 1998–2015; data were drawn from national health registers. Across a median follow-up of 9.7 years, 18,374 (1.6%) children were diagnosed with ASD.

There were 168 maternal nonchronic diagnoses with a prevalence of at least 0.05% during the 12 months before childbirth and 68 maternal chronic diagnoses with a prevalence of at least 0.1% in the 48 months before childbirth. In Cox regression analyses that adjusted for a wide range of sociodemographic variables, 37 of 168 nonchronic and 32 of 68 chronic diagnoses were significantly associated with ASD. After adjusting for multiple hypothesis testing, these numbers reduced to 20 and 22, respectively. These 42 diagnoses included psychiatric, neurological, cardiometabolic, oncological, orthopedic, and other conditions.

In the next step of analysis, all 42 diagnoses along with the sociodemographic covariates were examined together in a single analysis; thus, each diagnosis adjusted for the rest in an exploratory analysis. In this multidiagnosis model, 30 diagnoses, that is, 15 nonchronic and 15 chronic diagnoses, remained significantly associated with ASD.

In the direct sibling analyses, after adjusting for covariates, about three-quarters of the 42 diagnoses were significantly associated with ASD. However, in the exposure-discordant sibling pair analysis, only 3 diagnoses (fracture of the skull and facial bones, maternal care for other fetal problems, and mental disorder, not otherwise specified) remained significantly associated with ASD, suggesting that almost all the associations between maternal diagnoses and ASD could be explained by genetic and environmental risk factors shared between mother and child.

Finally, in the paternal negative control analysis, for 13 out of 17 diagnoses studied, the relationship between parental diagnosis and ASD in offspring was closely similar between mothers and fathers. These results also suggested that almost all the associations between maternal diagnoses and ASD could be explained by genetic and environmental risk factors shared between parents and offspring.

The take-home message from this study67 is that many maternal diagnoses are associated with the risk of ASD in offspring, but the risks appear to be driven by genetic and environmental variables rather than by the diagnoses, themselves. The most important limitation of this study is that it examined maternal diagnoses with no a priori hypotheses based on theoretical cause-effect considerations.

Importantly, the identities of the shared genetic and environmental variables could not be determined in this study.67 Also importantly, the take-home message of this study (see above) cannot be generalized to most of the other risk factors for ASD considered in earlier sections of this article because these risk factors were not maternal diagnoses that were studied by the authors.67

Not Risk Factors

Despite widespread fear in the lay population, data from meta-analyses show that thimerosal in vaccines,43 vaccines in general,68 and the MMR vaccine, in particular,69 are not associated with an increased risk of ASD.

Risk Factors: General Comments

The risk factors listed in this article are not exhaustive; there are exposures examined in occasional studies, not all of which have been associated with increased risk, and these are too many to list. There are also risk factors within a group that have been studied separately (eg, different pollutants or pesticides under the general umbrella of air pollution or pesticides) that, with a view to reducing information overload, have deliberately not been separately presented in this article.

Many risk factors aggregate, such as low socioeconomic status, maternal malnutrition, inadequate maternal weight gain during pregnancy, low levels of nutrients in maternal blood, etc; or, preterm birth, small for gestational age, and low birthweight. Such groupings can perhaps be represented by a single construct. It may also not be meaningful to deconstruct gestational, labor, or neonatal adversities into individual events and experiences unless there is a theoretical reason to do so; it is possible that physiological stresses increase the risk of ASD through shared or overlapping mediatory pathways.

Many risk factors studied are not necessarily risk factors; they may be either markers of risk or mediators of risk. As an example, maternal autoimmune disease, maternal infection, and fever during pregnancy; maternal use of antibiotics and acetaminophen during pregnancy; changes in levels of immune and inflammatory molecules; and changes in the gut microbiome have all been associated with ASD risk. However, although speculation is possible, it cannot be asserted with certainty which of these are the primary risk factors, which are merely markers, and which are mechanisms. It is also uncertain to what extent significant findings are due to confounding by genetic factors, confounding by indication or the severity thereof, and confounding by unmeasured and unknown risk factors. Readers may wish to refer to general reviews on the subject.70,71

The referencing of meta-analyses and studies in previous sections is not an endorsement of infallibility. No meta-analysis, no study in a meta-analysis, and no standalone study is perfect. Every study needs to be understood in the context of its sample and the population that the sample represents; in its methodological context, and in the context of its strengths and limitations. As a special point, there is much difference between the concept of autism in early studies and the concept of ASD in current research. Therefore, the interpretation of all findings must necessarily be nuanced. This, of course, is true of all research but is especially important in the context of the etiopathogenesis of ASD because of the enormous heterogeneity evident herein.

Furthermore, on the subject of nuanced interpretations, in meta-analysis,38 gestational exposure to antidepressants was associated with an increased risk of ASD in offspring; however, in the same meta-analysis, prepregnancy exposure to antidepressants was also associated with increased risk. This implies that genetic or environmental factors, shared between mother and child, rather than antidepressant exposure, drive the ASD risk. As another example, evidence associating maternal smoking with ASD risk is indirect. In a meta-analysis,34 maternal smoking during pregnancy increased the risk of ASD in offspring, but the risk narrowly missed statistical significance. However, when population-level smoking metrics were included in meta-regression, the risk was statistically significant. Separately, in a large cohort study,72 the risk of ASD associated with gestational exposure to cannabis was reduced by about 60% in tobacco smokers, suggesting that tobacco use also plays a substantial role as a risk factor for ASD.

Parting Notes

This article has made no attempt to speculate on how different risk factors can be integrated in the etiopathogenesis of ASD; current understanding of ASD is insufficient to undertake such a task. This article has deliberately refrained from presenting values for risk for individual risk factors; that is, odds ratios, hazard ratios, and their 95% confidence intervals. This is deliberate because the subject is important and will be addressed in the next article in this column.

Article Information

Published Online: April 14, 2025. https://doi.org/10.4088/JCP.25f15878
© 2025 Physicians Postgraduate Press, Inc.
To Cite: Andrade C. Autism spectrum disorder, 1: genetic and environmental risk factors. J Clin Psychiatry 2025;86(2):25f15878.
Author Affiliations: Department of Psychiatry, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India; Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Corresponding Author: Chittaranjan Andrade, MD, Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India ([email protected]).
Relevant Financial Relationships: None.
Funding/Support: None.

Each month in his online column, Dr Andrade considers theoretical and practical ideas in clinical psychopharmacology with a view to update the knowledge and skills of medical practitioners who treat patients with psychiatric conditions.

Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India. Please contact Chittaranjan Andrade, MD, at Psychiatrist.com/contact/andrade.

Financial disclosure and more about Dr Andrade.

  1. Gillberg C. Maternal age and infantile autism. J Autism Dev Disord. 1980;10(3):293–297.
  2. Yan X, Li Y, Li Q, et al. Prevalence of autism spectrum disorder among children and adolescents in the United States from 2021 to 2022. J Autism Dev Disord. 2024. Online ahead of print. doi:10.1007/s10803-024-06390-7. CrossRef
  3. Talantseva OI, Romanova RS, Shurdova EM, et al. The global prevalence of autism spectrum disorder: a three-level meta-analysis. Front Psychiatry. 2023;14:1071181.
  4. Hansen SN, Schendel DE, Parner ET. Explaining the increase in the prevalence of autism spectrum disorders: the proportion attributable to changes in reporting practices. JAMA Pediatr. 2015;169(1):56–62. PubMed CrossRef
  5. Chiarotti F, Venerosi A. Epidemiology of autism spectrum disorders: a review of worldwide prevalence estimates since 2014. Brain Sci. 2020;10(5):274.
  6. Russell G, Stapley S, Newlove-Delgado T, et al. Time trends in autism diagnosis over 20 years: a UK population-based cohort study. J Child Psychol Psychiatry. 2022;63(6):674–682.
  7. Solmi M, Song M, Yon DK, et al. Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries. Mol Psychiatry. 2022;27(10):4172–4180.
  8. Zeidan J, Fombonne E, Scorah J, et al. Global prevalence of autism: a systematic review update. Autism Res. 2022;15(5):778–790.
  9. Qiu S, Qiu Y, Li Y, et al. Genetics of autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses. Transl Psychiatry. 2022;12(1):249.
  10. Ramaswami G, Geschwind DH. Genetics of autism spectrum disorder. Handb Clin Neurol. 2018;147:321–329.
  11. Manoli DS, State MW. Autism spectrum disorder genetics and the search for pathological mechanisms. Am J Psychiatry. 2021;178(1):30–38.
  12. Rosenthal SB, Willsey HR, Xu Y, et al. A convergent molecular network underlying autism and congenital heart disease. Cell Syst. 2021;12(11):1094–1107.e6.
  13. Cross-Disorder Group of the Psychiatric Genomics Consortium; Cross-Disorder Group of the Psychiatric Genomics Consortium. Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell. 2019;179(7):1469–1482.e11.
  14. Andrade C. Genes as unmeasured and unknown confounds in studies of neurodevelopmental outcomes after antidepressant prescription during pregnancy. J Clin Psychiatry. 2020;81(3):20f13463.
  15. Wu S, Wu F, Ding Y, et al. Advanced parental age and autism risk in children: a systematic review and meta-analysis. Acta Psychiatr Scand. 2017;135(1):29–41. PubMed CrossRef
  16. Dehesh T, Mosleh-Shirazi MA, Jafari S, et al. A assessment of the effects of parental age on the development of autism in children: a systematic review and a meta-analysis. BMC Psychol. 2024;12(1):685.
  17. Nijsten K, Jansen LAW, Limpens J, et al. Long-term health outcomes of children born to mothers with hyperemesis gravidarum: a systematic review and meta analysis. Am J Obstet Gynecol. 2022;227(3):414–429.e17.
  18. Gardner RM, Brynge M, Sjöqvist H, et al. Maternal immune activation and autism in offspring: what is the evidence for causation? Biol Psychiatry. 2024;S0006–3223(24):01760–01768.
  19. Tioleco N, Silberman AE, Stratigos K, et al. Prenatal maternal infection and risk for autism in offspring: a meta-analysis. Autism Res. 2021;14(6):1296–1316.
  20. Antoun S, Ellul P, Peyre H, et al. Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta analysis. Mol Autism. 2021;12(1):60.
  21. Zhen Lim TX, Pickering TA, Lee RH, et al. Hypertensive disorders of pregnancy and occurrence of ADHD, ASD, and epilepsy in the child: a meta-analysis. Pregnancy Hypertens. 2023;33:22–29.
  22. Wu D, Li Y, Chen L, et al. Maternal gestational weight gain and offspring’s neurodevelopmental outcomes: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2023;153:105360.
  23. Sanchez CE, Barry C, Sabhlok A, et al. Maternal pre-pregnancy obesity and child neurodevelopmental outcomes: a meta-analysis. Obes Rev. 2018;19(4):464–484. PubMed CrossRef
  24. Katsigianni M, Karageorgiou V, Lambrinoudaki I, et al. Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta analysis. Mol Psychiatry. 2019;24(12):1787–1797. PubMed CrossRef
  25. Dubey P, Thakur B, Rodriguez S, et al. A systematic review and meta-analysis of the association between maternal polycystic ovary syndrome and neuropsychiatric disorders in children. Transl Psychiatry. 2021;11(1):569.
  26. Garza-Martínez MJ, Á Hernández-Mariano J, Hurtado-Salgado EM, et al. Maternal diabetes during pregnancy and offspring’s risk of autism spectrum disorder: a systematic review and meta-analysis. J Psychiatr Res. 2025;182:100–115.
  27. Ge GM, Leung MTY, Man KKC, et al. Maternal thyroid dysfunction during pregnancy and the risk of adverse outcomes in the offspring: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2020;105(12):dgaa555.
  28. Mazzone PP, Hogg KM, Weir CJ, et al. Comparison of neurodevelopmental, educational and adult socioeconomic outcomes in offspring of women with and without epilepsy: a systematic review and meta-analysis. Seizure. 2024;117:213–221.
  29. He S, Zhou F, Tian G, et al. Effect of anesthesia during pregnancy, delivery, and childhood on autism spectrum disorder: a systematic review and meta-analysis. J Autism Dev Disord. 2024;54(12):4540–4554.
  30. Chen M, Lin Y, Yu C, et al. Effect of cesarean section on the risk of autism spectrum disorders/attention deficit hyperactivity disorder in offspring: a meta analysis. Arch Gynecol Obstet. 2024;309(2):439–455.
  31. Guo BQ, Li HB, Zhai DS, et al. Prevalence of autism spectrum disorder diagnosis by birth weight, gestational age, and size for gestational age: a systematic review, meta analysis, and meta-regression. Eur Child Adolesc Psychiatry. 2024;33(7):2035–2049.
  32. García-Serna AM, Morales E. Neurodevelopmental effects of prenatal vitamin D in humans: systematic review and meta-analysis. Mol Psychiatry. 2020;25(10):2468–2481.
  33. Liu X, Zou M, Sun C, et al. Prenatal folic acid supplements and offspring’s autism spectrum disorder: a meta-analysis and meta-regression. J Autism Dev Disord. 2022;52(2):522–539.
  34. Jung Y, Lee AM, McKee SA, et al. Maternal smoking and autism spectrum disorder: meta-analysis with population smoking metrics as moderators. Sci Rep. 2017;7(1):4315. PubMed CrossRef
  35. Tadesse AW, Dachew BA, Ayano G, et al. Prenatal cannabis use and the risk of attention deficit hyperactivity disorder and autism spectrum disorder in offspring: a systematic review and meta-analysis. J Psychiatr Res. 2024;171:142–151.
  36. Masarwa R, Levine H, Gorelik E, et al. Prenatal exposure to acetaminophen and risk for attention deficit hyperactivity disorder and autistic spectrum disorder: a systematic review, meta-analysis, and meta-regression analysis of cohort studies. Am J Epidemiol. 2018;187(8):1817–1827.
  37. Lee E, Cho J, Kim KY. The association between autism spectrum disorder and pre- and postnatal antibiotic exposure in childhood-a systematic review with meta analysis. Int J Environ Res Public Health. 2019;16(20):4042.
  38. Leshem R, Bar-Oz B, Diav-Citrin O, et al. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) during pregnancy and the risk for autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in the offspring: a true effect or a bias? A systematic review & meta-analysis. Curr Neuropharmacol. 2021;19(6):896–906.
  39. Andrade C, Varadharajan N, Bascarane S, et al. Gestational exposure to valproate and autism spectrum disorder or attention-deficit/hyperactivity disorder in offspring: systematic review and meta-analysis. Acta Psychiatr Scand. 2025;9. Online ahead of print. doi:10.1111/acps.13797. CrossRef
  40. Honybun E, Cockle E, Malpas CB, et al. Neurodevelopmental and functional outcomes following in utero exposure to antiseizure medication: a systematic review. Neurology. 2024;102(8):e209175.
  41. Wang Z, Yuen AS, Wong KH, et al. Association between prenatal antipsychotic exposure and the risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2024;160:105635.
  42. Andrade C, Varadharajan N, Bascarane S, et al. Gestational exposure to benzodiazepines or z-hypnotics and neurodevelopmental disorders in offspring: systematic review and meta-analysis. Acta Psychiatr Scand. 2024;150(2):65–77.
  43. Yoshimasu K, Kiyohara C, Takemura S, et al. A meta-analysis of the evidence on the impact of prenatal and early infancy exposures to mercury on autism and attention deficit/hyperactivity disorder in the childhood. Neurotoxicology. 2014;44:121–131. PubMed CrossRef
  44. Dutheil F, Comptour A, Morlon R, et al. Autism spectrum disorder and air pollution: a systematic review and meta-analysis. Environ Pollut. 2021;278:116856.
  45. Xu Y, Yang X, Chen D, et al. Maternal exposure to pesticides and autism or attention-deficit/hyperactivity disorders in offspring: a meta-analysis. Chemosphere. 2023;313:137459.
  46. Dou JF, Schmidt RJ, Volk HE, et al. 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. Environ Health. 2024;23(1):62.
  47. Zhang J, Yuan M, Liu Y, et al. Bisphenol A exposure and neurodevelopmental disorders and problems in children under 12 years of age: a systematic review and meta-analysis. J Hazard Mater. 2025;490:137731.
  48. Duque-Cartagena T, Dalla MDB, Mundstock E, et al. Environmental pollutants as risk factors for autism spectrum disorders: a systematic review and meta-analysis of cohort studies. BMC Public Health. 2024;24(1):2388.
  49. Tartaglione AM, Camoni L, Calamandrei G, et al. The contribution of environmental pollutants to the risk of autism and other neurodevelopmental disorders: a systematic review of case-control studies. Neurosci Biobehav Rev. 2024;164:105815.
  50. Zhang J, Li X, Shen L, et al. Trace elements in children with autism spectrum disorder: a meta-analysis based on case-control studies. J Trace Elem Med Biol. 2021;67:126782.
  51. Chen LC, Chen MH, Hsu JW, et al. Association of parental depression with offspring attention deficit hyperactivity disorder and autism spectrum disorder: a nationwide birth cohort study. J Affect Disord. 2020;277:109–114. PubMed CrossRef
  52. Gong T, Lundholm C, Rejnö G, et al. Parental asthma and risk of autism spectrum disorder in offspring: a population and family-based case-control study. Clin Exp Allergy. 2019;49(6):883–891.
  53. Rosman NP, Vassar R, Doros G, et al. Association of prenatal ultrasonography and autism spectrum disorder. JAMA Pediatr. 2018;172(4):336–344.
  54. Laugesen K, Skajaa N, Petersen I, et al. Mental disorders among offspring prenatally exposed to systemic glucocorticoids. JAMA Netw Open. 2025;8(1):e2453245.
  55. Chae J, Cho GJ, Oh MJ, et al. In utero exposure to ritodrine during pregnancy and risk of autism in their offspring until 8 years of age. Sci Rep. 2021;11(1):1146.
  56. Gidaya NB, Lee BK, Burstyn I, et al. In utero exposure to β-2-adrenergic receptor agonist drugs and risk for autism spectrum disorders. Pediatrics. 2016;137(2):e20151316.
  57. Wiegersma AM, Dalman C, Lee BK, et al. Association of prenatal maternal anemia with neurodevelopmental disorders. JAMA Psychiatry. 2019;76(12):1294–1304.
  58. Kosidou K, Karlsson H, Arver S, et al. Maternal steroid hormone levels in early pregnancy and autism in the offspring: a population-based, nested case-control study. Biol Psychiatry. 2024;96(2):147–158.
  59. Chen S, Fan M, Lee BK, et al. Rates of maternal weight gain over the course of pregnancy and offspring risk of neurodevelopmental disorders. BMC Med. 2023;21(1):108.
  60. Lyall K, Westlake M, Musci RJ, et al. Association of maternal fish consumption and ω-3 supplement use during pregnancy with child autism-related outcomes: results from a cohort consortium analysis. Am J Clin Nutr. 2024;120(3):583–592.
  61. Liew Z, Meng Q, Yan Q, et al. Association between estimated geocoded residential maternal exposure to lithium in drinking water and risk for autism spectrum disorder in offspring in Denmark. JAMA Pediatr. 2023;177(6):617–624.
  62. Geier DA, Geier MR. Fetal alcohol syndrome and the risk of neurodevelopmental disorders: a longitudinal cohort study. Brain Dev. 2022;44(10):706–714.
  63. Sourander A, Silwal S, Surcel HM, et al. Maternal serum vitamin B12 during pregnancy and offspring autism spectrum disorder. Nutrients. 2023;15(8):2009.
  64. Gardner RM, Lee BK, Brynge M, et al. Neonatal levels of acute phase proteins and risk of autism spectrum disorder. Biol Psychiatry. 2021;89(5):463–475.
  65. Gardener H, Spiegelman D, Buka SL. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry. 2009;195(1):7–14. PubMed CrossRef
  66. Gardener H, Spiegelman D, Buka SL. Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics. 2011;128(2):344–355. PubMed CrossRef
  67. Khachadourian V, Arildskov ES, Grove J, et al. Familial confounding in the associations between maternal health and autism. Nat Med. 2025;31(3):996–1007.
  68. Taylor LE, Swerdfeger AL, Eslick GD. Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Vaccine. 2014;32(29):3623–3629. PubMed CrossRef
  69. Di Pietrantonj C, Rivetti A, Marchione P, et al. Vaccines for measles, mumps, rubella, and varicella in children. Cochrane Database Syst Rev. 2020;4(4):CD004407. PubMed CrossRef
  70. Lyall K, Croen L, Daniels J, et al. The changing epidemiology of autism spectrum disorders. Annu Rev Public Health. 2017;38:81–102.
  71. Love C, Sominsky L, O’Hely M, et al. Prenatal environmental risk factors for autism spectrum disorder and their potential mechanisms. BMC Med. 2024;22(1):393.
  72. Tadesse AW, Ayano G, Dachew BA, et al. Exposure to maternal cannabis use disorder and risk of autism spectrum disorder in offspring: a data linkage cohort study. Psychiatry Res. 2024;337:115971.
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