The Iranian Journal of Obstetrics, Gynecology and Infertility

The Iranian Journal of Obstetrics, Gynecology and Infertility

The Relationship between Maternal Polycystic Ovary Syndrome and Autism Spectrum Disorder in Offspring: A Systematic Review

Document Type : Review Article

Authors
Mansoureh Rafaei 1
Fahimeh Ezzati Arasteh 2
Hadis Sourinejad 3
Roya Najafi Vosough 4
Soodabeh Aghababaei 1
Arezoo Shayan 5
1 Associate Professor, Department of Maternal and Child Health, Mother and Child Care Research Center, Institute of Health Sciences and Technologies, School of Nursing and Midwifery, Hamadan University of Medical Sciences, Hamadan, Iran.
2 PhD Candidate in Midwifery, Department of Midwifery and Reproductive Health, Mother and Child Care Research Center, School of Nursing and Midwifery, Hamadan University of Medical Sciences, Hamadan, Iran.
3 Assistant Professor, Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Lorestan University of Medical Sciences, Khorramabad, Iran.
4 PhD in Biostatistics, Health Sciences Research Center, Health Sciences and Technologies Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran.
5 Lecturer, Department of Midwifery and Reproductive Health, Mother and Child Care Research Center, School of Nursing and Midwifery, Hamadan University of Medical Sciences, Hamadan, Iran.
10.22038/ijogi.2026.94010.6655
Abstract
Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. Increasing evidence suggests that this syndrome, in addition to affecting maternal reproductive health, may be associated with adverse neurodevelopmental outcomes in offspring. Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a rising prevalence, and the role of maternal factors during preconception and pregnancy periods in its development has received growing attention. The present study was conducted with aim to systematically review and evaluate the available evidence on the association between maternal PCOS and the risk of ASD in offspring.
Methods: This systematic review was conducted in accordance with the PRISMA guidelines. PubMed, Scopus, Web of Science, Google Scholar, SID, and Magiran were searched for studies published between 2000 and July 2024 using Persian and English search terms combined with the Boolean operators AND and OR. Original observational studies, including cohort and case-control designs, which examined the association between maternal PCOS and ASD in offspring, were included. Articles lacking sufficient data, non-original publications, and low-quality studies were excluded. Study quality was assessed using the Newcastle–Ottawa Scale.
Results: Of the 1,240 records identified, 9 eligible studies involving a total of 1,766,553 individuals were included in the review. These included 4 cohort and 5 case-control studies. Most studies reported a positive association between maternal PCOS and an increased risk of ASD in offspring. In terms of quality, 8 studies were rated as high and 1 as moderate quality.
Conclusion: The available evidence indicates that maternal PCOS is associated with an increased risk of ASD in offspring; however, heterogeneity across studies, potential diagnostic bias, and residual confounding limit causal inference. Further longitudinal studies with rigorous control of confounding factors and investigation of the underlying biological pathways are needed.
Keywords
Autism Spectrum Disorder
Neurodevelopmental Disorder
Polycystic Ovary Syndrome
Systematic Review
Subjects
1.     Shukla A, Rasquin LI, Anastasopoulou C. Polyendocrine metabolic ovarian syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan– [updated 2025 Jul 7; cited 2026 Sep 16]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459251/
2.     Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Human reproduction 2016; 31(12):2841-55.
3.     World Health Organization. Polycystic ovary syndrome [Internet]. Geneva: World Health Organization; 2025 Feb 7 [cited 2026 Aug 3]. Available from: https://www.who.int/news-room/fact-sheets/detail/polycystic-ovary-syndrome.
4.     Lin T, Xie B, Yang J, Xu J, Chen F. Changes in the global burden of polycystic ovary syndrome from 1990 to 2021. Reproductive Health 2025; 22(1):86.
5.     Wang J, Wang B, Li C, Meng T, Liu C, Chen J, et al. Evolving global trends in PCOS burden: a three-decade analysis (1990–2021) with projections to 2036 among adolescents and young adults. Frontiers in endocrinology 2025; 16:1569694.
6.     Meng Y, Zhao T, Zhang R, Zhu X, Ma C, Shi Q. Global burden of polycystic ovary syndrome among women of childbearing age, 1990–2021: a systematic analysis using the global burden of disease study 2021. Frontiers in Public Health 2025; 13:1514250.
7.     Dubey P, Thakur B, Rodriguez S, Cox J, Sanchez S, Fonseca A, et al. A systematic review and meta-analysis of the association between maternal polycystic ovary syndrome and neuropsychiatric disorders in children. Translational psychiatry 2021; 11(1):569.
8.     Shaw KA. Prevalence and early identification of autism spectrum disorder among children aged 4 and 8 years—Autism and Developmental Disabilities Monitoring Network, 16 Sites, United States, 2022. MMWR. Surveillance Summaries 2025; 74.
9.     Issac A, Halemani K, Shetty A, Thimmappa L, Vijay VR, Koni K, et al. The global prevalence of autism spectrum disorder in children: a systematic review and meta-analysis. Osong Public Health and Research Perspectives 2025; 16(1):3.
10.  Kosidou K, Dalman C, Widman L, Arver S, Lee BK, Magnusson C, et al. Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden. Molecular psychiatry 2016; 21(10):1441-8.
11.  Mkhitaryan M, Avetisyan T, Yeritsyan H, Harutyunyan H, Yenkoyan K. Unraveling the Genetic and Environmental Risk Factors of Autism Spectrum Disorder Through a Case‐Control Study in Armenia. Health Science Reports 2025; 8(5):e70801.
12.  Khachadourian V, Arildskov ES, Grove J, O’Reilly PF, Buxbaum JD, Reichenberg A, et al. Familial confounding in the associations between maternal health and autism. Nature medicine 2025; 31(3):996-1007.
13.  Jiang L, Tian L, Yuan J, Xu X, Qu F, Zhang R, et al. Associations between sex hormone levels and autistic traits in infertile patients with polycystic ovary syndrome and their offspring. Frontiers in endocrinology 2022; 12:789395.
14.  Baron-Cohen S, Auyeung B, Nørgaard-Pedersen B, Hougaard DM, Abdallah MW, Melgaard L, et al. Elevated fetal steroidogenic activity in autism. Molecular psychiatry 2015; 20(3):369-76.
15.  Lombardo MV, Ashwin E, Auyeung B, Chakrabarti B, Taylor K, Hackett G, et al. Fetal testosterone influences sexually dimorphic gray matter in the human brain. The Journal of neuroscience 2012; 32(2):674-80.
16.  Mamidala MP, Polinedi A, Kumar PP, Rajesh N, Vallamkonda OR, Udani V, et al. Maternal hormonal interventions as a risk factor for autism spectrum disorder: an epidemiological assessment from India. Journal of biosciences 2013; 38(5):887-92.
17.  Kahn LG, Hipwell AE, Charifson M, Ling R, Cajachagua-Torres KN, Ghassabian A. Maternal polycystic ovarian syndrome and offspring psychopathology and neurodevelopment. Human Reproduction 2025; 40(7):1257-65.
18.  Abu-Zaid A, Bhagavathula AS, Rahmani J, Alyoubi RA, Alomar O, Baradwan S, et al. Maternal polycystic ovary syndrome and the potential risk of attention-deficit/hyperactivity disorder and autism spectrum disorder in the offspring: a systematic review and meta-analysis. The European Journal of Contraception & Reproductive Health Care 2022; 27(3):253-60.
19.  Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. bmj 2021; 372.
20.  Margulis AV, Pladevall M, Riera-Guardia N, Varas-Lorenzo C, Hazell L, Berkman ND, et al. Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle–Ottawa scale and the RTI item bank. Clinical epidemiology. 2014 Oct 10:359-68.
21.  Berni TR, Morgan CL, Berni ER, Rees DA. Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes. The Journal of Clinical Endocrinology & Metabolism 2018; 103(6):2116-25.
22.  Cesta CE, Öberg AS, Ibrahimson A, Yusuf I, Larsson H, Almqvist C, et al. Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?. Psychological medicine 2020; 50(4):616-24.
23.  Chen X, Kong L, Piltonen TT, Gissler M, Lavebratt C. Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study. Human Reproduction 2020; 35(10):2336-47.
24.  Cherskov A, Pohl A, Allison C, Zhang H, Payne RA, Baron-Cohen S. Polycystic ovary syndrome and autism: a test of the prenatal sex steroid theory. Translational psychiatry 2018; 8(1):136.
25.  Lee BK, Arver S, Widman L, Gardner RM, Magnusson C, Dalman C, Kosidou K. Maternal hirsutism and autism spectrum disorders in offspring. Autism Research. 2017 Sep;10(9):1544-6.
26.  Schieve LA, Drews-Botsch C, Harris S, Newschaffer C, Daniels J, DiGuiseppi C, et al. Maternal and paternal infertility disorders and treatments and autism spectrum disorder: findings from the study to explore early development. Journal of Autism and Developmental Disorders 2017; 47(12):3994-4005.
27.  Palm CV, Glintborg D, Find LG, Larsen PV, Dalgaard CM, Boye H, et al. Prenatal androgen exposure and traits of autism spectrum disorder in the offspring: Odense child cohort. Journal of autism and developmental disorders 2023; 53(3):1053-65.
28.  Kosidou K, Dalman C, Widman L, Arver S, Lee BK, Magnusson C, et al. Maternal polycystic ovary syndrome and risk for attention-deficit/hyperactivity disorder in the offspring. Biological psychiatry 2017; 82(9):651-9.
29.  Rotem RS, Nguyen VT, Chodick G, Davidovitch M, Shalev V, Hauser R, et al. Associations of maternal androgen-related conditions with risk of autism spectrum disorder in progeny and mediation by cardiovascular, metabolic, and fertility factors. American journal of epidemiology 2021; 190(4):600-10.
 
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 29, Issue 4
June 2026
Pages 68-85