Meta Analysis: Effects of Polycystic Ovarian Syndrome and Maternal Diabetes on the Risk of Autism in Children


  • Laksmy Dewi Sukmakarti Master's Program in Public Health, Universitas Sebelas Maret
  • Bhisma Murti Master's Program in Public Health, Universitas Sebelas Maret
  • Rita Benya Adriani Masters Program in Public Health, Universitas Sebelas Maret



Background: Autism is a condition of developmental abnormalities in social, communication and behavior aspects. Polycystic ovary syndrome and maternal diabetes during pregnancy contribute more than 50% to the risk of ASD offspring. This study aims to analyze and estimate the influence of polycystic ovarian syndrome and maternal diabetes on autism in children.
Subjects and Method: The meta-analysis was carried out according to the PRISMA flow chart and the PICO model. Q: Child, I: Mother with PCOS and maternal diabetes, C: T Mother without PCOS and maternal diabetes, O: Autism. Search for articles in this study through databases that include Google Scholar, Pubmed, ScienceDirect and Sage Journal. With keywords including: Polycystic Ovarian Syndrome” AND “Maternal Diabetes” OR “Gestational Diabetes Mellitus” AND “Autism” OR “Autism Spectrum Disorder” AND “Cohort”. A full paper article with an observational cohort study, the research subject was a child, the size of the relationship used was the adjusted odds ratio, the research outcome was autism. Analysis was performed with Revman 5.3.
Results: There were 13 articles with cohort designs originating from America, Denmark, England, Sweden, Israel, China with a total of 4,641,483 research samples. A meta-analysis of 13 cohort studies concluded that children of pregnant women with PCOS had a 1.36 times greater risk of developing autism than those without PCOS, and the effect was statistically significant (aOR= 1.36; 95% CI= 1.24 to 1.49; p<0.001). In addition, pregnant women with maternal diabetes have a 1.24 times higher risk of having a child with autism than those without maternal diabetes, and this effect is statistically significant (aOR= 1.24; 95% CI= 1.08 to 1.43; p=0.002).
Conclusion: Pregnant women who have PCOS and maternal diabetes increase the risk of autism in children.

Keywords: polycystic ovarian syndrome, maternal diabetes, autism.

Correspondence: Laksmy Dewi Sukmakarti. Master's Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: Mobile: +628773-8298156.


Alves JM, Angelo BC, Negriff S, Luo SH, Chow T, Cabeen R, Carter SA, et al. (2022). Prenatal exposure to gesta-tional diabetes mellitus and autistic traits among typically developing children. Diabetes. 71(1): 602-P.

Aviel-Shekler K, Hamshawi Y, Sirhan W, Getselter D, Srikanth KD, Malka A, Piran R, et al. (2020). Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring. Transl. Psychiatry, 10(1).

Baio J, Wiggins L, Christensen DL, Maenner M J, Daniels J, Warren Z, Kurzius-Spencer M, et al. (2018). Centers for Disease Control and Prevention MMWR. MMWR Surveill. Summ, 67(6): 1–23.

Baxter AJ, Brugha TS, Erskine HE, Scheurer RW, Vos T, Scott JG (2015). The epidemiology and global burden of autism spectrum disorders. Psychol. Med. 45(3): 601–613.

Bell GA, Sundaram R, Mumford SL, Park H, Mills J, Bell EM, Broadney M, et al. (2018) Maternal polycystic ovarian syndrome and early offspring development. Hum Reprod. 33(7).

Berni TR, Morgan CL, Berni ER, Rees DA (2018). Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes. J Clin Endocr. 103(6): 2116–2125.

BPS (2020). Badan pusat statistik Indone-sia, Provinsi Bengkulu, dan Kabupaten Seluma (Central Bureau of Statistics of Indonesia, Bengkulu Province, and Seluma Districts). Badan Pusat Statistik Kabupaten Seluma.

Carter SA, Lin JC, Chow T, Yu X, Rahman MM, Martinez MP, Feldman K, et al. (2022). Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring. Autism. 1177/13623613221118430

Chang YS, Chen LW, Yu T, Lin SH, Kuo PL (2023). Preterm birth and weight-for-gestational age for risks of autism spectrum disorder and intellectual disability: A nationwide population-based cohort study. J Formos Med Assoc, 122(6), 493–504.

Chen S, Zhao S, Dalman C, Karlsson H, Gardner R (2022). Association of maternal diabetes with neurodevelopmental disorders: autism spectrum disorders, attention-deficit/ hyperactivity disorder and intellectual disability. Int J Epidemiol. 50(2): 459–474. ije/dyaa212

Cherskov A, Pohl A, Allison C, Zhang H, Payne RA, Baron-Cohen S (2018). Polycystic ovary syndrome and autism: A test of the prenatal sex steroid theory. Transl. Psychiatry, 8(1).

Cochrane (2014). RevMan 5.3 User Guide. The Cochrane Collaboration.

Cordero C, Windham GC, Schieve LA, Fallin MD, Croen LA, Siega-Riz AM, Engel SM, et al. (2019). Maternal diabetes and hypertensive disorders in association with autism spectrum disorder. Autism Res., 12(6): 967–975.

Critical Appraisal Skills Programme (2018). CASP (Cohort Study) Checklist. documents/CASP-Cohort-Study-Checklis-t/CASP-Cohort-Study-Checklist_2018.pdf

Dewi R, Inayatillah, Yullyana R (2018). Pengalaman orangtua dalam mengasuh anak autis di Kota Banda Aceh (Parents' experiences in raising autistic children in Banda Aceh City). Psikoislamedia Jurnal Psikologi, 3(2): 288–301.

Etminan-Baksh M, Tadi S, Hatami M, Darabi R (2020). Prevalence of gestational diabetes mellitus and its associated risk factors in Boo-Ali Hospital, Theran. Galen Med. 9: e1642.

Greger HK, Hanem LGE, Østgård HF, Vanky E (2020). Cognitive function in metformin exposed children, born to mothers with PCOS - follow-up of an RCT. BMC Pediatrs, 20(1).

Hernawan AD, Diningrum A, Jati SN, Nasip M (2018). Risk factors of autism spectrum disorder (ASD). Unnes Journal of Public Health. 7(2): 104–112.

Hisle-Gorman E, Susi A, Stokes T, Gorman G, Erdie-Lalena C, Nylund C M (2018). Prenatal, perinatal, and neonatal risk factors of autism spectrum disorder. Pediatr. Res. 84(2): 190–198.

Homburg R, Gudi A, Shah A, Layton AM (2017). A novel method to demonstrate that pregnant women with polycystic ovary syndrome hyper-expose their fetus to androgens as a possible stepping stone for the developmental theory of PCOS. A pilot study. Reprod. Biol. Endocrinol., 15(1): 15–18. 801702821

Katsigianni M, Karageorgiou V, Lambrinoudaki I, Siristatidis C (2019). Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis. Mol. Psychiatry, 24(12): 1787–1797. https://

Kelley AS, Puttabyatappa M, Ciarelli JN, Zeng L, Smith YR, Lieberman R, Pennathur S, et al. (2019). Prenatal testosterone excess disrupts placental function in a sheep model of polycystic ovary syndrome. Endocrinology (United States), 160(11).

Kosidou K, Dalman C, Widman L, Arver S, Lee BK, Magnusson C, Gardner RM (2016). Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden. Mol Psychiatry. 21(10). https://doi. org/10.1038/mp.2015.183

Li Y, Ren X, He L, Li J, Zhang S, Chen W (2020). Maternal age and the risk of gestational diabetes mellitus: A systematic review and meta-analysis of over 120 million participants. Diabetes Res. Clin. Pract. 162. https://doi. org/10.1016/j.diabres.2020.108044

Lu J, Wang Z, Liang Y, Yao P (2022). Rethinking autism: the impact of maternal risk factors on autism development. Am. J. Transl. Res., 14(2): 1136–1145. http://www.ncbi.nlm.

Modabbernia A, Velthorst E, Reichenberg A (2017). Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol, 8(1): 1–16.

Mohsen FAT, Lauszus FF (2022). Gestationel diabetes mellitus og autisme spek trum for styrrelse hos barnet. Ugeskr Laeger, 184:1–7.

Murti B (2018). Prinsip dan metode riset epidemiologi (5th ed) (Epidemiological research principles and methods (5th ed)). Program studi ilmu kesehatan masyarakat, program pascasarjana, Universitas Sebelas Maret.

Nahum Sacks K, Friger M, Shoham-Vardi I, Abokaf H, Spiegel E, Sergienko R, Landau D, et al. (2016). Prenatal exposure to gestational diabetes mellitus as an independent risk factor for longterm neuropsychiatric morbidity of the offspring. Am. J. Obstet. Gynecol., 215(3): 380.e1-380.e7.

Palm CVB, Glintborg D, Find LG, Larsen PV, Dalgaard CM, Boye H, Jensen TK, et al. (2023). Prenatal androgen exposure and traits of autism spectrum disorder in the offspring: odense child cohort. J Autism Dev Disord., 53(3): 1053–1065.

Rotem RS, Nguyen VT, Chodick G, Davidovitch M, Shalev V, Hauser R, Coull BA, et al. (2021). Associations of maternal androgen-related conditions with risk of autism spectrum disorder in progeny and mediation by cardiovascular, metabolic, and fertility factors. Am. J. Epidemiol. 90(4): 600–610.

Schieve LA, Drews-Botsch C, Harris S, Newschaffer C, Daniels J, DiGuiseppi C, Croen LA, et al. (2018). Maternal and paternal infertility disorders and treatments and autism spectrum disorder: findings from the study to explore early development. J Autism Dev Disord. 47(12): 3994–4005.

Sultana Z, Uddin SN, Ahmed A (2017). Role of environmental and genetic factors in autism spectrum disorder. Bangabandhu Sheikh Mujib Med. Univ. J. 10(2): 76.

Sun M, Sun B, Qiao S, Feng X, Li Y, Zhang S, Lin, et al. (2020). Elevated maternal androgen is associated with dysfunctional placenta and lipid disorder in newborns of mothers with polycystic ovary syndrome. Fertil. Steril. 113(6).

Zhu B, Deng F, Yan S, Huang K, Wu X, Tao X, Wang S, et al. (2021). Gestational diabetes mellitus, autistic traits and ADHD symptoms in toddlers: Placental inflammatory and oxidative stress cytokines do not play an intermediary role. Psychoneuroendocrinology, 134 (October). /10.1016/j.psyneuen.2021.105435.




How to Cite

Sukmakarti, L. D., Murti, B., & Adriani, R. B. (2023). Meta Analysis: Effects of Polycystic Ovarian Syndrome and Maternal Diabetes on the Risk of Autism in Children. Journal of Maternal and Child Health, 8(5), 599–612.