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Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis

Molecular Psychiatry volume 24, pages 1787–1797 (2019)Cite this article

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Abstract

There is evidence showing a positive correlation between prenatal androgens and their effect on the development of central nervous system and the autistic spectrum disorder (ASD) phenotype in offspring of mothers with polycystic ovary syndrome (PCOS). We applied a systematic review to investigate whether women with PCOS have increased odds of having a child with ASD, while, secondarily, if these women themselves are at high risk of having the disease. Major databases from inception until 14th October 2018 were searched. The primary outcome measure was the odds of an ASD diagnosis in children of mothers with diagnosed PCOS, while the secondary outcome was the odds of ASD diagnosis in women with PCOS. Scheduled subgroup analyses were according to the time of birth and maternal age. We assessed the odds ratio (OR), using a random-effects model; heterogeneity was assessed by I2 and τ2 statistics. The quality of the evidence was evaluated using the Newcastle–Ottawa Scale. Ten studies were eligible for inclusion, including a total of 33,887 ASD children and 321,661 non-ASD children. Diagnosed PCOS was associated with a 1.66 times increase in the odds of ASD in the offspring [95% CI: 1.51, 1.83, p = 1.99 × 10−25, 7 studies, I2 = 0%, τ2 = 0]. Women with PCOS were 1.78 times more likely to be diagnosed with ASD (95% CI: 1.10, 2.87, p = 0.0179, 5 studies, I2 = 85.4%, τ2 = 0.2432). Additional analyses did not change the initial result. The overall quality of the evidence was high. The pooled effects size displayed low heterogeneity (I2 = 0%) for the primary outcome. While the heterogeneity in the secondary outcome appears to attenuate when only high quality studies are synthesized, still the result exhibits significant heterogeneity. Τhe available data allowed a subgroup analysis only for classification system for PCOS diagnosis and showed a significant increase of ASD diagnosis in the offspring of women with Read Code and ICD diagnosed PCOS. In conclusion, the available evidence suggests that women with PCOS have increased odds of having a child with ASD, an effect size estimate based on a large number of patients from studies of good quality. Regarding the evidence on the prevalence of ASD in PCOS women, results suggest that women with PCOS are more likely to be diagnosed with ASD.

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References

  1. Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18:737–54.

    PubMed  Google Scholar 

  2. Azziz R, Marin C, Hoq L, Badamgarav E, Song P. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab. 2005;90:4650–8.

    CAS  Google Scholar 

  3. Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, et al. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod. 2011;26:3123–9.

    CAS  PubMed  Google Scholar 

  4. Fauser BCJM, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97:28–38.

    PubMed  Google Scholar 

  5. Huerta M, Bishop SL, Duncan A, Hus V, Lord C. Application of DSM-5 criteria for autism spectrum disorder to three samples of children with DSM-IV diagnoses of pervasive developmental disorders. Am J Psychiatry. 2012;169:1056–64.

    PubMed  PubMed Central  Google Scholar 

  6. Christensen DL, Baio J, Van Naarden Braun K, Bilder D, Charles J, Constantino JN, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR Surveill Summ. 2016;65:1–23.

    PubMed  Google Scholar 

  7. Chapman E, Baron-Cohen S, Auyeung B, Knickmeyer R, Taylor K, Hackett G. Fetal testosterone and empathy: evidence from the empathy quotient (EQ) and the “reading the mind in the eyes” test. Soc Neurosci. 2006;1:135–48.

    PubMed  Google Scholar 

  8. Doherty DA, Newnham JP, Bower C, Hart R. Implications of polycystic ovary syndrome for pregnancy and for the health of offspring. Obstet Gynecol. 2015;125:1397–406.

    PubMed  Google Scholar 

  9. Knickmeyer R, Baron-Cohen S, Fane BA, Wheelwright S, Mathews GA, Conway GS, et al. Androgens and autistic traits: a study of individuals with congenital adrenal hyperplasia. Horm Behav. 2006;50:148–53.

    CAS  PubMed  Google Scholar 

  10. Baron-Cohen S, Knickmeyer RC, Belmonte MK. Sex differences in the brain: implications for explaining autism. Science. 2005;310:819–23.

    CAS  PubMed  Google Scholar 

  11. Baron-Cohen S. The extreme male brain theory of autism. Trends Cogn Sci. 2002;6:248–54.

    PubMed  Google Scholar 

  12. Manson JE. Prenatal exposure to sex steroid hormones and behavioral/cognitive outcomes. Metabolism. 2008;57:S16–21.

    CAS  PubMed  Google Scholar 

  13. Krakowiak P, Walker CK, Bremer AA, Baker AS, Ozonoff S, Hansen RL, et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics. 2012;129:e1121–8.

    PubMed  PubMed Central  Google Scholar 

  14. O’Keane V, Scott J. From “obstetric complications” to a maternal–foetal origin hypothesis of mood disorder. Br J Psychiatry. 2005;186:367–8.

    PubMed  Google Scholar 

  15. Chakrabarti B, Dudbridge F, Kent L, Wheelwright S, Hill-Cawthorne G, Allison C, et al. Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism Res. 2009;2:157–77.

    CAS  PubMed  Google Scholar 

  16. Hu VW, Nguyen A, Kim KS, Steinberg ME, Sarachana T, Scully MA, et al. Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis. PLoS ONE. 2009;4:e5775.

    PubMed  PubMed Central  Google Scholar 

  17. Wang C, Geng H, Liu W, Zhang G. Prenatal, perinatal, and postnatal factors associated with autism: a meta-analysis. Medicine. 2017;96:e6696.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Krakowiak P, Walker CK, Tancredi D, Hertz-Picciotto I, Van de Water J. Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism Res. 2017;10:89–98.

    PubMed  Google Scholar 

  19. 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. J Neurosci. 2012;32:674–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Palomba S, Marotta R, Di Cello A, Russo T, Falbo A, Orio F, et al. Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study. Clin Endocrinol. 2012;77:898–904.

    CAS  Google Scholar 

  21. Hergüner S, Harmancı H, Hergüner A, Toy H. Autistic traits in women with polycystic ovary syndrome. Res Autism Spectr Disord. 2012;6:1019–22.

    Google Scholar 

  22. Homburg R, Gudi A, Shah A, M Layton A. 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. 2017;15:61. https://doi.org/10.1186/s12958-017-0282-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gore AC, Martien KM, Gagnidze K, Pfaff D. Implications of prenatal steroid perturbations for neurodevelopment, behavior, and autism. Endocr Rev. 2014;35:961–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Malaeb S, Dammann O. Fetal inflammatory response and brain injury in the preterm newborn. J Child Neurol. 2009;24:1119–26.

    PubMed  PubMed Central  Google Scholar 

  25. Schwarz E, Guest PC, Rahmoune H, Wang L, Levin Y, Ingudomnukul E, et al. Sex-specific serum biomarker patterns in adults with Asperger’s syndrome. Mol Psychiatry. 2011;16:1213–20.

    CAS  PubMed  Google Scholar 

  26. Auyeung B, Taylor K, Hackett G, Baron-Cohen S. Foetal testosterone and autistic traits in 18 to 24-month-old children. Mol Autism. 2010;1:11

    PubMed  PubMed Central  Google Scholar 

  27. Ingudomnukul E, Baron-Cohen S, Wheelwright S, Knickmeyer R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav. 2007;51:597–604.

    CAS  PubMed  Google Scholar 

  28. Baron-Cohen S, Knickmeyer RC, Belmonte MK. Sex differences in the brain: implications for explaining autism. Science. 2005;310:819–23.

    CAS  PubMed  Google Scholar 

  29. Knickmeyer RC, Baron-Cohen S. Topical review: fetal testosterone and sex differences in typical social development and in autism. J Child Neurol. 2006;21:825–45.

    PubMed  Google Scholar 

  30. Geschwind N, Galaburda AM. Cerebral lateralization. Biological mechanisms, associations, and pathology: II. A hypothesis and a program for research. Arch Neurol. 1985;42:521–52.

    CAS  PubMed  Google Scholar 

  31. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62:e1–34.

    Google Scholar 

  32. Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.

    PubMed  Google Scholar 

  33. Barthold JS, González R. The epidemiology of congenital cryptorchidism, testicular ascent and orchiopexy. J Urol. 2003;170:2396–401.

    PubMed  Google Scholar 

  34. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Google Scholar 

  35. Dersimonian R, Laird N. Meta-analysis in clinical trials [Internet]. Available from: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.331.2969&rep=rep1&type=pdf. Cited 08 Nov 2018.

  36. Ioannidis JPA, Trikalinos TA. The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. Can Med Assoc J. 2007;176:1091–6.

    Google Scholar 

  37. Olkin I, Dahabreh IJ, Trikalinos TA. GOSH—a graphical display of study heterogeneity. Res Synth Methods. 2012;3:214–23.

    PubMed  Google Scholar 

  38. Baujat B, Mahe C, Pignon J-P, Hill C. A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials. Stat Med. 2002;21:2641–52.

    PubMed  Google Scholar 

  39. Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.

    Google Scholar 

  40. Pohl A, Cassidy S, Auyeung B, Baron-Cohen S. Uncovering steroidopathy in women with autism: a latent class analysis. Mol Autism. 2014;5:27.

    PubMed  PubMed Central  Google Scholar 

  41. Mamidala MP, Polinedi A, Kumar PTVP, Rajesh N, Vallamkonda OR, Udani V, et al. Maternal hormonal interventions as a risk factor for autism spectrum disorder: an epidemiological assessment from India. J Biosci. 2013;38:887–92.

    CAS  PubMed  Google Scholar 

  42. Cesta CE, Månsson M, Palm C, Lichtenstein P, Iliadou AN, Landén M. Polycystic ovary syndrome and psychiatric disorders: co-morbidity and heritability in a nationwide Swedish cohort. Psychoneuroendocrinology. 2016;73:196–203.

    PubMed  Google Scholar 

  43. 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. J Autism Dev Disord. 2017;47:3994–4005.

    PubMed  PubMed Central  Google Scholar 

  44. 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. Mol Psychiatry. 2016;21:1441–8.

    CAS  PubMed  Google Scholar 

  45. Hisle-Gorman E, Susi A, Stokes T, Gorman G, Erdie-Lalena C, Nylund CM. Prenatal, perinatal, and neonatal risk factors of autism spectrum disorder. Pediatr Res. 2018;84:190–8.

    PubMed  Google Scholar 

  46. 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. Transl Psychiatry. 2018;8:136.

    PubMed  PubMed Central  Google Scholar 

  47. Berni TR, Morgan CL, Berni ER, Rees DA. Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes. J Clin Endocrinol Metab. 2018;103:2116–25.

    PubMed  Google Scholar 

  48. Abdoli A, Dalimi A. Are there any relationships between latent Toxoplasma gondii infection, testosterone elevation, and risk of autism spectrum disorder? Front Behav Neurosci. 2014;8:339.

    PubMed  PubMed Central  Google Scholar 

  49. Aisaka K, Kaneda S, Tsuzuki H, Tawada T, Kokuho K, Toriya Y, et al. [Comprehensive approach to clinical background and effect of bromocriptine administration in patients with endocrinological polycystic ovarian disease]. Nihon Naibunpi Gakkai Zasshi. 1990;66:101–12.

    CAS  PubMed  Google Scholar 

  50. 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. Biol Psychiatry. 2017;82:651–9.

    PubMed  Google Scholar 

  51. Lee BK, Arver S, Widman L, Gardner RM, Magnusson C, Dalman C, et al. Maternal hirsutism and autism spectrum disorders in offspring. Autism Res. 2017;10:1544–6.

    PubMed  Google Scholar 

  52. Lyall K, Pauls DL, Spiegelman D, Santangelo SL, Ascherio A. Fertility therapies, infertility and autism spectrum disorders in the nurses’ health study II. Paediatr Perinat Epidemiol. 2012;26:361–72. https://doi.org/10.1111/j.1365-3016.2012.01294.x.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Ronald A, Happé F, Price TS, Baron-Cohen S, Plomin R. Phenotypic and genetic overlap between autistic traits at the extremes of the general population. J Am Acad Child Adolesc Psychiatry. 2006;45:1206–14.

    PubMed  Google Scholar 

  54. Ruta L, Ingudomnukul E, Taylor K, Chakrabarti B, Baron-Cohen S. Increased serum androstenedione in adults with autism spectrum conditions. Psychoneuroendocrinology. 2011;36:1154–63.

    CAS  PubMed  Google Scholar 

  55. Sabuncuoglu O. Towards a further understanding of prenatal thyroid theory of homosexuality: autoimmune thyroiditis, polycystic ovary syndrome, autism and low birth weight. Ment Illn. 2017;9:7325.

    PubMed  PubMed Central  Google Scholar 

  56. Takahashi K, Eda Y, Abu-Musa A, Okada S, Yoshino K, Kitao M. Transvaginal ultrasound imaging, histopathology and endocrinopathy in patients with polycystic ovarian syndrome. Hum Reprod. 1994;9:1231–6.

    CAS  PubMed  Google Scholar 

  57. Whitehouse AJ, Mattes E, Maybery MT, Dissanayake C, Sawyer M, Jones RM, et al. Perinatal testosterone exposure and autistic-like traits in the general population: a longitudinal pregnancy-cohort study. J Neurodev Disord. 2012;4:25.

    PubMed  PubMed Central  Google Scholar 

  58. Andrade C. Major malformation risk, pregnancy outcomes, and neurodevelopmental outcomes associated with metformin use during pregnancy. J Clin Psychiatry. 2016;77:e411–4.

    PubMed  Google Scholar 

  59. Bilder DA, Bakian AV, Viskochil J, Clark EAS, Botts EL, Smith KR, et al. Maternal prenatal weight gain and autism spectrum disorders. Pediatrics. 2013;132:e1276–83.

    PubMed  PubMed Central  Google Scholar 

  60. Brown L, Burns YR, Watter P, Gibbons KS, Gray PH. Motor performance, postural stability and behaviour of non-disabled extremely preterm or extremely low birth weight children at four to five years of age. Early Hum Dev. 2015;91:309–15.

    PubMed  Google Scholar 

  61. Deng W, Zou X, Deng H, Li J, Tang C, Wang X, et al. The relationship among genetic heritability, environmental effects, and autism spectrum disorders. J Child Neurol. 2015;30:1794–9. https://doi.org/10.1177/0883073815580645.

    Article  PubMed  Google Scholar 

  62. Dinsdale NL, Crespi BJ. Revisiting the wandering womb: oxytocin in endometriosis and bipolar disorder. Horm Behav. 2017;96:69–83.

    CAS  PubMed  Google Scholar 

  63. Hauth I, de Bruijn YGE, Staal W, Buitelaar JK, Rommelse NN. Testing the extreme male brain theory of autism spectrum disorder in a familial design. Autism Res. 2014;7:491–500.

    PubMed  Google Scholar 

  64. Shen D, Wang F, Jiang Z, Qu F. [Long-term effects of polycystic ovary syndrome on the offspring]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2017;46:300–4.

    PubMed  Google Scholar 

  65. Lassek WD, Gaulin SJC. Waist–hip ratio and cognitive ability: is gluteofemoral fat a privileged store of neurodevelopmental resources? Evol Hum Behav. 2008;29:26–34.

    Google Scholar 

  66. Chang B-H, Hoaglin DC. Meta-analysis of odds ratios. Med Care. 2017;55:328–35.

    PubMed  PubMed Central  Google Scholar 

  67. Yu H-F, Chen H-S, Rao D-P, Gong J. Association between polycystic ovary syndrome and the risk of pregnancy complications: a PRISMA-compliant systematic review and meta-analysis. Medicine. 2016;95:e4863.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I. Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr. 2015;169:154.

    PubMed  PubMed Central  Google Scholar 

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

    Google Scholar 

  70. Yip BHK, Leonard H, Stock S, Stoltenberg C, Francis RW, Gissler M, et al. Caesarean section and risk of autism across gestational age: a multi-national cohort study of 5 million births. Int J Epidemiol. 2016;46:dyw336.

    Google Scholar 

  71. Qin JZ, Pang LH, Li MJ, Fan XJ, Huang RD, Chen HY. Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2013;11:56.

    PubMed  PubMed Central  Google Scholar 

  72. Rice TR. Postnatal testosterone may be an important mediator of the association between prematurity and male neurodevelopmental disorders: a hypothesis. Int J Adolesc Med Health. 2017;29. https://doi.org/10.1515/ijamh-2015-0047.

  73. Mouridsen SE, Rich B, Isager T. Sibling sex ratio of individuals diagnosed with autism spectrum disorder as children. Dev Med Child. 2010;52:289–92.

    Google Scholar 

  74. Mouridsen SE, Rich B, Isager T. The sex ratio of full and half siblings of people diagnosed with an autism spectrum disorder: a Danish Nationwide Register Study. Child Psychiatry Hum Dev. 2014;45:493–9.

    PubMed  Google Scholar 

  75. Loomes R, Hull L, Mandy WPL. What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2017;56:466–74.

    PubMed  Google Scholar 

  76. Baron-Cohen S. Empathizing, systemizing, and the extreme male brain theory of autism. Prog Brain Res. 2010;186:167–75.

  77. Mezzelani A, Raggi ME, Marabotti A, Milanesi L. Ochratoxin A as possible factor trigging autism and its male prevalence via epigenetic mechanism. Nutr Neurosci. 2016;19:43–6.

    CAS  PubMed  Google Scholar 

  78. Beggiato A, Peyre H, Maruani A, Scheid I, Rastam M, Amsellem F, et al. Gender differences in autism spectrum disorders: divergence among specific core symptoms. Autism Res. 2017;10:680–9.

    PubMed  Google Scholar 

  79. Werling DM, Geschwind DH. Sex differences in autism spectrum disorders. Curr Opin Neurol. 2013;26:146–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Day F, Karaderi T, Jones MR, Meun C, He C, Drong A, et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet. 2018;14:e1007813.

  81. Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium. Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. Mol Autism. 2017;8:21.

    Google Scholar 

  82. Ding T, Hardiman PJ, Petersen I, Wang F-F, Qu F, Baio G. The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: a systematic review and meta-analysis. Oncotarget. 2017;8:96351–8.

    PubMed  PubMed Central  Google Scholar 

  83. Baptiste CG, Battista M-C, Trottier A, Baillargeon J-P. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2010;122:42–52.

    CAS  PubMed  Google Scholar 

  84. Sir-Petermann T, Maliqueo M, Angel B, Lara HE, Pérez-Bravo F, Recabarren SE. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod. 2002;17:2573–9.

    CAS  PubMed  Google Scholar 

  85. Maliqueo M, Lara HE, Sánchez F, Echiburú B, Crisosto N, Sir-Petermann T. Placental steroidogenesis in pregnant women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;166:151–5.

    CAS  PubMed  Google Scholar 

  86. Barry JA, Kay AR, Navaratnarajah R, Iqbal S, Bamfo JEAK, David AL, et al. Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels. J Obstet Gynaecol. 2010;30:444–6.

    CAS  PubMed  Google Scholar 

  87. Sandin S, Hultman CM, Kolevzon A, Gross R, MacCabe JH, Reichenberg A. Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2012;51:477–86.

    PubMed  Google Scholar 

  88. Zheng Z, Zhang L, Li S, Zhao F, Wang Y, Huang L, et al. Association among obesity, overweight and autism spectrum disorder: a systematic review and meta-analysis. Sci Rep. 2017;7:11697.

    PubMed  PubMed Central  Google Scholar 

  89. Rücker G, Schwarzer G, Carpenter JR, Schumacher M. Undue reliance on I(2) in assessing heterogeneity may mislead. BMC Med Res Methodol. 2008;8:79.

    PubMed  PubMed Central  Google Scholar 

  90. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97–111.

    PubMed  Google Scholar 

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  1. Menopause Clinic, 2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece

    Maria Katsigianni & Irene Lambrinoudaki

  2. Assisted Reproduction Unit, Third Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, “Attikon Hospital”, 1 Rimini Street, Chaidari, 12642, Athens, Greece

    Vasilios Karageorgiou & Charalampos Siristatidis

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Katsigianni, M., Karageorgiou, V., Lambrinoudaki, I. et al. Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 24, 1787–1797 (2019). https://doi.org/10.1038/s41380-019-0398-0

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