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Prenatal Glucocorticoid Exposure and Autism Spectrum Disorder: Current Evidence, Mechanisms, and Clinical Implications Cover

Prenatal Glucocorticoid Exposure and Autism Spectrum Disorder: Current Evidence, Mechanisms, and Clinical Implications

Open Access
|Jul 2026

References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed, text rev (DSM-5-TR). Washington, DC: American Psychiatric Association; 2022. doi:10.1176/appi.books.9780890425787
  2. Zwaigenbaum L, Bauman ML, Stone WL, et al. Early identification of autism spectrum disorder: recommendations for practice and research. Pediatrics. 2015;136 Suppl 1(Suppl 1):S10–S40. doi:10.1542/peds.2014-3667C
  3. Hyman SL, Levy SE, Myers SM; COUNCIL ON CHILDREN WITH DISABILITIES, SECTION ON DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS. Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics. 2020;145(1):e20193447. doi:10.1542/peds.2019-3447
  4. Salari N, Rasoulpoor S, Rasoulpoor S, et al. The global prevalence of autism spectrum disorder: a comprehensive systematic review and meta-analysis. Ital. J. Pediatr. 2022;48(1). Doi:10.1186/s13052-022-01310-w
  5. Maenner MJ, Shaw KA, Baio J, et al. Prevalence of autism spectrum disorder among children aged 8 years — Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2016. MMWR Surveillance Summaries. 2020;69(4):1–12. Doi:10.15585/mmwr.ss6904a1
  6. Talantseva OI, Romanova RS, Shurdova EM, et al. The global prevalence of autism spectrum disorder: A three-level meta-analysis. Front. Psychiatry. 2023;14. Doi:10.3389/fpsyt.2023.1071181
  7. Masini E, Loi E, Vega-Benedetti AF, et al. An overview of the main genetic, epigenetic and environmental factors involved in autism spectrum disorder focusing on synaptic activity. Int. J. Mol. Sci. 2020;21(21):8290. Doi:10.3390/ijms21218290
  8. Bandoli G, Palmsten K, Smith CJF, Chambers CD. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum. Dis. Clin. N. Am. 2017;43(3):489–502. Doi:10.1016/j.rdc.2017.04.013
  9. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al. Antenatal betamethasone for women at risk for late preterm delivery. N. Engl. J. Med. 2016;374(14):1311–1320. Doi:10.1056/nejmoa1516783
  10. Stutchfield P, Whitaker R, Russell I; Antenatal Steroids for Term Elective Caesarean Section (ASTECS) Research Team. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331(7518):662. doi:10.1136/bmj.38547.416493.06
  11. Tao S, Du J, Chi X, et al. Associations between antenatal corticosteroid exposure and neurodevelopment in infants. Am. J. Obstet. Gynecol. 2022;227(5):759.e1–759.e15. doi:10.1016/j.ajog.2022.05.060
  12. Blencowe H, Cousens S, Chou D, et al. Born Too Soon: The global epidemiology of 15 million preterm births. Reprod. Health. 2013;10(S1). Doi:10.1186/1742-4755-10-s1-s2
  13. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics. 1972;50(4):515–525. Doi:10.1542/peds.50.4.515
  14. McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Libr. 2020;2021(2). Doi:10.1002/14651858.cd004454.pub4
  15. Jobe AH, Goldenberg RL. Antenatal corticosteroids: an assessment of anticipated benefits and potential risks. Am. J. Obstet. Gynecol. 2018;219(1):62–74. Doi:10.1016/j.ajog.2018.04.007
  16. Guidelines Review Committee. WHO recommendations on interventions to improve preterm birth outcomes. Published November 1, 2015. https://www.who.int/publications/i/item/9789241508988
  17. Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am. J. Obstet. Gynecol. 1995;173(1):254–262. Doi:10.1016/0002-9378(95)90210-4
  18. Kemp MW, Saito M, Usuda H, et al. Maternofetal pharmacokinetics and fetal lung responses in chronically catheterized sheep receiving constant, low-dose infusions of betamethasone phosphate. Am. J. Obstet. Gynecol. 2016;215(6):775.e1–775.e12. doi:10.1016/j.ajog.2016.08.017
  19. Bartholomew J, Kovacs L, Papageorgiou A. Review of the antenatal and postnatal use of steroids. Indian J. Pediatr. 2014;81(5):466–472. Doi:10.1007/s12098-014-1376-9
  20. Haas DM, Lehmann AS, Skaar T, et al. The impact of drug metabolizing enzyme polymorphisms on outcomes after antenatal corticosteroid use. Am. J. Obstet. Gynecol. 2012;206(5):447.e17–447.e24. doi:10.1016/j.ajog.2012.02.016
  21. Schoenmakers S, Li L, Kluivers ACM, et al. Pharmacokinetics of betamethasone in pre-eclampsia: An in vivo and ex vivo study. Br J Clin Pharmacol. 2025;91(8):2327–2339. doi:10.1002/bcp.70035
  22. Jobe AH, Milad MA, Peppard T, Jusko WJ. Pharmacokinetics and pharmacodynamics of intramuscular and oral betamethasone and dexamethasone in reproductive age women in India. American Journal of Obstetrics and Gynecology. Clin Transl Sci. 2020;13(2):391–399. doi:10.1111/cts.12724
  23. Williams MJ, Ramson JA, Brownfoot FC. Different corticosteroids and regimens for accelerating fetal lung maturation for babies at risk of preterm birth. Cochrane Libr. 2022;2022(8). Doi:10.1002/14651858.cd006764.pub4
  24. Ainsworth S. Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life. 7th ed. Oxford, UK: Oxford University Press; 2020. Doi:10.1093/med/9780198840787.001.0001
  25. Van Der Merwe JL, Sacco A, Toelen J, Deprest J. Long-term neuropathological and/or neurobehavioral effects of antenatal corticosteroid therapy in animal models: a systematic review. Pediatr. Res. 2019;87(7):1157–1170. Doi:10.1038/s41390-019-0712-1
  26. Aviram A, Murphy K, McDonald S, et al. Antenatal corticosteroids and neurodevelopmental outcomes in late preterm births. Arch. Dis. Child. Fetal Neonatal Ed. 2021;107(3):250–255. Doi:10.1136/archdischild-2021-322152
  27. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and Early-Life conditions on adult health and disease. N. Engl. J. Med. 2008;359(1):61–73. Doi:10.1056/nejmra0708473
  28. Liauw J, Campbell KSJ, Foggin H, et al. Antenatal corticosteroids and child neurodevelopment. Obstet. Gynecol. Published online June 5, 2025. Doi:10.1097/aog.000000000000595
  29. Ninan K, Liyanage SK, Murphy KE, Asztalos EV, McDonald SD. Evaluation of long-term outcomes associated with pre-term exposure to antenatal corticosteroids. JAMA Pediatrics. 2022;176(6):e220483. Doi:10.1001/jamapediatrics.2022.0483
  30. Altman J, A. Bayer S. Atlas of Human Central Nervous System Development. Routledge. https://www.routledge.com/Atlas-of-Human-Central-Nervous-System-Development/book-series/CRCAHCNSD?publishedFilter=alltitles&pd=published,forthcoming&pg=1&pp=12&so=pub&view=list?publishedFilter=alltitles&pd=published,forthcoming&pg=1&pp=12&so=pub&view=list
  31. Kwan KY, Lam MMS, Johnson MB, et al. Species-Dependent posttranscriptional regulation of NOS1 by FMRP in the developing cerebral cortex. Cell. 2012;149(4):899–911. Doi:10.1016/j.cell.2012.02.060
  32. Huttenlocher PR, Dabholkar AS. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol. 1997;387(2):167–178. Doi:10.1002/(sici)1096-9861(19971020)387:2<;167::aid-cne1>3.0.co;2-z
  33. Noorlander CW, Tijsseling D, Hessel EVS, et al. Antenatal glucocorticoid treatment affects hippocampal development in mice. PLoS ONE. 2014;9(1):e85671. Doi:10.1371/journal.pone.0085671
  34. Laugesen K, Skajaa N, Petersen I, et al. Mental disorders among offspring prenatally exposed to systemic glucocorticoids. JAMA Network Open. 2025;8(1):e2453245. Doi:10.1001/jamanetworkopen.2024.53245
  35. Räikkönen K, Gissler M, Kajantie E. Associations between maternal antenatal corticosteroid treatment and mental and behavioral disorders in children. JAMA. 2020;323(19):1924. Doi:10.1001/jama.2020.3937
  36. Ram S, Howland MA, Sandman CA, Davis EP, Glynn LM. Prenatal risk for autism spectrum disorder (ASD): Fetal cortisol exposure predicts child ASD symptoms. Clin. Psychol. Sci. 2018;7(2):349–361. Doi:10.1177/2167702618811079
  37. Wapner RJ, Sorokin Y, Mele L, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. N Engl J Med. 2007;357(12):1190–1198. doi:10.1056/NEJMoa071453
  38. Dalziel SR, Lim VK, Lambert A, et al. Antenatal exposure to beta-methasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ. 2005;331(7518):665. doi:10.1136/bmj.38576.494363.E0
  39. Committee Opinion No. 713 Summary: Antenatal corticosteroid therapy for fetal maturation. Obstet. Gynecol. 2017;130(2):493–494. Doi:10.1097/aog.0000000000002231
  40. Blankenship SA, Brown KE, Simon LE, Stout MJ, Tuuli MG. Antenatal corticosteroids in preterm small-for-gestational age infants: a systematic review and meta-analysis. Am J Obstet Gynecol MFM. 2020;2(4):100215. Doi:10.1016/j.ajogmf.2020.100215
  41. Li T, Shen W, Wu F, et al. Antenatal corticosteroids is associated with better postnatal growth outcomes of very preterm infants: A national multicenter cohort study in China. Front Pediatr. 2023;10:1086920. Published 2023 Jan 11. Doi:10.3389/fped.2022.1086920
  42. Yang X, Ewald ER, Huo Y, et al. Glucocorticoid-induced loss of DNA methylation in non-neuronal cells and potential involvement of DNMT1 in epigenetic regulation of Fkbp5. Biochem Biophys Res Commun. 2012;420(3):570–575. Doi:10.1016/j.bbrc.2012.03.035
  43. Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol. 2000;20(18):6891–6903. Doi:10.1128/MCB.20.18.6891-6903.2000
  44. Bartlett AA, Lapp HE, Hunter RG. Epigenetic mechanisms of the glucocorticoid receptor. Trends Endocrinol Metab. 2019;30(11):807–818. Doi:10.1016/j.tem.2019.07.003
  45. Paes T, Feelders RA, Hofland LJ. Epigenetic mechanisms modulated by glucocorticoids with a focus on Cushing syndrome. J Clin Endocrinol Metab. 2024;109(6):e1424–e1433. Doi:10.1210/clinem/dgae151
  46. Rakers F, Schleußner E, Muth I, et al. Association between antenatal glucocorticoid exposure and the activity of the stress system, cognition, and behavior in 8- to 9-year-old children: A prospective observational study. Acta Obstet Gynecol Scand. 2022;101(9):996–1006. Doi:10.1111/aogs.14386
  47. Ma SL, Chen LH, Lee CC, et al. Genetic overlap between attention deficit/hyperactivity disorder and autism spectrum disorder in SHANK2 gene. Front Neurosci. 2021;15:649588. Published 2021 Apr 27. Doi:10.3389/fnins.2021.649588
  48. Irwin JL, Meyering AL, Peterson G, et al. Maternal prenatal cortisol programs the infant hypothalamic-pituitary-adrenal axis. Psychoneuroendocrinol. 2021;125:105106. Doi:10.1016/j.psyneuen.2020.105106
  49. Komoltsev IG, Gulyaeva NV. Brain trauma, glucocorticoids and neuroinflammation: dangerous liaisons for the hippocampus. Biomedicines. 2022;10(5):1139. Published 2022 May 15. Doi:10.3390/biomedicines10051139
  50. Banker SM, Gu X, Schiller D, Foss-Feig JH. Hippocampal contributions to social and cognitive deficits in autism spectrum disorder. Trends Neurosci. 2021;44(10):793–807. Doi:10.1016/j.tins.2021.08.005
  51. Knezevic E, Nenic K, Milanovic V, Knezevic NN. The role of cortisol in chronic stress, neurodegenerative diseases, and psychological disorders. Cells. 2023;12(23):2726. Published 2023 Nov 29. Doi:10.3390/cells12232726
  52. Bilder DA, Worsham W, Sullivan S, et al. Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism. Mol Autism. 2023;14(1):30. Published 2023 Aug 12. Doi:10.1186/s13229-023-00562-5
  53. Kashanian M, Faghankhani M, YousefzadehRoshan M, Ehsani-Pour M, Sheikhansari N. Woman's perceived stress during pregnancy; stressors and pregnancy adverse outcomes. J Matern Fetal Neonatal Med. 2021;34(2):207–215. Doi:10.1080/14767058.2019.1602600
  54. Alexandraki KI, Kaltsas GA, Chrousos GP. Adrenal Suppression. [Updated 2018 Oct 1]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MD-Text.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279047/
  55. Harrewijn A, Vidal-Ribas P, Clore-Gronenborn K, et al. Associations between brain activity and endogenous and exogenous cortisol – A systematic review. Psychoneuroendocrinol. 2020;120:104775. Doi:10.1016/j.psyneuen.2020.104775
  56. Pofi R, Tomlinson JW. Glucocorticoids in pregnancy. Obstet Med. 2020;13(2):62–69. Doi:10.1177/1753495X19847832
  57. Ilg L, Klados M, Alexander N, Kirschbaum C, Li SC. Long-term impacts of prenatal synthetic glucocorticoids exposure on functional brain correlates of cognitive monitoring in adolescence. Sci. Rep. 2018 May 16;8(1):7715.
  58. Carelli MCB, Peixoto-Filho FM, Velarde LGC, de Sá RAM, Monteiro V, Araujo Júnior E. Effects of antenatal corticosteroids on fetal hemodynamics: a longitudinal study. Radiol Bras. 2024;57:e20230129. Published 2024 May 7. Doi:10.1590/0100-3984.2023.0129
  59. Mbarek H, et al. Prenatal exposure to topical and systemic corticosteroids and risk of congenital malformations: a cohort study. Eur J Epidemiol. 2022;37(9):951–962.
  60. Sigmon ER, Kelleman M, Susi A, Nylund CM, Oster ME. Congenital heart disease and autism: a case-control study. Pediatrics. 2019;144(5):e20184114. Doi:10.1542/peds.2018-4114
  61. Shimanoe C, Matsumoto A, Hara M, et al. Perceived stress, depressive symptoms, and cortisol-to-cortisone ratio in spot urine in 6878 older adults. Psychoneuroendocrinol. 2021;125:105125. Doi:10.1016/j.psyneuen.2020.105125
  62. Stalder T, Kirschbaum C. Analysis of cortisol in hair-state of the art and future directions. Brain Behav Immun. 2012;26(7):1019–1029. doi:10.1016/j.bbi.2012.02.002
  63. Jahnke JR, Terán E, Murgueitio F, Cabrera H, Thompson AL. Maternal stress, placental 11β-hydroxysteroid dehydrogenase type 2, and infant HPA axis development in humans: Psychosocial and physiological pathways. Placenta. 2021;104:179–187. Doi:10.1016/j.placenta.2020.12.008
  64. Deng J, Chalhoub NE, Sherwin CM, Li C, Brunner HI. Glucocorticoids pharmacology and their application in the treatment of childhood-onset systemic lupus erythematosus. Semin Arthritis Rheum. 2019;49(2):251–259. Doi:10.1016/j.semarthrit.2019.03.010
  65. Martinez GJ, Appleton M, Kipp ZA, Loria AS, Min B, Hinds TD Jr. Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries. Physiol Rev. 2024;104(1):473–532. Doi:10.1152/physrev.00021.2023
  66. Levitt DG. Pharmacokinetics/pharmacodynamics of glucocorticoids: modeling the glucocorticoid receptor dynamics and dose/response of commonly prescribed glucocorticoids. ADMET DMPK. 2024;12(6):971–989. Published 2024 Oct 19. Doi:10.5599/admet.2414
  67. He Y, Yi W, Suino-Powell K, et al. Structures and mechanism for the design of highly potent glucocorticoids. Cell Res. 2014;24(6):713–726. Doi:10.1038/cr.2014.52
  68. Timmermans S, Souffriau J, Libert C. A general introduction to glucocorticoid biology. Front Immunol. 2019;10:1545. Published 2019 Jul 4. Doi:10.3389/fimmu.2019.01545
  69. Panettieri RA, Schaafsma D, Amrani Y, Koziol-White C, Ostrom R, Tliba O. Non-genomic effects of glucocorticoids: an updated view. Trends Pharmacol Sci. 2019;40(1):38–49. Doi:10.1016/j.tips.2018.11.002
  70. Nethathe GD, Lipman J, Anderson R, Fuller PJ, Feldman C. Glucocorticoids with or without fludrocortisone in septic shock: a narrative review from a biochemical and molecular perspective. Br J Anaesth. 2024;132(1):53–65. Doi:10.1016/j.bja.2023.10.034
  71. Yasir M, Goyal A, Sonthalia S. Corticosteroid Adverse Effects. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 3, 2023.
  72. Fowden AL, Vaughan OR, Murray AJ, Forhead AJ. Metabolic consequences of glucocorticoid exposure before birth. Nutrients. 2022;14(11):2304. Published 2022 May 30. Doi:10.3390/nu14112304
  73. Bontempo AC. Patient attitudes toward clinicians' communication of diagnostic uncertainty and its impact on patient trust. SSM Qual. Res. Health. 2022;3:100214. Doi:10.1016/j.ssmqr.2022.100214
  74. Vidaeff AC, Belfort MA, Kemp MW, et al. Updating the balance between benefits and harms of antenatal corticosteroids. Am J Obstet Gynecol. 2023;228(2):129–132. Doi:10.1016/j.ajog.2022.10.002
  75. WHO recommendations on: Antenatal corticosteroids for improving preterm birth outcomes. Geneva: World Health Organization; 2022.
  76. Main EK, et al. Reduction of severe maternal morbidity and mortality through a statewide collaborative quality improvement initiative. Am J Obstet Gynecol. 2022;226(2):248.e1–248.e13.
  77. De Costa A, Oladapo OT, Gupta S, et al. Antenatal corticosteroids for early preterm birth: implementation strategy lessons from the WHO ACTION-I trial. Health Res Policy Syst. 2022;20(1):141. Published 2022 Dec 28. Doi:10.1186/s12961-022-00941-z
  78. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2017;3(3):CD004454. Published 2017 Mar 21. Doi:10.1002/14651858.CD004454.pub3
  79. NICE. Overview | Preterm labour and birth | Guidance | NICE. Published November 20, 2015. https://www.nice.org.uk/guidance/ng25
  80. Melamed N, Shah J, Soraisham A, et al. Association between antenatal corticosteroid administration-to-birth interval and outcomes of preterm neonates. Obstet Gynecol. 2015;125(6):1377–1384. Doi:10.1097/AOG.0000000000000840
  81. Norberg H, Kowalski J, Maršál K, Norman M. Timing of antenatal corticosteroid administration and survival in extremely preterm infants: a national population-based cohort study. BJOG. 2017;124(10):1567–1574. Doi:10.1111/1471-0528.14545
  82. Melamed N, Asztalos E, Murphy K, et al. Neurodevelopmental disorders among term infants exposed to antenatal corticosteroids during pregnancy: a population-based study. BMJ Open. 2019;9(9):e031197. Published 2019 Sep 30. Doi:10.1136/bmjopen-2019-031197
  83. Crowther CA, Middleton PF, Voysey M, et al. Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis. PLoS Med. 2019;16(4):e1002771. Published 2019 Apr 12. Doi:10.1371/journal.pmed.1002771
  84. Frändberg J, Sandblom J, Bruschettini M, Maršál K, Kristensen K. Antenatal corticosteroids: a retrospective cohort study on timing, indications and neonatal outcome. Acta Obstet Gynecol Scand. 2018;97(5):591–597. Doi:10.1111/aogs.13301
  85. Levin HI, Ananth CV, Benjamin-Boamah C, Siddiq Z, Son M, Friedman AM. Clinical indication and timing of antenatal corticosteroid administration at a single centre. BJOG. 2016;123(3):409–414. Doi:10.1111/1471-0528.13730
  86. Alsayegh E, Barrett J, Melamed N. Optimal timing of antenatal corticosteroids in women with bleeding placenta previa or low-lying placenta. J. Matern. Fetal Neonatal Med. 2018;32(12):1971–1977. Doi:10.1080/14767058.2017.1422713
DOI: https://doi.org/10.34763/jmotherandchild.20263001.d-26-00003 | Journal eISSN: 2719-535X | Journal ISSN: 2719-6488
Language: English
Page range: 129 - 144
Submitted on: Jan 6, 2026
Accepted on: Apr 2, 2026
Published on: Jul 18, 2026
Published by: Institute of Mother and Child
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2026 Saim Mahmood Khan, Jawairya Muhammad Hussain, Yousif Daud Channa, Syed Zawiar Muhammad, Afnan Shaikh, Uzair Virk, Abdullah Aftab Khan, Muhammad Ali Shahzad, Surraiya Riaz Mahmood Khan, published by Institute of Mother and Child
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