Cognitive development and neuropsychic health of children conceived by assisted reproductive technologies

Lokshin V.N., Ilmuratova S.Kh.

PERSONA International Clinical Center for Reproductology, Almaty, Kazakhstan
Objective: To carry out a systematic analysis of current publications on the assessment of a risk for neuropsychiatric disorders in children conceived by assisted reproductive technologies (ART).
Materials and methods: This review includes an analysis of foreign articles found in the online databases Medline, PubMed, and Springer and published in the past 5 years.
Results: Despite the encouraging results of studies on the long-term potential consequences of ART on the neuropsychiatric health of children, information is limited due to the presence of independent risk factors for nervous system diseases that are directly unrelated to reproductive technologies, such as multiple pregnancies, preterm birth, and no comparison group of children conceived spontaneously and born to mothers with a history of infertility.
Conclusion: Considering the pace of development and introduction of up-to-date technologies in reproductology, it is necessary to further investigate the potential impact of ART on neuropsychiatric health, taking into account amendments for an adequate risk assessment. Neonatal nervous system diseases are probably more associated with multiple pregnancies and abnormal pregnancy and childbirth.

Keywords

IVF
ART
children
offspring
cognitive development
neurological disorders
nervous system diseases
attention deficit/hyperactivity disorder
autism spectrum disorders
cerebral palsy
autism

References

  1. Opdahl S., Henningsen A.A., Bergh C., Gissler M., Romundstad L.B., Petzold M. et al. Data resource profile: Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) cohort. Int. J. Epidemiol. 2020; 49(2): 365-6f. https://dx.doi.org/10.1093/ije/dyz228.
  2. ESHRE. ART fact sheet 2022. Updated January 2022. Available at:https://www.eshre.eu/Europe/Factsheets-and-infographics
  3. Wyns C., Bergh C., Calhaz-Jorge C., De Geyter C., Kupka M.S., Motrenko T. et al.; European IVF-monitoring Consortium (EIM)‡ for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2016: results generated from European registries by ESHRE. Hum. Reprod. Open. 2020; 2020(3): hoaa032. https://dx.doi.org/10.1093/hropen/hoaa032.
  4. De Geyter C., Calhaz-Jorge C., Kupka M.S., Wyns C., Mocanu E., Motrenko T. et al.; European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum. Reprod. 2018; 33(9): 1586-601. https://dx.doi.org/10.1093/humrep/dey242.
  5. Adamson G.D., de Mouzon J., Chambers G.M., Zegers-Hochschild F., Mansour R., Ishihara O. et al. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011. Fertil. Steril. 2018; 110(6): 1067-80. https://dx.doi.org/10.1016/j.fertnstert.2018.06.039.
  6. Roychoudhury S., Lodha A., Synnes A., Abou Mehrem A., Canning R., Banihani R. et al.; Canadian Neonatal Network; Canadian Preterm Birth Network; Canadian Neonatal Follow-Up Network Investigators. Neurodevelopmental outcomes of preterm infants conceived by assisted reproductive technology. Am. J. Obstet. Gynecol. 2021; 225(3): 276.e1-276.e9. https://dx.doi.org/10.1016/j.ajog.2021.03.027.
  7. Hoyos L., R., Ory S.J. The influence of assisted reproductive technologies on obstetric and perinatal outcomes: the chicken, the egg, or both? Fertil. Steril. 2021; 115(4): 884-5. https://dx.doi.org/10.1016/J.FERTNSTERT.2021.01.022.
  8. Ganer Herman H., Mizrachi Y., Shevach Alon A., Farhadian Y., Gluck O., Bar J. et al. Obstetric and perinatal outcomes of in vitro fertilization and natural pregnancies in the same. Fertil. Steril. 2021; 115(4): 940-6. https://dx.doi.org/10.1016/J.FERTNSTERT.2020.10.060.
  9. Hwang S.S., Dukhovny D., Gopal D., Cabral H., Missmer S., Diop H. et al. Health of infants after ART-treated, subfertile, and fertile deliveries. Pediatrics. 2018; 142(2): e20174069. https://dx.doi.org/10.1542/peds.2017-4069.
  10. Molinaro T.A. Taking a second look at obstetrical outcomes after assisted reproductive technologies. Fertil. Steril. Rep. 2021; 2: 368-9.https://dx.doi.org/10.1016/j.xfre.2021.08.014.
  11. Luke B., Brown M.B., Wantman E., Forestieri N.E., Browne M.L., Fisher S.C. et al. The risk of birth defects with conception by ART. Hum. Reprod. 2021; 36(1): 116-29. https://dx.doi.org/10.1093/humrep/deaa272.
  12. Wessel J.A., Mol F., Danhof N.A., Betjes H., de Bruin J.P., Cantineau A.E.P. et al. Birthweight and other perinatal outcomes of singletons conceived after assisted reproduction compared to natural conceived singletons in couples with unexplained subfertility: follow-up of two randomized clinical trials. Hum. Reprod. 2021; 36(3): 817-25. https://dx.doi.org/10.1093/humrep/deaa298.
  13. Huang X., Fu J. Association between assisted reproductive technology and white matter Injury in premature infants: A case-control study. Front. Pediatr. 2021; 9: 686670. https://dx.doi.org/10.3389/fped.2021.686670.
  14. Levin S., Sheiner E., Wainstock T., Walfisch A., Segal I., Landau D. et al. Infertility treatments and long-term neurologic morbidity of the offspring. Am. J. Perinatol. 2019; 36(9): 949-54. https://dx.doi.org/10.1055/s-0038-1675159.
  15. Hansen M., Greenop K.R., Bourke J., Baynam G., Hart R.J., Leonard H. Intellectual disability in children conceived using assisted reproductive technology. Pediatrics. 2018; 142(6): e20181269. https://dx.doi.org/10.1542/peds.2018-1269.
  16. Norrman E., Petzold M., Bergh C., Wennerholm U.-B. School performance in singletons born after assisted reproductive technology. Hum. Reprod. 2018; 33(10): 1948-59. https://dx.doi.org/10.1093/humrep/dey273.
  17. Luke B., Brown M.B., Ethen M.K., Canfield M.A., Watkins S., Wantman E. et al. Third grade academic achievement among children conceived with the use of in vitro fertilization: a population-based study in Texas. Fertil. Steril. 2020; 113(6): 1242-50. https://dx.doi.org/10.1016/j.fertnstert.2020.01.015.
  18. Norrman E., Petzold M., Bergh C., Wennerholm U.B. School performance in children born after intracytoplasmic sperm injection (ICSI). Hum. Reprod. 2020; 35(2): 340-54. https://dx.doi.org/10.1093/humrep/dez281.
  19. Spangmose A.L., Malchau S.S., Schmidt L., Vassard D., Rasmussen S., Loft A. et al. Academic performance in adolescents born after ART-a nationwide registry-based cohort study. Hum. Reprod. 2017; 32(2): 447-56.https://dx.doi.org/10.1093/humrep/dew334.
  20. Spangmose A.L., Malchau S.S., Henningsen A.A., Forman J.L., Rasmussen S., Loft A. et al. Academic performance in adolescents aged 15–16 years born after frozen embryo transfer compared with fresh embryo transfer: a nationwide registry-based cohort study. BJOG. 2019; 126(2): 261-9. https://dx.doi.org/10.1111/1471-0528.15484.
  21. Farhi A., Gabis L.V., Frank S., Glasser S., Hirsh-Yechezkel G., Brinton L. et al. Cognitive achievements in school-age children born following assisted reproductive technology treatments: a prospective study. Early Hum. Dev. 2021; 155: 105327. https://dx.doi.org/10.1016/j.earlhumdev.2021.105327.
  22. Jenabi E., Seyedi M., Hamzehei R., Bashirian S., Rezaei M., Razjouyan K. et al. Association between assisted reproductive technology and autism spectrum disorders in Iran: a case-control study. Clin. Exp. Pediatr. 2020; 63(9): 368-72. https://dx.doi.org/10.3345/cep.2020.00073.
  23. Farhi A., Glasser S., Gabis L.V., Hirsh-Yechezkel G., Frank S., Brinton L. et al. How are they doing? Neurodevelopmental outcomes at school age of children born following assisted reproductive treatments. J. Child Neurol. 2021; 36(4): 262-71. https://dx.doi.org/10.1177/0883073820967169.
  24. Davidovitch M., Chodick G., Shalev V., Eisenberg V.H., Dan U., Reichenberg A. et al. Infertility treatments during pregnancy and the risk of autism spectrum disorder in the offspring. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2018; 86: 175-9. https://dx.doi.org/10.1016/j.pnpbp.2018.05.022.
  25. Diop H., Cabral H., Gopal D., Cui X., Stern J.E., Kotelchuck M. Early autism spectrum disorders in children born to fertile, subfertile, and ART-treated women. Matern. Child Health J. 2019; 23(11): 1489-99.https://dx.doi.org/10.1007/s10995-019-02770-z.
  26. Bergh C., Wennerholm U.B. Long-term health of children conceived after assisted reproductive technology. Ups. J. Med. Sci. 2020; 125(2): 152-7.https://dx.doi.org/10.1080/03009734.2020.1729904.
  27. Smithers-Sheedy H., Mcintyre S., Badawi N., Goldsmith S., Balde I., Gibson C. et al. Australian Cerebral Palsy Register Report, 2018.
  28. Александрова Н.В., Баев О.Р, Иванец Т.Ю. Преждевременные роды при беременности, наступившей с использованием вспомогательных репродуктивных технологий. Пути профилактики. Акушерство и гинекология. 2012; 4-2: 33-8. [Aleksandrova N.V, Bayev O.R,. Ivanets T.Yu. Premature birth in assisted reproductive technology pregnancy: ways of prevention. Obstetrics and Gynecology. 2012; 4-2: 33-8. (in Russian)].
  29. Goldsmith S,. McIntyre S., Badawi N., Hansen M. Cerebral palsy after assisted reproductive technology: a cohort study. Dev. Med. Child Neurol. 2018; 60(1): 73-80. https://dx.doi.org/10.1111/dmcn.13577.
  30. Djuwantono T., Aviani J.K., Permadi W., Achmad T.H., Halim D. Risk of neurodevelopmental disorders in children born from different ART treatments: a systematic review and meta-analysis. J. Neurodev. Disord. 2020; 12(1): 33. https://dx.doi.org/10.1186/s11689-020-09347-w.
  31. Wang F.F., Yu T., Chen X.L., Luo R., Mu D.Z. Cerebral palsy in children born after assisted reproductive technology: a meta-analysis. World J. Pediatr. 2021; 17(4): 364-74. https://dx.doi.org/10.1007/s12519-021-00442-z.
  32. Spangmose A.L., Christensen L.H., Henningsen A.A., Forman J., Opdahl S., Romundstad L.B. et al. Cerebral palsy in ART children has declined substantially over time: a Nordic study from the CoNARTaS group. Hum. Reprod. 2021; 36(8): 2358-70. https://dx.doi.org/ 10.1093/humrep/deab122.
  33. Rissanen E., Gissler M., Lehti V., Tiitinen A. The risk of psychiatric disorders among Finnish ART and spontaneously conceived children: Finnish population-based register study. Eur. Child Adolesc. Psychiatry. 2020; 29(8): 1155-64. https://dx.doi.org/10.1007/s00787-019-01433-2.
  34. Wang C., Johansson A.L.V., Rodriguez-Wallberg K.A., Landén M., Almqvist C., Hernández-Díaz S., Oberg A.S. Long-term follow-up of psychiatric disorders in children and adolescents conceived by assisted reproductive techniques in Sweden. JAMA Psychiatry. 2022; 79(2): 133-42. https://dx.doi.org/10.1001/jamapsychiatry.2021.3647.
  35. La Rovere M., Franzago M., Stuppia L. Epigenetics and neurological disorders in ART. Int. J. Mol. Sci. 2019; 20(17): 4169. https://dx.doi.org/10.3390/ijms20174169.

Received 26.07.2022

Accepted 01.09.2022

About the Authors

Vyacheslav N. Lokshin, Dr. Med. Sci., Professor, member of National Academy of Science Republic of Kazakhstan, President of Kazakhstan Association of the Reproductive Medicine, managing director of the PERSONA International Clinical Center for Reproductology, +7(727)382-77-77, v_lokshin@persona-ivf.kz,
https://orcid.org/0000-0002-4792-53807-050060, 050000, Kazakhstan, Almaty, Utepova str., 32a.
Sevara Kh. Ilmuratova, pediatrician, Ph.D. candidate KSPH, PERSONA International Clinical Center for Reproductology, +7(777)801-73-05, i.sevarochka@mail.ru,
https://orcid.org/0000-0001-5445-8293, 050000, Kazakhstan, Almaty, Utepova str., 32a.
Corresponding author: Sevara Kh. Ilmuratova, i.sevarochka@mail.ru

Authors’ contributions: Lokshin V.N. – the concept and design of the investigation; Ilmuratova S.Kh. – material collection and processing; Lokshin V.N., Ilmuratova S.Kh. – writing the text.
Conflicts of interest: The authors declare that there are no possible conflicts of interest.
Funding: This study was conducted within the framework of the scientific and engineering project ИРН AP14872103 "Somatic and psychosocial status of children after ART determination with the development of prediction model and principles of child management" (Targeted Financing from the Ministry of Healthcare of the Republic of Kazakhstan).
For citation: Lokshin V.N., Ilmuratova S.Kh. Cognitive development and neuropsychic health of children conceived by assisted reproductive technologies.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 11: 31-36 (in Russian)
https://dx.doi.org/10.18565/aig.2022.11.31-36

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.