Skip to main content

Maternal use of hormonal contraception and risk of childhood ADHD: a nationwide population-based cohort study

Abstract

Although maternal use of hormones has been suspected of increasing the risk for childhood attention-deficit/hyperactivity disorder (ADHD), no study has examined hormonal contraception use in this context. We examined the association between maternal hormonal contraception use before or during pregnancy and ADHD risk in children. This nationwide population-based cohort study included 1,056,846 children born in Denmark between 1998 and 2014. Prescriptions for hormonal contraceptives redeemed by the mother was categorized as: no use, previous use (> 3 months before pregnancy), and recent use (≤ 3 months before or during pregnancy). Children were followed for ADHD, from birth until 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During 9,819,565 person-years of follow-up (median: 9.2), ADHD was diagnosed or a prescription for ADHD medication redeemed for 23,380 children (2.2%). The adjusted HR for ADHD was higher in children of mothers who had previously (HR 1.23; 95% CI 1.18–1.28) or recently (HR 1.30; 95% CI 1.24–1.37) used hormonal contraception than in those of mothers with no use. The highest estimates were seen for use of non-oral progestin products with HRs of 1.90 (95% CI 1.59–2.26) for previous use, 2.23 (95% CI 1.96–2.54) for recent use, and 3.10 (95% CI 1.62–5.91) for use during pregnancy. Maternal use of hormonal contraception was associated with an increased risk for ADHD in the offspring; more pronounced for non-oral progestin-only than other products.

This is a preview of subscription content, access via your institution.

References

  1. Wittchen HU, Jacobi F, Rehm J, et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21:655–79.

    Article  CAS  Google Scholar 

  2. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164:942–98.

    Article  Google Scholar 

  3. World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992.

    Google Scholar 

  4. Tarver J, Daley D, Sayal K. Attention-deficit hyperactivity disorder (ADHD): an updated review of the essential facts. Child Care Health Dev. 2014;40:762–74.

    Article  CAS  Google Scholar 

  5. Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet. 2016;387:1240–50.

    Article  Google Scholar 

  6. Hvolgaard Mikkelsen S, Olsen J, Bech BH, Obel C. Parental age and attention-deficit/hyperactivity disorder (ADHD). Int J Epidemiol. 2017;46:409–20.

    PubMed  Google Scholar 

  7. Hjern A, Weitoft GR, Lindblad F. Social adversity predicts ADHD-medication in school children - a national cohort study. Acta Paediatr. 2010;99:920–4.

    Article  CAS  Google Scholar 

  8. Andersen CH, Thomsen PH, Nohr EA, Lemcke S. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. Eur Child Adolesc Psychiatry. 2017;27:139–48.

    Article  Google Scholar 

  9. Lindh I, Skjeldestad FE, Gemzell-Danielsson K, et al. Contraceptive use in the Nordic countries. Acta Obstet Gynecol Scand. 2017;96:19–28.

    Article  CAS  Google Scholar 

  10. Hargreave M, Mørch LS, Andersen KK, Winther JF, Schmiegelow K, Kjaer SK. Maternal use of hormonal contraception and risk of childhood leukaemia: a nationwide, population-based cohort study. Lancet Oncol. 2018;19:1307–14.

    Article  CAS  Google Scholar 

  11. Strifert K. The link between oral contraceptive use and prevalence in autism spectrum disorder. Med Hypotheses. 2014;83:718–25.

    Article  CAS  Google Scholar 

  12. Strifert K. An epigenetic basis for autism spectrum disorder risk and oral contraceptive use. Med Hypotheses. 2015;85:1006–11.

    Article  Google Scholar 

  13. Strifert K. The case for epidemiological investigation of the possible link between combined oral contraceptives and autism spectrum disorder. Endocrinol Metabol Syndr. 2015;4:1000165.

    Google Scholar 

  14. Svahn MF, Hargreave M, Nielsen TS, et al. Mental disorders in childhood and young adulthood among children born to women with fertility problems. Hum Reprod. 2015;30:2129–37.

    Article  CAS  Google Scholar 

  15. Bay B, Mortensen EL, Hvidtjorn D, Kesmodel US. Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study. BMJ. 2013;347:f3978.

    Article  Google Scholar 

  16. Kallen AJ, Finnstrom OO, Lindam AP, Nilsson EM, Nygren KG, Otterblad Olausson PM. Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization? Eur J Paediatr Neurol. 2011;15:247–53.

    Article  Google Scholar 

  17. Beydoun HA, Sicignano N, Beydoun MA, et al. A cross-sectional evaluation of the first cohort of young adults conceived by in vitro fertilization in the United States. Fertil Steril. 2010;94:2043–9.

    Article  Google Scholar 

  18. Lacal I, Ventura R. Epigenetic inheritance: concepts, mechanisms and perspectives. Front Mol Neurosci. 2018;11:292.

    Article  CAS  Google Scholar 

  19. Kioumourtzoglou M, Coull BA, O’Reilly ÉJ, Ascherio A, Weisskopf MG. Association of exposure to diethylstilbestrol during pregnancy with multigenerational neurodevelopmental deficits. JAMA Pediatr. 2018;172:670–7.

    Article  Google Scholar 

  20. Bliddal M, Broe A, Pottegard A, Olsen J, Langhoff-Roos J. The Danish Medical Birth Register. Eur J Epidemiol. 2018;33:27–36.

    Article  Google Scholar 

  21. Kildemoes HW, Sorensen HT, Hallas J. The Danish National Prescription Registry. Scand J Public Health. 2011;39:38–41.

    Article  Google Scholar 

  22. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health. 2011;39:30–3.

    Article  Google Scholar 

  23. Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol. 1993;138:923–36.

    Article  CAS  Google Scholar 

  24. Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989;129:125–37.

    Article  CAS  Google Scholar 

  25. Williams RL. A note on robust variance estimation for cluster-correlated data. Biometrics. 2000;56:645–6.

    Article  CAS  Google Scholar 

  26. Sundhedsstyrelsen. Vejledning om medikamentel behandling af børn og unge med psykiske lidelser. https://www.retsinformation.dk/Forms/R0710.aspx?id=146409. Accessed 27 May 2019.

  27. Sundhedsdatastyrelsen, Sundhedsanalyser og Lægemiddelstatistik. Kommunale forskelle i brug af ADHD-medicin. https://sundhedsdatastyrelsen.dk/-/media/sds/filer/find-tal-og-analyser/laegemidler/kvartalets-medicinsalg/medicinforbrugindblik_2016_kommunale-forskelle-adhd.pdf. Accessed 27 May 2019.

  28. Stigning i forbruget af nødprævention. Danmarks Apotekerforening. 2017. https://www.apotekerforeningen.dk/-/media/apotekerforeningen/analysersundhed/04082017-noedpraevention.pdf. Accessed 10 March 2020.

  29. Starck M, Grunwald J, Schlarb AA. Occurrence of ADHD in parents of ADHD children in a clinical sample. Neuropsychiatr Dis Treat. 2016;12:581–8.

    PubMed  PubMed Central  Google Scholar 

  30. Hankoff LD, Darney PD. Contraceptive choices for behaviorally disordered women. Am J Obstet Gynecol. 1993;168:1986–9.

    Article  CAS  Google Scholar 

  31. Skoglund C, Kopp Kallner H, Skalkidou A, et al. Association of attention-deficit/hyperactivity disorder with teenage birth among women and girls in Sweden. JAMA Netw Open. 2019;2:e1912463.

    Article  Google Scholar 

  32. Hamza M, Halayem S, Bourgou S, Daoud M, Charfi F, Belhadj A. Epigenetics and ADHD: toward an integrative approach of the disorder pathogenesis. J Atten Disord. 2019;23:655–64.

    Article  Google Scholar 

  33. Bergman Å, Heindel J, Jobling S, Kidd AK, Zoeller RT. State of the science of endocrine disrupting chemicals. Nairobi, Geneva: United Nations Environment Programme; World Health Organization; 2013.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  35. Li L, Li M, Lu J, et al. Prenatal progestin exposure is associated with autism spectrum disorders. Front Psychiatry. 2018;9:611.

    Article  Google Scholar 

  36. Ghirardi L, Pettersson E, Taylor MJ, et al. Genetic and environmental contribution to the overlap between ADHD and ASD trait dimensions in young adults: a twin study. Psychol Med. 2019;49:1713–21.

    Article  Google Scholar 

Download references

Funding

No specific funding was obtained for the project which was supported by internal funding from the Unit Virus, Lifestyle and Genes at the Danish Cancer Society Research Center.

Author information

Authors and Affiliations

Authors

Contributions

MH, LSM and SKK initiated the study. MH, LSM, SKK and CHH designed the study. CHH and MH analysed the data; they are guarantors for the paper. CHH wrote the initial manuscript and all authors interpreted the results and revised the manuscript critically. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Corresponding author

Correspondence to Marie Hargreave.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Danish Data Protection Agency (Registration Number 2017-41-5221). As this study is based solely on data from electronic databases and registries, informed consents are not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 42 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hemmingsen, C.H., Kjaer, S.K., Jezek, A.H. et al. Maternal use of hormonal contraception and risk of childhood ADHD: a nationwide population-based cohort study. Eur J Epidemiol 35, 795–805 (2020). https://doi.org/10.1007/s10654-020-00673-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10654-020-00673-w

Keywords

  • Attention-deficit/hyperactivity disorder
  • ADHD
  • Hormonal contraception
  • Cohort study