Oral Presentation Society of Obstetric Medicine of Australia and New Zealand ASM 2026

Consensus Guidance: Reproductive safety and use of sodium valproate (141654)

Viandro Borja 1 , Treasure M McGuire 2 3 4 , James Dwyer 5 , Alka Garg 6 , Tamara Lebedevs 7 , Judy Longworth 8 , Katie Ho 5 , Kate Luttrell 9 , Suzanne Newman 10 , Lisa Robertson 9
  1. Pharmacy, Alfred Health, Melbourne, Victoria, Australia
  2. Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia
  3. Mater Pharmacy , Mater Health, SEQ , Brisbane, Queensland, Australia
  4. School of Pharmacy and Pharmaceutical Sciences, The University of Queensland, Brisbane, Queensland, Australia
  5. Pharmacy, Mercy Health, Melbourne, Victoria, Australia
  6. Pharmacy, Women’s and Children’s Health Network, Adelaide, South Australia, Australia
  7. Pharmacy Department, King Memorial Hospital, Perth, Western Australia, Australia
  8. Psychological Medicine, The Sydney Childrens Hospital Network , Childrens Hospital Westmead, Sydney, New South Wales, Australia
  9. Statewide Hospital Pharmacy, Tasmanian Health Service, Hobart, Tasmania, Australia
  10. Advanced Pharmacy Australia, Melbourne, Victoria, Australia

Background: Sodium valproate is indicated for epilepsy and bipolar disorder, with widespread use for neuropathic pain and migraine prophylaxis. However, well‑established dose-related teratogenic and neurodevelopmental risks during maternal use1,2 and controversial evidence suggesting possible paternal-mediated effects3-6 necessitate stringent reproductive safety practices. Despite longstanding national safety alerts and education efforts, risk-mitigation implementation strategies remain variable and inconsistent.7,8

 Objective: To develop evidence-based, consensus-driven guidance to support Australian healthcare professionals provide consistent, accurate, and patient‑centred advice regarding the reproductive risks of sodium valproate.

 Method:  Guidance development comprised pharmacists with relevant expertise (medication safety, mental health, newborn, women’s health and paediatrics) from a national member organisation, with stakeholder consultation from pharmacy and medical networks/organisations, to ensure guidance aligns with frontline practice, addresses current knowledge and policy gaps, and supports a standardised approach to risk mitigation across services. The working group undertook:

  1. comprehensive literature review with retrieved citations and clinical practice guidelines screened for relevance by two independent reviewers;
  2. working group preliminary recommendation categorisation using a modified NHMRC Grades of Recommendations9; and
  3. a Delphi10 consensus determination of recommendations ranked as ‘strong’, ‘weak’ or ‘good practice point’.

 Results: The final guidance comprises consensus statements across key domains including key practice points; indications/contraindications; informed consent/counselling; contraception/pregnancy prevention processes; monitoring/scheduled reviews; when pregnancy is suspected/confirmed; paternal exposure; and guidance implementation.

 Conclusion: This national cross-speciality initiative addresses practice variation and offers a practical evidence‑informed framework to support valproate use in the reproductive setting.

  1. Bromley R, Adab N, Bluett-Duncan M, Clayton-Smith J, Christensen J, Edwards K, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Epilepsy Group, editor. Cochrane Database Syst Rev. 2023(8). doi:10.1002/14651858.CD010224.pub3
  2. Medicines and Healthcare products Regulatory Agency. Valproate: review of safety data and expert advice on risk minimisation measures [Internet]. London (UK): MHRA; 2023 [cited 2025 Nov 20]. Available from: https://assets.publishing.service.gov.uk/media/65660310312f400013e5d508/Valproate-report-review-and-expert-advice.pdf
  3. Valproate EU consortium. A post-authorisation safety study (PASS) to evaluate the paternal exposure to valproate and the risk of neurodevelopmental disorders including autism spectrum disorder as well as congenital abnormalities in offspring – a population-based retrospective study [Internet]. IQVIA; 2023. Available from: https://catalogues.ema.europa.eu/system/files/2024-02/Valproate_PASS_Abstract_V2.0_0.pdf
  4. European Medicines Agency. European Medicines Agency [Internet]. 2024 [cited 2026 Apr 3]. Potential risk of neurodevelopmental disorders in children born to men treated with valproate medicines: PRAC recommends precautionary measures. Available from: https://www.ema.europa.eu/en/news/potential-risk-neurodevelopmental-disorders-children-born-men-treated-valproate-medicines-prac-recommends-precautionary-measures
  5. Christensen J, Trabjerg BB, Dreier JW. Risk of Neurodevelopmental Disorders and Paternal Use of Valproate During Spermatogenesis. JAMA Netw Open 2025;8(5):e2512139. doi:10.1001/jamanetworkopen.2025.12139
  6. Honybun E, Rayner G, Malpas CB, O’Brien TJ, Vajda FJ, Perucca P, et al. Paternal exposure to antiseizure medications and offspring outcomes: a systematic review. J Neurol Neurosurg Psychiatry 2025;96(1):15–25. doi:10.1136/jnnp-2024-334077
  7. Davies P, Reuber M, Grunewald R, Howell S, Dickson J, Dennis G, et al. The impact and challenges of the 2018 MHRA statement on the use of sodium valproate in women of childbearing age during the first year of implementation, in a UK epilepsy centre. Seizure 2020;79:8-13. doi:10.1016/j.seizure.2020.03.015
  8. Begum M, Giles L, Ilomaki J, Rumbold A, Davies M, Grzeskowiak LE, et al. Longitudinal Australian trends in the initiation of valproate medication among women of reproductive age and concurrent use of prescription contraceptives. Womens Health 2026 ;22:17455057251414916. doi:10.1177/17455057251414916
  9. National Health and Medical Research Council. Additional levels of evidence and grades for recommendations for developers of guidelines: Stage 2 consultation (early 2008–end June 2009) [Internet]. National Health and Medical Research Council; 2009. Available from: https://www.mja.com.au/sites/default/files/NHMRC.levels.of.evidence.2008-09.pdf
  10. Nasa P, Jain R, Juneja D. Delphi methodology in healthcare research: How to decide its appropriateness. World J Methodol 2021 20;11(4):116–29. doi:10.5662/wjm.v11.i4.116