Medicine & Health

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  • (2023) Raichand, Smriti
    Background: Teratogenic medicines when used in pregnancy increase the risk of foetal defects. The doses above which these risks increase are published for some medicines including four antiepileptics. Among antiepileptics, valproate is associated with the highest risk of foetal harm. It is, therefore, important to understand the utilisation of teratogenic medicines among pregnant women and women of child-bearing age. Study 1 in this thesis measured the prevalence of teratogenic medicine utilisation before and during pregnancy. Study 2 estimated utilisation of teratogenic antiepileptics as average daily doses (ADDs) dispensed to women of child-bearing age. Study 3 examined valproate utilisation in pregnancy, factors associated with continuation in pregnancy, and recent trends in women of child-bearing age. Methods: In Study 1 and Study 3 we used linked administrative health records, which contained pregnancy-related details and mothers’ health service use, including dispensed prescription medicines. The cohorts comprised concessional beneficiaries who gave birth in New South Wales in 2004-2012. To examine medicine utilisation among women of child-bearing age (Study 2, Study 3) we used medicine dispensing records for 10% of the Australian population in 2012-2020. We presented prevalence as percentages and n per 1000 women, ADDs as mg/day, and associations as odds ratios (ORs). Results: The prevalence of teratogenic medicine utilisation at any time during pregnancy was 2.0%, steadily decreasing from first trimester through to birth. Teratogenic antiepileptics (carbamazepine, lamotrigine, and valproate) except phenobarbital, were dispensed at ADDs below the published high-risk dose thresholds, to women of child-bearing age. Prevalence of valproate utilisation was 5.2 in 1000 pregnant women, and approximately 24% continued use in pregnancy. Having a diagnosis of epilepsy (OR 10.2, 95% CI 5.7-18.4) was significantly associated with valproate continuation in pregnancy. Valproate utilisation among women of child-bearing age decreased from 5.8 to 3.5 per 1000 women in 2013-2020. Conclusions: Taken together, our findings on teratogenic medicine use among pregnant women, antiepileptic ADDs among women of child-bearing age and valproate exposure in these populations suggest that Australian prescribers and patients were aware of the potential harms posed by these medicines.