Understanding antiepileptic drug exposure in pregnancy: the consequences for mother and child

Abstract

Background: Antiepileptic drugs (AEDs) are used to manage several neurological conditions and continued use throughout pregnancy is often necessary. AED use during pregnancy has been linked to elevated obstetric risk and prenatal AED exposure has been associated with an increased risk of major congenital malformations and the potential for negative effects on neurodevelopment. There have been few interventions undertaken in New Zealand for women or health professionals to ensure optimal use of these medicines in pregnancy. Aim: Investigate AED use in pregnant women, the developmental outcomes for children prenatally exposed to AEDs and explore a way to optimize AED use for women. Methods: Using encrypted individual identifiers, we linked the National Minimum Dataset, the Pharmaceutical Collection, the Laboratory Claims database and the Before School Check (B4SC; a database of childhood developmental screening results). We identified women who had given birth and had been dispensed one or more AEDs during pregnancy to investigate pregnancy outcomes in addition to dose adjustment and therapeutic drug monitoring (TDM) during pregnancy. We described data collected on the development of New Zealand four-year-olds during the B4SC and reported on the outcomes and referral rates of the B4SC measures for children prenatally exposed to AEDs. Stata and SPSS statistical software were used to determine rates of AED use, time trends, dose changes and rates of TDM. Logistic regression was used to estimate adjusted risk ratios for adverse developmental outcomes following prenatal exposure to AEDs. A use case method was employed to develop a health information technology (IT) solution for AED medicine management in women and the design was presented to health professionals, regulatory groups and consumers for feedback. Main findings: 1. There was an increase in the number of women of child-bearing potential prescribed AEDs over time. Pregnant women dispensed an AED had an increased prevalence of spontaneous abortion compared to women not dispensed an AED. 2. Contrary to guidelines, doses of lamotrigine and levetiracetam were not increased during pregnancy in 40% of the study population, TDM was infrequent and less than half of the adjusted doses were reduced postpartum. 3. Less than five percent of all New Zealand children had abnormal scores in developmental screening questionnaires, with children in areas with the highest deprivation scores more likely to require referral for further assessment than those living in areas with the lowest deprivation scores. 4. Prenatal exposure to sodium valproate and lamotrigine monotherapy and any AED polytherapy was associated with an increased risk of abnormal neurodevelopmental screening compared with no prenatal AED exposure. 5. An overarching theme of the feedback received on the patient-portal tool design was to involve patient groups in the development of the tool to help construct a patient-centred tool that women would engage with. Conclusion: AED use during pregnancy was associated with an increased rate of spontaneous abortion, there were potential problems with AED medicine management during pregnancy, and there was an increased risk of adverse neurodevelopment in children prenatally exposed to some AEDs. A patient-portal based health IT tool could mitigate some of these risks by ensuring optimal use of AEDs by women before and during pregnancy.