The use of parent-completed questionnaires to investigate developmental outcomes in large populations of children exposed to antiseizure medications in pregnancy.

OBJECTIVE: This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives. METHODS: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases. RESULTS: The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%). SIGNIFICANCE: Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3.

Neurodevelopment of babies born to mothers with epilepsy: A prospective observational cohort study.

OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded child development data are still limited. The NaME (Neurodevelopment of Babies Born to Mothers With Epilepsy) Study prospectively recruited a new cohort of women with epilepsy and their offspring for longitudinal follow-up. METHODS: Pregnant women of <21 weeks gestation (n = 401) were recruited from 21 hospitals in the UK. Data collection occurred during pregnancy (recruitment, trimester 3) and at 12 and 24 months of age. The primary outcome was blinded assessment of infant cognitive, language, and motor development on the Bayley Scales of Infant and Toddler Development (3rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2nd edition). RESULTS: There were 394 live births, with 277 children (70%) completing the Bayley assessment at 24 months. There was no evidence of an association of prenatal exposure to monotherapy lamotrigine (-.74, SE = 2.9, 95% confidence interval [CI] = -6.5 to 5.0, p = .80) or levetiracetam (-1.57, SE = 3.1, 95% CI = -4.6 to 7.7, p = .62) with poorer infant cognition, following adjustment for other maternal and child factors in comparison to nonexposed children. Similar results were observed for language and motor scores. There was no evidence of an association between increasing doses of either lamotrigine or levetiracetam. Nor was there evidence that higher dose folic acid supplementation (≥5 mg/day) or convulsive seizure exposure was associated with child development scores. Continued infant exposure to antiseizure medications through breast milk was not associated with poorer outcomes, but the number of women breastfeeding beyond 3 months was low. SIGNIFICANCE: These data are reassuring for infant development following in utero exposure to monotherapy lamotrigine or levetiracetam, but child development is dynamic, and future follow-up is required to rule out later emerging effects.

Prenatal exposure to anti-epileptic drugs: the need for preconception counselling.

There is accumulating evidence that prenatal exposure to antiepileptic drugs (AEDs) poses an increased risk to the fetus. There is robust evidence surrounding the incidence of major congenital malformations following exposure to some commonly prescribed AEDs, and growing evidence that prenatal exposure to certain AEDs is also associated with a reduction in cognitive functioning and an increase in neurodevelopmental disorders in childhood. This article discusses some of the findings in regards to pregnancy outcome after exposure to AEDs, the possible implications for the child and, given recent findings, the need for preconception counselling for women with epilepsy of childbearing potential.

The effectiveness of preconception counseling to reduce adverse pregnancy outcome in women with epilepsy: what's the evidence?

OBJECTIVE: The purpose of this Cochrane review was to determine the effectiveness of delivering preconception counseling interventions to women with epilepsy (WWE) as a means of reducing adverse pregnancy outcomes, increasing knowledge, and increasing intentions to plan pregnancy. METHODS: Two hundred twenty-five citations were retrieved from a systematic search of the Cochrane Library and electronic databases: Medline (OVID), Scopus, CINAHL, PsychINFO, and ASSIA, and hand searches of relevant epilepsy and obstetric journals. RESULTS: The search strategy identified 11 studies for consideration for inclusion. However, none met the required criteria for inclusion. CONCLUSIONS: There is no robust evidence to inform the content, methods of delivery, or likely effectiveness of preconception counseling to improve pregnancy outcomes for WWE and their offspring. The value of counseling WWE prior to conception remains uncertain and requires evaluation in well-designed studies, appropriately powered to detect changes likely associated with both maternal and infant outcomes.

Preconception counselling for women with epilepsy to reduce adverse pregnancy outcome.

BACKGROUND: The provision of preconception counselling to women with epilepsy (WWE) has become established as recommended practice and includes a review of drug treatment and the provision of information and advice on both seizure and treatment-related risks to both mother and child. In this review we assess the evidence regarding the effectiveness of preconception counselling for WWE. OBJECTIVES: To determine the effectiveness of preconception counselling for WWE, measured by a reduction in adverse pregnancy outcome in both mother and child; increased knowledge of preconception issues in WWE and increasing intention to plan pregnancy. SEARCH STRATEGY: We searched the Epilepsy Group's Specialized Register (30/01/2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4), and electronic databases: MEDLINE (OVID) (1950-February 2008); SCOPUS (1966-March 2008); CINAHL (1982-March 2008); PsyclNFO (1806-March 2008); ASSIA (1987-March 2008). SELECTION CRITERIA: Randomised control trials; including cluster and quasi-randomised trials, prospective cohorts, controlled before and after studies, and interrupted time series that compared the outcomes in mothers with epilepsy and infants of mothers with epilepsy who received preconception counselling, to the outcomes of mothers with epilepsy and their infants who received standard care or no intervention. DATA COLLECTION AND ANALYSIS: The methodological quality of potentially relevant studies were assessed to determine appropriate inclusion. Where necessary, study authors were contacted for additional information. No studies met the review inclusion criteria. MAIN RESULTS: The search strategy identified 11 studies for consideration of inclusion. However, none met the required criteria for inclusion. AUTHORS' CONCLUSIONS: There is no evidence to inform the content, methods of delivery or effectiveness of preconception counselling to improve pregnancy outcomes for WWE and their offspring. The value of counselling delivered to WWE prior to conception, with the intention of reducing the risks of adverse outcome in mother and child, requires evaluation in well-designed studies, appropriately powered to detect changes in both maternal and infant outcome.