Exposure to antiepileptic drugs in pregnancy: The need for a family factor framework

Huber‐Mollema, Yfke; Iterson, Loretta van; Sander, Josemir W.; Oort, Frans J.; Lindhout, Dick; Rodenburg, Roos

doi:10.1016/j.yebeh.2018.06.043

Cited by 3 publications

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“…In this study we did not consider the role of active maternal epilepsy during infant and child development. It will be worthwhile examining these aspects in future studies as they are of importance for developing interventions [48]. This may ultimately enhance the quality of life of children who have been exposed to AEDs in utero, their mothers, and their families.…”

Section: Discussionmentioning

confidence: 99%

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure

et al. 2020

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Objective To examine neurocognitive functioning of children exposed prenatally to carbamazepine, lamotrigine, levetiracetam or valproate monotherapy. Methods In a prospective observational study, children aged 6 or 7 years, identified from the European Registry of Antiepileptic Drugs and Pregnancy database in The Netherlands, were assessed using the Wechsler Intelligence Scale for Children and the developmental neuropsychological assessment. Maternal IQ was measured using Wechsler Adult Intelligence Scale. Assessors were blinded to drug exposures. Results One hundred and sixty-one children (one set of twins and 21 sibling pairs) of 139 mothers were included. As a group, children achieved average scores on neurocognitive outcomes. Children exposed to valproate (n = 22) performed lower on all six neurocognitive domains, especially language, than those exposed to carbamazepine (n = 32), lamotrigine (n = 82) or levetiracetam (n = 25). After controlling for maternal IQ and drug dose, the verbal IQ of valproate-exposed children was on average 9.1 points lower than those exposed to carbamazepine (95% confidence interval [CI] 1.3-17.0; p = 0.023), 10.3 lower than lamotrigine-exposed children (CI 3.4-17.3; p = 0.004) and 13.4 lower than levetiracetam-exposed children (CI 5.2-21.6; p = 0.002). No significant dose-effect was found. Virtually no significant differences were found between lamotrigine and levetiracetam or lamotrigine and carbamazepine exposed children. Conclusions Consistent with previous research, valproate-exposed children experienced more problems compared to three other common antiepileptic drugs, while children exposed to lamotrigine, carbamazepine or levetiracetam revealed little to no problems. This illustrates the need for systematic follow-up of prenatally exposed children, to support pre-pregnancy counseling and treatment decisions in women of reproductive age.

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Section: Discussionmentioning

confidence: 99%

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure

et al. 2020

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“…As children of mothers with epilepsy bear multiple risks, 35 it is of importance to consider other possible contributing factors (eg, impact of maternal epilepsy on the child) to behavioral outcomes. Therefore, some of the associations found might be spurious.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings are of clinical importance and require replication. As children of mothers with epilepsy bear multiple risks, 35 it is of importance to consider other possible contributing factors (eg, impact of maternal epilepsy on the child) to behavioral outcomes. Further research into child development in the context of prenatal AED exposure is necessary to understand the (ir)reversibility of the exposure; to what extent is the behavioral teratogenic risk that occurred susceptible to adjustments?…”

Section: Discussionmentioning

confidence: 99%

Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy

et al. 2019

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ObjectiveTo examine the behavioral functioning of children prenatally exposed to carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproate (VPA) monotherapy.MethodsIn collaboration with the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), the Dutch EURAP & Development study was designed, a prospective observational study. Between January 2015 and March 2018, the Child Behavior Checklist and the Social Emotional Questionnaire were used to examine the nature and severity of behavioral problems. VPA‐exposed children were compared to children exposed to CBZ, LTG, or LEV, taking potential confounders into account. A direct comparison was also made between LTG and LEV, as these are first‐choice treatments for many women with epilepsy of childbearing potential.ResultsOf the 405 invited, 181 children were included; 26 were exposed to VPA, 37 to CBZ, 88 to LTG, and 30 to LEV. For most children, both parents completed the behavioral questionnaires. Across all four antiepileptic drug (AED) exposure groups, high percentages of children with clinically relevant behavior problems were found, with behavioral problems occurring in 32% of VPA‐exposed children, 14% of CBZ, 16% of LTG, and 14% of LEV. After controlling for potential confounders, VPA‐exposed children had significantly more social problems than those exposed to LTG (−2.8, 95% confidence interval [CI] = −5.2 to −0.4; P = 0.022) or LEV (−3.2, CI: −6.1 to −0.3; P = 0.028), and significantly more attention problems than LEV‐exposed children (−3.7, CI: −6.7 to −0.8; P = 0.013). LTG‐exposed children had significantly more attention deficit (−9.2, CI: −17.3 to 1.1; P = 0.026), but significantly less anxious behavior when compared to LEV‐exposed children (9.0, CI: 0.3‐17.6; P = 0.042).SignificanceCompared to population norms, a high proportion of children of mothers with epilepsy exposed prenatally to monotherapy with four common AEDs had clinical behavioral problems reported by parents. Different patterns were seen, with some but not all subscales raised for all AED exposure groups. It is important that prenatally AED‐exposed children are regularly screened for behavioral problems so that appropriate help can be provided.

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“…Children of mothers with epilepsy are at higher risk of behavioral problems [1,2]. Multiple risk factors may contribute to child behavioral problems, including possible teratogenic effects of prenatal exposure to antiepileptic drugs (AEDs) and family factors [3]. We previously showed that there were no significant differences on child internalizing and externalizing problems between different AED exposure types [2].…”

Section: Introductionmentioning

confidence: 99%

“…Having a mother with a chronic medical condition may also contribute to child development: epilepsy-related factors and possible psychiatric comorbidities or AED side effects may be involved [6][7][8][9]. Research into children of mothers with epilepsy has paid little attention to the influence of distinct family factors on child behavioral development [3]. The few studies that have been published show that mothers with epilepsy have problems with caring for themselves and for the child and experience more parenting stress [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Maternal epilepsy and behavioral development of the child: Family factors do matter

Huber‐Mollema

Oort

Lindhout

et al. 2019

Epilepsy & Behavior

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The purpose of the study was to examine whether mothers with epilepsy experience family problems and to investigate the possible mediating role of distinct family factors in the relationship between maternal epilepsy and child behavioral problems, in which it is also investigated whether more proximal family factors mediate the more distal family factors. Methods: In an observational study, with children identified from the European Registry of Antiepileptic Drugs and Pregnancy database in the Netherlands (EURAP-NL), parents completed questionnaires on maternal epilepsy, family factors (proximal, distal, contextual, global), and child behavior. Hierarchical multilevel regression analyses were performed to examine the relative contribution of epilepsy-related and family factors on child internalizing and externalizing problems. Results: Between January 2015 and March 2018, the questionnaires were completed for 175 children. Mothers with epilepsy showed significantly more parenting stress and problems with parenting than mothers from the general population. Family factors were significantly associated with child behavioral problems. For internalizing problems, maternal epilepsy, global, contextual, and distal family factors were each found to have significant added value. Distal family factors contributed most to internalizing problems and showed a mediating role for epilepsy-related factors and previous added family factors in the model. Global, contextual, distal, and proximal factors were all found to be significant contributors to externalizing problems, with the factor most proximal to the child (quality of parent-child interaction) showing the largest effect. Discussion: Including family factors in research regarding children of mothers with epilepsy is important as they can have a contribution additional to the teratogenic risks of prenatal exposure to antiepileptic drugs (AEDs). Family factors, in particular distal and proximal family factors, can weaken or strengthen child development and may provide starting points for interventions.

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Exposure to antiepileptic drugs in pregnancy: The need for a family factor framework

Cited by 3 publications

References 33 publications

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure

Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy

Maternal epilepsy and behavioral development of the child: Family factors do matter

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