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Behavioral Outcomes and Neurodevelopmental Disorders Among Children of Women With Epilepsy
Morris J Cohen1, Kimford J Meador2, David W Loring3
1Pediatric Neuropsychology International LLC, Augusta, Georgia.
Insights
Fetal exposure to antiseizure medications (ASMs) did not impact overall childhood adaptive functioning. However, higher ASM blood concentrations in the third trimester were linked to decreased adaptive functioning in children. Psychiatric screening for mothers with epilepsy and their offspring is recommended.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- The developmental effects of fetal exposure to antiseizure medications (ASMs) are not fully understood.
- Understanding these associations is crucial for managing epilepsy during pregnancy and ensuring optimal child development.
Purpose of the Study:
- To investigate the association between fetal ASM exposure and adaptive, behavioral, emotional, and neurodevelopmental outcomes in children at ages 2, 3, and 4.5 years.
- To compare outcomes between children of mothers with and without epilepsy.
Main Methods:
- Prospective observational cohort study (MONEAD) involving 456 pregnant women (with and without epilepsy) across 20 US epilepsy centers.
- Children were assessed at multiple time points, with primary outcome being adaptive functioning (ABAS-3 GAC score) at 4.5 years.
- Statistical analyses compared outcomes between groups and assessed the association of ASM blood concentrations and dosage with outcomes.
Main Results:
- Overall adaptive functioning at 4.5 years did not significantly differ between children of mothers with and without epilepsy.
- However, adjusted analyses revealed a significant decrease in adaptive functioning with increasing third-trimester ASM blood concentrations.
- This decrease was particularly evident for levetiracetam and lamotrigine exposure.
Conclusions:
- While overall adaptive functioning may not differ, there is an exposure-dependent association between ASMs and child functioning.
- The findings suggest a need for careful consideration of ASM exposure during pregnancy.
- Psychiatric or psychological screening and referral for women with epilepsy and their children are recommended.
Importance:
The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated.
Objective:
To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age.
Design, Setting, And Participants:
The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023.
Exposures:
Exposures included mother's epilepsy status as well as mother's ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen.
Main Outcomes And Measures:
The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures.
Results:
Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, -2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, -7.8 [95% CI, -12.6 to -3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, -18.9 [95% CI, -26.8 to -10.9]; P < .001) and lamotrigine (PE, -12.0 [95% CI, -23.7 to -0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose.
Conclusions And Relevance:
This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.
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