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

NaME Study Group; Rebecca L Bromley; Philip Bullen; Ellen Campbell; John Craig; Amy Ingham; Beth Irwin; Cerain Jackson; Teresa Kelly; James Morrow; Sarah Rushton; Marta García-Fiñana; David M Hughes; Janine Winterbottom; Amanda Wood; Laura M Yates; Jill Clayton-Smith

doi:10.1111/epi.17709

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

NaME Study Group, Rebecca L Bromley, Philip Bullen, Ellen Campbell, John Craig, Amy Ingham, Beth Irwin, Cerain Jackson, Teresa Kelly, James Morrow, Sarah Rushton, Marta García-Fiñana, David M Hughes, Janine Winterbottom, Amanda Wood, Laura M Yates, Jill Clayton-Smith

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded, child development data are still limited. The Neurodevelopment of babies born to mothers with epilepsy (NaME) 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 (3 rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2 nd 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 with lamotrigine (-0.74, SE 2.9, 95% 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 non-exposed 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. Neither was there evidence that higher dose folic acid supplementation (=/> 5mg/d) or convulsive seizure exposure were associated with child development scores. Continued infant exposure to antiseizure medications through breastmilk 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.

Original language	English
Pages (from-to)	2454-2471
Number of pages	18
Journal	Epilepsia
Volume	64
Issue number	9
Early online date	5 Jul 2023
DOIs	https://doi.org/10.1111/epi.17709
Publication status	Published - 19 Sept 2023

Keywords

antiseizure medication
development
epilepsy
pharmacovigilance
pregnancy

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NaME Study Group, Bromley, R. L., Bullen, P., Campbell, E., Craig, J., Ingham, A., Irwin, B., Jackson, C., Kelly, T., Morrow, J., Rushton, S., García-Fiñana, M., Hughes, D. M., Winterbottom, J., Wood, A., Yates, L. M., & Clayton-Smith, J. (2023). Neurodevelopment of babies born to mothers with epilepsy: a prospective observational cohort study. Epilepsia, 64(9), 2454-2471. https://doi.org/10.1111/epi.17709

@article{d7ab5bb1488b42199509c04b58513b7d,

title = "Neurodevelopment of babies born to mothers with epilepsy: a prospective observational cohort study",

abstract = "OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded, child development data are still limited. The Neurodevelopment of babies born to mothers with epilepsy (NaME) 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 (3 rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2 nd 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 with lamotrigine (-0.74, SE 2.9, 95% 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 non-exposed 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. Neither was there evidence that higher dose folic acid supplementation (=/> 5mg/d) or convulsive seizure exposure were associated with child development scores. Continued infant exposure to antiseizure medications through breastmilk 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.",

keywords = "antiseizure medication, development, epilepsy, pharmacovigilance, pregnancy",

author = "{NaME Study Group} and Bromley, {Rebecca L} and Philip Bullen and Ellen Campbell and John Craig and Amy Ingham and Beth Irwin and Cerain Jackson and Teresa Kelly and James Morrow and Sarah Rushton and Marta Garc{\'i}a-Fi{\~n}ana and Hughes, {David M} and Janine Winterbottom and Amanda Wood and Yates, {Laura M} and Jill Clayton-Smith",

note = "{\textcopyright} 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.",

year = "2023",

month = sep,

day = "19",

doi = "10.1111/epi.17709",

language = "English",

volume = "64",

pages = "2454--2471",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "John Wiley & Sons Ltd",

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}

NaME Study Group, Bromley, RL, Bullen, P, Campbell, E, Craig, J, Ingham, A, Irwin, B, Jackson, C, Kelly, T, Morrow, J, Rushton, S, García-Fiñana, M, Hughes, DM, Winterbottom, J, Wood, A, Yates, LM & Clayton-Smith, J 2023, 'Neurodevelopment of babies born to mothers with epilepsy: a prospective observational cohort study', Epilepsia, vol. 64, no. 9, pp. 2454-2471. https://doi.org/10.1111/epi.17709

TY - JOUR

T1 - Neurodevelopment of babies born to mothers with epilepsy

T2 - a prospective observational cohort study

AU - NaME Study Group

AU - Bromley, Rebecca L

AU - Bullen, Philip

AU - Campbell, Ellen

AU - Craig, John

AU - Ingham, Amy

AU - Irwin, Beth

AU - Jackson, Cerain

AU - Kelly, Teresa

AU - Morrow, James

AU - Rushton, Sarah

AU - García-Fiñana, Marta

AU - Hughes, David M

AU - Winterbottom, Janine

AU - Wood, Amanda

AU - Yates, Laura M

AU - Clayton-Smith, Jill

PY - 2023/9/19

Y1 - 2023/9/19

N2 - OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded, child development data are still limited. The Neurodevelopment of babies born to mothers with epilepsy (NaME) 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 (3 rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2 nd 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 with lamotrigine (-0.74, SE 2.9, 95% 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 non-exposed 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. Neither was there evidence that higher dose folic acid supplementation (=/> 5mg/d) or convulsive seizure exposure were associated with child development scores. Continued infant exposure to antiseizure medications through breastmilk 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.

AB - OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded, child development data are still limited. The Neurodevelopment of babies born to mothers with epilepsy (NaME) 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 (3 rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2 nd 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 with lamotrigine (-0.74, SE 2.9, 95% 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 non-exposed 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. Neither was there evidence that higher dose folic acid supplementation (=/> 5mg/d) or convulsive seizure exposure were associated with child development scores. Continued infant exposure to antiseizure medications through breastmilk 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.

KW - antiseizure medication

KW - development

KW - epilepsy

KW - pharmacovigilance

KW - pregnancy

U2 - 10.1111/epi.17709

DO - 10.1111/epi.17709

M3 - Article

C2 - 37403560

SN - 0013-9580

VL - 64

SP - 2454

EP - 2471

JO - Epilepsia

JF - Epilepsia

IS - 9

ER -

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

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