Breastfeeding in children of women taking antiepileptic drugs: Cognitive outcomes at age 6 years

Kimford J. Meador, Gus A. Baker, Nancy Browning, Morris J. Cohen, Rebecca L. Bromley, Jill Clayton-Smith, Laura A. Kalayjian, Andres M Kanner, Joyce D. Liporace, Page B. Pennell, Michael Privitera, David W. Loring

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapymay be harmful.We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES Differential Ability Scales IQwas the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS In total, 42.9%of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95%CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95%CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95%CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95%CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95%CI, 0-7] points higher for breastfed children, P = .03). CONCLUSIONS AND RELEVANCE No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00021866.

Original languageEnglish (US)
Pages (from-to)729-736
Number of pages8
JournalJAMA Pediatrics
Volume168
Issue number8
DOIs
StatePublished - 2014

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Breast Feeding
Anticonvulsants
Aptitude
Mothers
Pharmaceutical Preparations
Valproic Acid
Folic Acid
Linear Models
Executive Function
Carbamazepine
Phenytoin
Human Milk
Cognition
Multicenter Studies
Observational Studies
Pregnant Women
Epilepsy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Meador, K. J., Baker, G. A., Browning, N., Cohen, M. J., Bromley, R. L., Clayton-Smith, J., ... Loring, D. W. (2014). Breastfeeding in children of women taking antiepileptic drugs: Cognitive outcomes at age 6 years. JAMA Pediatrics, 168(8), 729-736. https://doi.org/10.1001/jamapediatrics.2014.118

Breastfeeding in children of women taking antiepileptic drugs : Cognitive outcomes at age 6 years. / Meador, Kimford J.; Baker, Gus A.; Browning, Nancy; Cohen, Morris J.; Bromley, Rebecca L.; Clayton-Smith, Jill; Kalayjian, Laura A.; Kanner, Andres M; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

In: JAMA Pediatrics, Vol. 168, No. 8, 2014, p. 729-736.

Research output: Contribution to journalArticle

Meador, KJ, Baker, GA, Browning, N, Cohen, MJ, Bromley, RL, Clayton-Smith, J, Kalayjian, LA, Kanner, AM, Liporace, JD, Pennell, PB, Privitera, M & Loring, DW 2014, 'Breastfeeding in children of women taking antiepileptic drugs: Cognitive outcomes at age 6 years', JAMA Pediatrics, vol. 168, no. 8, pp. 729-736. https://doi.org/10.1001/jamapediatrics.2014.118
Meador, Kimford J. ; Baker, Gus A. ; Browning, Nancy ; Cohen, Morris J. ; Bromley, Rebecca L. ; Clayton-Smith, Jill ; Kalayjian, Laura A. ; Kanner, Andres M ; Liporace, Joyce D. ; Pennell, Page B. ; Privitera, Michael ; Loring, David W. / Breastfeeding in children of women taking antiepileptic drugs : Cognitive outcomes at age 6 years. In: JAMA Pediatrics. 2014 ; Vol. 168, No. 8. pp. 729-736.
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abstract = "IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapymay be harmful.We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES Differential Ability Scales IQwas the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS In total, 42.9{\%}of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95{\%}CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95{\%}CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95{\%}CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95{\%}CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95{\%}CI, 0-7] points higher for breastfed children, P = .03). CONCLUSIONS AND RELEVANCE No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00021866.",
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T2 - Cognitive outcomes at age 6 years

AU - Meador, Kimford J.

AU - Baker, Gus A.

AU - Browning, Nancy

AU - Cohen, Morris J.

AU - Bromley, Rebecca L.

AU - Clayton-Smith, Jill

AU - Kalayjian, Laura A.

AU - Kanner, Andres M

AU - Liporace, Joyce D.

AU - Pennell, Page B.

AU - Privitera, Michael

AU - Loring, David W.

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N2 - IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapymay be harmful.We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES Differential Ability Scales IQwas the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS In total, 42.9%of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95%CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95%CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95%CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95%CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95%CI, 0-7] points higher for breastfed children, P = .03). CONCLUSIONS AND RELEVANCE No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00021866.

AB - IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapymay be harmful.We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES Differential Ability Scales IQwas the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS In total, 42.9%of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95%CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95%CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95%CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95%CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95%CI, 0-7] points higher for breastfed children, P = .03). CONCLUSIONS AND RELEVANCE No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00021866.

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