Kimford J Meador1, Gus A Baker2, Nancy Browning3, Morris J Cohen4, Rebecca L Bromley5, Jill Clayton-Smith5, Laura A Kalayjian6, Andres Kanner7, Joyce D Liporace8, Page B Pennell9, Michael Privitera10, David W Loring11. 1. Department of Neurology and Neurological Sciences, Stanford University, Stanford, California. 2. Walton Centre for Neurology and Neurosurgery, University of Liverpool, Merseyside, England. 3. The EMMES Corporation, Rockville, Maryland. 4. Departments of Neurology, Pediatrics, and Psychiatry, Georgia Regents University, Augusta. 5. Institute of Human Development, University of Manchester, and Central Manchester University Hospitals National Health Service Foundation Trust, Manchester, England. 6. Department of Neurology, University of Southern California, Los Angeles. 7. Department of Neurology, University of Miami, Miami, Florida. 8. Department of Neurology, Riddle Health Care, Media, Pennsylvania. 9. Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts. 10. Department of Neurology, University of Cincinnati, Cincinnati, Ohio. 11. Departments of Neurology and Pediatrics, Emory University, Atlanta, Georgia.
Abstract
IMPORTANCE: Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may 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 IQ was 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.
IMPORTANCE: Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may 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 IQ was 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]), periconceptionfolate 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.
Authors: K J Meador; G A Baker; N Browning; J Clayton-Smith; D T Combs-Cantrell; M Cohen; L A Kalayjian; A Kanner; J D Liporace; P B Pennell; M Privitera; D W Loring Journal: Neurology Date: 2010-11-24 Impact factor: 9.910
Authors: Jonathan Y Bernard; Maria De Agostini; Anne Forhan; Toni Alfaiate; Mercedes Bonet; Valérie Champion; Monique Kaminski; Blandine de Lauzon-Guillain; Marie-Aline Charles; Barbara Heude Journal: J Pediatr Date: 2013-01-11 Impact factor: 4.406
Authors: Kimford J Meador; Gus A Baker; Nancy Browning; Morris J Cohen; Rebecca L Bromley; Jill Clayton-Smith; Laura A Kalayjian; Andres Kanner; Joyce D Liporace; Page B Pennell; Michael Privitera; David W Loring Journal: Lancet Neurol Date: 2013-01-23 Impact factor: 44.182
Authors: D Jeffrey Newport; Page B Pennell; Martha R Calamaras; James C Ritchie; Melanee Newman; Bettina Knight; Adele C Viguera; Joyce Liporace; Zachary N Stowe Journal: Pediatrics Date: 2008-06-30 Impact factor: 7.124
Authors: Mandy B Belfort; Sheryl L Rifas-Shiman; Ken P Kleinman; Lauren B Guthrie; David C Bellinger; Elsie M Taveras; Matthew W Gillman; Emily Oken Journal: JAMA Pediatr Date: 2013-09 Impact factor: 16.193