Kelsey K Wiggs1, Martin E Rickert2, Ayesha C Sujan2, Patrick D Quinn2, Henrik Larsson2, Paul Lichtenstein2, A Sara Oberg2, Brian M D'Onofrio2. 1. From the Department of Psychological & Brain Sciences (K.K.W., M.E.R., A.C.S., B.M.D.) and Department of Applied Health Science (P.D.Q.), School of Public Health, Indiana University-Bloomington; Department of Medical Epidemiology and Biostatistics (H.L., P.L., A.S.O., B.M.D.), Karolinska Institutet, Stockholm; School of Medical Sciences (H.L.), Örebro University, Sweden; and Department of Epidemiology (A.S.O.), T.H. Chan School of Public Health, Harvard, Boston, MA. kkwiggs@indiana.edu. 2. From the Department of Psychological & Brain Sciences (K.K.W., M.E.R., A.C.S., B.M.D.) and Department of Applied Health Science (P.D.Q.), School of Public Health, Indiana University-Bloomington; Department of Medical Epidemiology and Biostatistics (H.L., P.L., A.S.O., B.M.D.), Karolinska Institutet, Stockholm; School of Medical Sciences (H.L.), Örebro University, Sweden; and Department of Epidemiology (A.S.O.), T.H. Chan School of Public Health, Harvard, Boston, MA.
Abstract
OBJECTIVE: To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors. METHODS: We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication. RESULTS: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53). CONCLUSIONS: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.
OBJECTIVE: To determine whether children born to women who use antiseizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors. METHODS: We used Swedish register data (n = 14,614 children born 1996-2011 and followed up through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%) and the 3 most commonly reported individual drugs (valproic acid 4.8%, lamotrigine 6.8%, and carbamazepine 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication. RESULTS: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.53-3.47) and ADHD (HR 1.74, 95% CI 1.28-2.38). Whereas a small, nonstatistically significant association with ASD (HR 1.25, 95% CI = 0.88-1.79) and ADHD (HR 1.18, 95% CI 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53). CONCLUSIONS: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of ASD and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggests that certain ASMs may be safer than others in pregnancy.
Authors: Amir Sariaslan; Niklas Långström; Brian D'Onofrio; Johan Hallqvist; Johan Franck; Paul Lichtenstein Journal: Int J Epidemiol Date: 2013-08 Impact factor: 7.196
Authors: Morris J Cohen; Kimford J Meador; Nancy Browning; Ryan May; Gus A Baker; Jill Clayton-Smith; Laura A Kalayjian; Andres Kanner; Joyce D Liporace; Page B Pennell; Michael Privitera; David W Loring Journal: Epilepsy Behav Date: 2013-09-05 Impact factor: 2.937