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Antiseizure medication use during pregnancy and risk of ASD and ADHD in children
Kelsey K Wiggs1, Martin E Rickert2, Ayesha C Sujan2
1From 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.
Insights
Maternal use of valproic acid during pregnancy is linked to increased risks of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children. Other antiseizure medications (ASMs) like lamotrigine showed no such risks.
Area of Science:
- Neurodevelopmental disorders
- Pharmacology
- Pregnancy safety
Background:
- Antiseizure medications (ASMs) are crucial for managing epilepsy in pregnant women.
- The potential neurodevelopmental effects of prenatal ASM exposure, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), require thorough investigation.
- Understanding these risks is vital for informed clinical decision-making during pregnancy.
Purpose of the Study:
- To investigate the association between prenatal exposure to antiseizure medications (ASMs) and the risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring.
- To determine if these associations persist after accounting for potential confounding factors.
- To compare the risks associated with specific ASMs used during pregnancy.
Main Methods:
- Utilized Swedish register data from 14,614 children born between 1996 and 2011, with follow-up through 2013.
- Examined maternal first-trimester use of any ASM, valproic acid, lamotrigine, and carbamazepine.
- Diagnosed ASD and ADHD using ICD-10 codes and ADHD medication prescriptions, adjusting for confounders.
Main Results:
- Maternal valproic acid use was significantly associated with an increased risk of ASD (HR 2.30) and ADHD (HR 1.74) in children.
- Carbamazepine use showed weak, non-significant associations with ASD and ADHD.
- Lamotrigine exposure did not show any statistically significant association with ASD or ADHD after adjusting for confounders.
Conclusions:
- Maternal valproic acid use during pregnancy is linked to elevated risks of ASD and ADHD in offspring.
- Lamotrigine and carbamazepine appear to have a lower risk profile compared to valproic acid for these neurodevelopmental outcomes.
- Findings suggest differential safety profiles among ASMs, emphasizing the need for careful selection during 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.
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