Antiseizure medication use during pregnancy and risk of ASD and ADHD in children.
Antiseizure medication use during pregnancy and risk of ASD and ADHD in children.
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DOI：
10.1212/wnl.0000000000010993
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发表时间：
2020-12-15
期刊：
影响因子：
9.9
通讯作者：
D'Onofrio BM
中科院分区：
文献类型：
--
作者：
Wiggs KK;Rickert ME;Sujan AC;Quinn PD;Larsson H;Lichtenstein P;Oberg AS;D'Onofrio BM
确定怀孕期间使用抗癫痫药物（asm）的妇女所生的孩子是否具有独立于混杂因素的自闭症谱系障碍（ASD）和注意力缺陷/多动障碍（ADHD）的更高风险。我们使用瑞典的登记数据（n = 14,614名1996-2011年出生的儿童，随访至2013年），使用迄今为止最大的样本，并对一系列测量的混杂因素进行了调整，以检查癫痫女性儿童的关联。我们检查了母亲报告的妊娠早期使用任何ASM（22.7%）和3种最常见的单独药物（丙戊酸4.8%，拉莫三嗪6.8%和卡马西平9.7%）。我们用ICD-10诊断确定ASD，用ICD-10诊断确定ADHD，或者用ADHD药物处方确定ADHD。对单个药物的检查显示，在调整混杂因素后，丙戊酸的使用与ASD（风险比[HR] 2.30, 95%可信区间[CI] 1.53-3.47）和ADHD（风险比[HR] 1.74, 95%可信区间[CI] 1.28-2.38）相关。尽管卡马西平与ASD （HR 1.25, 95% CI = 0.88-1.79）和ADHD （HR 1.18, 95% CI 0.91-1.52）的关联较小，但混杂解释了与拉莫三嗪的所有关联（HRASD 0.86, 95% CI 0.67-1.53; HRADHD 1.01, 95% CI 0.67-1.53）。我们没有发现与拉莫三嗪暴露相关的风险证据，然而我们观察到与母亲使用丙戊酸相关的ASD和ADHD风险升高。与卡马西平的相关性较弱，无统计学意义。我们的发现增加了越来越多的证据，表明某些asm在怀孕期间可能比其他asm更安全。
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. 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. 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). 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.