Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Medicine, Volda Hospital, Volda, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Am J Clin Nutr. 2023 Jul;118(1):303-313. doi: 10.1016/j.ajcnut.2023.05.023. Epub 2023 May 20.
Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment.
To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy.
We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits.
We included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5-8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34).
In this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.
产前接触抗癫痫药物（ASM）可能导致血浆叶酸浓度降低，并与儿童神经发育受损有关。
研究母体叶酸缺乏的遗传易感性是否与癫痫女性所生孩子的语言障碍和自闭症特征风险相关。
我们纳入了挪威母婴队列研究中患有和不患有癫痫且有可用遗传数据的妇女的孩子。ASM 使用、叶酸补充剂使用和剂量、饮食叶酸摄入量、儿童自闭症特征和儿童语言障碍信息来自家长报告的调查问卷。我们使用逻辑回归，检验了产前 ASM 暴露与母体叶酸缺乏遗传易感性（表示为低叶酸浓度的多基因风险评分或母体 rs1801133 基因型（CC 或 CT/TT））之间的相互作用，以评估其对语言障碍或自闭症特征的风险。
我们纳入了 96 名患有 ASM 治疗性癫痫的妇女的孩子、131 名患有 ASM 未治疗性癫痫的妇女的孩子和 37249 名未患有癫痫的妇女的孩子。与 ASM 未暴露的儿童相比，低叶酸浓度的多基因风险评分与 ASM 暴露的癫痫妇女的孩子的语言障碍或自闭症特征的 ASM 相关风险之间没有相互作用，年龄为 1.5-8 岁。无论母体 rs1801133 基因型如何，ASM 暴露的儿童都有神经发育不良的风险增加（8 岁时语言障碍的调整后比值比[aOR]为 2.88[95%置信区间（CI）：1.00，8.26]，如果 CC 基因型，则 aOR 为 2.88[95% CI：1.10，7.53]）。在 3 岁的未患有癫痫的妇女的孩子中，与 CC 基因型相比，具有母体 rs1801133 CT/TT 基因型的儿童有语言障碍的风险增加（aOR：1.18；95% CI：1.05，1.34）。
在本项孕妇队列研究中，叶酸补充剂的广泛使用，母体叶酸缺乏的遗传易感性并没有显著影响 ASM 相关的神经发育受损风险。
