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孕期单独或联合使用曲坦类药物与其他偏头痛药物及其后代神经发育结局的关联。

Association of Prenatal Exposure to Triptans, Alone or Combined With Other Migraine Medications, and Neurodevelopmental Outcomes in Offspring.

作者信息

Camanni Margherita, van Gelder Marleen M H J, Cantarutti Anna, Nordeng Hedvig, Lupattelli Angela

机构信息

Unit of Biostatistics, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Italy.

Department of Pharmacy, Faculty of Mathematics and Natural Sciences, PharmacoEpidemiology and Drug Safety Research Group, University of Oslo, Norway.

出版信息

Neurology. 2025 Jun 24;104(12):e213678. doi: 10.1212/WNL.0000000000213678. Epub 2025 May 21.

Abstract

BACKGROUND AND OBJECTIVES

The long-term reproductive safety of migraine medications remains uncertain. This study sought to examine the effect of different intensities and durations of prenatal exposure to triptans, alone and combined with other preventive migraine medications, on neurodevelopmental disorders (NDDs) in children.

METHODS

This nationwide health registry study in Norway included pregnancies of women with migraine before pregnancy and followed up their children up to 14 years of age. Single and multiple group-based trajectory models and group-based multitrajectory models were applied to cluster triptan exposure alone and combined with preventive antimigraine medications. Child outcomes, based on specialist outpatient and inpatient diagnoses, included autism spectrum and behavioral disorders, learning and intellectual disabilities, speech/language and developmental coordination disorders, and attention-deficit hyperactivity disorders (ADHDs). We fit adjusted and weighted pooled logistic regression models and standardized risk curves using propensity score-based overlap weighting.

RESULTS

We included 26,210 pregnancies of women with migraine; 4,929 and 21,281 were, respectively, nonmedicated and medicated with triptans in the year of prepregnancy. In the latter group, we identified 4 group-based trajectories of triptans alone and combined with preventive medications: () (41.5%, 47.0%), () (31.3%, 28.8%), () (21.3%, 9.1%), and () (5.9%, 15.2%). Overall, 1,140 children (4.3%) had a NDD (mean follow-up time: 8 years). Children born to women with any triptan trajectory had a slightly higher risk of NDD compared with children of nonmedicated women (magnitude range of the weighted hazard ratio [wHR]: 1.05-1.16). These risks decreased to the null when () acted as a comparator (magnitude of wHR: 0.94-1.01) or when analyzing speech/language disorders or ADHD (magnitude of wHR: 0.82-1.14). There was a slightly elevated risk of autism disorders with both triptan late discontinuation trajectories (wHR 1.24, 95% CI [0.78-1.97]; wHR 1.30, 95% CI [0.66-2.56]), but the 95% CI crossed the null and the weighted risk difference remained low.

DISCUSSION

Our findings indicate that prenatal exposure to triptans, alone or combined with other migraine medications, does not substantially increase the risk of a broad range of neurodevelopmental outcomes in children up to adolescence.

摘要

背景与目的

偏头痛药物的长期生殖安全性仍不确定。本研究旨在探讨孕期单独使用曲坦类药物以及与其他预防性偏头痛药物联合使用时,不同强度和持续时间的暴露对儿童神经发育障碍(NDDs)的影响。

方法

这项在挪威进行的全国性健康登记研究纳入了孕前患有偏头痛的女性的妊娠情况,并对其子女进行了长达14年的随访。基于单组和多组的轨迹模型以及基于组的多轨迹模型被用于对单独使用曲坦类药物以及与预防性抗偏头痛药物联合使用的情况进行聚类分析。基于专科门诊和住院诊断的儿童结局包括自闭症谱系和行为障碍、学习和智力残疾、言语/语言和发育协调障碍以及注意力缺陷多动障碍(ADHDs)。我们使用基于倾向评分的重叠加权法拟合了调整后的加权合并逻辑回归模型和标准化风险曲线。

结果

我们纳入了26210例患有偏头痛的女性的妊娠情况;在孕前一年,分别有4929例和21281例未使用药物和使用了曲坦类药物。在后者组中,我们确定了单独使用曲坦类药物以及与预防性药物联合使用的4种基于组的轨迹:()(41.5%,47.0%),()(31.3%,28.8%),()(21.3%,9.1%),以及()(5.9%,15.2%)。总体而言,1140名儿童(4.3%)患有神经发育障碍(平均随访时间:8年)。与未使用药物女性的子女相比,任何曲坦类药物轨迹的女性所生子女患神经发育障碍的风险略高(加权风险比[wHR]的幅度范围:1.05 - 1.16)。当以()作为对照时(wHR幅度:0.94 - 1.01),或者在分析言语/语言障碍或ADHD时(wHR幅度:0.82 - 1.14),这些风险降至零。两种曲坦类药物延迟停药轨迹的自闭症谱系障碍风险略有升高(wHR 1.24,95% CI [0.78 - 1.97];wHR 1.30,95% CI [0.66 - 2.56]),但95% CI包含零值,且加权风险差异仍然较低。

讨论

我们的研究结果表明,孕期单独或与其他偏头痛药物联合使用曲坦类药物,在青春期前儿童中不会显著增加广泛的神经发育结局的风险。

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