Wiggs Kelsey Kathleen, Sujan Ayehsa C, Rickert Martin E, Quinn Patrick D, Larsson Henrik, Lichtenstein Paul, D'Onofrio Brian M, Oberg A Sara
From the Department of Psychological & Brain Sciences (K.K.W., M.E.R., B.M.D.) and Department of Applied Health Science, School of Public Health (P.D.Q.), Indiana University, Bloomington; Kaiser Permanente Northern California Division of Research (A.C.S.), Oakland; Department of Medical Epidemiology and Biostatistics (H.L., P.L., B.M.D., A.S.O.), 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.
Neurology. 2022 Jun 6;98(23):e2329-e2336. doi: 10.1212/WNL.0000000000200516.
To evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy.
We used Swedish register-based data to examine associations between maternal reported use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in pregnancy and diagnosis of neonatal seizures or epilepsy in >1.2 million children. To account for systematic differences between exposed and unexposed children, we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression or anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, comorbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy).
Compared with all other children, children of women who reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR] 1.41, 95% CI 1.03-1.94; hazard ratio [HR] 1.21, 95% CI 1.03-1.43, respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR 1.30, 95% CI 0.94-1.80; HR 1.13, 95% CI 0.95-1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR 1.10, 95% CI 0.79-1.53; HR 0.96, 95% CI 0.81-1.14).
We found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children's risk for neonatal seizures or epilepsy.
This study provides Class II evidence that exposure to SSRIs/SNRIs in the first trimester of pregnancy is not associated with an increased incidence of neonatal seizures/epilepsy.
评估孕期使用血清素能抗抑郁药的女性所生子女发生新生儿惊厥和癫痫的风险是否更高。
我们利用瑞典基于登记的数据,研究了120多万名儿童的母亲报告的孕期使用选择性5-羟色胺再摄取抑制剂(SSRI)或5-羟色胺去甲肾上腺素再摄取抑制剂(SNRI)与新生儿惊厥或癫痫诊断之间的关联。为了考虑暴露组和未暴露组儿童之间的系统差异,我们对一系列测量的混杂因素进行了调整。在首先评估母亲使用SSRI/SNRI的指征(即抑郁或焦虑)和父母癫痫的作用后,我们对其余的父母背景因素(如年龄、合并症、教育程度和家庭社会经济指数)以及特定于妊娠的特征(如母亲在妊娠早期使用其他精神药物和吸烟)进行了调整。
与所有其他儿童相比,报告孕期使用SSRI/SNRI的女性所生子女发生新生儿惊厥和癫痫的风险升高(风险比[RR]为1.41,95%可信区间为1.03 - 1.94;风险率[HR]为1.21,95%可信区间为1.03 - 1.43)。通过对母亲使用SSRI/SNRI的指征进行调整,关联估计值有所减弱(RR为1.30,95%可信区间为0.94 - 1.80;HR为1.13,95%可信区间为0.95 - 1.33),但对父母癫痫病史进行额外调整后并未减弱。对所有测量的父母和特定于妊娠的因素进行全面调整后,剩余关联大幅减弱(RR为1.10,95%可信区间为0.79 - 1.53;HR为0.96,95%可信区间为0.81 - 1.14)。
我们没有找到证据支持孕期母亲使用SSRI/SNRI会增加儿童发生新生儿惊厥或癫痫风险的担忧。
本研究提供了二级证据,即妊娠早期暴露于SSRI/SNRI与新生儿惊厥/癫痫发病率增加无关。