Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Nordsjaellands Hospital, Hillerød, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Acta Psychiatr Scand. 2022 Jun;145(6):557-567. doi: 10.1111/acps.13431. Epub 2022 Apr 1.
To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes.
A register-based nationwide cohort study was conducted including all registered pregnancies in Denmark from 1997 to 2016. Mirtazapine-exposed pregnancies were compared with mirtazapine unexposed pregnancies in a 1:4 ratio matched according to propensity scores. Outcomes were major congenital malformations analyzed using log binomial models, and spontaneous abortion, stillbirth and neonatal death analyzed using Cox proportional hazard regression.
From a source population of 1,650,649 pregnancies, the propensity score-matched cohort included 4475 pregnancies (895 mirtazapine exposed) in the analysis of major congenital malformations. The analyses of spontaneous abortion included 9 500 pregnancies (1900 mirtazapine exposed), and for the analyses of stillbirths and neonatal deaths 9725 (1 945 mirtazapine-exposed) and 4485 pregnancies (897 mirtazapine-exposed) were included, respectively. Thirty-one (3.5%) children were diagnosed with major congenital malformation among the mirtazapine exposed compared with 152 (4.3%) among the unexposed pregnancies (OR=0.81, 95% CI 0.55-1.20). Spontaneous abortion occurred in 237 (12.5%) of the mirtazapine exposed compared with 931 (12.3%) of the unexposed pregnancies (HR = 1.04%, 95% CI 0.91-1.20). The analyses revealed no increased risk of stillbirth (HR = 0.88%, 95% CI 0.34-2.29) or neonatal death (HR = 0.60%, 95% CI 0.18-2.02).
In this nationwide Danish register study, mirtazapine exposure in pregnancy was not associated with major congenital malformations, spontaneous abortion, stillbirth, or neonatal death. Clinicians and patients can be reassured that mirtazapine is safe in pregnancy.
研究妊娠期间米氮平暴露与特定不良妊娠结局风险之间的关系。
本研究采用基于登记的全国性队列研究，纳入了 1997 年至 2016 年期间丹麦所有的注册妊娠。将米氮平暴露妊娠与米氮平未暴露妊娠按照倾向评分进行 1:4 匹配对照。采用对数二项式模型分析主要先天性畸形结局，采用 Cox 比例风险回归分析自然流产、死胎和新生儿死亡结局。
在一个由 1650649 例妊娠组成的源人群中，倾向评分匹配队列分析中纳入了 4475 例（895 例米氮平暴露）主要先天性畸形。自然流产分析纳入了 9500 例妊娠（1900 例米氮平暴露），死胎和新生儿死亡分析分别纳入了 9725 例（1945 例米氮平暴露）和 4485 例（897 例米氮平暴露）妊娠。在米氮平暴露组中，有 31 例（3.5%）儿童被诊断为先天性畸形，而在未暴露组中，有 152 例（4.3%）（OR=0.81，95% CI 0.55-1.20）。在米氮平暴露组中，有 237 例（12.5%）发生自然流产，而在未暴露组中，有 931 例（12.3%）（HR=1.04%，95% CI 0.91-1.20）。分析结果未显示死胎（HR=0.88%，95% CI 0.34-2.29）或新生儿死亡（HR=0.60%，95% CI 0.18-2.02）风险增加。
在这项丹麦全国性登记研究中，妊娠期间米氮平暴露与主要先天性畸形、自然流产、死胎或新生儿死亡无关。临床医生和患者可以放心，米氮平在妊娠期间是安全的。
