Department of Obstetrics and Gynecology, Aarhus University Hospital, Palle Juul-Jensens Blvd 99, 8200 Aarhus N, Denmark. e-mail:
Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.
J Clin Psychiatry. 2021 Jan 5;82(1):20m13458. doi: 10.4088/JCP.20m13458.
Attention-deficit/hyperactivity disorder (ADHD) medications are increasingly used in pregnancy. Studies on the pregnancy safety of these medications that are restricted to live births may underestimate severe teratogenic effects that cause fetal demise or termination of pregnancy. The present study addresses this limitation by including data from both prenatal and postnatal diagnoses of major malformations.
A nationwide registry-based study was conducted of 364,012 singleton pregnancies in Denmark from November 1, 2007, to February 1, 2014. Exposures to ADHD medication were obtained from redeemed prescriptions from the Danish Health Services Prescription Database. Outcome data included prenatally diagnosed malformations from the Danish Fetal Medicine Database and postnatally diagnosed malformations from the Danish National Patient Registry. The primary outcome was major malformations overall, and secondary outcomes were malformations of the central nervous system and cardiac malformations. The comparison group was pregnancies with no redeemed prescriptions for ADHD medication. We defined severe cardiac malformations (SCM) as concurrent diagnoses of a cardiac malformation with miscarriage, termination, stillbirth, postnatal death, or cardiac surgery within 1 year of birth.
The prevalence of first-trimester exposure to ADHD medication increased during the study period from 0.05% in 2008 to 0.27% in 2013, with the majority (473/569) of the exposures being to methylphenidate. There were 5.1% malformations overall and 2.1% cardiac malformations among the exposed compared to 4.6% and 1.0%, respectively, among the unexposed. For methylphenidate, the adjusted prevalence ratios (PRs) were 1.04 (95% confidence interval [CI], 0.70-1.55) for malformations overall and 1.65 (95% CI, 0.89-3.05) for any cardiac malformations (number needed to harm [NNH] = 92), with septum defects in 10 out of 12 cases. The PR for ventricular septal defect was 2.74 (95% CI, 1.03-7.28) and for SCM, 2.59 (95% CI, 0.98-6.90).
Exposure to methylphenidate was not associated with an increased risk of malformations overall in data that included information from both prenatal and postnatal diagnoses of major malformations. There was an increased risk of cardiac malformations with NNH of 92 based on 12 cases among the exposed. More data are needed on other types of ADHD medication.
注意力缺陷/多动障碍（ADHD）药物在妊娠期间的使用越来越多。这些药物的妊娠安全性研究仅限于活产，可能会低估导致胎儿死亡或终止妊娠的严重致畸作用。本研究通过纳入产前和产后主要畸形诊断的数据来解决这一局限性。
这是一项基于全国注册的研究，纳入了 2007 年 11 月 1 日至 2014 年 2 月 1 日期间丹麦的 364012 例单胎妊娠。ADHD 药物的暴露情况来自丹麦卫生服务处方数据库中已兑换的处方。结局数据包括来自丹麦胎儿医学数据库的产前诊断畸形和来自丹麦国家患者登记处的产后诊断畸形。主要结局是总体主要畸形，次要结局是中枢神经系统畸形和心脏畸形。对照组为无 ADHD 药物兑换处方的妊娠。我们将严重心脏畸形（SCM）定义为心脏畸形同时伴有流产、终止妊娠、死胎、产后死亡或出生后 1 年内心脏手术的并存诊断。
研究期间，妊娠早期暴露于 ADHD 药物的比例从 2008 年的 0.05%上升至 2013 年的 0.27%，其中大部分（473/569）暴露于哌醋甲酯。与未暴露组相比，暴露组的总体畸形发生率为 5.1%，心脏畸形发生率为 2.1%；未暴露组的总体畸形发生率为 4.6%，心脏畸形发生率为 1.0%。对于哌醋甲酯，调整后的比值比（PR）分别为 1.04（95%置信区间[CI]，0.70-1.55）和任何心脏畸形（需要治疗的人数[NNH] = 92）为 1.65（95% CI，0.89-3.05），12 例中有 10 例为室间隔缺损。室间隔缺损的 PR 为 2.74（95% CI，1.03-7.28），SCM 的 PR 为 2.59（95% CI，0.98-6.90）。
在纳入产前和产后主要畸形诊断信息的数据中，哌醋甲酯暴露与整体畸形风险增加无关。暴露组有 12 例心脏畸形，NNH 为 92，风险增加。还需要更多关于其他类型 ADHD 药物的数据。
