Department of Medicine Solna, Center for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Acta Obstet Gynecol Scand. 2021 Nov;100(11):2111-2118. doi: 10.1111/aogs.14251. Epub 2021 Aug 28.
For phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, the only approved indication in women is for pulmonary arterial hypertension. These drugs are increasingly being proposed and tested for treatment of female infertility and complications in pregnancy. However, the extent of use of PDE5 inhibitors in the general pregnant population over the last decades is unknown. Therefore, we conducted a descriptive cohort study using data from the population health registers in the Scandinavian countries.
By linking the Medical Birth Registers and the Prescribed Drug Registers in Denmark (1997-2017), Norway (2004-2017), and Sweden (2006-2016), women with filled prescriptions of PDE5 inhibitors in outpatient settings in the 90 days before the date of last menstrual period and/or during pregnancies were identified. With additional linkage to the National Patient Registers, information on maternal, pregnancy, and infant characteristics, co-morbidities, and co-medication was collected and described.
Among over 3 million singleton pregnancies, only 77 were pregnancies in women who had at least one filled prescription of a PDE5 inhibitor within the 90 days before the start of pregnancy to delivery. Prescription fills most often occurred before the last menstrual period and in the first trimester, with very few occurring later in pregnancy. Sildenafil was the most used PDE5 inhibitor. Among pregnant women using PDE5 inhibitors, 44% were 35 years of age or older, eight had a cardiovascular diagnosis, and three specifically had a diagnosis of pulmonary arterial hypertension. Among the infants born to mothers using PDE5 inhibitors, nine were born preterm, six were small-for-gestational age, five had an Apgar score at 5 minutes below 8, 18 were admitted to the Neonatal Intensive Care Unit, and eight had respiratory and cardiovascular conditions.
Few women used PDE5 inhibitors in outpatient settings before or during pregnancy in the Scandinavian countries in the last decades. Only a small proportion had a diagnosis for pulmonary arterial hypertension, suggesting off-label use in the remaining users. Use was predominantly in mothers over age 35 years. The safety of fetal exposure to sildenafil and other PDE5 inhibitors in pregnancy has not been established. As maternal age continues to increase and additional uses of PDE5 inhibitors are investigated, the safety of these drugs in pregnancy should be thoroughly evaluated.
对于磷酸二酯酶 5 型（PDE5）抑制剂，如西地那非，其在女性中的唯一批准适应症是肺动脉高压。这些药物越来越多地被提议并测试用于治疗女性不孕和妊娠并发症。然而，过去几十年中，PDE5 抑制剂在普通孕妇人群中的使用程度尚不清楚。因此，我们使用斯堪的纳维亚国家的人群健康登记处的数据进行了描述性队列研究。
通过将丹麦（1997-2017 年）、挪威（2004-2017 年）和瑞典（2006-2016 年）的医疗出生登记处和处方药物登记处进行链接，确定了在末次月经前 90 天内在门诊处开具 PDE5 抑制剂处方的女性和/或在妊娠期间开具 PDE5 抑制剂处方的女性。通过进一步与国家患者登记处链接，收集并描述了母亲、妊娠和婴儿特征、合并症和合并用药的信息。
在超过 300 万例单胎妊娠中，只有 77 例妊娠的女性在妊娠开始至分娩前的 90 天内至少有一次开具 PDE5 抑制剂处方。处方填写最常发生在末次月经前和妊娠早期，很少发生在妊娠后期。西地那非是使用最广泛的 PDE5 抑制剂。在使用 PDE5 抑制剂的孕妇中，44%的孕妇年龄在 35 岁或以上，8 人患有心血管疾病，3 人患有特发性肺动脉高压。在使用 PDE5 抑制剂的母亲所生的婴儿中，有 9 人早产，6 人出生体重小于胎龄，5 人在第 5 分钟时的阿普加评分低于 8 分，18 人被送入新生儿重症监护病房，8 人有呼吸和心血管疾病。
在过去几十年中，斯堪的纳维亚国家的门诊处很少有女性在妊娠前或妊娠期间使用 PDE5 抑制剂。只有一小部分患有肺动脉高压的诊断，这表明其余使用者为标签外使用。使用者主要为 35 岁以上的母亲。胎儿暴露于西地那非和其他 PDE5 抑制剂在妊娠中的安全性尚未确定。随着产妇年龄的继续增加和对 PDE5 抑制剂的额外使用的研究，这些药物在妊娠中的安全性应进行彻底评估。
