Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Division of Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):6291-6296. doi: 10.1080/14767058.2021.1910669. Epub 2021 Apr 29.
The U.S. Food and Drug Administration (FDA) approved Makena (hydroxyprogesterone caproate [HPC] injection) in February 2011 for reducing the risk of preterm birth (PTB) in women with a singleton pregnancy who had a history of singleton spontaneous PTB (sPTB). Makena was approved under accelerated approval and required a postmarketing study to verify its clinical benefits. However, the postmarketing trial (PROLONG) failed to verify Makena's clinical benefit to neonates and substantiate its effect on reducing the risk of recurrent PTB. This study examined the utilization of HPC, along with another progestogen (vaginal progesterone) used to reduce the risk of sPTB during pregnancy, to inform the landscape of HPC use in the United States.
We included pregnant women aged 10-54 years with a live birth delivery from 1 January, 2008 to 31 December, 2018 in the Sentinel Distributed Database (SDD). We examined the prevalence of injectable HPC (Makena and its generics), compounded HPC, and vaginal progesterone use during the second and third trimesters during the study period. We also assessed the proportion of these HPC-exposed pregnancies with obstetrical conditions of interest as potential reasons for use: (1) history of preterm delivery; (2) cervical shortening in the current pregnancy; and (3) preterm labor in the current pregnancy.
We identified a total of 3,445,739 live-birth pregnancies (among 2.9 million women) between 2008 and 2018 in the SDD. Of these pregnancies, 6.5 per 1,000 pregnancies used injectable HPC, 2.3 per 1,000 pregnancies used compounded HPC, and 1.5 per 1,000 pregnancies used vaginal progesterone during the second and/or third trimesters. The yearly uptakeof pregnancies with injectable HPC use increased during the study period from 2.1 per 1,000 pregnancies in 2012 to 12.6 per 1,000 pregnancies in 2018; use of compounded HPC decreased from 3.3 per 1,000 pregnancies to 0.25 per 1,000 pregnancies over the same period. Of 16,524 pregnancies with injectable HPC use, 12,054 (73%) had at least one related obstetrical condition, including 6,439 (39%) with a recorded history of preterm delivery. In addition, 4,665 (28%) had a PTB recorded as the outcome for the current pregnancy.
We found modest use of HPC during the second and/or third trimesters among all live-birth pregnancies in SDD. The majority of pregnancies with injectable HPC use had at least one of three obstetrical indications of interest recorded before or during the pregnancy.
美国食品和药物管理局（FDA）于 2011 年 2 月批准 Makena（己酸羟孕酮[HPC]注射液）用于减少有单胎自发性早产（sPTB）史的单胎妊娠女性的早产风险。Makena 是在加速审批下获得批准的，需要进行上市后研究以验证其临床益处。然而，上市后试验（PROLONG）未能验证 Makena 对新生儿的临床益处，并证实其对降低复发性早产风险的影响。本研究检查了 HPC 的使用情况，以及另一种用于降低妊娠期间 sPTB 风险的孕激素（阴道孕酮）的使用情况，以了解美国 HPC 使用情况。
我们纳入了年龄在 10-54 岁之间的、2008 年 1 月 1 日至 2018 年 12 月 31 日之间活产分娩的 Sentinel 分布式数据库（SDD）中的孕妇。我们检查了研究期间第二和第三孕期注射用 HPC（Makena 及其仿制药）、复合 HPC 和阴道孕酮的使用情况。我们还评估了这些 HPC 暴露妊娠中存在以下产科情况的比例，这些情况可能是使用 HPC 的原因：（1）早产史；（2）当前妊娠的宫颈缩短；（3）当前妊娠的早产。
我们在 SDD 中总共确定了 3445739 例活产妊娠（290 万例女性）。这些妊娠中，6.5%的妊娠使用注射用 HPC，2.3%的妊娠使用复合 HPC，1.5%的妊娠在第二和/或第三孕期使用阴道孕酮。在研究期间，使用注射用 HPC 的妊娠比例逐年增加，从 2012 年的每 1000 例妊娠 2.1 例增加到 2018 年的每 1000 例妊娠 12.6 例；同期使用复合 HPC 的比例从每 1000 例妊娠 3.3 例降至 0.25 例。在 16524 例使用注射用 HPC 的妊娠中，有 12054 例（73%）至少有一种相关的产科情况，其中 6439 例（39%）有早产史。此外，4665 例（28%）的妊娠记录为当前妊娠的早产。
我们发现 SDD 中所有活产妊娠中，第二和/或第三孕期 HPC 的使用量适中。使用注射用 HPC 的妊娠中，大多数至少有一种在妊娠前或妊娠期间记录的三种感兴趣的产科指征。
