Kuon Ruben-J, Berger Richard, Rath Werner
Universitätsklinikum Heidelberg, Abteilung für Gynäkologische Endokrinologie und Fertilitätsstörungen, Frauenklinik, Heidelberg, Germany.
Marienhausklinikum, Frauenklinik, Neuwied, Germany.
Geburtshilfe Frauenheilkd. 2021 Jan;81(1):61-69. doi: 10.1055/a-1295-0752. Epub 2021 Jan 19.
Prior spontaneous preterm birth is a strong risk factor for the recurrence of spontaneous preterm birth in a subsequent pregnancy and has been evaluated in prevention studies using progesterone (natural progesterone administered orally or vaginally, and 17-hydroxyprogesterone caproate [17-OHPC]) as a selection criterion. Based on the findings of a randomized, placebo-controlled study, 17-OHPC was approved for use in 2011 by the Food and Drug Administration in the USA for the prevention of recurrent preterm birth. The approval was granted with qualification that a subsequent confirmatory study would need to be carried out, the results of which have just been published (PROLONG trial). A systematic literature search for the period from 1970 to April 2020 using the search terms "preterm birth" and "17-OHPC" or "progesterone" was carried out. Only randomized, placebo-controlled studies of women with singleton pregnancies who received 17-OHPC to prevent recurrent preterm birth were included in the subsequent meta-analysis. The relative risk and associated 95% confidence intervals were calculated. The heterogeneity between studies was evaluated with I statistics. In addition to the original study used for the approval and the PROLONG trial, only one other study was found which met the inclusion criteria (total number of patients: 2221). With considerable heterogeneity between the studies, particularly with respect to the risk factors for preterm birth, the comparison between 17-OHPC and placebo showed no significant reduction in preterm birth rates before 37, 35 and 32 weeks of gestation and no significant differences with regard to the prevalence of miscarriage before 20 weeks of gestation or fetal deaths (antepartum or intrapartum) after 20 weeks of gestation and neonatal morbidity. Based on the currently available data, 17-OHPC cannot be recommended for the prevention of recurrent preterm birth. Further randomized, placebo-controlled studies with clearly defined, comparable risk factors are required to identify the group of pregnant women which could benefit from the use of 17-OHPC to prevent preterm birth.
既往自发性早产是后续妊娠中自发性早产复发的一个重要危险因素，并且在预防研究中已将其作为使用孕激素（口服或阴道给予天然孕激素以及己酸羟孕酮[17-OHPC]）的选择标准进行了评估。基于一项随机、安慰剂对照研究的结果，2011年美国食品药品监督管理局批准17-OHPC用于预防复发性早产。批准时附带条件，即需要开展一项后续确证性研究，其结果刚刚发表（PROLONG试验）。使用检索词“早产”和“17-OHPC”或“孕激素”对1970年至2020年4月期间进行了系统的文献检索。后续的荟萃分析仅纳入了接受17-OHPC预防复发性早产的单胎妊娠女性的随机、安慰剂对照研究。计算了相对风险及相关的95%置信区间。使用I²统计量评估研究之间的异质性。除了用于批准的原始研究和PROLONG试验外，仅发现另一项符合纳入标准的研究（患者总数：2221）。由于研究之间存在相当大的异质性，尤其是在早产危险因素方面，17-OHPC与安慰剂之间的比较显示，在妊娠37、35和32周之前早产率没有显著降低，在妊娠20周之前流产患病率或妊娠20周之后（产前或产时）胎儿死亡以及新生儿发病率方面也没有显著差异。基于目前可得的数据，不推荐使用17-OHPC预防复发性早产。需要开展进一步的随机、安慰剂对照研究，明确界定可比的危险因素，以确定可能从使用17-OHPC预防早产中获益 的孕妇群体。
