Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California.
Department of Obstetrics and Gynecology, The Sheba Medical Center, Tel HaShomer, Israel and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Am J Perinatol. 2023 Aug;40(11):1158-1162. doi: 10.1055/a-2081-2573. Epub 2023 Apr 26.
The frequency of intrahepatic cholestasis of pregnancy (ICP) peaks during the third trimester of pregnancy when plasma progesterone levels are the highest. Furthermore, twin pregnancies are characterized by higher progesterone levels than singletons and have a higher frequency of cholestasis. Therefore, we hypothesized that exogenous progestogens administered for reducing the risk of spontaneous preterm birth may increase the risk of cholestasis. Utilizing the large IBM MarketScan Commercial Claims and Encounters Database, we investigated the frequency of cholestasis in patients treated with vaginal progesterone or intramuscular 17α-hydroxyprogesterone caproate for the prevention of preterm birth.
We identified 1,776,092 live-born singleton pregnancies between 2010 and 2014. We confirmed second and third trimester administration of progestogens by cross-referencing the dates of progesterone prescriptions with the dates of scheduled pregnancy events such as nuchal translucency scan, fetal anatomy scan, glucose challenge test, and Tdap vaccination. We excluded pregnancies with missing data regarding timing of scheduled pregnancy events or progesterone treatment prescribed only during the first trimester. Cholestasis of pregnancy was identified based on prescriptions for ursodeoxycholic acid. We used multivariable logistic regression to estimate adjusted (for maternal age) odds ratios for cholestasis in patients treated with vaginal progesterone, and in patients treated with 17α-hydroxyprogesterone caproate compared with those not treated with any type of progestogen (the reference group).
The final cohort consisted of 870,599 pregnancies. Among patients treated with vaginal progesterone during the second and third trimester, the frequency of cholestasis was significantly higher than the reference group (0.75 vs. 0.23%, adjusted odds ratio [aOR]: 3.16, 95% confidence interval [CI]: 2.23-4.49). In contrast, there was no significant association between 17α-hydroxyprogesterone caproate and cholestasis (0.27%, aOR: 1.12, 95% CI: 0.58-2.16) CONCLUSION: Using a robust dataset, we observed that vaginal progesterone but not intramuscular 17α-hydroxyprogesterone caproate was associated with an increased risk for ICP.
· Previous studies have been underpowered to detect potential association between progesterone and ICP.. · Vaginal progesterone was significantly associated with ICP.. · Intramuscular 17α-hydroxyprogesterone was not associated with ICP..
当血浆孕酮水平处于最高水平时，妊娠肝内胆汁淤积症（ICP）的频率在妊娠的第三个三个月达到高峰。此外，双胎妊娠的孕酮水平高于单胎妊娠，且胆汁淤积症的发生率更高。因此，我们假设用于降低自发性早产风险的外源性孕激素可能会增加胆汁淤积症的风险。利用大型 IBM MarketScan 商业索赔和就诊数据库，我们研究了接受阴道孕酮或肌内 17α-羟孕酮己酸酯预防早产的患者中胆汁淤积症的发生频率。
我们确定了 2010 年至 2014 年间 1776092 例活产单胎妊娠。通过将孕酮处方日期与颈透明层扫描、胎儿解剖扫描、葡萄糖挑战试验和 Tdap 疫苗等预定妊娠事件的日期进行交叉引用，证实了第二和第三个三个月孕激素的使用。我们排除了有关预定妊娠事件时间或仅在第一个三个月开处方的孕激素治疗数据缺失的妊娠。根据熊去氧胆酸的处方确定妊娠胆汁淤积症。我们使用多变量逻辑回归来估计接受阴道孕酮治疗的患者和接受 17α-羟孕酮己酸酯治疗的患者与未接受任何类型孕激素治疗的患者（参考组）的胆汁淤积症校正（按母亲年龄调整）比值比。
最终队列包括 870599 例妊娠。在第二和第三个三个月接受阴道孕酮治疗的患者中，胆汁淤积症的发生率明显高于参考组（0.75%比 0.23%，调整比值比[aOR]：3.16，95%置信区间[CI]：2.23-4.49）。相比之下，17α-羟孕酮己酸酯与胆汁淤积症之间无显著关联（0.27%，aOR：1.12，95%CI：0.58-2.16）。
使用强大的数据集，我们观察到阴道孕酮但不是肌内 17α-羟孕酮己酸酯与 ICP 风险增加相关。
·以前的研究在检测孕激素与 ICP 之间的潜在关联方面能力不足。·阴道孕酮与 ICP 显著相关。·肌内 17α-羟孕酮与 ICP 无关。
