Sawady Joram, Mercer Brian M, Wapner Ronald J, Zhao Yuan, Sorokin Yoram, Johnson Francee, Dudley Donald J, Spong Catherine Y, Peaceman Alan M, Leveno Kenneth J, Harper Margaret, Caritis Steve N, Miodovnik Menachem, Thorp John M, Ramin Susan, Carpenter Marshall W, Rouse Dwight J
Department of Pathology, Metro Health Medical Center, Case Western Reserve University, Cleveland, OH, USA.
Am J Obstet Gynecol. 2007 Sep;197(3):281.e1-8. doi: 10.1016/j.ajog.2007.06.041.
In utero exposure to repeated doses of antenatal corticosteroids (ACSs) has been shown to reduce fetal growth. Our goal was to evaluate whether weekly betamethasone (R-ACS) alters placental growth and histologic findings.
In a multicenter randomized controlled trial of R-ACS vs a single course of ACS followed by weekly placebo (S-ACS), placentas were weighed after removal of the membranes and umbilical cord. A single pathologist who was masked to study group and pregnancy outcomes performed histologic evaluation for placental calcifications, infarction, fibrin deposition, and hemorrhage or thrombus formation, acute and chronic chorioamnionitis, fibromuscular vascular hyperplasia, nucleated red blood cells, and villous crowding, edema, fibrosis, or fibrinoid necrosis. Findings were compared between study groups and according to the number of courses of ACS.
One hundred ninety-four placentas were available for evaluation. Univariable analyses revealed no differences between study groups in any of the 19 evaluated histologic parameters between R-ACS and S-ACS groups overall or in analyses that were restricted to deliveries at < 32 or > or = 32 weeks of gestation. Calcifications were more common (P = .045) in the R-ACS group after controlling for other factors. Multivariable analysis revealed increasing gestational age at delivery, but not increasing ACS courses, to be associated with decreasing chorionic inflammation, villous edema, and fibrosis and with increasing villus crowding, fibrin deposition, and calcifications. Ninety-three placentas were weighed before formalin fixation. After controlling for delivery gestation and infant gender, placental weight was significantly lower in the R-ACS group (P = .017) and was related inversely to the number of ACS courses (P = .037). This finding was confirmed only for deliveries at > or = 32 weeks of gestation (525 vs 441 g for R-ACS and S-ACS group, respectively; P = .036).
Repeated antenatal corticosteroid treatments in pregnancy are associated with decreased placental growth in a dose-dependent fashion, but not with evident differences in histologic markers of placental inflammation, ischemia, or infarction. Histologic placental abnormalities should not be attributed to repeated courses of corticosteroids.
已表明子宫内反复暴露于产前皮质类固醇（ACSs）会降低胎儿生长。我们的目标是评估每周使用倍他米松（R-ACS）是否会改变胎盘生长及组织学表现。
在一项R-ACS与单次使用ACS后每周使用安慰剂（S-ACS）的多中心随机对照试验中，去除胎膜和脐带后对胎盘进行称重。一名对研究组和妊娠结局不知情的病理学家对胎盘钙化、梗死、纤维蛋白沉积、出血或血栓形成、急慢性绒毛膜羊膜炎、纤维肌性血管增生、有核红细胞以及绒毛拥挤、水肿、纤维化或类纤维蛋白坏死进行组织学评估。在研究组之间以及根据ACS疗程数对结果进行比较。
194个胎盘可供评估。单变量分析显示，总体上R-ACS组和S-ACS组在19项评估的组织学参数中的任何一项上均无差异，在仅限于妊娠<32周或≥32周分娩的分析中也无差异。在控制其他因素后，钙化在R-ACS组中更常见（P = 0.045）。多变量分析显示，分娩时孕周增加，但不是ACS疗程增加，与绒毛膜炎症、绒毛水肿和纤维化减少以及绒毛拥挤、纤维蛋白沉积和钙化增加有关。93个胎盘在福尔马林固定前称重。在控制分娩孕周和婴儿性别后，R-ACS组的胎盘重量显著较低（P = 0.017），并且与ACS疗程数呈负相关（P = 0.037）。这一发现仅在妊娠≥32周分娩时得到证实（R-ACS组和S-ACS组分别为525 g和441 g；P = 0.036）。
孕期反复进行产前皮质类固醇治疗与胎盘生长呈剂量依赖性降低有关，但与胎盘炎症、缺血或梗死的组织学标志物无明显差异。胎盘组织学异常不应归因于反复使用皮质类固醇疗程。
