Placental histopathology in early-onset fetal growth restriction with use of sildenafil, a secondary analysis of the Dutch STRIDER study

IF 3 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2024-11-12 DOI:10.1016/j.placenta.2024.10.024

Marjon E. Feenstra , Mirthe H. Schoots , Romy Bezemer , Lotte-Elisabeth van der Meeren , Peter GJ. Nikkels , Harry van Goor , Jan-Luuk Hillebrands , Jelmer R. Prins , Wessel Ganzevoort , Sanne J. Gordijn

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引用次数: 0

Abstract

Objectives

Placental pathology lesions are common in early-onset fetal growth restriction (eoFGR). Therapeutic interventions to improve eoFGR outcomes are needed. In the international STRIDER trials (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) sildenafil didn't improve perinatal outcomes of eoFGR. We aimed to study the underlying placental pathology in the Dutch STRIDER trial and the effects of sildenafil on placental histopathology by describing the associations with sildenafil treatment, placental-dysfunction serum biomarkers and markers of oxidative stress.

Methods

The Dutch STRIDER trial was a randomized controlled trial of sildenafil versus placebo in 216 singleton pregnancies complicated by eoFGR, included between 20+0- and 29+6-weeks’ gestation. In 158 cases, placental histology was available. Lesions were classified independently by three perinatal pathologists blinded for clinical data, according to the international criteria of the Amsterdam Placental Workshop Group Consensus Statement. Blood samples taken at inclusion were analyzed for free thiols (FT), placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1, n = 85).

Results

The ‘big four’ placental lesions (maternal and fetal vascular malperfusion, and chronic or acute inflammatory lesions) were equally distributed in both groups. However, massive perivillous fibrin deposition (MPFD) and chronic histiocytic intervillositis (CHIV) were less common in the sildenafil-treated group compared to the placebo-treated group (p = 0.026 and p = 0.043). FT, PlGF and sFlt-1 at inclusion were not discriminative for placental lesions.

Conclusions

Sildenafil had no effect on common placental lesions. The lower incidence of MPFD and CHIV after sildenafil exposure merits more research on the interaction between sildenafil and the immune system.

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西地那非对早发性胎儿生长受限的胎盘组织病理学影响，荷兰STRIDER研究的二次分析

目的早发型胎儿生长受限（eoFGR）常见胎盘病理病变。需要采取治疗干预措施来改善eoFGR结果。在国际STRIDER试验（西地那非治疗预后不佳的早发性宫内生长限制）中，西地那非没有改善eoFGR的围产期结局。我们旨在通过描述西地那非治疗、胎盘功能障碍血清生物标志物和氧化应激标志物之间的关系，研究荷兰STRIDER试验中潜在的胎盘病理学和西地那非对胎盘组织病理学的影响。方法荷兰STRIDER试验是一项随机对照试验，在216例合并eoFGR的单胎妊娠中使用西地那非与安慰剂，包括妊娠20+0 ~ 29+6周。158例有胎盘组织学资料。根据阿姆斯特丹胎盘研讨会小组共识声明的国际标准，由三名围产期病理学家对临床数据进行盲法独立分类。纳入时采集的血样分析游离硫醇（FT）、胎盘生长因子（PlGF）和可溶性fms样酪氨酸激酶-1 （sFlt-1, n = 85）。结果两组胎盘“四大”病变（母胎血管灌注不良、慢性或急性炎性病变）分布均匀。然而，与安慰剂治疗组相比，西地那非治疗组的大量绒毛周围纤维蛋白沉积（MPFD）和慢性组织细胞绒毛间炎（CHIV）较少见（p = 0.026和p = 0.043）。纳入时的FT、PlGF和sFlt-1对胎盘病变没有区别性。结论西地那非对常见胎盘病变无影响。西地那非暴露后MPFD和CHIV发生率较低，值得进一步研究西地那非与免疫系统的相互作用。

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来源期刊

Placenta 医学-发育生物学

CiteScore

6.30

自引率

10.50%

发文量

391

审稿时长

78 days

期刊介绍： Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.