Placenta-associated biomarkers and pregnancy outcome in HPA-1a alloimmunization: A prospective cohort study

IF 3 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2024-10-24 DOI:10.1016/j.placenta.2024.10.014

Nora Hersoug Nedberg , Mona Nystad , Maria Therese Ahlen , Eirin Listau Bertelsen , Katarzyna Guz , Małgorzata Uhrynowska , Marzena Dębska , Agnieszka Gierszon , Agnieszka Orzińska , Anne Husebekk , Ewa Brojer , Anne Cathrine Staff , Heidi Tiller

{"title":"Placenta-associated biomarkers and pregnancy outcome in HPA-1a alloimmunization: A prospective cohort study","authors":"Nora Hersoug Nedberg , Mona Nystad , Maria Therese Ahlen , Eirin Listau Bertelsen , Katarzyna Guz , Małgorzata Uhrynowska , Marzena Dębska , Agnieszka Gierszon , Agnieszka Orzińska , Anne Husebekk , Ewa Brojer , Anne Cathrine Staff , Heidi Tiller","doi":"10.1016/j.placenta.2024.10.014","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from parental incompatibility in human platelet antigens (HPA) and subsequent maternal sensitization. The HPA-1a epitope is also expressed on placental tissue. Chronic placental inflammation and lower birth weight is observed more often in HPA-1a alloimmunized pregnancies, suggesting a placental component in the pathophysiology of FNAIT. Today, prediction of FNAIT severity is limited. The aim of the study was to investigate whether dysregulated maternal angiogenic proteins are associated with neonatal outcome in HPA-1a alloimmunized pregnancies.</div></div><div><h3>Material and methods</h3><div>Eighty-seven HPA-1a negative pregnant women were identified from a large prospective screening study in Poland (PREVFNAIT) including 43 HPA-1a immunized and 44 non-immunized controls. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal plasma from 2nd and 3rd trimester by enzyme-linked immunosorbent assay and levels/ratios were compared between study groups, using uni- and multivariable analyses. Main outcome measures were either classic FNAIT-related (severe thrombocytopenia, petechia, intracranial hemorrhage), placenta-related (small for gestational age) or a composite variable combining them all.</div></div><div><h3>Results</h3><div>There were no significant differences in plasma concentrations of sFlt-1, PlGF, sEng nor sFlt-1/PlGF ratio when comparing immunized and non-immunized pregnancies. Among HPA-1a alloimmunized pregnancies, increasing levels of the sFlt-1 protein in 3rd trimester were significantly associated with lower neonatal platelet count (multivariable linear regression, p = 0.024). Increased sFlt-1 and sFlt-1/PlGF ratio in 3rd trimester were significantly associated with higher odds of a composite adverse neonatal outcome in alloimmunized pregnancies (multivariable logistic regression, p = 0.029 and p = 0.019, respectively).</div></div><div><h3>Conclusion</h3><div>An anti-angiogenic profile in HPA-1a alloimmunized mothers is associated with a composite adverse neonatal outcome. This suggests that sFlt-1 and the sFlt-1/PlGF ratio may assist in predelivery risk stratification and clinical management decisions for FNAIT.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"158 ","pages":"Pages 185-191"},"PeriodicalIF":3.0000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Placenta","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143400424006878","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from parental incompatibility in human platelet antigens (HPA) and subsequent maternal sensitization. The HPA-1a epitope is also expressed on placental tissue. Chronic placental inflammation and lower birth weight is observed more often in HPA-1a alloimmunized pregnancies, suggesting a placental component in the pathophysiology of FNAIT. Today, prediction of FNAIT severity is limited. The aim of the study was to investigate whether dysregulated maternal angiogenic proteins are associated with neonatal outcome in HPA-1a alloimmunized pregnancies.

Material and methods

Eighty-seven HPA-1a negative pregnant women were identified from a large prospective screening study in Poland (PREVFNAIT) including 43 HPA-1a immunized and 44 non-immunized controls. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal plasma from 2nd and 3rd trimester by enzyme-linked immunosorbent assay and levels/ratios were compared between study groups, using uni- and multivariable analyses. Main outcome measures were either classic FNAIT-related (severe thrombocytopenia, petechia, intracranial hemorrhage), placenta-related (small for gestational age) or a composite variable combining them all.

Results

There were no significant differences in plasma concentrations of sFlt-1, PlGF, sEng nor sFlt-1/PlGF ratio when comparing immunized and non-immunized pregnancies. Among HPA-1a alloimmunized pregnancies, increasing levels of the sFlt-1 protein in 3rd trimester were significantly associated with lower neonatal platelet count (multivariable linear regression, p = 0.024). Increased sFlt-1 and sFlt-1/PlGF ratio in 3rd trimester were significantly associated with higher odds of a composite adverse neonatal outcome in alloimmunized pregnancies (multivariable logistic regression, p = 0.029 and p = 0.019, respectively).

Conclusion

An anti-angiogenic profile in HPA-1a alloimmunized mothers is associated with a composite adverse neonatal outcome. This suggests that sFlt-1 and the sFlt-1/PlGF ratio may assist in predelivery risk stratification and clinical management decisions for FNAIT.

查看原文本刊更多论文

胎盘相关生物标志物与 HPA-1a 同种免疫的妊娠结局：前瞻性队列研究

导言胎儿和新生儿同种免疫血小板减少症（FNAIT）是由于父母的人类血小板抗原（HPA）不相容以及随后的母体致敏造成的。HPA-1a 表位也在胎盘组织上表达。在 HPA-1a 同种免疫妊娠中更常观察到慢性胎盘炎症和较低的出生体重，这表明 FNAIT 的病理生理学中存在胎盘成分。目前，对 FNAIT 严重程度的预测还很有限。该研究旨在探讨母体血管生成蛋白失调是否与 HPA-1a 同种免疫妊娠的新生儿结局有关。材料和方法从波兰的一项大型前瞻性筛查研究（PREVFNAIT）中确定了 87 名 HPA-1a 阴性孕妇，其中包括 43 名 HPA-1a 免疫对照和 44 名非免疫对照。通过酶联免疫吸附法测定了怀孕第二和第三季度母体血浆中的胎盘生长因子（PlGF）、可溶性瘤样酪氨酸激酶-1（sFlt-1）和可溶性内胚叶素（sEng），并使用单变量和多变量分析比较了研究组之间的水平/比率。主要结果指标为典型的 FNAIT 相关（严重血小板减少、瘀斑、颅内出血）、胎盘相关（胎龄小）或综合所有指标的复合变量。结果免疫妊娠与非免疫妊娠的血浆中 sFlt-1、PlGF、sEng 或 sFlt-1/PlGF 比值无显著差异。在HPA-1a同种免疫妊娠中，怀孕三个月时sFlt-1蛋白水平的升高与新生儿血小板计数的降低显著相关（多变量线性回归，p = 0.024）。结论 HPA-1a 同种免疫母亲的抗血管生成特征与新生儿综合不良结局相关。这表明，sFlt-1 和 sFlt-1/PlGF 比值可能有助于对 FNAIT 进行分娩前风险分层和临床管理决策。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.