早孕期胎盘生物标志物与不良妊娠结局的相关性：一项前瞻性队列研究。

Association between adverse pregnancy outcome and placental biomarkers in the first trimester: A prospective cohort study.

机构信息

Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.

Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research (CTR), University of Cambridge, Cambridge, UK.

出版信息

BJOG. 2024 May;131(6):823-831. doi: 10.1111/1471-0528.17691. Epub 2023 Oct 12.

DOI:10.1111/1471-0528.17691

PMID:37822261

Abstract

OBJECTIVE

To determine the inter-relationships between five first-trimester biomarkers (pregnancy associated plasma protein A [PAPP-A], alpha-fetoprotein [AFP], beta human chorionic gonadotrophin [beta-hCG], placenta growth factor [PlGF] and soluble fms-like tyrosine kinase receptor-1 [sFlt-1]) and a range of adverse pregnancy outcomes (APOs).

DESIGN

Prospective cohort study of nulliparous singleton pregnancy.

SETTING

Cambridge, UK.

POPULATION OR SAMPLE

4056 pregnancy outcome prediction study participants.

METHODS

The biomarker concentrations were measured in maternal serum at ~12 weeks of gestation. Univariable analysis of APOs was performed using logistic regression. Multivariable analysis used best subsets logistic regression with cross-validation.

MAIN OUTCOME MEASURES

Pre-eclampsia (PE), small for gestational age (SGA), including severe SGA (birthweight <3rd), fetal growth restriction (FGR), preterm birth (PTB, both induced and spontaneous [iPTB and sPTB, respectively]), pre-viable loss and stillbirth, plus combinations of outcomes.

RESULTS

Lower values of PAPP-A, PlGF and sFlt-1 and higher values of AFP were associated with FGR (OR for 1 SD higher value 0.59 [95% CI 0.48-0.74], OR 0.56 [95% CI 0.44-0.70], OR 0.68 [95% CI 0.54-0.87] and OR 1.53 [95% CI 1.25-1.88]), severe SGA (OR 0.59 [95% CI 0.49-0.72], OR 0.71 [95% CI 0.57-0.87], OR 0.74 [95% CI 0.60-0.91] and OR 1.41 [95% CI 1.17-1.71]), sPTB (OR 0.61 [95% CI 0.50-0.73], OR 0.79 [95% CI 0.66-0.96], OR 0.57 [95% CI 0.47-0.70] and OR 1.41 [95% CI 1.18-1.67]) and iPTB (OR 0.72 [95% CI 0.57-0.91], OR 0.62 [95% CI 0.49-0.78], OR 0.71 [95% CI 0.56-0.90] and OR 1.44 [95% CI 1.16-1.78]), respectively. When combinations of biomarkers were assessed, PAPP-A and AFP were independently associated with severe SGA; PAPP-A alone with PE + PTB; PlGF alone with severe PE; PlGF, beta-hCG, AFP and PAPP-A with the combination of PE and SGA; AFP and sFlt-1 with sPTB; and AFP and PlGF with iPTB.

CONCLUSIONS

Combinations of first-trimester placental biomarkers are associated with APOs. However, the patterns vary for different types of APO, indicating heterogeneity in the underlying pathophysiological pathways.

摘要

目的

确定五个早孕生物标志物（妊娠相关血浆蛋白 A [PAPP-A]、甲胎蛋白 [AFP]、β人绒毛膜促性腺激素 [β-hCG]、胎盘生长因子 [PlGF]和可溶性 fms 样酪氨酸激酶受体 1 [sFlt-1]）与一系列不良妊娠结局（APO）之间的相互关系。

设计

前瞻性队列研究，纳入初产妇单胎妊娠。

地点

英国剑桥。

人群或样本

4056 名妊娠结局预测研究参与者。

方法

在孕 12 周左右测量母体血清中的生物标志物浓度。使用逻辑回归对 APO 进行单变量分析。使用具有交叉验证的最佳子集逻辑回归进行多变量分析。

主要观察指标

子痫前期（PE）、小于胎龄儿（SGA），包括严重 SGA（出生体重 <3 个百分位）、胎儿生长受限（FGR）、早产（PTB，包括诱导性和自发性 [iPTB 和 sPTB]）、未存活流产和死胎，以及结局组合。

结果

PAPP-A、PlGF 和 sFlt-1 值较低，AFP 值较高与 FGR 相关（1 SD 值升高的 OR 为 0.59 [95% CI 0.48-0.74]、OR 0.56 [95% CI 0.44-0.70]、OR 0.68 [95% CI 0.54-0.87]和 OR 1.53 [95% CI 1.25-1.88]）、严重 SGA（OR 0.59 [95% CI 0.49-0.72]、OR 0.71 [95% CI 0.57-0.87]、OR 0.74 [95% CI 0.60-0.91]和 OR 1.41 [95% CI 1.17-1.71]）、sPTB（OR 0.61 [95% CI 0.50-0.73]、OR 0.79 [95% CI 0.66-0.96]、OR 0.57 [95% CI 0.47-0.70]和 OR 1.41 [95% CI 1.18-1.67]）和 iPTB（OR 0.72 [95% CI 0.57-0.91]、OR 0.62 [95% CI 0.49-0.78]、OR 0.71 [95% CI 0.56-0.90]和 OR 1.44 [95% CI 1.16-1.78]）。当评估生物标志物组合时，PAPP-A 和 AFP 与严重 SGA 独立相关；PAPP-A 单独与 PE+PTB 相关；PlGF 单独与严重 PE 相关；PlGF、β-hCG、AFP 和 PAPP-A 与 PE 和 SGA 的组合相关；AFP 和 sFlt-1 与 sPTB 相关；AFP 和 PlGF 与 iPTB 相关。