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利用血管生成生物标志物谱对胎儿生长受限患者进行风险分层。

Use of the angiogenic biomarker profile to risk stratify patients with fetal growth restriction.

机构信息

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology (Drs Arenas and Perdigao, Ms Kaur, Dr Abramowicz, Ms Mussatt, and Dr Rana).

Department of Pathology (Drs Tang and Yeo), University of Chicago, Chicago, IL.

出版信息

Am J Obstet Gynecol MFM. 2021 Jul;3(4):100394. doi: 10.1016/j.ajogmf.2021.100394. Epub 2021 May 12.

Abstract

BACKGROUND

Novel angiogenic biomarker profiles have demonstrated emerging evidence for predicting preeclampsia onset, severity, and adverse outcomes. Limited data exist in screening patients with fetal growth restriction for preeclampsia development using angiogenic biomarkers.

OBJECTIVE

The objective of this study was to risk stratify patients with fetal growth restriction using a soluble fms-like tyrosine kinase-1 to placental growth factor ratio. Previously published cutoff of 38 was used to predict preeclampsia development and severity as well as adverse maternal or neonatal outcomes within a 2-week time period.

STUDY DESIGN

This was a prospective observational cohort study performed in a single tertiary hospital. Patients with a singleton fetal growth restriction pregnancy between 24 and 37 weeks' gestation were evaluated using serial 2-week encounters from the time of enrollment to delivery. Pregnancies with proven genetic or infectious etiology of fetal growth restriction or congenital anomalies were excluded. Ultrasound growth and Doppler measurements were obtained at the start of every encounter with routine preeclampsia laboratory tests and blood pressure checks when clinically indicated. Maternal serum was collected for all serial encounters and measured for soluble fms-like tyrosine kinase-1 and placental growth factor after delivery in a double-blinded fashion. Maternal charts were reviewed for baseline demographic characteristics, pregnancy diagnoses and outcomes, and neonatal outcomes.

RESULTS

A total of 45 patients were enrolled for a total of 77 encounters, with the median (quartile 1, quartile 3) gestational age of the study enrolled at 31.43 (28.14-33.57) weeks. Patients were divided into low-risk (ratio of <38) and high-risk (ratio of ≥38) groups. Baseline characteristics of patients did not show any marked differences, including preeclampsia labs or ultrasound parameters, between the 2 groups. Systolic and diastolic blood pressures upon enrollment were statistically elevated when soluble fms-like tyrosine kinase-1 to placental growth factor ratio was ≥38 (P=.02 and P=.01, respectively). Compared to patients with a low ratio, patients with a high ratio had a greater proportion of preeclampsia diagnosis, higher rates of preterm delivery under 34 and 37 weeks gestation, smaller neonatal birthweight, and a shorter time to delivery from testing to delivery.

CONCLUSION

Among patients with fetal growth restriction, the soluble fms-like tyrosine kinase-1 to placental growth factor ratio may serve as a potential biomarker for identifying at risk patients for developing preeclampsia and subsequently preterm delivery.

摘要

背景

新型血管生成生物标志物的研究成果为预测子痫前期的发病、严重程度和不良结局提供了新的证据。目前,利用血管生成生物标志物对胎儿生长受限的患者进行子痫前期发病筛查的相关数据有限。

目的

本研究旨在利用可溶性 fms 样酪氨酸激酶 1 与胎盘生长因子比值对胎儿生长受限患者进行风险分层。该比值的截断值为 38,曾被用于预测子痫前期的发病和严重程度,以及在 2 周内发生不良母婴或新生儿结局的风险。

研究设计

这是一项在一家三级医院进行的前瞻性观察性队列研究。纳入妊娠 24 至 37 周且患有单胎胎儿生长受限的患者,从入组至分娩,每 2 周进行一次连续评估。排除因遗传或感染病因导致胎儿生长受限或先天性异常的妊娠。在每次就诊时均进行超声生长和多普勒测量,并在临床需要时进行常规子痫前期实验室检查和血压检查。在每次就诊时收集母体血清,在分娩后采用双盲法测量可溶性 fms 样酪氨酸激酶 1 和胎盘生长因子。回顾产妇病历以获取基线人口统计学特征、妊娠诊断和结局以及新生儿结局等信息。

结果

共有 45 例患者入组,共进行了 77 次就诊,研究入组时的中位(四分位距 1,四分位距 3)孕周为 31.43(28.14-33.57)周。患者被分为低风险(比值<38)和高风险(比值≥38)组。两组患者的基线特征,包括子痫前期实验室检查或超声参数,均无明显差异。可溶性 fms 样酪氨酸激酶 1 与胎盘生长因子比值≥38 时,患者的收缩压和舒张压在入组时即出现统计学升高(分别为 P=.02 和 P=.01)。与比值较低的患者相比,比值较高的患者子痫前期的诊断比例更大,<34 周和<37 周早产的发生率更高,新生儿出生体重更小,从检测到分娩的时间更短。

结论

在胎儿生长受限的患者中,可溶性 fms 样酪氨酸激酶 1 与胎盘生长因子比值可能成为一种潜在的生物标志物,用于识别有发生子痫前期和随后早产风险的患者。

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