使用母体 PlGF 和 sFlt-1/PlGF 比值预测生长受限和适于胎龄儿的早产：一项前瞻性研究。

Prediction of preterm birth in growth-restricted and appropriate-for-gestational-age infants using maternal PlGF and the sFlt-1/PlGF ratio-A prospective study.

机构信息

Mater Research Institute, University of Queensland, South Brisbane, Queensland, Australia.

Faculty of Medicine, The University of Queensland, Herston, Queensland, Australia.

出版信息

BJOG. 2024 Jul;131(8):1089-1101. doi: 10.1111/1471-0528.17752. Epub 2024 Jan 9.

DOI:10.1111/1471-0528.17752

PMID:38196326

Abstract

OBJECTIVE

To assess the utility of placental growth factor (PlGF) levels and the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA).

DESIGN

Prospective, observational cohort study.

SETTING

Tertiary maternity hospital in Australia.

POPULATION

There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32 weeks) and 109 (30.0%) late FGR (≥32 weeks).

METHODS

Maternal serum PlGF and sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt-1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt-1/PlGF ratio to the time of birth or censoring.

MAIN OUTCOME MEASURES

The primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained.

RESULTS

The early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p < 0.001) and higher median sFlt-1 levels (2774 ng/L versus 2096 ng/L, p < 0.001) and sFlt-1/PlGF ratio higher (35 versus 10, p < 0.001). Both PlGF <100 ng/L and elevated sFlt-1/PlGF ratio were strongly predictive for PTB as well as PTB within 1, 2 and 3 weeks of diagnosis. For both FGR and AGA groups, PlGF <100 ng/L or raised sFlt-1/PlGF ratio were strongly associated with increased risk for medically indicated PTB. The highest RR was seen in the FGR cohort when PlGF was <100 ng/L (RR 35.20, 95% CI 11.48-175.46).

CONCLUSIONS

Low maternal PlGF levels and elevated sFlt-1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies.

摘要

目的

评估胎盘生长因子（PlGF）水平和可溶性 fms 样酪氨酸激酶-1/胎盘生长因子（sFlt-1/PlGF）比值预测胎儿生长受限（FGR）胎儿早产（PTB）的效用，以及适用于胎龄（AGA）的胎儿。

设计

前瞻性观察队列研究。

地点

澳大利亚的一家三级妇产医院。

人群

共有 320 例单胎妊娠：141 例（44.1%）AGA，83 例（25.9%）早期 FGR（<32 周）和 109 例（30.0%）晚期 FGR（≥32 周）。

方法

从招募到分娩，每 4 周测量一次母体血清 PlGF 和 sFlt-1/PlGF 比值。低值母体 PlGF 水平和高 sFlt-1/PlGF 比值定义为<100ng/L 和<28 周<5.78 时>38 周。使用 Cox 比例风险模型。分析期定义为从首次测量 PlGF 和 sFlt-1/PlGF 比值到分娩或截止时间的时间。

主要结果测量

主要研究结果为总 PTB。还确定了出生在 1、2 和 3 周内以及医学指示和自发性 PTB 的相对风险（RR）。

结果

早期 FGR 队列的中位数 PlGF 水平较低（54 与 229ng/L，p<0.001），中位数 sFlt-1 水平较高（2774ng/L 与 2096ng/L，p<0.001），sFlt-1/PlGF 比值较高（35 与 10，p<0.001）。PlGF<100ng/L 和 sFlt-1/PlGF 比值升高均强烈预测 PTB 以及诊断后 1、2 和 3 周内的 PTB。对于 FGR 和 AGA 两组，PlGF<100ng/L 或 sFlt-1/PlGF 比值升高与医学指示性 PTB 风险增加密切相关。当 PlGF<100ng/L 时，FGR 队列的 RR 最高（RR 35.20，95%CI 11.48-175.46）。