目的:评估胎盘生物标志物(胎盘生长因子(PlGF)和可溶性fms样酪氨酸激酶-1(sFlt-1)/PlGF比率)与胎儿胎盘多普勒-脐动脉搏动指数(UAPI)和子宫动脉搏动指数(UtA)在各种组合中对胎儿生长受限的早产(PTB)可能性的关联。
方法:一项妊娠合并FGR的前瞻性队列研究。母体血清PlGF水平,sFlt-1/PlGF比值,从招募到交付,每4周测量一次UAPI和UtAPI。Harrell的一致性统计用于评估胎盘生物标志物和胎儿胎盘多普勒的各种组合,以确定预测PTB的理想组合(<37周)。多变量Cox回归用作时变协变量。
结果:研究队列中有320例妊娠-179例(55.9%)为FGR,141例(44.1%)为AGA。在FGR队列中,低PlGF水平和升高的sFlt-1/PlGF比率均显着影响PTB的时间。低PlGF比sFlt-1/PlGF比率或PlGF和sFlt-1/PlGF比率的组合更好地预测PTB(分别为Harrell的C0.81、0.79、0.75)。同样,尽管妊娠的UAPI和UtAPI>95百分位数都显着影响了PTB的时间,结合起来,它们比单独的任何一种方法都是更好的预测因子(哈雷尔的C分别为0.82、0.75、0.76)。当PlGF<100ng/L时,预测效用最高,UAPI和UtAPI>95百分位数合并(哈雷尔C0.88)(HR32.9995%CI10.74,101.32)。
结论:低母体PlGF水平(<100ng/L)和胎儿胎盘多普勒异常(UAPI和UtAPI>95百分位数)在合并FGR的PTB妊娠中具有最大的预测效用,可能有助于指导这些复杂妊娠的临床管理。本文受版权保护。保留所有权利。
OBJECTIVE: To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Doppler indices (umbilical artery (UA) pulsatility index (PI) and uterine artery (UtA) PI) in various combinations for predicting preterm birth (PTB) in pregnancies complicated by fetal growth restriction (FGR).
METHODS: This was a prospective observational cohort study, performed at Mater Mother\'s Hospital in Brisbane, Queensland, Australia, from May 2022 to June 2023, of pregnancies complicated by FGR and appropriate-for-gestational-age (AGA) pregnancies. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA-PI and UtA-PI were measured at 2-4-weekly intervals from recruitment until delivery. Harrell\'s concordance statistic (Harrell\'s C) was used to evaluate multivariable Cox proportional hazards regression models featuring various combinations of placental biomarkers and fetoplacental Doppler indices to ascertain the best combination to predict PTB (< 37 weeks). Multivariable Cox regression models were used with biomarkers as time-varying covariates.
RESULTS: The study cohort included 320 singleton pregnancies, comprising 179 (55.9%) affected by FGR, defined according to a Delphi consensus, and 141 (44.1%) with an AGA fetus. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio were associated with significantly shorter time to PTB. Low PlGF was a better predictor of PTB than was either sFlt-1/PlGF ratio or a combination of PlGF and sFlt-1/PlGF ratio (Harrell\'s C, 0.81, 0.78 and 0.79, respectively). Although both Doppler indices were significantly associated with time to PTB, in combination they were better predictors of PTB than was either UA-PI > 95th centile or UtA-PI > 95th centile alone (Harrell\'s C, 0.82, 0.75 and 0.76, respectively). Predictive utility for PTB was best when PlGF < 100 ng/L, UA-PI > 95th centile and UtA-PI > 95th centile were combined (Harrell\'s C, 0.88) (hazard ratio, 32.99; 95% CI, 10.74-101.32).
CONCLUSIONS: Low maternal serum PlGF level (< 100 ng/L) and abnormal fetoplacental Doppler indices (UA-PI > 95th centile and UtA-PI > 95th centile) in combination have the greatest predictive utility for PTB in pregnancies complicated by FGR. Their assessment may help guide clinical management of these complex pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.