Soluble fms‐like tyrosine kinase to placental growth factor ratio in different stages of early‐onset fetal growth restriction and small for gestational age

• Published in: Acta obstetricia et gynecologica Scandinavica Vol. 100; no. 1; pp. 119 - 128
• Main Authors: Garcia‐Manau, Pablo, Mendoza, Manel, Bonacina, Erika, Garrido‐Gimenez, Carmen, Fernandez‐Oliva, Antoni, Zanini, Julia, Catalan, Marina, Tur, Helena, Serrano, Berta, Carreras, Elena
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2021
• Subjects: Adult; adverse pregnancy outcomes; angiogenic factors; Biomarkers - blood; Biometry; Case-Control Studies; Clinical outcomes; Female; fetal growth restriction; Fetal Growth Retardation - blood; Fetuses; Gestational Age; Growth disorders; Growth factors; Humans; Infant, Newborn; Infant, Small for Gestational Age - blood; Placenta Growth Factor - blood; placental growth factor; Predictive Value of Tests; Pregnancy; Pregnancy - blood; Pregnancy Proteins - blood; Prenatal development; Prospective Studies; small for gestational age; soluble fms‐like tyrosine kinase 1; Ultrasonic imaging; Ultrasonography, Prenatal; Vascular Endothelial Growth Factor Receptor-1 - blood; placental growth factor; soluble fms-like tyrosine kinase 1; angiogenic factors; adverse pregnancy outcomes; fetal growth restriction; small for gestational age
• ISSN: 0001-6349; 1600-0412
• DOI: 10.1111/aogs.13978

Introduction Increased soluble fms‐like tyrosine kinase to placental growth factor ratio (sFlt‐1/PlGF) has been demonstrated in early‐onset fetal growth restriction (FGR) and small for gestational age (SGA). sFlt‐1/PlGF cut‐offs have been described to assess preeclampsia severity; however, sFlt‐1/PlGF values present in early‐onset SGA and different FGR severity stages remain unknown. Hence, the objective of this study was to describe and compare the sFlt‐1/PlGF values and pregnancy outcomes among early‐onset SGA/FGR stages. Material and methods This is a prospective case‐control study conducted at Vall d’Hebron University Hospital. Singleton pregnancies with estimated fetal weight <10th centile and a control group of uncomplicated pregnancies between 20+0 and 31+6 weeks of gestation were enrolled. Study women were classified at diagnosis into different stages, according to estimated fetal weight centile and Doppler ultrasound. sFlt‐1/PlGF serum concentrations were measured at diagnosis and, together with pregnancy outcomes, were compared among FGR severity stages, SGA, and controls. Finally, correlations between sFlt‐1/PlGF values and time to delivery, gestational age at delivery, days of neonatal admission, and birthweight z‐scores were investigated. Results Among the 207 women enrolled, 32 (15.4%) had uncomplicated pregnancies, 49 (23.7%) pregnancies showed SGA, and 126 (60.9%) involved FGR (92 being stage I, 17 stage II, and 17 stage III). SGA and controls had similar median sFlt‐1/PlGF values (25.7 vs 27.1, P > .05) and pregnancy outcomes. However, all FGR stages had significantly poorer outcomes and greater sFlt‐1/PlGF values than those of SGA and controls. Furthermore, median values differed significantly among all FGR severity stages (9.76 for stage I; 284.3 for stage II, and 625.02 for stage III, P < .05) increasing with FGR severity as well as the frequency of adverse pregnancy outcomes. Additionally, a significant correlation was found between greater sFlt‐1/PlGF ratio values and gestational age at delivery, time from diagnosis to delivery, birthweight z‐scores, and time in neonatal intensive care unit (r = −.637, r = −.576, r = −.161, and r = .311, respectively). Conclusions Values of sFlt‐1/PlGF at diagnosis permit early‐onset FGR/SGA severity classification with good correlation with Doppler ultrasound findings and the occurrence of adverse outcomes. Thus, sFlt‐1/PlGF could aid in early‐onset FGR/SGA severity classification and clinical management when Doppler assessment is not feasible.