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

Abstract

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.

sFlt-1/PlGF Ratio in Prediction of Short-Term Neonatal Outcome of Small for Gestational Age Neonates

“…The authors found significant correlation between greater sFlt-1/PlGF ratio values and gestational age at delivery, time from diagnosis to delivery, birthweight z-scores, and time in NICU (r = −0.637, r = −0.576, r = −0.161, and r = 0.311, respectively). Therefore, they concluded that sFlt-1/PlGF could aid in early-onset FGR/SGA severity classification and clinical management when Doppler assessment is not feasible [16]. In our study sFlt-1/PlGF ratio was significantly related to birthweight and NICU hospitalization as well.…”

Association of sFlt-1 and C-reactive protein with outcomes in severe preeclampsia

“…Overexpression of sFlt-1, either naturally or caused by experimental mutant adenoviral injection in preeclamptic pregnant models, has been shown to be associated with hypertension, glomerular endotheliosis, delivery of growth-restricted offspring, and fetoplacental Doppler abnormalities. [24][25][26] Accordingly, in our study, sFlt-1 was elevated in severe PE compared to normal pregnant women and was more prominently elevated in those with composite adverse maternal outcomes. In addition, we demonstrated a correlation between sFlt-1 and fullPIERS scores, a previously validated model in our institution that was used to predict adverse maternal outcomes in PE.…”

Adverse Neonatal Outcome of Pregnancies Complicated by Preeclampsia

“…There are reports that preeclampsia is linked to longer hospitalizations of neonates in the neonatal intensive care units (NICU) [ 19 ]. Other authors have shown that a longer stay in the neonatal care unit may be related to an elevated sFlt-1/PlGF ratio or to an increased sFlt concentration or a decreased PlGF content alone [ 30 , 31 ]. In our study, the sFlt-1/PlGF ratio demonstrated similar correlations, with the neonates born to mothers with higher ratios spending more time in hospital.…”