Maternal sFlt-1/PlGF Ratio to Distinguish Pathological Fetal Growth Restriction From Constitutional Smallness: Systematic Review.

Abstract

<h4>Background</h4>Distinguishing pathological fetal growth restriction (FGR) from constitutionally small-for-gestational-age (SGA) fetuses remains clinically challenging. The maternal soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio reflects placental angiogenic imbalance and may assist recognition of placental insufficiency.<h4>Objectives</h4>To assess the performance of the maternal sFlt-1/PlGF ratio for differentiating FGR from SGA and appropriate-for-gestational-age (AGA) pregnancies.<h4>Search strategy</h4>PubMed, Scopus, Web of Science, Embase, Cochrane CENTRAL and Google Scholar were searched from inception to 14 January 2025 using MeSH and text terms for "sFlt-1", "PlGF", "fetal growth restriction", and "small-for-gestational-age".<h4>Selection criteria</h4>Peer-reviewed human studies reporting maternal sFlt-1/PlGF ratios in pregnancies classified as FGR, SGA or AGA.<h4>Data collection and analysis</h4>Two reviewers independently screened records; one reviewer extracted data and assessed quality with second-reviewer verification (> 30%). Owing to heterogeneity, findings were synthesised narratively, with a meta-analysis restricted to studies directly comparing FGR and SGA.<h4>Main results</h4>Forty observational studies (> 25 000 pregnancies) were included. Across gestation, FGR consistently showed higher sFlt-1/PlGF ratios than AGA. SGA exhibited modest or no elevation. Four studies (n = 614) enabled pooling: log-transformed ratios were significantly higher in FGR than SGA (SMD 0.58, 95% CI 0.35-0.81) with low heterogeneity. Ratios were most discriminatory in early-onset placental FGR.<h4>Conclusions</h4>The sFlt-1/PlGF ratio is best considered an adjunctive indicator of placental insufficiency. Normal results can support expectant management in SGA when ultrasound and Doppler are reassuring, whereas elevated values warrant closer surveillance.