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Maternal sFlt-1/PlGF Ratio to Distinguish Pathological Fetal Growth Restriction From Constitutional Smallness:
Zoe Byrne1,2, Sonja Brennan1,2, David Watson1,2
1Maternal-Fetal Medicine Unit, Townsville University Hospital, Townsville, Queensland, Australia.
BJOG : an International Journal of Obstetrics and Gynaecology
|January 5, 2026
Summary
The maternal soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio helps distinguish fetal growth restriction (FGR) from small-for-gestational-age (SGA) fetuses. Elevated ratios indicate placental insufficiency, guiding closer surveillance in FGR pregnancies.
Area of Science:
- Obstetrics and Gynecology
- Maternal-Fetal Medicine
- Reproductive Biology
Background:
- Distinguishing pathological fetal growth restriction (FGR) from constitutionally small-for-gestational-age (SGA) fetuses is a significant clinical challenge.
- The maternal soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio serves as a biomarker for placental angiogenic imbalance and insufficiency.
Purpose of the Study:
- To evaluate the diagnostic performance of the maternal sFlt-1/PlGF ratio in differentiating FGR from SGA and appropriate-for-gestational-age (AGA) pregnancies.
- To assess the utility of the sFlt-1/PlGF ratio in identifying placental insufficiency.
Main Methods:
- A comprehensive literature search was conducted across major databases (PubMed, Scopus, Web of Science, Embase, Cochrane CENTRAL, Google Scholar) up to January 14, 2025.
- Forty observational studies, encompassing over 25,000 pregnancies, were included, reporting maternal sFlt-1/PlGF ratios in FGR, SGA, or AGA classifications.
- Data extraction and quality assessment were performed by two independent reviewers, with findings synthesized narratively and a meta-analysis conducted for studies directly comparing FGR and SGA.
Main Results:
- Fetal growth restriction (FGR) cases consistently demonstrated higher sFlt-1/PlGF ratios compared to appropriate-for-gestational-age (AGA) pregnancies across gestation.
- Small-for-gestational-age (SGA) fetuses showed only modest or no elevation in sFlt-1/PlGF ratios.
- A meta-analysis of four studies (n=614) revealed significantly higher log-transformed sFlt-1/PlGF ratios in FGR compared to SGA (SMD 0.58, 95% CI 0.35-0.81) with low heterogeneity.
Conclusions:
- The maternal sFlt-1/PlGF ratio is a valuable adjunctive marker for placental insufficiency.
- Normal sFlt-1/PlGF ratios can support expectant management in SGA pregnancies with reassuring ultrasound and Doppler findings.
- Elevated sFlt-1/PlGF ratios in FGR pregnancies necessitate closer maternal and fetal surveillance.
