Design: Systematic review and meta-analysis of 22 observational studies
Population: Singleton pregnancies without pre-eclampsia, sampled before 29 weeks
Primary outcome: Angiogenic markers in later growth restriction or SGA vs unaffected
Effect: PlGF SMD -0.38 (95% CI -0.63 to -0.13); sensitivity 0.29, specificity 0.86

Placental growth factor (PlGF) and sFlt-1 are established in pre-eclampsia assessment. This meta-analysis of 22 observational studies asked whether they also flag growth restriction or small-for-gestational-age birth in pregnancies that never develop pre-eclampsia, using samples taken before 29 weeks.

PlGF was lower in pregnancies later found to be affected (SMD -0.38, 95% CI -0.63 to -0.13; 19 studies). sFlt-1 did not differ, and the higher sFlt-1/PlGF ratio seemed to be driven by the low PlGF. Across five accuracy studies, PlGF had a sensitivity of 0.29 and a specificity of 0.86.

Heterogeneity was very high (I² up to 92%), so the size of the difference is uncertain. A test that misses seven in ten affected pregnancies is not a screen on its own.

The value is as a component of future multimarker models. For now, growth surveillance by ultrasound and risk factors remains the standard.

Low PlGF before 29 weeks was the most consistent early marker of later growth restriction without pre-eclampsia.
PlGF alone detected only about 29% of affected pregnancies.
sFlt-1 did not differ, so the ratio adds little here beyond PlGF.
Keep ultrasound growth surveillance as the standard for growth restriction.
A low PlGF result in a normotensive woman is worth a closer look at fetal growth.

Why it matters

It tempers the hope that a pre-eclampsia biomarker can double as an early growth-restriction screen.

The statistics, in plain English

A standardised mean difference of -0.38 is a small-to-moderate shift. I² of 92% means the studies disagreed a great deal about its size. Sensitivity of 0.29 means about seven in ten affected pregnancies had a normal PlGF.