Prediction of preterm birth in growth‐restricted and appropriate‐for‐gestational‐age infants using maternal PlGF and the sFlt‐1/PlGF ratio—A prospective study

Abstract

ObjectiveTo assess the utility of placental growth factor (PlGF) levels and the soluble fms‐like tyrosine kinase‐1/placental growth factor (sFlt‐1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA).DesignProspective, observational cohort study.SettingTertiary maternity hospital in Australia.PopulationThere were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32+0 weeks) and 109 (30.0%) late FGR (≥32+0 weeks).MethodsMaternal serum PlGF and sFlt‐1/PlGF ratio were measured at 4‐weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt‐1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt‐1/PlGF ratio to the time of birth or censoring.Main outcome measuresThe primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained.ResultsThe early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p < 0.001) and higher median sFlt‐1 levels (2774 ng/L versus 2096 ng/L, p < 0.001) and sFlt‐1/PlGF ratio higher (35 versus 10, p < 0.001). Both PlGF <100 ng/L and elevated sFlt‐1/PlGF ratio were strongly predictive for PTB as well as PTB within 1, 2 and 3 weeks of diagnosis. For both FGR and AGA groups, PlGF <100 ng/L or raised sFlt‐1/PlGF ratio were strongly associated with increased risk for medically indicated PTB. The highest RR was seen in the FGR cohort when PlGF was <100 ng/L (RR 35.20, 95% CI 11.48–175.46).ConclusionsLow maternal PlGF levels and elevated sFlt‐1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies.