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.

Objective: To 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).

Design: Prospective, observational cohort study.

Setting: Tertiary maternity hospital in Australia.

Population: There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32 weeks) and 109 (30.0%) late FGR (≥32 weeks).

Methods: Maternal 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 Measures: The 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.

Results: The 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).

Conclusions: Low maternal PlGF levels and elevated sFlt-1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies.