Angiogenic Factors and Doppler Evaluation in Normally Growing Fetuses at Routine Third-Trimester Scan: Prediction of Subsequent Low Birth Weight.

ABSTRACT

OBJECTIVE: To evaluate in normally growing fetuses at routine 32-36 weeks scan the performance of maternal angiogenic factors, Doppler and ultrasound indices in predicting smallness for gestational age (SGA) at birth. METHODS: A cohort of 1,000 singleton pregnancies with normal estimated fetal weight (EFW, ≥10th centile) at 32-36 weeks scan was included. At inclusion, Doppler indices (mean uterine artery pulsatility index [mUtA-PI], cerebroplacental ratio and normalized umbilical vein blood flow by EFW (ml/min/kg) were evaluated, and blood samples were collected and frozen. Nested in this cohort, maternal circulating placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by enzyme-linked immunosorbent assay in all cases with a birth weight <10th centile by customized standards and in an equivalent number of controls (birth weight ≥10th centile). RESULTS: 160 cases were included (80 SGA and 80 controls). EFW (2,128 vs. 2,279 g, p < 0.001), mUtA-PI z-values (-0.25 vs. -0.65, p = 0.034) and sFlt-1/PlGF ratio (11.10 vs. 6.74, p < 0.005) were lower in SGA. The combination of sFlt-1/PlGF ratio and EFW resulted in a 66.3% detection rate for subsequent SGA, with 20% of false-positives. Fetal Doppler indices were not predictive of SGA. CONCLUSIONS: In normally growing fetuses, maternal angiogenic factors add to ultrasound parameters in predicting subsequent SGA at birth. This supports further research to investigate composite scores in order to improve the definition and identification of fetal growth restriction.