Changes in uterine artery Doppler velocimetry and circulating angiogenic factors in the first half of pregnancies delivering small-for-gestational age neonates: Placental Doppler and biomarker slopes in smallness-for-gestational age

Objective To assess the relationship between longitudinal changes in placental Doppler indices and maternal circulating angiogenic factors in the first half of pregnancy and delivery of a small-for-gestational-age (SGA) neonate, and ascertain whether longitudinal evaluation of these variables improves the prediction achieved by second-trimester cross-sectional evaluation. Methods From a prospective cohort of unselected singleton pregnancies undergoing first-trimester screening for aneuploidy, 138 were included in this study. Of these, 46 were complicated by SGA (delivering after 34 weeks’ gestation with a birth weight< 10th centile) and 92 were appropriate-for-gestational-age (AGA) pregnancies, which were included as controls (ratio 1:2). First-to-second trimester longitudinal changes in uterine artery (UtA) Doppler indices and maternal circulating levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed. Results Compared with the AGA group, SGA pregnancies had significantly higher UtA impedance in the first (Z-score: 0.46 vs –0.57; P< 0.001) and second (Z-score: 1.71 vs –0.75; P< 0.001) trimesters. Likewise, the sFlt-1/PlGF ratio was significantly higher in SGA than in AGA pregnancies in the first (98.0 vs 67.9; P=0.01) and early second (22.4 vs 8.8; P< 0.001) trimesters. The predictive performance of the longitudinal changes in UtA Doppler indices for SGA was significantly lower than that of second-trimester cross-sectional values (area Correspondence to: Dr S. Triunfo, Maternal-Fetal Medicine Department, Hospital Clinic, University of Barcelona, Sabino de Arana 1, 08028 Barcelona, Spain (e-mail: [email protected]) Accepted: 25 May 2016 under receiver–operating characteristics curve (AUC), 60.8% vs 84.3%; P= 0.0035). The detection rate of SGA, at a 10% false-positive rate (FPR), was 17.7% by longitudinal changes in UtA Doppler and 56.2% by second-trimester cross-sectional UtA Doppler values. Similarly, the predictive performance of the longitudinal changes in PlGF was significantly lower than that of early second-trimester cross-sectional values (AUC, 71.4% vs 76.5%; P= 0.008). The detection rate of SGA at a 10% FPR was 40.6% when screening by longitudinal changes in PlGF and 52.1% when screening by early second-trimester cross-sectional values. Conclusions Firstand second-trimester UtA Doppler velocimetry and maternal circulating angiogenic markers have clinical utility as a cross-sectional assessment for the identification of pregnancies at high risk of delivering a SGA neonate, however, they do not improve prediction when their longitudinal changes are used. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.