First-trimester screening for fetal growth restriction using Doppler color flow analysis of the uterine artery and serum PAPP-A levels in unselected pregnancies

Purpose: To explore an early diagnostic model for fetal growth restriction (FGR) at 11-13 (+6 days) gestational weeks using Doppler analysis of the uterine artery and measurements of pregnancy-associated plasma protein-A (PAPP-A). Methods: This was a prospective study which included 1796 singleton pregnant women, who received routine pregnancy examination at 11-13 (+6 days) gestational weeks in Shanghai Changning Maternity and Infant Health Hospital between 1 June 2017 and 31 July 2018. Uterine artery pulsatility index (PI), uterine resistance index (RI), and notching were recorded using the Doppler ultrasound detector (Voluson E8; GE Healthcare, Kretztechnik, Zipf, Austria). Maternal serum PAPP-A was assayed using time-resolved fluorescence immunoassay (Perkin-Elmer Life Sciences, Waltham, MA, USA) and analyzed using Fetal Medicine Foundation software. Maternal and neonatal outcomes were followed. Results: Out of 1796 pregnant women aged 18-42 years, 76 (4.2%) mothers had FGR fetus. In the FGR fetuses, the mean uterine artery PI and RI were higher, the PAPP-A levels were 0.42-fold lower (all p values < .05), and notching was 40% higher (p < .0001) than in non-FGR fetuses. The sensitivity and specificity of early diagnosis of FGR and the area under the curve for the combination of uterine artery PI and PAPP-A were 0.788 (95% CI: 0.735, 0.842), 0.816, and 0.758, respectively. A combination of PAPP-A and Doppler analysis of uterine artery was better than individual measurements for predicting FGR (all p values < .05), and the specificity was significantly improved after including serum PAPP-A. Conclusion: The combination of uterine artery PI and PAPP-A measured at 11-13 (+6 days) gestational weeks provides a sensitive and specific predictor for early diagnosis of FGR.