Prenatal prediction of neonatal respiratory distress syndrome using uteroplacental Doppler and placental microvascular perfusion indices: development of a risk model

Background: Neonatal respiratory distress syndrome (NRDS) is a leading cause of neonatal morbidity and mortality; however, current antenatal risk assessments lack physiological specificity. This study aimed to evaluate the early predictive value of mid-pregnancy placental perfusion indices derived from three-dimensional power Doppler (3D-PD) imaging—the vascularization index (VI), flow index (FI), and vascularization flow index (VFI)—together with conventional Doppler parameters [e.g., the uterine artery pulsatility index (UtA-PI), cerebroplacental ratio (CPR)] and maternal clinical factors for NRDS, and to develop and validate a nomogram for individualized risk stratification.

Methods: In this retrospective study, pregnant women who underwent second-trimester ultrasound at a tertiary hospital in Xiangyang between January 2021 and December 2024 and had traceable delivery outcomes were screened (n=610). After applying the exclusion criteria, 362 women were included in the study (NRDS group, n=58; control group, n=304). Maternal variables and UtA-PI, umbilical artery PI (UA-PI), middle cerebral artery PI (MCA-PI), and CPR were collected; VI, FI, and VFI were computed offline after placental volume acquisition. The primary outcome was NRDS, defined as the need for ≥24 hours of oxygen/respiratory support and neonatal intensive care unit (NICU) admission. Univariate and multivariate logistic regression analyses were performed to identify independent predictors; a nomogram was constructed from the final model. Discrimination, calibration, and clinical utility were assessed using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA), with internal validation by bootstrap resampling.

Results: Compared with the control group, the NRDS group showed higher UtA-PI (1.15±0.38 vs. 1.02±0.35, P<0.05), lower CPR (1.53±0.27 vs. 1.62±0.30, P=0.003), and reduced VI and VFI (both P<0.05). In the multivariate analysis, UtA-PI [odds ratio (OR) =1.52, 95% confidence interval (CI): 1.14–2.02], CPR (OR =0.70, 95% CI: 0.57–0.86), VFI (OR =0.75, 95% CI: 0.63–0.90), and gestational hypertension (OR =3.08, 95% CI: 1.44–6.59) were independent predictors of NRDS. The combined nomogram achieved an area under the curve (AUC) of 0.849 (95% CI: 0.745–0.871) with good calibration (mean absolute error: 0.046). DCA demonstrated higher net benefit across threshold probabilities of 0.05–0.75.

Conclusions: Integrating uteroplacental macrocirculatory resistance (UtA-PI and CPR) with microcirculatory perfusion (VFI) and key maternal factors enables effective early risk stratification for NRDS. The proposed nomogram is intuitive and practical, exhibits good discriminatory performance, and may guide delivery planning, perinatal monitoring, and timely intervention.