Ophthalmic artery Doppler as potential surrogate marker of angiogenic imbalance in near‐term pregnancy
Year: 2026
Type: article
Abstract: OBJECTIVES: First, to evaluate whether the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is associated with hemodynamic changes in ophthalmic artery (OA) Doppler in near-term pregnancy. Second, to assess the performance of OA Doppler to rule in and rule out angiogenic factor imbalance. METHODS: This was a cross-sectional cohort study nested within the PE37 randomized controlled trial, involving nulliparous women recruited between January 2023 and January 2025 who underwent sFlt-1/PlGF ratio measurement between 35 + 0 and 36 + 6 weeks' gestation. We included a subsample of women who underwent OA Doppler evaluation, including measurement of OA peak systolic velocity (PSV) ratio and OA pulsatility index (PI), as well as assessment of mean arterial pressure (MAP) and mean uterine artery (UtA) PI. The operator was blinded to sFlt-1/PlGF ratio values. Trends in median values of OA and maternal-fetal Doppler parameters across sFlt-1/PlGF tertiles were analyzed using the Jonckheere-Terpstra test and quantile regression, adjusting for maternal body mass index, age and smoking status. The predictive performance of the OA-PSV ratio for sFlt-1/PlGF ratio ≥ 38 was evaluated using receiver-operating-characteristics-curve analysis. RESULTS: We included 203 women, of whom 62, 71 and 70 were in the lowest, middle and highest tertiles of the sFlt-1/PlGF ratio, respectively. With increasing sFlt-1/PlGF ratio tertile, there was a significant increase in the OA-PSV ratio (median, 0.45 (interquartile range (IQR), 0.39-0.53) vs 0.48 (IQR, 0.41-0.58) vs 0.59 (IQR, 0.50-0.66); adjusted P < 0.001), a significant decrease in OA-PI (median, 2.20 (IQR, 1.92-2.61) vs 2.13 (IQR, 1.86-2.37) vs 1.86 (IQR, 1.60-2.26); adjusted P = 0.031) and a significant increase in MAP (median, 87.0 (IQR, 82.7-92.0) mmHg vs 88.7 (IQR, 83.7-93.7) mmHg vs 94.7 (IQR, 89.3-100.0) mmHg; adjusted P < 0.001). In contrast, no significant trend was observed in mean UtA-PI across sFlt-1/PlGF ratio tertiles. Among those individuals with an OA-PSV ratio < 0.61, 90.5% truly had a sFlt-1/PlGF ratio < 38, at a 15% false-positive rate. CONCLUSIONS: This study provides new evidence of a significant association between the sFlt-1/PlGF ratio and OA Doppler parameters in near-term pregnancies, suggesting that OA Doppler indices, particularly the PSV ratio, reflect angiogenic imbalance. Given its non-invasive nature, accessibility and low cost, OA Doppler emerges as a promising surrogate tool for ruling out angiogenic imbalance. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
DOI: 10.1002/uog.70270
Institutions: Hospital Sant Joan de Déu Barcelona, Hospital Clínic de Barcelona, Universitat de Barcelona, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Agostino Gemelli University Polyclinic, Centre for Biomedical Network Research on Rare Diseases, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Institut de Recerca Sant Joan de Déu, Instituto de Salud Carlos III, Red de Salud Materno Infantil y del Desarrollo
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,940
Funder: Instituto de Salud Carlos III
OpenAlex ID: W7166555178
