PO:14:200 | Placental markers of angiogenesis in pregnant women with antiphospholipid syndrome: predictive role of SFLT-1, PLGF, and uterine artery doppler in preeclampsia

Maria Bernadette Cilona¹, Valentina Canti¹, Martina Beschi², Federica Pasi³, Serena Girardelli³, Mirko Pozzoni³, Maria Teresa Castiglioni³, Paolo Cavoretto³, Patrizia Rovere-Querini^1|2 | ¹Unit of Internal Medicine and Division of Immunology, Transplantation and Infectious diseases, IRCCS San Raffaele Hospital Milan, Italy; ²Vita-Salute San Raffaele University Milan, Italy; ³Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute Milan, Italy

Aim of the study. Abnormal placentation, inflammation, complement activation, and angiogenic imbalance especially involving sFlt-1 and PLGF, are key factors in the pathogenesis of O-APS. Uterine artery Doppler can identify increased resistance due to impaired spiral artery remodeling, a common feature in O-APS contributing to adverse outcomes. This study aimed to evaluate the predictive value of uterine artery Doppler (mean pulsatility index, PI) and angiogenic biomarkers (sFlt-1/PLGF ratio) for the early detection of preeclampsia and other obstetric complications in O-APS patients treated with standard therapy, with or without hydroxychloroquine (HCQ).

Methods. A monocentric, retrospective cohort study was conducted including pregnant patients aged 18–45 diagnosed with primary O-APS, based on the 2006 revised Sydney criteria, and a control group of healthy pregnant individuals. All participants were prospectively followed throughout gestation. O-APS patients received standard treatment with or without HCQ. Uterine artery Doppler (mean PI) and maternal serum levels of sFlt-1/PLGF were assessed in each trimester. Pregnancy outcomes, including birth weight and occurrence of preeclampsia or fetal loss, were recorded. Multiple regression analysis was used to evaluate the association between biomarker values and neonatal birth weight.

Results. A total of 31 pregnant individuals were included: 19 with O-APS and 12 healthy controls. Median age was 34 years (IQR 30–37) in the O-APS group and 32 years (IQR 29–35) in controls. sFlt-1/PlGF ratios were higher in O-APS across all trimesters, but differences were not statistically significant. Mean PI declined physiologically in both groups, but remained consistently higher in O-APS. Second-trimester PI was significantly lower in patients treated with HCQ compared to those receiving standard therapy alone [0.63 (0.54–0.79) vs 1.22 (0.91–1.55), p=0.04]. Seventeen of 19 O-APS pregnancies reached term, with a median birth weight of 2965g (2760–3260) vs 3460g (2825–3745) in controls (p=0.15). Two adverse outcomes occurred in the O-APS group: one severe early-onset preeclampsia with IUGR and one spontaneous miscarriage. These patients showed markedly elevated first-trimester sFlt-1/PlGF ratios [222 (137.5–306.5)] compared to those with successful outcomes [41.5 (23.75–56.25), p=0.14]. In multivariate analysis, first-trimester sFlt-1/PlGF ratio significantly predicted birth weight (R²=0.29).

Conclusions. Elevated sFlt-1/PLGF ratios and higher uterine artery PI in the first trimester may serve as early markers of adverse pregnancy outcomes in O-APS. The addition of HCQ may improve placental vascular resistance. These findings support the potential role of these biomarkers in early risk stratification, which should be validated in larger prospective studies.