Serum sFlt-1/PlGF ratio combined with ANXA2 correlates with adverse pregnancy outcomes in women with suspected preeclampsia.

OBJECTIVE

Preeclampsia (PE) is a hypertensive disorder of pregnancy, and its occurrence is strongly associated with an imbalance in the sFlt-1/PlGF ratio of placental origin. Although this ratio has been used for clinical risk stratification, a single index has limited ability to characterize complex placental pathology. This study aimed to improve the early warning efficacy of adverse outcomes (PE progression, serious complications, and neonatal outcomes) in pregnant women with suspected PE, based on changes in circulating levels of the key regulator of placental vascular remodeling, annexin A2 (ANXA2), in conjunction with sFlt-1/PlGF ratio.

METHODS

This was a prospective cohort study that included 146 pregnant women with suspected PE at 20-33 weeks of gestation. The closest adverse outcome event or the last measurement before delivery (sFlt-1/PlGF, ANXA2) was analyzed. Composite adverse outcomes were defined as PE progression, severe maternal complications (HELLP syndrome, eclampsia, etc.), and neonatal outcomes (preterm labor, RDS, etc.). sFlt-1/PlGF ratios in combination with ANXA were used to stratify subjects. sFlt-1/PlGF ratios ≥ 85 and ANXA2 levels < 6.13 served as the high-risk group ( = 22), sFlt-1/PlGF ratio ≥ 85 or ANXA2 level < 6.13 as intermediate-risk group ( = 36), and the remaining as low-risk group ( = 88). The predictive value of the sFlt-1/PlGF ratio combined with ANXA2 for adverse pregnancy outcomes was assessed by ROC curve.

RESULTS

Maternal adverse outcomes, including HELLP syndrome, renal failure, pulmonary edema, DIC, and eclampsia were not significantly correlated with the sFlt-1/PlGF ratio (all  > 0.05). Adverse neonatal outcomes, PE/IUGR leading to early delivery (before 34 weeks) and the incidence of RDS were highest in the group with a sFlt-1/PlGF ratio > 85 (all  < 0.001). Subjects with adverse pregnancy outcomes were characterized by a higher sFlt-1/PlGF ratio and lower ANXA2 levels. The proportion of maternal HELLP syndrome was higher in the high-risk group (23.26%, 10/22,  < 0.001); neonatal RDS had the highest incidence in the high-risk group (23.26%, 10/22,  < 0.001). And three cases of placental abruption and one neonatal death occurred in the high-risk group. The combination of the two indicators had a high predictive value for adverse pregnancy outcomes in women with suspected PE (AUC 0.858, 95CI% 0.785-0.931).

CONCLUSION

An sFlt-1/PlGF ratio ≥ 85 combined with circulating ANXA2 < 6.13 ng/mL accurately identifies those at high risk for PE-related adverse outcomes, and its early warning efficacy is significantly superior to current single-biomarker strategies. This model provides a quantitative tool based on placental pathology for the timing of intervention in pregnant women with suspected PE and has potential for clinical translation.