Related Experiment Video
Updated: Jul 13, 2025
Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Cluster analysis of antiphospholipid antibodies-associated adverse pregnancy outcome patients: based on a 13-years
Yin Long1, Can Huang1,2,3,4, Yixin Cui1
1Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Wangfu Jing Street, Beijing, 100730, China.
Insights
Antiphospholipid antibodies (aPLs) are linked to adverse pregnancy outcomes (APOs). Cluster analysis identified four patient subtypes, aiding in risk stratification for better obstetric outcomes in antiphospholipid syndrome (APS).
Area of Science:
- Reproductive Immunology
- Obstetrics and Gynecology
- Clinical Pathology
Background:
- Antiphospholipid antibodies (aPLs) are a significant cause of adverse pregnancy outcomes (APOs).
- Obstetric Antiphospholipid Syndrome (APS) requires improved risk stratification for better patient management.
- Distinct clinical phenotypes among aPLs-positive patients with APOs are not well-defined.
Purpose of the Study:
- To identify distinct clinical phenotypes in patients with aPLs-associated adverse pregnancy outcomes (APOs) using cluster analysis.
- To facilitate risk stratification and improve pregnancy outcomes in obstetric Antiphospholipid Syndrome (APS).
- To correlate identified subtypes with specific pregnancy complications and placental pathology.
Main Methods:
- Retrospective analysis of a persistent aPLs-positive women cohort.
- Hierarchical cluster analysis incorporating demographic data, clinical manifestations, previous APOs, and antibody profiles.
- Histopathologic examination of placentae from a subset of patients.
Main Results:
- Four distinct clusters were identified among 209 patients and 477 pregnancies.
- Cluster 1 (triple aPLs positivity) showed high rates of gestational hypertension and preterm delivery.
- Cluster 2 (lupus anticoagulant positivity) indicated a high risk of overall gestational APOs.
- Cluster 3 (isolated aPLs-IgM) was associated with early miscarriage (60.92%).
- Cluster 4 (aPLs-IgG) presented with placenta insufficiency (22.73%).
- Live birth rates were lower in clusters 1 and 2 (69.20%); placental damage was most severe in cluster 1.
Conclusions:
- Cluster analysis successfully identified four clinical subtypes of aPLs-associated APOs.
- Triple aPLs positivity or high-risk lupus anticoagulant profiles are associated with gestational hypertension and preterm delivery.
- Isolated lupus anticoagulant, anticardiolipin, or anti-beta2-glycoprotein I positivity correlate with early fetal loss.
Abstract:
Antiphospholipid antibodies (aPLs) are the leading causes of adverse pregnancy outcomes (APOs). We conducted cluster analysis to identify distinct phenotypes among aPLs-associated APOs patients. This approach aims to facilitate risk stratification and improve pregnancy outcomes for obstetric APS. This was a retrospective study of persistent aPLs positive women cohort in Peking Union Medical College Hospital. Baseline demographic characteristics, clinical manifestation, previous APOs and antibodies profiles were included for hierarchical cluster analysis. Placentae from portions of patients were collected and performed the histopathologic diagnoses. Four clusters among 209 patients with 477 pregnancies were identified. Cluster 1 comprised patients with triple aPLs positivity and demonstrates a high incidence of gestational hypertension (34.92%, P < 0.05) and preterm delivery (20.63%, P < 0.05). Patients in cluster 2 were characterized by lupus anticoagulant (LA) positivity, with high risk of whole gestational APOs. Cluster 3 included patients with isolated aPLs-IgM isotype combined with early miscarriage (60.92%, P = 0.016). Patients in cluster 4 majorly presented aPLs-IgG isotype combined with placenta insufficiency (22.73%). During the follow-up, the live birth rate in cluster 1 and 2 was only 69.20%. Placenta pathology revealed the most severe impairment within cluster 1, whereas clusters 3 and 4 exhibited relatively milder damage. By cluster analysis, we identified four clinical subtypes of aPLs-associated APOs patients. Patients with triple antibodies or high-risk lupus characteristics were prone to occurred gestational hypertension and premature delivery. Isolated LA or aCL/aβ2GPI positivity were found to be more frequently associated with early-stage fetal loss.
