What is the clinical evidence from this study?

Study design: Cohort. Population: Preeclampsia (n=1124). Intervention: High HDL subtype (HHS) vs. High triglyceride subtype (HTS). Primary outcome: Low birth weight (OR 6.271, 95% CI 2.478-15.87, p=<0.001).

What question did this study set out to answer?

The study aims to identify distinct maternal circulating lipid metabolic subtypes in women with preeclampsia and their association with clinical outcomes.

June 27, 2026BMC Pregnancy and Childbirth0 citationsOpen Access

Maternal circulating lipid metabolic heterogeneity in preeclampsia: machine learning identifies clinically distinct subtypes

Q: What are the key findings of this study?

The high HDL subtype of preeclampsia was associated with a significantly higher risk of low birth weight compared to the high triglyceride subtype (19.8% vs 3.8%, OR 6.271).

Q: What question did this study set out to answer?

The study aims to identify distinct maternal circulating lipid metabolic subtypes in women with preeclampsia and their association with clinical outcomes.

JGJianfeng GanObstetrics and Gynecology Hospital of Fudan University LCLi CaoFudan University JSJ SHAOMinistry of Agriculture

Key Result

The high HDL subtype of preeclampsia was associated with a significantly higher risk of low birth weight compared to the high triglyceride subtype (19.8% vs 3.8%, OR 6.271).

Key Points

The study aims to identify distinct maternal circulating lipid metabolic subtypes in women with preeclampsia and their association with clinical outcomes.
Conducted a retrospective cohort study involving 1,124 women with preeclampsia from 2018-2022.
Analyzed third-trimester serum lipids including total cholesterol, triglycerides, HDL-C, and LDL-C.
Utilized unsupervised k-means clustering to identify lipid metabolic subtypes.
Identified four lipid metabolic subtypes: low metabolic subtype (33.5%), high HDL subtype (35.0%), high triglyceride subtype (11.7%), and high metabolic subtype (19.8%).
The high triglyceride subtype had the lowest rates of preterm birth (3.1%, p = 0.016) and low birth weight (3.8%, p < 0.001).
The high metabolic subtype displayed the highest blood pressure and proteinuria levels.

Study Design

Type

Cohort (n=1,124)

Multicenter

Structured PICO

Do distinct maternal circulating lipid metabolic subtypes associate with different clinical outcomes in women with preeclampsia?

Population

1,124 pregnant women with preeclampsia evaluated in the third trimester to identify distinct maternal circulating lipid metabolic subtypes and their association with clinical outcomes.

Exposure

Stratification into lipid metabolic subtypes using unsupervised k-means clustering of third-trimester serum lipids (total cholesterol, triglycerides, HDL-C, and LDL-C)

Comparator

Comparison across the four identified lipid metabolic clusters

Outcome

Clinical characteristics and pregnancy outcomes (including preterm birth, low birth weight, blood pressure, and proteinuria)hard clinical

Machine learning-based clustering of third-trimester serum lipids identifies four distinct subtypes of preeclampsia with different clinical trajectories and pregnancy outcomes.

Main Result

Odds Ratio: 6.271 (95% CI 2.478–15.87)

Absolute Event Rate: 19.8% vs 3.8%

p-value: p=<0.001

Limitations

Lipid measurements were obtained in the third trimester without recording the exact gestational week at sampling.
Reliance on four conventional lipid markers may oversimplify the complexity of placental and maternal lipid metabolism.
Potential unmeasured confounders such as dietary lipids, pre-pregnancy dyslipidemia, medication use, and clinical management decisions.
Conducted at a single tertiary referral center, which may overrepresent severe or atypical cases and limit generalizability.
Absence of a normotensive control group prevents direct comparison to uncomplicated pregnancies.

Abstract

Preeclampsia is associated with dyslipidemia. Maternal circulating lipid profiles may reflect underlying placental-metabolic interactions. We aimed to identify distinct maternal circulating lipid metabolic subtypes and assess their association with clinical outcomes among preeclamptic women. A retrospective cohort study of 1,124 women with preeclampsia (2018–2022) was conducted. Third-trimester serum lipids (total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)) were analyzed. Unsupervised k-means clustering (Euclidean distance, k = 4 optimized by consensus culmulative distribution function) was used to identify subtypes. Clinical characteristics and pregnancy outcomes were compared across clusters. We identified four lipid metabolic subtypes of preeclampsia with distinct clinical profiles. Four subtypes were identified: Cluster 1 (low metabolic subtype, LMS, 33.5%), Cluster 2 (high HDL subype, HHS, 35.0%), Cluster 3 (high triglyceride subtype, HTS, 11.7%), and Cluster 4 (high metabolic subtype, HMS, 19.8%). The HTS subtype with elevated triglycerides and highest pre-pregnancy body mass index (median 23.92 kg/m 2 ), had the lowest rates of preterm birth (3.1%, p = 0.016) and low birth weight (3.8%, p < 0.001). Conversely, the HMS subtype exhibited the highest blood pressure and proteinuria levels. This study establishes lipid-driven subtypes of preeclampsia with distinct clinical trajectories, suggesting placental lipid handling may be a key modulator in disorder heterogeneity. This heterogeneity underscores the importance of lipid-based stratification for understanding placental dysfunction in preeclampsia.

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