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Free leptin index and PAPP-A: a first trimester maternal serum screening test for pre-eclampsia
Paula L Hedley1, Sophie Placing, Karen Wøjdemann
1Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
Insights
First-trimester screening for pre-eclampsia (PE) can be improved by combining free leptin index (fLI) and PAPP-A. This combined approach enhances detection rates for PE, aiding early intervention strategies.
Area of Science:
- Obstetrics and Gynecology
- Maternal-Fetal Medicine
- Biomarker Discovery
Background:
- Pre-eclampsia (PE) is a significant pregnancy complication.
- Early detection of PE in the first trimester is crucial for timely intervention, such as low-dose aspirin prophylaxis.
- Maternal serum screening offers a non-invasive method for assessing PE risk.
Purpose of the Study:
- To evaluate the performance of first-trimester maternal serum screening for pre-eclampsia (PE).
- To assess the utility of free leptin index (fLI) and PAPP-A as biomarkers for PE detection.
- To determine if combining fLI and PAPP-A improves screening accuracy.
Main Methods:
- Analysis of first-trimester serum samples from 126 PE pregnancies and 289 controls.
- Calculation of gestational age and maternal weight-independent log MoM values for fLI and PAPP-A.
- Utilizing receiver-operator-characteristics curves to assess marker performance.
- Employing Monte Carlo simulation for estimating population screening performance.
Main Results:
- Free leptin index (fLI) was significantly elevated in PE pregnancies compared to controls (p < 0.001).
- PAPP-A levels were significantly reduced in PE pregnancies compared to controls (p < 0.001).
- Combined screening with fLI and PAPP-A demonstrated improved detection rates (22-35%) at various false positive rates (6-12%).
Conclusions:
- The combination of PAPP-A and fLI offers superior screening performance for pre-eclampsia compared to using either marker alone.
- This combined biomarker approach holds promise for enhancing early detection of PE.
- Improved screening can facilitate earlier prophylactic interventions, potentially reducing PE incidence and severity.
Background:
Prophylaxis with low-dose aspirin may reduce the risk of pre-eclampsia (PE) if introduced in first trimester. The performance of first trimester maternal serum screening for PE using free leptin index (fLI) and PAPP-A, where fLI = leptin/leptin soluble receptor was studied.
Methods:
First trimester serum samples from 126 PE pregnancies and 289 control pregnancies were studied. fLI and PAPP-A were converted into gestational age and maternal weight independent log MoM values of PAPP-A and fLI. The screening performance of markers was studied by receiver-operator-characteristics curves. The performance of population screening was estimated by Monte Carlo simulation.
Results:
fLI was significantly (p < 0.001) elevated [mean log MoM 0.2165 (SD: 0.2604)] compared to controls [mean log MoM -0.0368 (SD: 0.3132)] and PAPP-A was significantly (p < 0.001) reduced [mean log MoM -0.0133 (SD: 0.2661)] compared to controls [mean log MoM 0.0474 (SD: 0.2521)] in PE pregnancies. There was no correlation between fLI and PAPP-A in control or PE pregnancies. Combined fLI and PAPP-A screening for PE had estimated population detection rates of 22% and 35% for false positives rates of 6% and 12%, respectively.
Conclusion:
Combining PAPP-A and fLI improves screening performance for PE compared to single marker screening.
