Prediction of Preeclampsia in Nulliparous Women according to First Trimester Maternal Factors and Serum Markers

Fetal Diagn Ther. 2020;47(4):277-283. doi: 10.1159/000503229. Epub 2019 Oct 17.

Abstract

Objective: To evaluate the performance of maternal risk factors (BMI and mean arterial pressure [MAP]) and first-trimester maternal serum markers in the early prediction of preeclampsia (PE) in nulliparous women.

Material and methods: This was a case-cohort study based on a cohort of 14,207 nulliparous women. A total of 213 cases with term PE (from 37 weeks + 0 days) and 55 cases with preterm PE (before 37 weeks + 0 days) were identified and validated. Randomly, 449 controls were selected. Serum samples previously collected for the double test (pregnancy-associated plasma protein A [PAPP-A] and free β human chorionic gonadotrophin [hCGβ]) as part of the first-trimester screening program were retrieved and analyzed for placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL). Concentrations were transformed to multiples of the median (MoM). Multivariate regression analysis was used for prediction models. Receiver-operating characteristics (ROC) curves were used for evaluation of the screening performance.

Results: In preterm PE, the PlGF (0.79 MoM), sFlt-1 (0.86 MoM), NGAL (1.15 MoM), and PAPP-A (0.89 MoM) medians were significantly altered. In term PE, PlGF (0.90 MoM) and NT-proBNP (0.86 MoM) medians were significantly reduced. The combination of MAP and PlGF yielded a 39% detection rate of preterm PE for a 10% false-positive rate. The combination of MAP, BMI, and PlGF yielded a 33% detection rate of term PE with a 10% false-positive rate.

Conclusion: First-trimester MAP, maternal serum PlGF, and NGAL are markers of preterm PE. Maternal serum sFlt-1 is a significant marker of preterm PE, but only early in the first trimester. First-trimester maternal serum NT-proBNP is not a predictor of PE. Screening performance for PE with these markers individually or in combination is modest.

Keywords: First trimester; Maternal serum; Preeclampsia.

MeSH terms

  • Adult
  • Arterial Pressure / physiology*
  • Biomarkers / blood
  • Chorionic Gonadotropin, beta Subunit, Human / blood
  • Female
  • Humans
  • Lipocalin-2 / blood*
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Placenta Growth Factor / blood*
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis*
  • Pregnancy
  • Pregnancy Trimester, First / blood*
  • Pregnancy-Associated Plasma Protein-A / metabolism
  • Risk Factors
  • Vascular Endothelial Growth Factor Receptor-1 / blood*

Substances

  • Biomarkers
  • Chorionic Gonadotropin, beta Subunit, Human
  • Lipocalin-2
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Pregnancy-Associated Plasma Protein-A