First trimester hyperglycosylated human chorionic gonadotrophin in serum - a marker of early-onset preeclampsia

Placenta. 2013 Nov;34(11):1059-65. doi: 10.1016/j.placenta.2013.08.006. Epub 2013 Aug 28.

Abstract

Introduction: Recent studies indicate that treatment with low-dose aspirin may reduce the risk of preeclampsia. Thus, early prediction of preeclampsia is needed. Low serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG-h) are associated with early pregnancy loss. We therefore studied whether it may serve as an early marker of preeclampsia.

Methods: A nested case-control study included 158 women with subsequent preeclampsia, 41 with gestational hypertension, 81 normotensive women giving birth to small-for-gestational-age (SGA) infants and 427 controls participating in first trimester screening for Down's syndrome between 8 and 13 weeks of gestation. Gestational-age-adjusted multiples of medians (MoMs) were calculated for serum concentrations of hCG-h, the free beta subunit of hCG (hCGβ) and pregnancy-associated plasma placental protein A (PAPP-A) and the proportion of hCG-h to hCG (%hCG-h). Clinical risk factors including mean arterial pressure (MAP) and parity were also included in the risk calculation.

Results: In women with subsequent preeclampsia %hCG-h was lower than in controls (median MoM 0.92, P < 0.001), especially in 29 cases with early-onset preeclampsia (0.86, P < 0.001), in which PAPP-A also was reduced (0.95, P = 0.001). At 90% specificity for prediction of early-onset preeclampsia, sensitivity was 56% (95% confidence interval, 52-61%) for %hCG-h, 33% (28-37%) for PAPP-A, and 69% (51-83%) for the combination of these with first trimester MAP and parity. The area under the receiver-operating characteristic (ROC) curve for the combination of all these was 0.863 (0.791-0.935).

Conclusions: hCG-h is a promising first trimester marker for early-onset preeclampsia. Addition of PAPP-A and maternal risk factors may improve the results.

Keywords: Hyperglycosylated human chorionic gonadotrophin; Preeclampsia; Pregnancy-associated plasma protein A; Sensitivity and specificity; Small-for-gestational-age.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Chorionic Gonadotropin / blood*
  • Down-Regulation*
  • Female
  • Fetal Growth Retardation / blood
  • Fetal Growth Retardation / diagnosis
  • Fetal Growth Retardation / epidemiology
  • Finland / epidemiology
  • Glycosylation
  • Hospitals, University
  • Humans
  • Hypertension, Pregnancy-Induced / blood
  • Hypertension, Pregnancy-Induced / diagnosis
  • Hypertension, Pregnancy-Induced / epidemiology
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Male
  • Maternal Serum Screening Tests
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis*
  • Pre-Eclampsia / epidemiology
  • Pregnancy
  • Pregnancy Trimester, First
  • Pregnancy-Associated Plasma Protein-A / analysis
  • Principal Component Analysis
  • Risk Factors
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers
  • Chorionic Gonadotropin
  • Pregnancy-Associated Plasma Protein-A
  • PAPPA protein, human