title: First trimester hyperglycosylated human chorionic gonadotrophin in serum - a marker of early-onset preeclampsia.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Biomedicum Helsinki, PB 700, 00029 Helsinki, Finland. Electronic address: elina.keikkala@hus.fi.
authors.forename: E
authors.initials: E
authors.lastname: Keikkala
authors.forename: P
authors.initials: P
authors.lastname: Vuorela
authors.forename: H
authors.initials: H
authors.lastname: Laivuori
authors.forename: J
authors.initials: J
authors.lastname: Romppanen
authors.forename: S
authors.initials: S
authors.lastname: Heinonen
authors.forename: U-H
authors.initials: UH
authors.lastname: Stenman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D005387:Finland / Q000453:epidemiology; D006031:Glycosylation; D006785:Hospitals, University; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D062145:Maternal Serum Screening Tests; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D025341:Principal Component Analysis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Hyperglycosylated human chorionic gonadotrophin; Preeclampsia; Pregnancy-associated plasma protein A; Sensitivity and specificity; Small-for-gestational-age