title: Maternal serum PAPP-A and free β-hCG at 12, 22 and 32 weeks' gestation in screening for pre-eclampsia.
abstract: OBJECTIVE
  To examine the distribution of maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG) at 12, 22 and 32 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of these biomarkers in screening for PE.
  
  
  METHODS
  Serum PAPP-A and free β-hCG were measured in 94 989 cases at 11-13 weeks, 7597 at 19-24 weeks and 8088 at 30-34 weeks' gestation. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with PAPP-A and free β-hCG. The empirical and model-based performance of screening for preterm PE requiring delivery < 37 weeks' gestation and term PE with delivery ≥ 37 weeks was estimated.
  
  
  RESULTS
  Combined screening with maternal factors and serum PAPP-A at 11-13 and 30-34 weeks and with maternal factors and serum free β-hCG at 19-24 and 30-34 weeks improved the prediction provided by maternal factors alone for preterm PE. The detection rate, at a 10% false-positive rate, for preterm PE by screening with maternal factors was about 45% which improved to 51% and 53% by combined screening with PAPP-A at 11-13 weeks and 30-34 weeks, respectively, and 55% and 54% by combined screening with free β-hCG at 19-24 weeks and 30-34 weeks, respectively. Measurement of serum PAPP-A and free β-hCG was not useful in the prediction of term PE.
  
  
  CONCLUSIONS
  Measurement of serum PAPP-A and free β-hCG could improve the prediction of preterm PE provided by maternal characteristics and medical history alone. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Institute of Health Research, University of Exeter, Exeter, UK.
authors.forename: A
authors.initials: A
authors.lastname: Wright
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Guerra
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Pellegrino
authors.affiliation: Institute of Health Research, University of Exeter, Exeter, UK.
authors.forename: D
authors.initials: D
authors.lastname: Wright
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood; D011263:Pregnancy Trimester, Third / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Bayes' theorem; free β-human chorionic gonadotropin; impaired placentation; pre-eclampsia; pregnancy-associated plasma protein-A; pyramid of pregnancy care; screening