title: First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery.
abstract: OBJECTIVE
  To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict preterm delivery.
  
  
  METHODS
  We examined 54 722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the median (MoM) of the expected normal median for a pregnancy of the same gestation and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length. The association between free beta-hCG, PAPP-A and delta NT and the incidence of preterm delivery before 37 weeks or early preterm delivery before 34 weeks was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratios (LR) for preterm delivery and early preterm delivery were also calculated after excluding other adverse pregnancy complications.
  
  
  RESULTS
  The risk of preterm delivery increased with decreasing maternal serum PAPP-A. In the 3132 cases delivering before 37 weeks the PAPP-A MoM was 0.91 and in the 1060 cases delivering before 34 weeks the PAPP-A MoM was 0.90. At the 5th centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for delivery before 37 weeks and before 34 weeks were 1.92 and 2.35, respectively. The respective values for the 5th centile of free beta-hCG (0.41 MoM) were 1.18 and 1.08 and for the 95th centile of delta NT they were 0.91 and 0.77, respectively.
  
  
  CONCLUSIONS
  Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk of preterm or early preterm delivery. The LR profiles provided at various levels of PAPP-A may be of some help in counseling women with such results and may raise awareness among healthcare professionals for increased surveillance in such cases.
authors.affiliation: Prenatal Screening Unit, Clinical Biochemistry Department, Harold Wood Hospital, Romford, Essex, UK. KevinSpencer1@aol.com
authors.forename: K
authors.initials: K
authors.lastname: Spencer
authors.forename: N J
authors.initials: NJ
authors.lastname: Cowans
authors.forename: F
authors.initials: F
authors.lastname: Molina
authors.forename: K O
authors.initials: KO
authors.lastname: Kagan
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D000782:Aneuploidy; D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism*; D005260:Female; D006801:Humans; D048208:Nuchal Translucency Measurement; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D047928:Premature Birth / Q000175:diagnosis*; D011446:Prospective Studies; D016216:Ultrasonography, Prenatal
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A