title: Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers.
abstract: OBJECTIVE
  Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3- to 4-fold, in open spina bifida. We assessed whether combined screening using BPD, AFP, and other serum markers at 11-13 weeks would increase detection.
  
  
  METHODS
  Maternal AFP levels were measured on serum stored at 11-13 weeks in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median (MoM) for gestational age. All samples had been measured for free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published.
  
  
  RESULTS
  The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P < .01, 1 tail). The median free β-hCG was significantly reduced to 0.820 MoM (P < .02), but the median PAPP-A was similar in cases and controls. Modeling predicted the following: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; and a combined test with BPD, AFP, and free β-hCG detects 58% for 5% or 70% for 10%.
  
  
  CONCLUSIONS
  Combining AFP and BPD with free β-hCG as part of first-trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.
authors.affiliation: Centre Hospitalier Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, and Société Française pour l'Amélioration des Pratiques Echographiques, Paris, France. bernardjeanpierre@me.com
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bernard
authors.forename: Howard S
authors.initials: HS
authors.lastname: Cuckle
authors.forename: Maguy A
authors.initials: MA
authors.lastname: Bernard
authors.forename: Christine
authors.initials: C
authors.lastname: Brochet
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Salomon
authors.forename: Yves
authors.initials: Y
authors.lastname: Ville
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D016137:Spina Bifida Cystica / Q000175:diagnosis* / Q000000981:diagnostic imaging; D016216:Ultrasonography, Prenatal; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; D011266:Pregnancy-Associated Plasma Protein-A
keywords: fetus; first trimester; neural tube defects; ultrasound