title: First-trimester maternal serum level of pregnancy-associated plasma protein-A is an independent predictor of fetal maxillary bone length.
abstract: OBJECTIVE
  To derive a nomogram of fetal maxillary bone length (MAX) for a Chinese population and to study whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) is an independent predictor of fetal MAX.
  
  
  METHODS
  This was a prospective observational study over 10 months examining Chinese women with a singleton pregnancy who attended the first-trimester screening program for Down syndrome. The subjects had the fetal crown-rump length (CRL), nuchal translucency, MAX, maternal serum PAPP-A and free beta-human chorionic gonadotropin (fbeta-hCG) levels measured. A nomogram of MAX was derived using normal pregnancies with reliable dates. The correlations between MAX, CRL, PAPP-A and fbeta-hCG levels were studied, after correction for gestational dependency using Z-score transformation for the ultrasound markers (Z-MAX and Z-CRL), and logarithmic transformation of multiple of gestation-specific medians for the biochemical markers (log10PAPP-A multiples of the median (MoM) and log10fbeta-hCG MoM), using the Pearson test and multiple regression analysis.
  
  
  RESULTS
  During the study period, 607 Chinese women met the inclusion criteria. The mean gestational age at the first-trimester screening was 12 + 4 weeks (SD, 4 days). Curve estimation analysis showed that a linear relationship fit best between MAX and CRL (MAX (mm) = -0.01 + 0.101 * CRL (mm); r = 0.826; P < 0.0001), and between MAX and gestational age (MAX (mm) = -8.465 + 0.170 * gestational age (day); r = 0.754; SD = 0.71; P < 0.0001). There were significant positive correlations between Z-MAX and Z-CRL (r = 0.627; P = < 0.0001), Z-MAX and log10PAPP-A MoM (r = 0.239; P = < 0.0001). Multiple regression analysis showed that both Z-CRL (P = < 0.0001) and log10 PAPP-A MoM (P = 0.048) were independent predictors for Z-MAX.
  
  
  CONCLUSIONS
  Both CRL and maternal levels of PAPP-A are independent predictors of the fetal MAX measured during the first trimester. The positive correlation between PAPP-A levels and fetal MAX is consistent with the known biological function of PAPP-A on bone growth. This association must be adjusted for when both PAPP-A and MAX are combined for screening of Down syndrome.
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China S.A.R.
authors.forename: T Y
authors.initials: TY
authors.lastname: Leung
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China S.A.R.
authors.forename: L W
authors.initials: LW
authors.lastname: Chan
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China S.A.R.
authors.forename: T N
authors.initials: TN
authors.lastname: Leung
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China S.A.R.
authors.forename: T Y
authors.initials: TY
authors.lastname: Fung
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China S.A.R.
authors.forename: D S
authors.initials: DS
authors.lastname: Sahota
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China S.A.R.
authors.forename: T K
authors.initials: TK
authors.lastname: Lau
mesh_terms: D044466:Asian People / Q000208:ethnology*; D015415:Biomarkers / Q000378:metabolism; D018568:Crown-Rump Length; D004314:Down Syndrome / Q000175:diagnosis* / Q000208:ethnology; D005260:Female; D006801:Humans; D008437:Maxilla / Q000196:embryology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis / Q000379:methods; D011446:Prospective Studies; D012016:Reference Values
chemical_list: D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A