First‐trimester maternal serum level of pregnancy‐associated plasma protein‐A is an independent predictor of fetal maxillary bone length

Abstract

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. 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. 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. 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.