First trimester maternal serum PAPP-A, beta-hCG and ADAM12 in prediction of small-for-gestational-age fetuses

Prenat Diagn. 2008 Dec;28(12):1131-5. doi: 10.1002/pd.2141.

Abstract

Objective: To examine the ability of predicting fetuses being small-for-gestational-age (SGA) at delivery with the maternal serum markers pregnancy-associated plasma protein A (PAPP-A), beta-human chorionic gonadotrophin (beta-hCG) and A disintegrin and metalloprotease 12 (ADAM12) in first trimester.

Methods: In all,36 cases being SGA (birth weight < 5th centile) and 108 controls being non-SGA were matched on ethnicity (only Caucasians), smoking status (only nonsmokers), body mass index (BMI), age and parity. Stored blood samples from PAPP-A and beta-hCG testing obtained at gestational age (GA) of 8 weeks to 13 weeks and 6 days were analyzed for ADAM12. Median MoM values were compared using Mann-Whitney test. Monte Carlo estimation and receiver-operator-characteristics curves were used to asses screening performance.

Results: Median MoM values of PAPP-A (0.64 vs 1.02, p < 0.001), beta-hCG (0.74 vs 1.04, p = 0.007) and ADAM12 (0.74 vs 0.97, p = 0.004) were significantly reduced in cases compared to controls. The combination of PAPP-A MoM and beta-hCG MoM yielded a detection rate (DR) for SGA of 26% for a 5% false-positive rate (FPR). Addition of ADAM12 only improved (28% DR for a 5% FPR) screening performance modestly.

Conclusion: Early prediction of fetuses being SGA is feasible with the combination of first trimester PAPP-A, beta-hCG and ADAM12. Screening performance is approaching clinical relevance. The inclusion of further markers is an attractive option.

Publication types

  • Evaluation Study

MeSH terms

  • ADAM Proteins / blood*
  • ADAM Proteins / metabolism
  • ADAM12 Protein
  • Adolescent
  • Adult
  • Case-Control Studies
  • Chorionic Gonadotropin, beta Subunit, Human / blood*
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism
  • Cohort Studies
  • Feasibility Studies
  • Female
  • Fetal Growth Retardation / blood
  • Fetal Growth Retardation / diagnosis
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age*
  • Membrane Proteins / blood*
  • Membrane Proteins / metabolism
  • Mothers
  • Pregnancy
  • Pregnancy Trimester, First / blood*
  • Pregnancy Trimester, First / metabolism
  • Pregnancy-Associated Plasma Protein-A / analysis*
  • Pregnancy-Associated Plasma Protein-A / metabolism
  • Prenatal Diagnosis / methods*
  • Young Adult

Substances

  • Chorionic Gonadotropin, beta Subunit, Human
  • Membrane Proteins
  • ADAM Proteins
  • ADAM12 Protein
  • ADAM12 protein, human
  • Pregnancy-Associated Plasma Protein-A