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

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 (β-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 β-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), β-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 β-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, β-hCG and ADAM12. Screening performance is approaching clinical relevance. The inclusion of further markers is an attractive option.