First trimester maternal serum PAPP-A, beta-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 (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.


CONCLUSIONS
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.
Pihl
Kasper
K
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark. Kasper_Pihl@dadlnet.dk
Larsen
Torben
T
Krebs
Lone
L
Christiansen
Michael
M
D051722:ADAM Proteins / Q000097:blood* / Q000378:metabolism; D000072199:ADAM12 Protein; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood* / Q000378:metabolism; D015331:Cohort Studies; D005240:Feasibility Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008565:Membrane Proteins / Q000097:blood* / Q000378:metabolism; D009035:Mothers; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood* / Q000378:metabolism; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis* / Q000378:metabolism; D011296:Prenatal Diagnosis / Q000379:methods*; D055815:Young Adult
D018997:Chorionic Gonadotropin, beta Subunit, Human; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D011266:Pregnancy-Associated Plasma Protein-A