This study describes a new competing-risks model based on a combination of maternal characteristics and medical history with serum pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation for prediction of a small-for-gestational-age (SGA) neonate. PAPP-A likelihood was expressed as a continuous function of both gestational age at delivery and birth-weight Z-score in the same model. What are the clinical implications of this work? Addition of serum PAPP-A improves the performance of screening for a SGA neonate achieved by maternal factors alone and demonstrates the methodology for incorporation of further biomarkers into a single model that can be used numerous times during the course of pregnancy to predict SGA of any severity of smallness and degree of prematurity.

Objectives To expand a new competing‐risks model for prediction of a small‐for‐gestational‐age (SGA) neonate, by the addition of pregnancy‐associated plasma protein‐A (PAPP‐A) and placental growth factor (PlGF), and to evaluate and compare PAPP‐A and PlGF in predicting SGA. Methods This was a prospective observational study of 60 875 women with singleton pregnancy undergoing routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation. We fitted a folded‐plane regression model for the PAPP‐A and PlGF likelihoods. A previously developed maternal history model and the likelihood models were combined, according to Bayes' theorem, to obtain individualized distributions for gestational age (GA) at delivery and birth‐weight Z‐score. We assessed the discrimination and calibration of the model. McNemar's test was used to compare the detection rates for SGA with, without or independently of pre‐eclampsia (PE) occurrence, of different combinations of maternal history, PAPP‐A and PlGF, for a fixed false‐positive rate. Results The distributions of PAPP‐A and PlGF depend on both GA at delivery and birth‐weight Z‐score, in the same continuous likelihood, according to a folded‐plane regression model. The new approach offers the capability for risk computation for any desired birth‐weight Z‐score and GA at delivery cut‐off. PlGF was consistently and significantly better than PAPP‐A in predicting SGA delivered before 37 weeks, especially in cases with co‐existence of PE. PAPP‐A had similar performance to PlGF for the prediction of SGA without PE. At a fixed false‐positive rate of 10%, the combination of maternal history, PlGF and PAPP‐A predicted 33.8%, 43.8% and 48.4% of all cases of a SGA neonate with birth weight < 10th percentile delivered at ≥ 37, < 37 and < 32 weeks' gestation, respectively. The respective values for birth weight < 3rd percentile were 38.6%, 48.7% and 51.0%. The new model performed well in terms of risk calibration. Conclusions The combination of PAPP‐A and PlGF values with maternal characteristics, according to Bayes' theorem, improves prediction of SGA. PlGF is a better predictor of SGA than PAPP‐A, especially when PE is present. The new competing‐risks model for SGA can be tailored to each pregnancy and to the relevant clinical requirements. © 2020 International Society of Ultrasound in Obstetrics and Gynecology

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