Competing-risks model for prediction of small-for-gestational-age neonate from maternal characteristics, serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation.

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.

Competing-risks model for prediction of small-for-gestational-age neonate from maternal characteristics and serum pregnancy-associated plasma protein-A at 11-13 weeks' gestation.

OBJECTIVES: To develop a continuous likelihood model for pregnancy-associated plasma protein-A (PAPP-A), in the context of a new competing-risks model for prediction of a small-for-gestational-age (SGA) neonate, and to compare the predictive performance of the new model for SGA to that of previous methods. 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. The dataset was divided randomly into a training dataset and a test dataset. The training dataset was used for PAPP-A likelihood model development. We used Bayes' theorem to combine the previously developed prior model for the joint Gaussian distribution of gestational age (GA) at delivery and birth-weight Z-score with the PAPP-A likelihood to obtain a posterior distribution. This patient-specific posterior joint Gaussian distribution of GA at delivery and birth-weight Z-score allows risk calculation for SGA defined in terms of different birth-weight percentiles and GA. The new model was validated internally in the test dataset and we compared its predictive performance to that of the risk-scoring system of the UK National Institute for Health and Care Excellence (NICE) and that of logistic regression models for different SGA definitions. RESULTS: PAPP-A has a continuous association with both birth-weight Z-score and GA at delivery according to a folded-plane regression. The new model, with the addition of PAPP-A, was equal or superior to several logistic regression models. The new model performed well in terms of risk calibration and consistency across different GAs and birth-weight percentiles. In the test dataset, at a false-positive rate of about 30% using the criteria defined by NICE, the new model predicted 62.7%, 66.5%, 68.1% and 75.3% of cases of a SGA neonate with birth weight < 10th percentile delivered at < 42, < 37, < 34 and < 30 weeks' gestation, respectively, which were significantly higher than the respective values of 46.7%, 55.0%, 55.9% and 52.8% achieved by application of the NICE guidelines. CONCLUSIONS: Using Bayes' theorem to combine PAPP-A measurement data with maternal characteristics improves the prediction of SGA and performs better than logistic regression or NICE guidelines, in the context of a new competing-risks model for the joint distribution of birth-weight Z-score and GA at delivery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.