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.
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.