Objectives: First, to investigate the additive value of second-trimester placental growth factor (PlGF) for the prediction of a small-for-gestational-age (SGA) neonate. Second, to examine second-trimester contingent screening strategies.
Methods: This was a prospective observational study in women with singleton pregnancy undergoing routine ultrasound examination at 19-24 weeks' gestation. We used the competing-risks model for prediction of SGA. The parameters for the prior model and the likelihoods for estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI) were those presented in previous studies. A folded-plane regression model was fitted in the dataset of this study to describe the likelihood of PlGF. We compared the prediction of screening by maternal risk factors against the prediction provided by a combination of maternal risk factors, EFW, UtA-PI and PlGF. We also examined the additive value of PlGF in a policy that uses maternal risk factors, EFW and UtA-PI.
Results: The study population included 40 241 singleton pregnancies. Overall, the prediction of SGA improved with increasing degree of prematurity, with increasing severity of smallness and in the presence of coexisting pre-eclampsia. The combination of maternal risk factors, EFW, UtA-PI and PlGF improved significantly the prediction provided by maternal risk factors alone for all the examined cut-offs of birth weight and gestational age at delivery. Screening by a combination of maternal risk factors and serum PlGF improved the prediction of SGA when compared to screening by maternal risk factors alone. However, the incremental improvement in prediction was decreased when PlGF was added to screening by a combination of maternal risk factors, EFW and UtA-PI. If first-line screening for a SGA neonate with birth weight < 10th percentile delivered at < 37 weeks' gestation was by maternal risk factors and EFW, the same detection rate of 90%, at an overall false-positive rate (FPR) of 50%, as that achieved by screening with maternal risk factors, EFW, UtA-PI and PlGF in the whole population can be achieved by reserving measurements of UtA-PI and PlGF for only 80% of the population. Similarly, in screening for a SGA neonate with birth weight < 10th percentile delivered at < 30 weeks, the same detection rate of 90%, at an overall FPR of 14%, as that achieved by screening with maternal risk factors, EFW, UtA-PI and PlGF in the whole population can be achieved by reserving measurements of UtA-PI and PlGF for only 70% of the population. The additive value of PlGF in reducing the FPR to about 10% with a simultaneous detection rate of 90% for a SGA neonate with birth weight < 3rd percentile born < 30 weeks, is gained by measuring PlGF in only 50% of the population when first-line screening is by maternal factors, EFW and UtA-PI.
Conclusions: The combination of maternal risk factors, EFW, UtA-PI and PlGF provides effective second-trimester prediction of SGA. Serum PlGF is useful for predicting a SGA neonate with birth weight < 3rd percentile born < 30 weeks after an inclusive assessment by maternal risk factors and biophysical markers. Similar detection rates and FPRs can be achieved by application of contingent screening strategies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Keywords: Bayes' theorem; estimated fetal weight; fetal growth restriction; likelihood; placental growth factor; pyramid of prenatal care; second-trimester screening; small-for-gestational age; survival model; uterine artery Doppler.
© 2021 International Society of Ultrasound in Obstetrics and Gynecology.