Prediction of Small-for-Gestation Neonates from Biophysical and Biochemical Markers at 11–13 Weeks

Abstract

Objective: To develop a model for prediction of small-for-gestational age (SGA) neonates in the absence of preeclampsia (PE) based on maternal factors and biophysical and biochemical markers at 11–13 weeks’ gestation. Methods: Screening study in 1,536 SGA and 31,314 non-SGA pregnancies based on maternal characteristics, fetal nuchal translucency (NT) thickness, serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotrophin (β-hCG). We also measured mean arterial pressure (MAP), uterine artery pulsatility index (PI) and performed case-control studies for measurement of maternal serum concentration of placental growth factor (PLGF), placental protein 13 (PP13) and A Disintegrin And Metalloprotease (ADAM12). Regression analysis was used to develop a model for the prediction of SGA. Results: In the SGA group, uterine artery PI and MAP were increased and serum PAPP-A, free β-hCG, PLGF, PP13, and ADAM12 and fetal NT were decreased. At a false positive rate of 10%, the estimated detection rate by a combination of maternal factors and biophysical and biochemical markers at 11–13 weeks was 73% for SGA requiring delivery before 37 weeks and 46% for those delivering at term. Conclusions: Half of pregnancies with SGA neonates in the absence of PE could potentially be identified at 11–13 weeks.

First trimester screening of maternal placental protein 13 for predicting preeclampsia and small for gestational age: In-house study and systematic review

“…[Sch] [9,12,[15][16][17][18] Of the 8 studies, only 4 reported raw PP13 concentrations in controls for assessment of normative levels in first trimester of pregnancy, [Sch] [16,17,19] and these were presented in various formats.…”

“…[17] In comparison, median level of PP13 among controls in the in-house study was 53.5 (IQR; 37.7-71.8) pg/ml for all woman, 54.7 (IQR; 39.8-72.1) pg/ml for nulliparous women and 53.9, 54.0, 52.5 pg/ml for gestational week 11-13, respectively. [Sch] Although, a number of the studies found a significant difference in PP13 MoM levels between cases and controls for preeclampsia, [Sch] [12] early-onset preeclampsia [12,15,16] and SGA; [Sch] [9] three studies found no association between PP13 levels and adverse pregnancy outcomes. [9,17,18] In most studies, diagnostic accuracy of each outcome was determined at fixed cut-points of false positive rates of 5%, 10% and 20%.…”

“…[7][8][9][10][11][12][13][14][15] However, less remarkable predictive properties have been reported in recent studies, with some describing a potential role of PP13 levels for predicting preeclampsia or small for gestational age (SGA) in combination with other biomarkers. [9,12,15] Variation in study design, population characteristics, numbers of cases and reporting of the diagnostic accuracy of PP13, have made it difficult to interpret the clinical significance of these results.…”

“…[7][8][9][10][11][12][13][14][15] However, less remarkable predictive properties have been reported in recent studies, with some describing a potential role of PP13 levels for predicting preeclampsia or small for gestational age (SGA) in combination with other biomarkers. [9,12,15] Variation in study design, population characteristics, numbers of cases and reporting of the diagnostic accuracy of PP13, have made it difficult to interpret the clinical significance of these results. [9,12,[15][16][17][18][19] The original objective of this study was to assess normative levels of PP13 in the first trimester of pregnancy and to examine the diagnostic accuracy for predicting adverse pregnancy outcomes in an unselected maternity population.…”

“…[9,12,15] Variation in study design, population characteristics, numbers of cases and reporting of the diagnostic accuracy of PP13, have made it difficult to interpret the clinical significance of these results. [9,12,[15][16][17][18][19] The original objective of this study was to assess normative levels of PP13 in the first trimester of pregnancy and to examine the diagnostic accuracy for predicting adverse pregnancy outcomes in an unselected maternity population. However, due to the discontinuation in the production of the PP13 assay after March 2011, the analysis was only possible for a small number of cases.…”