First‐trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early‐onset pre‐eclampsia

Abstract

Objective To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free b subunit of human chorionic gonadotrophin (fb-hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first-trimester identification of early-onset pre-eclampsia.Design Nested case-control study.Setting Routine first-trimester screening for trisomy 21 in the Netherlands.Population Eighty-eight women who developed pre-eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls.Methods PP13, PlGF and ADAM12 were measured in stored firsttrimester serum, previously tested for PAPP-A and fb-hCG. All marker levels were expressed in multiples of the gestation-specific normal median (MoMs). Model predicted detection rates for fixed false-positive rates were obtained for statistically significant markers alone and in combination.Main outcome measures Development of pre-eclampsia or HELLP syndrome.Results PP13 and PlGF were reduced in women with preeclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP-A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and fb-hCG did not differ between control women and those with pre-eclampsia. In pre-eclampsia complicated by a small-for-gestational-age fetus, all markers except fb-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted preeclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false-positive rate.Conclusion This study demonstrates that PP13 and PlGF in the first-trimester might be promising markers in risk assessment for early pre-eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.Keywords A desintegrin and metalloproteinase 12, first-trimester, placental growth factor, placental protein 13, pre-eclampsia.Please cite this paper as: Wortelboer E, Koster M, Cuckle H, Stoutenbeek P, Schielen P, Visser G. First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia.

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.…”