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

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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. BJOG 2010;117:1384–1389. Objective 

To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free β subunit of human chorionic gonadotrophin (fβ-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 first-trimester serum, previously tested for PAPP-A and fβ-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 pre-eclampsia, 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 fβ-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 fβ-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted pre-eclampsia 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.
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Keywords: A desintegrin and metalloproteinase 12; first-trimester; placental growth factor; placental protein 13; pre-eclampsia

Document Type: Research Article

Affiliations: 1: Department of Obstetrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands 2: Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands 3: Medical College of Columbia University, Department of Obstetrics and Gynecology, New York, NY, USA

Publication date: 2010-10-01

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