ADAM12s in maternal serum as a potential marker of pre‐eclampsia

Spencer, Kevin; Cowans, Nicholas J.; Stamatopoulou, Anastasia

doi:10.1002/pd.1957

Cited by 76 publications

(63 citation statements)

References 25 publications

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“…6,17,18 Our findings regarding ADAM12 support a previous study indicating that ADAM12 does not provide useful prediction of SGA, pre-eclampsia or preterm delivery 19 and contradict two previous reports showing that in pregnancies developing pre-eclampsia the serum ADAM12 concentration is reduced. 1,2 We only found a small, although significant, reduction of ADAM12 levels in pregnancies complicated by pre-eclampsia who subsequently delivered a SGA neonate. This may be explained by the fact that ADAM12 is a placental product involved in the control of fetal growth.…”

Section: Markermentioning

confidence: 83%

“…Previous studies have reported that in the first-trimester concentrations are reduced for placental protein 13 (PP13), anti-angiogenic factors such as placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12) in pregnancies with early-onset pre-eclampsia (delivery before 34 weeks of gestation) and pre-eclampsia later in pregnancy, with a higher predictive value in the former group. [1][2][3][4][5][6] However, the number of cases studied for early-onset pre-eclampsia was generally low, ranging from 6 to 34. Recently, a detection rate of 86% of early-onset pre-eclampsia has been predicted at a false-positive rate of 10%, by combining maternal characteristics, obstetrics history, serum PlGF and uterine artery pulsatility index at 11-14 weeks of gestation.…”

Section: Introductionmentioning

confidence: 99%

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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

Wortelboer

Koster

Cuckle

et al. 2010

BJOG

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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.

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Section: Markermentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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

Wortelboer

Koster

Cuckle

et al. 2010

BJOG

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“…Interestingly, decreased serum levels of ADAM12, another member of ADAM family, have been reported in PE. 47,48 In addition, multiple ADAMTS subtypes have been detected, albeit many at low levels, in total RNA lysates prepared from human term placenta or uterine tissues, suggesting that these metalloproteinases may play important roles in implantation and placentation. 49 A spliced form (2.4 kb of mRNA) of ADAMTS13 has also been identified in placenta, but the expression of the protein in the placenta or any specific cell in placenta has not been explored yet.…”

Section: Discussionmentioning

confidence: 99%

Von Willebrand Factor and ADAMTS13

Stépanian

Cohen-Moatti²,

Sanglier³

et al. 2011

ATVB

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Objective-The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery). Methods and Results-We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin- Key Words: hypertension Ⅲ pregnancy Ⅲ ADAMTS13 Ⅲ preeclampsia Ⅲ von Willebrand factor P reeclampsia (PE) is the most frequent medical complication during pregnancy, occurring in Ϸ2% to 7% of pregnancies worldwide. 1,2 It is a major cause of perinatal and maternal mortality and morbidity. PE is characterized clinically by new onset hypertension and proteinuria after 20 weeks of gestation (WG). The pathogenesis of PE involves inadequate cytotrophoblast invasion with subsequent abnormal placentation, resulting in placental hypoperfusion and ischemia with microthrombotic lesions. 3,4 The ischemic placenta releases various molecules, including cytokines, antiangiogenic peptides, free reactive oxygen species that induce systemic maternal endothelial dysfunction, and excessive general inflammatory responses. 5,6 The pathophysiology of the placental microthrombosis observed in PE is obviously multifactorial and likely involves both the endothelium and plasma proteins. Among the various plasma proteins involved in thrombosis, the von Willebrand factor (VWF)/a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) couple is interesting to focus on, considering this specific hemorheologic context. VWF is a large multimeric plasma glycoprotein that notably mediates platelet adhesion and aggregation at high shear stress conditions thanks to its multimeric structure. 7 It is synthesized in endothelial cells and megakaryocytes and respectively stored in Weibel-Palade bodies and ␣ granules; VWF is formed in these compartments as ultralarge and very active VWF multimers. ADAMTS13 is a zinc metalloprotease that specifically cleaves the bond between amino acids Tyr1605 and Met1606 in the A2 domain of VWF exposed by shear stress. This protease activity reduces VWF molecular weight and consequently also its platelet-tethering function. 7,8 A severely deficient ADAMTS13 activity (less than 5% of

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“…26 Laigaard et al and Spenceret al have shown reduced ADAM12 levels in pregnancies complicated by PE, and in both studies ADAM12 was suggested to be a potential PE marker(median ADAM12 MoM were 0.86, P = 0.008 and 0.49 P = 0.0001, respectively). 27 In contrast, Poonet al, and…”

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confidence: 95%

Predictive Value of Maternal Serum Markers for Preeclampsia

Kim

2012

KMJ

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The study performed a systematic review of screening for preeclampsia with the combination of vascular parameters and maternal serum markers in the first and early second trimester. We identified eligible studies through a search of Medline, and, for each included study, we focused on the relationship between the maternal serum markers and preeclampsia. In the selected literature, a combination of maternal serum markers was analyzed, also. Several tests suggested moderate or convincing prediction of early preeclampsia, but screening for late preeclampsia was poor. Literatures for serum markers were selected. Each serum marker was identified independently, and where relevant, a combination of these markers was analyzed. Encouraging results for the first trimester screening were observed when it was combined with other markers. Even in the first trimester of pregnancy, we can present the reliable results for the prediction of early preeclampsia. Detection rate for combination markers may yield higher detection rate and be promising to identify patients at high risk of developing preeclampsia.

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ADAM12s in maternal serum as a potential marker of pre‐eclampsia

Abstract: ADAM12s in addition to being a potential marker of aneuploidy may also be a marker of pre-eclampsia. Further studies are required to see if this can improve on the clinical discrimination already provided by PAPP-A in the early first trimester.

Cited by 76 publications

References 25 publications

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

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

Von Willebrand Factor and ADAMTS13

Predictive Value of Maternal Serum Markers for Preeclampsia

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