Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Abstract

Background Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies.Methods Maternal serum PAPP-A and free ß-human chorionic gonadotropin (ß-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47 770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ß-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated. ResultsIn the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free β-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified. ConclusionsThe graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.

Extracellular Nucleic Acids in Maternal Circulation as Potential Biomarkers for Placental Insufficiency

“…Using single biochemical markers usually has a low predictive value in the first trimester. PAPP-A, a glycoprotein synthesized in the placenta, has been shown to be a powerful predictive biochemical marker of PE when combined with Doppler ultrasound, reaching 70% sensitivity at 95% specificity (Spencer et al, 2008;Goetzinger et al, 2010;Anderson et al, 2011). However, some recent studies evaluating PAPP-A as a firsttrimester predictive marker for PE showed conflicting results that indicated no differentiation between complicated and uncomplicated pregnancies (Mikat et al, 2011;Stirnemann et al, 2011).…”

Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse

“…For example, unusually low levels of PAPPA in the first trimester may be indicative of increased risk of fetal genetic disorders such as Down's syndrome (Brambati et al 1993) and Cornelia de Lange syndrome (Aitken et al 1999). Furthermore, low circulating PAPPA levels are also associated with higher risk of low birth weight, IUGR, and preeclampsia , Kwik & Morris 2003, Dugoff et al 2004, Spencer et al 2008, which are characterized by impaired trophoblast invasion. Although PAPPA is highly expressed in human placenta (Tornehave et al 1984), this is not the case in the mouse (Qin et al 2002, Soe et al 2002.…”

Discovery of the serum biomarker proteins in severe preeclampsia by proteomic analysis

“…Various serum proteins are considered to contribute to the symptoms of PE, such as placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), soluble fms-like tyrosine kinase-1(sFlt-1), placental protein 13 (PP-13), pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotrophin (HCG), soluble endoglin (sEng), alpha fetoprotein (AFP), insulin like growth factor-1 and IGF-binding protein-1 (IGFBP-1) (Muller et al, 1996;Bersinger and Odegard, 2004;Audibert et al, 2005;Venkatesha et al, 2006;Baumann et al, 2007;Spencer et al, 2008;Teixeira et al, 2008). Various studies have shown that the expression levels of these proteins increase or decrease according to the disorder and its degree in PE (Baumann et al, 2007).…”