Combination of PAPPA, fhCGß, AFP, PlGF, sTNFR1, and Maternal Characteristics in Prediction of Early-onset Preeclampsia.

OBJECTIVE: To evaluate the efficacy of first-trimester markers-pregnancy-associated plasma protein A (PAPPA), free human chorionic gonadotropin ß (fhCGß), alpha-fetoprotein (AFP), placental growth factor (PlGF), and soluble tumor necrosis factor receptor-1 (sTNFR1) together with maternal characteristics (MC) for prediction of early-onset preeclampsia (EOPE). METHODS: During 2005-2010, the abovementioned biomarkers were analyzed with logistic regression analysis in 64 EOPE and 752 control subjects to determine whether these biomarkers separately and in combination with MC would predict development of EOPE. RESULTS: PAPPA, fhCGß, and PlGF levels were lower, whereas AFP and sTNFR1 levels were higher in mothers with EOPE compared to controls. The combination of all markers with MC (age, weight, and smoking status) detected 48% of the mothers with EOPE, with a 10% false-positive rate (FPR). CONCLUSIONS: First-trimester maternal serum levels of PAPPA, fhCGß, AFP, PlGF, and sTNFR1, together with MC, are predictive of development of subsequent EOPE. These markers, along with MC, form a suitable panel for predicting EOPE.

First trimester placental retinol-binding protein 4 (RBP4) and pregnancy-associated placental protein A (PAPP-A) in the prediction of early-onset severe pre-eclampsia.

OBJECTIVE: In a retrospective case-control study, we examined the levels of placental retinol-binding protein 4 (RBP4) and pregnancy-associated placental protein A (PAPP-A) in first-trimester maternal serum samples as well as maternal characteristics to predict early-onset and severe pre-eclampsia. METHODS: In this retrospective case-control study, we identified females who delivered a singleton pregnancy on or after 24 weeks' gestation from 2003 to 2010 at Oulu University Hospital and had a retrospective first trimester trisomy screening, including serum PAPP-A measurement. Within this cohort, we identified 65 females who experienced early onset pre-eclampsia (EO-PE) and 742 controls who had uncomplicated deliveries. Retrospectively, we thawed all previously collected serum samples to measure placental retinol binding protein 4 (RBP4). PAPP-A and RBP4 were measured using automatic immunoassay systems and converted to multiples of the median (MoMs). Logistic regression analysis was performed to determine whether these biomarkers separately and in combination with maternal characteristics (maternal age, weight and smoking status) can be used to predict the development of early onset pre-eclampsia. RESULTS: The expected log(10) PAPP-A concentration and the expected log(10) RBP4 concentration in the control group were both affected by maternal weight and smoking status. The expected log(10) PAPP-A concentration was also affected by gestational age (GA). RBP4 levels in first-trimester serum were significantly higher in females who subsequently developed EO-PE outcome compared to those with normal pregnancy outcome (1.14 vs. 1.01 MoMs, p<0.0001). Maternal serum PAPP-A levels from the same pregnancy period were significantly lower in the EO-PE group compared to controls (0.80 vs. 1.05 MoMs, p=0.005). The risk model including maternal characteristics with PAPP-A log(10) MoM and RBP4 log(10) MoM had the best EO-PE prediction ability. It detected 34% (23%-46%) of females with subsequent EO-PE with a 10% false positive rate. CONCLUSION: This study showed that first-trimester maternal serum RBP4 was significantly increased and that PAPP-A decreased in pregnancies that ended in EO-PE compared to normal pregnancies. Thus, these markers may be useful members in a panel of markers for the early detection of early-onset and severe pre-eclampsia.

Type IV collagen alpha6 chain-derived noncollagenous domain 1 (alpha6(IV)NC1) inhibits angiogenesis and tumor growth.

Type IV collagen is a major component of vascular basement membranes. The noncollagenous (NC1) domains of several alpha-chains of type IV collagen reveal a capacity to inhibit angiogenesis and tumor growth. Here, we demonstrate that the NC1 domain of the alpha6 chain of type IV collagen (alpha6NC1) is an endogenous inhibitor of angiogenesis and tumor growth. Recombinant alpha6NC1 inhibits human endothelial cell proliferation and neovascularization of Matrigel plugs in mice. The alpha6NC1 suppresses the growth of subcutaneously transplanted Lewis lung carcinoma and also spontaneous pancreatic insulinomas that develop in the Rip1Tag2 mice. Inhibition of tumor growth is associated with significantly diminished microvascular density. Collectively, our results demonstrate that alpha6NC1 is an endogenous inhibitor of angiogenesis and tumor growth.