title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics and Gynecology, Oulu University Hospital, Finland.
authors: Anna
authors: A
authors: Yliniemi
authors: Department of Obstetrics and Gynecology, Oulu University Hospital, Finland.
authors: Mona-Marika
authors: MM
authors: Nurkkala
authors: Department of Obstetrics and Gynecology, Oulu University Hospital, Finland.
authors: Sanni
authors: S
authors: Kopman
authors: PerkinElmer, Turku, Finland.
authors: Teemu
authors: T
authors: Korpimaki
authors: PerkinElmer, Turku, Finland.
authors: Heikki
authors: H
authors: Kouru
authors: Department of Obstetrics and Gynecology, Oulu University Hospital, Finland. Electronic address: markku.ryynanen@oulu.fi.
authors: Markku
authors: M
authors: Ryynanen
authors: Department of Obstetrics and Gynecology, Oulu University Hospital, Finland; Department of Dermatology & Cutaneous Biology, Thomas Jefferson University Hospital, Philadelphia, USA.
authors: Jaana
authors: J
authors: Marttala
mesh_terms: D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D042241:Early Diagnosis; D005260:Female; D005865:Gestational Age; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011379:Prognosis; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Early onset severe pre-eclampsia; First trimester screening; PAPP-A; Prediction of pre-eclampsia; RBP4