title: Combinations of maternal serum markers to predict preeclampsia, small for gestational age, and stillbirth: a systematic review.
abstract: OBJECTIVE
  Abnormal serum screening markers have been associated with adverse pregnancy outcomes. We sought to review the performance of combined abnormal first and/or second trimester maternal serum markers used in prenatal screening for aneuploidy and open neural tube defects for predicting preeclampsia (PET), small for gestational age (SGA), and stillbirth beyond 24 weeks' gestation.
  
  
  METHODS
  Medline, EMBASE, and Cochrane Library databases were searched for studies from 1970 to May 2010 that analyzed predictive abilities of combined serum markers for defined outcomes.
  
  
  METHODS
  Data were extracted independently by two authors, and 15 studies were included. Eight studies of 115,290 pregnancies, 11 studies of 144 853 pregnancies, and seven studies of 80 274 pregnancies examined PET, SGA, and stillbirth respectively. Because of the heterogeneity of marker combinations and thresholds, outcome definitions, and analytic methods, limited meta-analysis was possible for the outcomes of PET and SGA only. Three relatively homogeneous studies on prediction of PET, and two on prediction of SGA were meta-analyzed. Several single studies demonstrated utility in combining markers to predict adverse outcome; however, this effect was not confirmed after meta-analysis. The most common combination of markers evaluated was alpha fetoprotein and human chorionic gonadotrophin for all outcomes. The highest positive likelihood ratios for predicting PET (5.68; 95% CI 0.73 to 43.97) and SGA (6.18; 95% CI 1.84 to 20.85) were seen with combined alpha fetoprotein and human chorionic gonadotrophin (> 2.5 multiples of the median).
  
  
  CONCLUSIONS
  Currently, no identifiable combination of serum markers performs well as a screening test for preeclampsia, small for gestational age, and stillbirth beyond 24 weeks. Large cohort studies with standardized screening test parameters and outcomes are needed.
authors.affiliation: Maternal Fetal Medicine Division, Department of Obstetrics and Gynaecology, Sunnybrook Health Sciences Centre, Toronto ON.
authors.forename: Dini
authors.initials: D
authors.lastname: Hui
authors.affiliation: Maternal Fetal Medicine Division, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: Nan
authors.initials: N
authors.lastname: Okun
authors.affiliation: Maternal Fetal Medicine Division, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: Kellie
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Maternal Fetal Medicine Division, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON.
authors.forename: John
authors.initials: J
authors.lastname: Kingdom
authors.affiliation: Hospital Library and Archives, The Hospital for Sick Children, University of Toronto, Toronto ON.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Uleryk
authors.affiliation: Department of Paediatrics, Mount Sinai Hospital, University of Toronto, Toronto ON; Department of Health Policy, Management and Evaluation, University of Toronto, Toronto ON.
authors.forename: Prakesh S
authors.initials: PS
authors.lastname: Shah
mesh_terms: D000782:Aneuploidy; D015415:Biomarkers / Q000097:blood*; D006063:Chorionic Gonadotropin / Q000097:blood; D004964:Estriol / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood*; D007265:Inhibins / Q000097:blood; D009436:Neural Tube Defects / Q000175:diagnosis; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis / Q000379:methods; D050497:Stillbirth; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; C422362:inhibin A; D007265:Inhibins; D011266:Pregnancy-Associated Plasma Protein-A; D004964:Estriol