title: Population-based biomarker screening and the development of severe preeclampsia in California.
abstract: OBJECTIVE
  The purpose of this study was to examine the relationship between second-trimester maternal serum biomarkers and the development of early- and late-onset severe preeclampsia in euploid pregnancies.
  
  
  METHODS
  Included were 136,139 pregnancies that obtained second-trimester prenatal screening through the California Prenatal Screening Program with live births in 2006-2008. We identified severe preeclampsia diagnoses from hospital discharge records. We used log binomial regression to examine the association between abnormal second-trimester maternal serum biomarkers and the development of severe preeclampsia.
  
  
  RESULTS
  Approximately 0.9% of all women (n = 1208) in our sample experienced severe preeclampsia; 329 women at <34 weeks' gestation and 879 women ≥34 weeks' gestation. High levels of alpha fetoprotein (AFP), human chorionic gonadotropin, inhibin (multiple of the median, ≥95th percentile), and low unconjugated estriol (multiple of the median, ≤5th percentile), were associated with severe preeclampsia (relative risk, 2.5-11.7). Biomarkers were more predictive of early-onset severe preeclampsia (relative risk, 3.8-11.7). One in 9.5 pregnancies with combined high AFP, inhibin, and low unconjugated estriol levels experienced severe early-onset preeclampsia compared with 1 in 680.5 pregnancies without any abnormal biomarkers.
  
  
  CONCLUSIONS
  The risk of the development of severe preeclampsia increases for women with high second-trimester AFP, human chorionic gonadotropin, inhibin, and/or low unconjugated estriol; this is especially true for early-onset severe preeclampsia. When abnormal biomarkers co-occur, risk dramatically increases. Although the screening value of second-trimester biomarkers is low, abnormal biomarkers, especially when occurring in combination, appear to indicate placental dysfunction that is associated with the development of severe preeclampsia.
authors.affiliation: Division of Maternal-Fetal Medicine, University of California-Davis, Sacramento, CA. Electronic address: Veronique.tache@ucdmc.ucdavis.edu.
authors.forename: Véronique
authors.initials: V
authors.lastname: Taché
authors.affiliation: Genetic Disease Screening Program, California Department of Public Health, Richmond, CA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Baer
authors.affiliation: Genetic Disease Screening Program, California Department of Public Health, Richmond, CA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Currier
authors.affiliation: Department of Public Health Sciences, University of California-Davis, Sacramento, CA.
authors.forename: Chin-Shang
authors.initials: CS
authors.lastname: Li
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Hawaii School of Medicine, Honolulu, and John A. Burns School of Medicine, University of Hawaii at Manoa, Manoa, HI.
authors.forename: Dena
authors.initials: D
authors.lastname: Towner
authors.affiliation: Department of Obstetrics and Gynecology, University of California-Davis, Sacramento, CA.
authors.forename: L Elaine
authors.initials: LE
authors.lastname: Waetjen
authors.affiliation: Genetic Disease Screening Program, California Department of Public Health, Richmond, CA; Division of Preventive Medicine and Public Health, Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Jelliffe-Pawlowski
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002140:California; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood*; D012044:Regression Analysis; D018570:Risk Assessment; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: biomarker; early-onset severe preeclampsia; screening; serum analyte