title: First and second trimester immune biomarkers in preeclamptic and normotensive women.
abstract: BACKGROUND
  Circulating immune markers may be associated with preeclampsia but further investigations in early pregnancy and among preeclampsia subtypes are warranted. We examined immune markers in 208 preeclamptic women and 411 normotensive controls.
  
  
  METHODS
  Our study was nested within the Collaborative Perinatal Project. A total of 242 women had first trimester serum samples and 392 had second trimester serum samples. Preeclampsia was defined as hypertension >20weeks of gestation with proteinuria or pulmonary edema, oliguria, or convulsions. Preterm preeclampsia was defined as preeclampsia with delivery less than 37weeks of gestation. Associations between immune markers RANTES, interleukin (IL)-6, IL4, IL5, IL12, IL10, IL8, IL1-beta, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and beta, transforming growth factor (TGF)-beta and preeclampsia were explored using a modified version of cox regression developed to address data with non-detectable levels. Models were adjusted for body mass index, gestational age of blood sampling, fetal sex, smoking, socioeconomic status and maternal age.
  
  
  RESULTS
  In first trimester samples, IL-12 was associated with preeclampsia (p=0.0255). IFN-gamma (p=0.0063), IL1-beta (p=0.0006), IL5 (p=0.0422) and TNFr (p=0.0460) were associated with preterm preeclampsia only. In second trimester samples, IL1-beta was associated with preeclampsia (p=0.0180) and term preeclampsia (p=0.0454). After correction for multiple comparisons, only IL1-beta remained associated with preterm preeclampsia in the first trimester (p=0.0288).
  
  
  CONCLUSIONS
  Elevated first trimester IL1-beta appears to be associated with preterm preeclampsia. However, few associations were observed in the second trimester. Systemic immune markers alone may not be useful for preeclampsia prediction.
authors.affiliation: Department of Epidemiology and Biostatistics, Texas A&M University, School of Public Health, College Station, TX, United States; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: Taylor@sph.tamhsc.edu.
authors.forename: Brandie D
authors.initials: BD
authors.lastname: Taylor
authors.affiliation: University of Texas School of Public Health, Houston, TX, United States.
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.affiliation: The Research Institute at Nationwide Children's Hospital, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Klebanoff
authors.affiliation: Department of Epidemiology and Biostatistics, Texas A&M University, School of Public Health, College Station, TX, United States.
authors.forename: Roger
authors.initials: R
authors.lastname: Zoh
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Debra
authors.initials: D
authors.lastname: Bass
authors.affiliation: Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Danish Centre for Neonatal Screening, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Kristin
authors.initials: K
authors.lastname: Skogstrand
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Haggerty
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008233:Lymphotoxin-alpha / Q000097:blood; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011262:Pregnancy Trimester, Second / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018946:Chemokine CCL5; D016207:Cytokines; D053583:Interleukin-1beta; D015848:Interleukin-5; D015850:Interleukin-6; D016209:Interleukin-8; D008233:Lymphotoxin-alpha; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Inflammation; Preeclampsia; Pregnancy