title: Abnormal blood biomarkers in early pregnancy are associated with preeclampsia: a meta-analysis.
abstract: OBJECTIVE
  Our aim was to evaluate the strength of association between abnormal levels of first trimester maternal blood biomarkers and the risk of preeclampsia.
  
  
  METHODS
  We searched MEDLINE, EMBASE and Cochrane databases from inception until April 2013. Studies that assessed the association between any abnormal maternal blood biomarker in the first trimester and preeclampsia were included. Two independent reviewers selected studies, extracted data and assessed the quality. Results were summarized as pooled odds ratios with 95% confidence intervals.
  
  
  RESULTS
  From 1071 citations, we identified 30 studies (65,538 women) for inclusion. Twenty four studies assessed preeclampsia of any onset, 10 studied early onset preeclampsia and seven evaluated late onset preeclampsia (after 34 weeks of gestation). The biomarkers PAPP-A (OR 2.1, 95% CI 1.6, 2.6), PP13 (OR 4.4, 95% CI 2.9, 6.8), sFlt-1 (OR 1.3, 95% CI 2.9, 6.8), pentraxin (OR 5.3, 95% CI 1.9, 15.0) and inhibin-A (OR 3.6, 95% CI 1.7, 7.6) were significantly associated with any preeclampsia. The odds of early onset preeclampsia were significantly increased when the biomarkers PlGF (OR 3.4, 95% CI 1.6, 7.2), PAPP-A (OR 4.8, 95% CI 2.5, 22.5), PP13 (OR 7.5, 95% CI 2.5, 22.5), soluble endoglin (OR 18.5, 95% CI 8.4, 41.0) and inhibin-A (OR 4.1, 95% CI 1.9, 8.8) were abnormal. Two biomarkers, soluble endoglin (OR 2.1, 95% CI 1.9, 2.4) and inhibin-A (OR 1.9, 95% CI 1.4, 2.8) were significantly associated with late onset preeclampsia.
  
  
  CONCLUSIONS
  Abnormal maternal blood biomarkers in early pregnancy are significantly associated with preeclampsia, particularly early onset disease.
authors.affiliation: Fetal Medicine Centre, Barts Health NHS Trust, Royal London Hospital, Whitechapel, London E1 1BB, UK. Electronic address: rebecca_e_allen@yahoo.co.uk.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Allen
authors.affiliation: Women's Health Research Unit, Centre for Primary Care and Public Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Rogozinska
authors.affiliation: Fetal Medicine Centre, Barts Health NHS Trust, Royal London Hospital, Whitechapel, London E1 1BB, UK.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Cleverly
authors.affiliation: Fetal Medicine Centre, Barts Health NHS Trust, Royal London Hospital, Whitechapel, London E1 1BB, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Aquilina
authors.affiliation: Fetal Medicine Centre, Barts Health NHS Trust, Royal London Hospital, Whitechapel, London E1 1BB, UK; Women's Health Research Unit, Centre for Primary Care and Public Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
authors.forename: S
authors.initials: S
authors.lastname: Thangaratinam
mesh_terms: D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D000071063:Endoglin; D005260:Female; D005865:Gestational Age; D006801:Humans; D007265:Inhibins / Q000097:blood*; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000097:blood*; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D002097:C-Reactive Protein; D000071063:Endoglin; D007265:Inhibins; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins; D011266:Pregnancy-Associated Plasma Protein-A; D011956:Receptors, Cell Surface; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C064206:ENG protein, human; C000608036:PGF protein, human; C422362:inhibin A
keywords: Biomarkers; First-trimester; Prediction; Preeclampsia; Pregnancy