title: Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes.
abstract: OBJECTIVE
  To study associations of first trimester cell-free fetal DNA levels (in this paper referred to as cell-free placental DNA (cfpDNA) levels) and preeclampsia (PE), pregnancy-induced hypertension (PIH), gestational diabetes (GDM) and spontaneous preterm birth (sPB).
  
  
  METHODS
  A nested case-control study was conducted in first trimester samples (gestational age 8+0-13+6weeks). A total of 226 cases and 301 controls were included. CfpDNA levels were quantified in male-bearing pregnancies using real-time DYS14-PCRs on DNA isolated from maternal serum. CfpDNA multiples of the median (MoMs) were calculated based on associations with patient characteristics (body mass index, parity, ethnicity and smoking). Associations between MoMs and adverse outcomes were studied.
  
  
  RESULTS
  Cell-free placental DNA levels were negatively associated with body mass index (β = -0.297, p < 0.001) and smoking (β = -0.163, p = 0.006). MoMs were lower in women who later developed PIH (n = 84, p = 0.009) or GDM (n = 56, p = 0.037). There was no association between cfpDNA MoMs and PE (n = 37, p = 0.15) or sPB (n = 49, p = 0.19). CfpDNA was positively correlated with pregnancy-associated plasma protein A (r = 0.426, p < 0.001) but not with placental growth factor (r = 0.059, p = 0.179).
  
  
  CONCLUSIONS
  Adjusted first trimester cfpDNA levels are associated with PIH and GDM but probably not with PE or sPB. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Division of Women and Baby, Department of Obstetrics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Florentine F
authors.initials: FF
authors.lastname: Thurik
authors.affiliation: Division of Women and Baby, Department of Obstetrics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Lamain-de Ruiter
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Javadi
authors.affiliation: Division of Women and Baby, Department of Obstetrics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Kwee
authors.affiliation: Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Heleen
authors.initials: H
authors.lastname: Woortmeijer
authors.affiliation: Division of Women and Baby, Department of Obstetrics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Godelieve C M L
authors.initials: GC
authors.lastname: Page-Christiaens
authors.affiliation: Division of Women and Baby, Department of Obstetrics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Arie
authors.initials: A
authors.lastname: Franx
authors.affiliation: Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
authors.affiliation: Division of Women and Baby, Department of Obstetrics, University Medical Centre Utrecht, Utrecht, The Netherlands.|Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Maria P H
authors.initials: MP
authors.lastname: Koster
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004247:DNA / Q000097:blood*; D016640:Diabetes, Gestational / Q000453:epidemiology*; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology; D007231:Infant, Newborn; D000072483:Placenta Growth Factor / Q000378:metabolism; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D047928:Premature Birth / Q000453:epidemiology*
chemical_list: D000072483:Placenta Growth Factor; D004247:DNA; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human