title: The effect of exercise and metformin treatment on circulating free DNA in pregnancy.
abstract: BACKGROUND
  Some pregnancy complications are characterized by increased levels of cell-free fetal (cffDNA) and maternal DNA (cfmDNA), the latter may also be elevated during physical strain. This study aims at assessing the impact of exercise and metformin intervention in pregnancy, and to compare the levels of cell free DNA in pregnant women with or without PCOS diagnosis.
  
  
  METHODS
  Consecutive women from two previous randomized controlled trials in pregnancy were included. Women came from a trial with organized exercise vs. standard antenatal care in pregnancy and a trial of metformin vs. placebo in PCOS women. Levels of cffDNA, cfmDNA and cell-free total DNA (cftDNA) were measured by qPCR.
  
  
  RESULTS
  Training in pregnancy did not affect the levels of cffDNA, cfmDNA or cftDNA. PCOS-women treated with metformin had lower levels of cfmDNA and cftDNA at week 32 (mean ± SD: 301 ± 162 versus 570 ± 337, p = 0.012, 345 ± 173 versus 635 ± 370, p = 0.019); otherwise the levels were comparable to PCOS-controls. Metformin-treated PCOS-women had higher cffDNA at inclusion, in the 1st trimester; later on in pregnancy the levels in the metformin and placebo groups were equal. A comparison of pregnant women in the exercise study (TRIP) to placebo-treated pregnant PCOS-women, showed the levels of cffDNA, cfmDNA or cftDNA during mid-pregnancy (weeks 18-36) to be equal.
  
  
  CONCLUSIONS
  Training during pregnancy was not associated with altered levels of cffDNA cfmDNA or cftDNA, but metformin treatment may reduce cfmDNA and cftDNA in pregnant PCOS women.
authors.affiliation: Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Unit for Applied Clinical Research, Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: sverre.christiansen@ntnu.no.
authors.forename: S C
authors.initials: SC
authors.lastname: Christiansen
authors.affiliation: Department of Obstetrics and Gynecology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway; Institute of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Vanky
authors.affiliation: Institute of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Klungland
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway; Clinical Services, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
authors.forename: S N
authors.initials: SN
authors.lastname: Stafne
authors.affiliation: Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway; Clinical Services, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Mørkved
authors.affiliation: Institute of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway; Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: K Å
authors.initials: KÅ
authors.lastname: Salvesen
authors.affiliation: Institute of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Sæther
authors.affiliation: Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Unit for Applied Clinical Research, Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: S M
authors.initials: SM
authors.lastname: Carlsen
mesh_terms: D000293:Adolescent; D000328:Adult; D004247:DNA / Q000097:blood*; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D004247:DNA; D008687:Metformin
keywords: Cell-free fetal DNA; Cell-free maternal DNA; Cell-free total DNA training in pregnancy; Metformin; Polycystic ovary syndrome