title: Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth.
abstract: OBJECTIVE
  The purpose of this study was to investigate oxidative stress as a mechanism of preterm birth in human subjects; we examined associations between urinary biomarkers of oxidative stress that were measured at multiple time points during pregnancy and preterm birth.
  
  
  METHODS
  This nested case-control study included 130 mothers who delivered preterm and 352 mothers who delivered term who were originally recruited as part of an ongoing prospective birth cohort at Brigham and Women's Hospital. Two biomarkers that included 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks) during gestation.
  
  
  RESULTS
  Urinary concentrations of 8-isoprostane and 8-OHdG decreased and increased, respectively, as pregnancy progressed. Average levels of 8-isoprostane across pregnancy were associated with increased odds of spontaneous preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7), and associations were strongest with levels measured later in pregnancy. Average levels of 8-OHdG were protective against overall preterm birth (adjusted odds ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent differences in the protective effect in cases of spontaneous preterm birth compared with cases of placental origin. Odds ratios for overall preterm birth were more protective in association with urinary 8-OHdG concentrations that were measured early in pregnancy.
  
  
  CONCLUSIONS
  Maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy. The 2 biomarkers that were measured in the present study had opposite associations with preterm birth; an improved understanding of what each represents may help to identify more precisely important mechanisms in the pathway to preterm birth.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Ferguson
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: McElrath
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI.
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI.
authors.forename: Rita
authors.initials: R
authors.lastname: Loch-Caruso
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI.
authors.forename: Bhramar
authors.initials: B
authors.lastname: Mukherjee
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI. Electronic address: meekerj@umich.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Meeker
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D018384:Oxidative Stress; D011247:Pregnancy; D047928:Premature Birth / Q000652:urine*; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine
keywords: epidemiology; longitudinal; oxidative stress; preterm birth
references.citation: J Trop Pediatr. 2012 Aug;58(4):326-8
references.pmid: 21930665
references.citation: Free Radic Res. 2006 Apr;40(4):379-84
references.pmid: 16517502
references.citation: Am J Obstet Gynecol. 1996 Feb;174(2):754-9
references.pmid: 8623817
references.citation: Placenta. 2001 Apr;22 Suppl A:S38-44
references.pmid: 11312627
references.citation: Placenta. 2007 Apr;28 Suppl A:S33-40
references.pmid: 17140657
references.citation: JAMA Pediatr. 2014 Jan;168(1):61-67
references.pmid: 24247736
references.citation: J Matern Fetal Med. 2001 Jun;10(3):182-5
references.pmid: 11444787
references.citation: Clin Biochem. 2007 Jul;40(11):793-7
references.pmid: 17442295
references.citation: Reprod Sci. 2012 May;19(5):505-12
references.pmid: 22344728
references.citation: Appl Physiol Nutr Metab. 2006 Dec;31(6):661-74
references.pmid: 17213880
references.citation: Free Radic Res. 2008 Oct;42(10):841-8
references.pmid: 18985484
references.citation: Obstet Gynecol. 2010 Aug;116(2 Pt 1):393-401
references.pmid: 20664401
references.citation: Eur J Clin Nutr. 2014 Feb;68(2):215-22
references.pmid: 24327121
references.citation: Environ Health Perspect. 2009 Oct;117(10):1587-92
references.pmid: 20019910
references.citation: Free Radic Biol Med. 2000 Feb 15;28(4):505-13
references.pmid: 10719231
references.citation: Biomarkers. 2009 Sep;14(6):406-13
references.pmid: 19548773
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(23):9383-7
references.pmid: 2123555
references.citation: Ann Clin Biochem. 2011 Mar;48(Pt 2):147-54
references.pmid: 21292864
references.citation: Reprod Sci. 2009 Feb;16(2):206-15
references.pmid: 19208789
references.citation: Am J Clin Nutr. 2005 May;81(5):1218S-1222S
references.pmid: 15883455
references.citation: Clin Chim Acta. 2004 Jan;339(1-2):1-9
references.pmid: 14687888
references.citation: Free Radic Res. 1997 Jun;26(6):507-14
references.pmid: 9212344
references.citation: Hum Exp Toxicol. 2010 May;29(5):351-8
references.pmid: 20385707
references.citation: Reprod Sci. 2010 Apr;17(4):401-9
references.pmid: 20167745
references.citation: Clin Chem. 2006 Apr;52(4):601-23
references.pmid: 16484333
references.citation: Am J Epidemiol. 2008 Nov 1;168(9):980-9
references.pmid: 18756014
references.citation: J Clin Invest. 2013 Sep;123(9):4063-75
references.pmid: 23979163
references.citation: MMWR Suppl. 2011 Jan 14;60(1):78-9
references.pmid: 21430627
references.citation: Lancet. 2008 Jan 5;371(9606):75-84
references.pmid: 18177778
references.citation: Placenta. 2009 Mar;30 Suppl A:S43-8
references.pmid: 19081132