title: Urinary tract infection during pregnancy, angiogenic factor profiles, and risk of preeclampsia.
abstract: BACKGROUND
  Despite decades of research, and much progress in discernment of biomarkers in the maternal circulation, the pathogenesis of preeclampsia (PE) remains elusive. The pathophysiology of PE is believed to involve aberrant placentation and an associated increase in systemic inflammation. In this conceptualization, PE becomes more likely when the level of systemic inflammatory burden inherent in pregnancy itself exceeds the maternal capacity to compensate for this additional stress. If this is the case, then it is possible to hypothesize that conditions, such as infectious disease, that increase systemic inflammatory burden should also increase the risk of PE. As urinary tract infection (UTI) represents a common source of inflammation during pregnancy, we tested whether presence of UTI during pregnancy increased the odds of developing PE. Prior work has documented this association. However many of these studies were limited by small cohort sizes and insufficient control for covariates.
  
  
  OBJECTIVE
  The present study is a secondary analysis of a robust contemporary obstetrical cohort recruited to examine the ability of longitudinally sampled maternal angiogenic concentrations to predict PE. We hypothesize that the occurrence of UTI during a pregnancy is associated with the later occurrence of PE in that pregnancy. As PE is believed to be associated with aberrations in systemic angiogenic levels (placental growth factor and soluble isoform of VEGF receptor), we further hypothesize that there will be significant interactions between maternal angiogenic protein levels and the occurrence of UTI.
  
  
  METHODS
  Women aged ≥18 years (n = 2607) were recruited and followed up prospectively from the initiation of prenatal care through delivery at 3 regional academic centers. PE was defined by American Congress of Obstetricians and Gynecologists criteria and was independently validated by a panel of physicians. UTI was defined by the presence of clinical symptoms necessitating treatment in addition to supportive laboratory evidence. Multivariate logistic regression models were used and controlled for maternal age, race, parity, body mass index, hypertension, diabetes, in vitro fertilization, and smoking status.
  
  
  RESULTS
  There were 129 women with diagnosed UTIs and 235 with PE. Patients with UTI in pregnancy had higher rates of PE (31.1% vs 7.8%, P < .001) compared to those without reported UTI. The mean gestational age (SD) for UTI diagnosis in PE cases and controls was 25.6 (10.4) and 21.9 (10.9) weeks, respectively (P = .08). The unadjusted odds ratio for PE in the setting of UTI was 5.29 (95% confidence interval, 3.54-7.89). After controlling for confounders, UTI was associated with an odds ratio for PE of 3.2 (95% confidence interval, 2.0-5.1).
  
  
  CONCLUSIONS
  Presence of UTI in pregnancy, particularly in the third trimester, is strongly associated with PE. This association supports the hypothesis that the risk of PE is enhanced by an increased maternal inflammatory burden. Prophylaxis against UTI represents a potentially low-cost global intervention to slow or halt the development of PE.
authors.affiliation: Brigham and Women's Hospital/Massachusetts General Hospital Integrated Residency Program in Obstetrics and Gynecology, Boston, MA. Electronic address: sreaster@partners.org.
authors.forename: Sarah Rae
authors.initials: SR
authors.lastname: Easter
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA.
authors.forename: David E
authors.initials: DE
authors.lastname: Cantonwine
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Chloe A
authors.initials: CA
authors.lastname: Zera
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Kee-Hak
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Parry
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: McElrath
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D008875:Middle Aged; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000453:epidemiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000453:epidemiology*; D011257:Pregnancy Proteins / Q000097:blood*; D011264:Pregnancy Trimesters; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States; D014552:Urinary Tract Infections / Q000097:blood / Q000453:epidemiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1