There is evidence that afebrile women in premature labor can be infected. Organisms are present in the amniotic fluid of 10% of the women in premature labor. Organisms can be isolated from between the chorion and amnion of 60% of the women who deliver prematurely, in contrast to only 20% of women who deliver at term. The major objective of this study is to define the microbiology and histopathology of women in premature labor and to treat the women in premature labor with antibiotics.
The specific aims are: 1) define the vaginal/cervical, amniotic fluid and placental microbiology of women in premature labor, 2) study selected microbiologic factors associated with infection, 3) demonstrate that antibiotics given to women in premature labor will reduce premature deliveries compared to placebo treated women, 4) demonstrate that placental and decidual inflammation is highly correlated with both infection and preterm delivery, and 5) evaluate defense mechanisms which may protect against infection. We plan to conduct a case-control study in which cases consisting of afebrile women in premature labor with intact membranes will undergo vaginal/cervical and trans-abdominal amniotic fluid cultures. These women will be placed in a randomized double- blinded trial of intravenous mezlocillin and oral erythromycin or saline placebo. The control group will be stratified into women who deliver at 34-37 and greater than 37 weeks of pregnancy. After delivery, cultures of the chorion-amnion and histology of the placental and endometrium will be performed. To evaluate the effect of infection on pregnancy the presence of vaginal/cervical, endometrial, placental membrane and amniotic organisms and/or inflammation will be compared among 450 causes and 450 control women. We will evaluate whether high organism concentration or organism virulence will positively correlate with infection and whether selected organisms, amniotic fluid bacterial inhibitory factors and serum antibody will negatively correlate with infection. It is hoped that the result of these studies will demonstrate the microbiology and pathophysiology of infection among women in premature labor and that antibiotic therapy will reduce the rate of premature births.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031871-05
Application #
3146905
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1987-09-01
Project End
1996-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Allen-Daniels, Matthew Josiah; Serrano, Myrna G; Pflugner, Lindsey P et al. (2015) Identification of a gene in Mycoplasma hominis associated with preterm birth and microbial burden in intraamniotic infection. Am J Obstet Gynecol 212:779.e1-779.e13
Whidbey, Christopher; Harrell, Maria Isabel; Burnside, Kellie et al. (2013) A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta. J Exp Med 210:1265-81
Hitti, Jane; Lapidus, Jodi A; Lu, Xinfang et al. (2010) Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid. Am J Obstet Gynecol 203:32.e1-8
Pereira, Leonardo; Reddy, Ashok P; Alexander, Amanda L et al. (2010) Insights into the multifactorial nature of preterm birth: proteomic profiling of the maternal serum glycoproteome and maternal serum peptidome among women in preterm labor. Am J Obstet Gynecol 202:555.e1-10
Cauci, Sabina; Hitti, Jane; Noonan, Carolyn et al. (2002) Vaginal hydrolytic enzymes, immunoglobulin A against Gardnerella vaginalis toxin, and risk of early preterm birth among women in preterm labor with bacterial vaginosis or intermediate flora. Am J Obstet Gynecol 187:877-81
Hitti, J; Hillier, S L; Agnew, K J et al. (2001) Vaginal indicators of amniotic fluid infection in preterm labor. Obstet Gynecol 97:211-9
Gravett, M G; Hitti, J; Hess, D L et al. (2000) Intrauterine infection and preterm delivery: evidence for activation of the fetal hypothalamic-pituitary-adrenal axis. Am J Obstet Gynecol 182:1404-13
Roos, T; Martin, T R; Ruzinski, J T et al. (1997) Lipopolysaccharide binding protein and soluble CD14 receptor protein in amniotic fluid and cord blood in patients at term. Am J Obstet Gynecol 177:1230-7
Hitti, J; Krohn, M A; Patton, D L et al. (1997) Amniotic fluid tumor necrosis factor-alpha and the risk of respiratory distress syndrome among preterm infants. Am J Obstet Gynecol 177:50-6
Rabe, L K; Sheiness, D; Hillier, S L (1995) Comparison of the use of oligonucleotide probes, 4-methylumbelliferyl derivatives, and conventional methods for identifying Prevotella bivia. Clin Infect Dis 20 Suppl 2:S195-7

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