Polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, local midtrimester cytokine response to vaginal flora, and subsequent preterm birth.

OBJECTIVE: This study investigated the association between polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, midtrimester vaginal microflora, vaginal interleukin receptor antagonist and interleukin-1beta levels and subsequent spontaneous preterm birth. STUDY DESIGN: Vaginal samples from 212 women, collected at 18-22 weeks' gestation, were analyzed for the polymorphism in intron 2 of the interleukin-1 receptor antagonist gene by polymerase chain reaction, qualitative and quantitative vaginal microflora, and interleukin-1beta and interleukin-1ra concentrations by enzyme-linked immunosorbent assay. Pregnancy outcome data were subsequently obtained. RESULTS: Carriage of intron 2 of the interleukin-1 receptor antagonist allele 2 (IL1RN * 2) was associated with an elevated vaginal pH in black ( P < .001) and white ( P = .005) women, a reduced interleukin-1beta response to anaerobic Gram-negative rods and/or Gardnerella vaginalis ( P < .01), and a decreased rate of spontaneous preterm deliveries (6% versus 18%, P = .02). In black women, IL1RN * 2 carriage was associated with increased anaerobic Gram-negative rods, Mycoplasma, and Peptostreptococci and decreased Lactobacilli colonization. CONCLUSION: IL1RN * 2 carriage was associated with a blunted proinflammatory interleukin-1beta response to abnormal vaginal flora. This property may decrease susceptibility to infection-related preterm birth.

Mycoplasma hominis and Ureaplasma urealyticum in midtrimester amniotic fluid: association with amniotic fluid cytokine levels and pregnancy outcome.

OBJECTIVE: The association between the detection of Mycoplasma hominis or Ureaplasma urealyticum in midtrimester amniotic fluid and amniotic fluid cytokine concentrations and subsequent pregnancy outcome were examined. STUDY DESIGN: Amniocentesis was performed between 15 and 19 weeks of gestation in 179 asymptomatic women. Aliquots were assayed for M hominis and U urealyticum by polymerase chain reaction coupled to enzyme-linked immunosorbent assay. Intra-amniotic levels of interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, interleukin-6, and tumor necrosis factor-alpha were determined by enzyme-linked immunosorbent assay. Pregnancy outcomes were obtained after the completion of all testing. RESULTS: U urealyticum was detected in 22 of 172 amniotic fluids (12.8%); M hominis was present in 11 of 179 amniotic fluids (6.1%). There was no relationship between U urealyticum detection and the concentration of any cytokine. Detection of M hominis was associated with elevated intra-amniotic concentrations of interleukin-4 ( P = .01). Preterm premature rupture of membranes that was followed by preterm birth occurred in 5 women (2.8%); 5 women (2.8%) had a spontaneous preterm birth with intact membranes. All 5 of the women with preterm premature rupture of membranes (100%) tested positive for either U urealyticum or M hominis , as opposed to none of the women with spontaneous preterm birth and to 27 of 161 women (16.8%) with a term birth ( P = .0002). CONCLUSION: The detection of M hominis or U urealyticum in midtrimester amniotic fluid by polymerase chain reaction-enzyme-linked immunosorbent assay may be a risk factor for subsequent preterm premature rupture of membranes.

A disproportionate increase in IL-1beta over IL-1ra in the cervicovaginal secretions of pregnant women with altered vaginal microflora correlates with preterm birth.

OBJECTIVE: This purpose of this study was to investigate the association between vaginal microflora, concentrations of interleukin-1beta (IL-1beta), and its natural receptor antagonist (IL-1ra) in the cervicovaginal discharge, and spontaneous preterm birth. Study design Vaginal samples collected at 18 to 22 weeks' gestation from 207 women were analyzed to study qualitative and quantitative microbiologic aspects of vaginal microflora and IL-1beta and IL-1ra concentrations. RESULTS: Among women colonized with anaerobic Gram-negative rods and/or Gardnerella vaginalis, an elevated IL-1beta concentration, or a diminished IL-1ra:IL-1beta ratio were associated with preterm delivery. A cut-off IL-1ra:IL-1beta ratio of <8632:1 optimally discriminated the subjects with subsequent spontaneous preterm deliveries from subjects who delivered at term, with a sensitivity of 78%, specificity of 51%, positive predictive value of 21%, and negative predictive value of 95%. CONCLUSION: A disproportionate increase in IL-1beta over IL-1ra in response to vaginal colonization with anaerobic Gram-negative rods and/or G. vaginalis at 18 to 22 weeks' gestation is associated with spontaneous preterm delivery.