Nucleic acids coding inflammatory cytokines, and the microbiome are detectable in the circulation of pregnant women with intrauterine infection — ASN Events
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Nucleic acids coding inflammatory cytokines, and the microbiome are detectable in the circulation of pregnant women with intrauterine infection (#155)

Owen Stock 1 , Natalie Hannan 1 , Gabrielle Fleming 2 , Clare Whitehead 1 , Sue Walker 2 , Stephen Tong 1
  1. Translational Obstetrics Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Heidelberg, VIC, Australia
  2. University of Melbourne, Heidelberg, VIC, Australia

INTRODUCTION:  Preterm prelabour rupture of fetal membranes (PPROM) can lead to intrauterine infection (chorioamnionitis) and cerebral palsy. A non-invasive test that identifies evolving intrauterine infection could be a useful clinical test. Nucleic acids of placental origin can be measured in maternal blood. Therefore, we examined whether nucleic acids coding inflammatory cytokines and microbes are altered in blood from women with chorioamnionitis.

METHODS: Pregnant women with PPROM were recruited and serial blood samples taken until delivery (RNA stabilised in PAXgene tubes, QIAGEN). Placental samples were collected from a subset of women. mRNA expression of the following cytokines were measured using qPCR: IL1b, IL6, IL8 and TNFα. Next generation sequencing (Roche GS FLX (454)) was performed on blood samples with bioinformatics diversity profiling to investigate the microbiome.

RESULTS: Women with PPROM were recruited (n=34). Of these, 27 were diagnosed with chorioamnionitis. IL1b mRNA expression was 65% higher in blood of women with PPROM and chorioamnionitis at delivery compared to 12 gestationally matched controls without ruptured membranes and who delivered at term (p=0.03). Interestingly, in one case where the neonate suffered florid E. coli infection, there was a very significant rise in IL1b mRNA in serial samples preceding birth. IL6, IL8 and TNFα mRNA were not increased with choriomnionitis.

Surprisingly, DNA coding bacteria of diverse species was present in maternal blood of women with chorioamnionitis. Some bacterial species, such as streptococcus, were present in every blood sample from women with chorioamnionitis.

CONCLUSION: Measuring mRNA coding IL1b in maternal blood has potential as a clinical test for chorioamnionitis. Surprisingly, DNA coding the microbiome (of possible placental origin) is readily detectable in maternal blood. This may represent a novel diagnostic approach to identify organisms responsible for intrauterine infection while the fetus is still in utero.

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