The University of Western Australia
Development of a Microbiological Test for Infection-Associated Preterm Birth
Introduction. Preterm birth is a multifactorial syndrome; 20-40% of all early deliveries are caused by ascending intrauterine infection (IUI), particularly those born more than 2 months preterm. A number of microorganisms have been identified in the vaginal mucosa that can cause IUI, yet translating this knowledge into improved diagnostics for identifying women at risk of preterm birth has remained elusive. Problem Statement. We set out to identify a vaginal microbial signature that identifies women at high risk of spontaneous preterm birth (sPTB) in early-/mid-pregnancy. Procedures/Data/Observations. A thousand asymptomatic pregnant women (16-22 weeks’ gestation, singleton pregnancies) were recruited from antenatal clinics at KEMH; vaginal swabs were collected, DNA extracted and vaginal microbial profiles generated at the species, serovar and clade level using targeted PCR assays and custom PCR arrays (n=25 targets). Obstetric outcomes were then used to identify bacterial signatures that were predictive of preterm birth. Results. No individual microbial target was indicative of increased PTB risk. Women with high levels of protective lactobacilli (L. crispatus, L. gasseri or L. jensenii) were at very low risk of PTB. However, in women deficient in these lactobacilli, a combination of G. vaginalis (clade 4), L. iners and U. parvum (serovars 3 or 6), which we termed ‘GLU positive’, was indicative of significantly increased risk of sPTB. Risk prediction was improved if F. nucleatum detection was included in the GLU test algorithm. The final GLU test algorithm predicted 39% of sPTBs and 48% of early sPTBs <34 weeks, with odds ratios of 3.1 and 4.6, respectively. Conclusions. GLU-positive singleton women in mid-pregnancy are at increased risk of sPTB and may benefit from targeted antimicrobial therapy. A randomised clinical trial is now underway to determine the clinical efficacy of screening and treating women based on their GLU test status.
Jeff Keelan gained his PhD from the University of Auckland in 1994, moving from Auckland to Perth WA in 2007. Although his research was initially in the field of steroid biochemistry, where he specialised in assay development, his postdoctoral research has primarily focused on the study of the immunology, endocrinology and pharmacology of pregnancy. He is Professor of Obstetrics and Head of Laboratories at the Division of Obstetrics & Gynaecology at King Edward Memorial Hospital (KEMH), University of Western Australia, and Head of School of Biomedical Sciences (QEII Medical Centre). He is also Director of the Women and Newborn Health Research Network at KEMH and Deputy Director of WIRF (Women and Infants Research Foundation). He has supervised more than 43 postgraduate students. His has published almost 200 articles in the fields of immunology, pharmacology, obstetrics and endocrinology (>7700 citations; h-index 47) and received more than $18 M in competitive grant funding. His current research is centred on the pharmacological treatment of intra-amniotic infection/inflammation, nanoparticle-based drug delivery in pregnancy, the intrauterine microbial and endocrine environment, amniotic fluid metagenomics, lipidomics and toxicology.