title: The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk.
abstract: Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing, we undertook a prospective study in women at risk of preterm birth (n = 161) to assess (1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth risk and (2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix.
  
  
  
  Lactobacillus iners dominance at 16 weeks of gestation was significantly associated with both a short cervix <25 mm (n = 15, P < 0.05) and preterm birth <34+0weeks (n = 18; P < 0.01; 69% PPV). In contrast, Lactobacillus crispatus dominance was highly predictive of term birth (n = 127, 98% PPV). Cervical shortening and preterm birth were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28, and 34 weeks) was then undertaken in women receiving vaginal progesterone (400 mg/OD, n = 25) versus controls (n = 42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (<34 weeks).
  
  
  
  L. iners dominance of the vaginal microbiota at 16 weeks of gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about "infection risk" associated with the use of a vaginal pessary during high-risk pregnancy can be reassured.
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.|Queen Charlotte's Hospital, Imperial College Healthcare NHS Trust, London, UK.|Department of Obstetrics and Gynaecology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Kindinger
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.|Queen Charlotte's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Bennett
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.
authors.forename: Yun S
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Centre for Digestive and Gut Health, Department of Surgery and Cancer and the Institute of Global Health Innovation, Faculty of Medicine, Imperial College London, London, UK.|School of Biosciences, Cardiff University, Cardiff, UK.|Division of Computational Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Marchesi
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Smith
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cacciatore
authors.affiliation: Centre for Digestive and Gut Health, Department of Surgery and Cancer and the Institute of Global Health Innovation, Faculty of Medicine, Imperial College London, London, UK.|Division of Computational Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Centre for Digestive and Gut Health, Department of Surgery and Cancer and the Institute of Global Health Innovation, Faculty of Medicine, Imperial College London, London, UK.|Division of Computational Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.|Department of Obstetrics and Gynaecology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: T G
authors.initials: TG
authors.lastname: Teoh
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK. d.macintyre@imperial.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: MacIntyre
mesh_terms: D000328:Adult; D058491:Bacterial Load / Q000187:drug effects; D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000502:physiology; D003430:Cross-Sectional Studies; D064806:Dysbiosis / Q000139:chemically induced; D005260:Female; D006801:Humans; D007778:Lactobacillus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D064307:Microbiota / Q000187:drug effects*; D010570:Pessaries / Q000009:adverse effects; D011247:Pregnancy; D011256:Pregnancy Outcome; D018566:Pregnancy, High-Risk / Q000187:drug effects*; D047928:Premature Birth / Q000517:prevention & control*; D011374:Progesterone / Q000627:therapeutic use*; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D014621:Vagina / Q000382:microbiology*; D055815:Young Adult
chemical_list: D012336:RNA, Ribosomal, 16S; D011374:Progesterone
keywords: Cervical length; Lactobacillus; Preterm birth; Progesterone; Vaginal microbiome