Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study
IntroductionBacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria pre...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-02-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/2/e035186.full |
| _version_ | 1819135949691420672 |
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| author | John Kinuthia R Scott McClelland Erica M Lokken Walter Jaoko Sujatha Srinivasan David N Fredricks Barbra A Richardson Kishorchandra Mandaliya Sophia Lannon Hudson Alumera Arthur Kemoli Emily Fay G John-Stewart |
| author_facet | John Kinuthia R Scott McClelland Erica M Lokken Walter Jaoko Sujatha Srinivasan David N Fredricks Barbra A Richardson Kishorchandra Mandaliya Sophia Lannon Hudson Alumera Arthur Kemoli Emily Fay G John-Stewart |
| author_sort | John Kinuthia |
| collection | DOAJ |
| description | IntroductionBacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria present around conception may lead to SPTB by compromising the protective effects of cervical mucus, colonising the endometrial surface before fetal membrane development, and causing low-level inflammation in the decidua, placenta and fetal membranes. This protocol describes a prospective case-cohort study addressing this hypothesis.Methods and analysisHIV-seronegative Kenyan women with fertility intent are followed from preconception through pregnancy, delivery and early postpartum. Participants provide monthly vaginal specimens during the preconception period for vaginal microbiota assessment. Estimated date of delivery is determined by last menstrual period and first trimester obstetrical ultrasound. After delivery, a swab is collected from between the fetal membranes. Placenta and umbilical cord samples are collected for histopathology. Broad-range 16S rRNA gene PCR and deep sequencing of preconception vaginal specimens will assess species richness and diversity in women with SPTB versus term delivery. Concentrations of key bacterial species will be compared using quantitative PCR (qPCR). Taxon-directed qPCR will also be used to quantify bacteria from fetal membrane samples and evaluate the association between bacterial concentrations and histopathological evidence of inflammation in the fetal membranes, placenta and umbilical cord.Ethics and disseminationThis study was approved by ethics committees at Kenyatta National Hospital and the University of Washington. Results will be disseminated to clinicians at study sites and partner institutions, presented at conferences and published in peer-reviewed journals. The findings of this study could shift the paradigm for thinking about the mechanisms linking vaginal microbiota and prematurity by focusing attention on the preconception vaginal microbiota as a mediator of SPTB. |
| first_indexed | 2024-12-22T10:27:13Z |
| format | Article |
| id | doaj.art-055eb07ec8854423a9fc3d8d51e03ad8 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-12-22T10:27:13Z |
| publishDate | 2020-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-055eb07ec8854423a9fc3d8d51e03ad82022-12-21T18:29:26ZengBMJ Publishing GroupBMJ Open2044-60552020-02-0110210.1136/bmjopen-2019-035186Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort studyJohn Kinuthia0R Scott McClelland1Erica M Lokken2Walter Jaoko3Sujatha Srinivasan4David N Fredricks5Barbra A Richardson6Kishorchandra Mandaliya7Sophia Lannon8Hudson Alumera9Arthur Kemoli10Emily Fay11G John-Stewart12Research and Programs, Kenyatta National Hospital, Nairobi, KenyaDepartment of Epidemiology, University of Washington, Seattle, Washington, USADepartment of Epidemiology, University of Washington, Seattle, Washington, USAMedical Microbiology, University of Nairobi, Nairobi, KenyaVaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USAVaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USADepartment of Global Health, University of Washington, Seattle, Washington, USAPathCare Kenya, Mombasa, KenyaNorthwest Perinatal, Portland, Oregon, USAUniversity of Nairobi School of Dental Sciences, Nairobi, KenyaUniversity of Nairobi School of Dental Sciences, Nairobi, Kenya4 Brigham and Women’s Physician’s Organization, Brookline, Massachusetts, USA Department of Epidemiology, University of Washington, Seattle, Washington, USAIntroductionBacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria present around conception may lead to SPTB by compromising the protective effects of cervical mucus, colonising the endometrial surface before fetal membrane development, and causing low-level inflammation in the decidua, placenta and fetal membranes. This protocol describes a prospective case-cohort study addressing this hypothesis.Methods and analysisHIV-seronegative Kenyan women with fertility intent are followed from preconception through pregnancy, delivery and early postpartum. Participants provide monthly vaginal specimens during the preconception period for vaginal microbiota assessment. Estimated date of delivery is determined by last menstrual period and first trimester obstetrical ultrasound. After delivery, a swab is collected from between the fetal membranes. Placenta and umbilical cord samples are collected for histopathology. Broad-range 16S rRNA gene PCR and deep sequencing of preconception vaginal specimens will assess species richness and diversity in women with SPTB versus term delivery. Concentrations of key bacterial species will be compared using quantitative PCR (qPCR). Taxon-directed qPCR will also be used to quantify bacteria from fetal membrane samples and evaluate the association between bacterial concentrations and histopathological evidence of inflammation in the fetal membranes, placenta and umbilical cord.Ethics and disseminationThis study was approved by ethics committees at Kenyatta National Hospital and the University of Washington. Results will be disseminated to clinicians at study sites and partner institutions, presented at conferences and published in peer-reviewed journals. The findings of this study could shift the paradigm for thinking about the mechanisms linking vaginal microbiota and prematurity by focusing attention on the preconception vaginal microbiota as a mediator of SPTB.https://bmjopen.bmj.com/content/10/2/e035186.full |
| spellingShingle | John Kinuthia R Scott McClelland Erica M Lokken Walter Jaoko Sujatha Srinivasan David N Fredricks Barbra A Richardson Kishorchandra Mandaliya Sophia Lannon Hudson Alumera Arthur Kemoli Emily Fay G John-Stewart Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study BMJ Open |
| title | Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study |
| title_full | Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study |
| title_fullStr | Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study |
| title_full_unstemmed | Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study |
| title_short | Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study |
| title_sort | impact of preconception vaginal microbiota on women s risk of spontaneous preterm birth protocol for a prospective case cohort study |
| url | https://bmjopen.bmj.com/content/10/2/e035186.full |
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