A prospective cohort for the investigation of alteration in temporal transcriptional and microbiome trajectories preceding preterm birth: A study protocol

Tobias Brummaier, Basirudeen S. Kabeer, Stephen Lindow, Justin C. Konje, Sasithon Pukrittayaamee, Juerg Utzinger, Mohammed Toufiq, Antonios Antoniou, Alexandra K. Marr, Sangrawee Suriyakan, Tomoshige Kino, Souhaila M. Al Khodor, Annalisa Terranegra, François Nosten, Daniel H. Paris, Rose McGready, Damien J. Chaussabel

Research output: Contribution to journalArticle

Abstract

Introduction: Preterm birth (PTB) results from heterogeneous influences and is a major contributor to neonatal mortality and morbidity that continues to have adverse effects on infants beyond the neonatal period. This protocol describes the procedures to determine molecular signatures predictive of PTB through high-frequency sampling during pregnancy, at delivery and the postpartum period. Methods and analysis: Four hundred first trimester pregnant women from either Myanmar or Thailand of either Karen or Burman ethnicity, with a viable, singleton pregnancy will be enrolled in this non-interventional, prospective pregnancy birth cohort study and will be followed through to the postpartum period. Fortnightly finger prick capillary blood sampling will allow the monitoring of genome-wide transcript abundance in whole blood. Collection of stool samples and vaginal swabs each trimester, at delivery and postpartum will allow monitoring of intestinal and vaginal microbial composition. In a nested case-control analysis, perturbations of transcript abundance in capillary blood as well as longitudinal changes of the gut, vaginal and oral microbiome will be compared between mothers giving birth to preterm and matched cases giving birth to term neonates. Placenta tissue of preterm and term neonates will be used to determine bacterial colonisation as well as for the establishment of coding and non-coding RNA profiles. In addition, RNA profiles of circulating, non-coding RNA in cord blood serum will be compared with those of maternal peripheral blood serum at time of delivery. Ethics and dissemination: This research protocol that aims to detect perturbations in molecular trajectories preceding adverse pregnancy outcomes was approved by the ethics committee of the Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand (Ethics Reference: TMEC 15-062), the Oxford Tropical Research Ethics Committee (Ethics Reference: OxTREC: 33-15) and the local Tak Province Community Ethics Advisory Board. The results of this cooperative project will be disseminated in multiple publications staggered over time in international peer-reviewed scientific journals.

Original languageEnglish
Article numbere023417
JournalBMJ Open
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

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Microbiota
Premature Birth
Ethics
Postpartum Period
Untranslated RNA
Thailand
Pregnancy
Mothers
Parturition
Newborn Infant
Myanmar
Tropical Medicine
Ethics Committees
Research Ethics Committees
Infant Mortality
First Pregnancy Trimester
Pregnancy Outcome
Serum
Fetal Blood
Placenta

Keywords

  • fetal medicine
  • maternal medicine
  • obstetrics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A prospective cohort for the investigation of alteration in temporal transcriptional and microbiome trajectories preceding preterm birth : A study protocol. / Brummaier, Tobias; Kabeer, Basirudeen S.; Lindow, Stephen; Konje, Justin C.; Pukrittayaamee, Sasithon; Utzinger, Juerg; Toufiq, Mohammed; Antoniou, Antonios; Marr, Alexandra K.; Suriyakan, Sangrawee; Kino, Tomoshige; Al Khodor, Souhaila M.; Terranegra, Annalisa; Nosten, François; Paris, Daniel H.; McGready, Rose; Chaussabel, Damien J.

In: BMJ Open, Vol. 9, No. 1, e023417, 01.01.2019.

Research output: Contribution to journalArticle

Brummaier, Tobias ; Kabeer, Basirudeen S. ; Lindow, Stephen ; Konje, Justin C. ; Pukrittayaamee, Sasithon ; Utzinger, Juerg ; Toufiq, Mohammed ; Antoniou, Antonios ; Marr, Alexandra K. ; Suriyakan, Sangrawee ; Kino, Tomoshige ; Al Khodor, Souhaila M. ; Terranegra, Annalisa ; Nosten, François ; Paris, Daniel H. ; McGready, Rose ; Chaussabel, Damien J. / A prospective cohort for the investigation of alteration in temporal transcriptional and microbiome trajectories preceding preterm birth : A study protocol. In: BMJ Open. 2019 ; Vol. 9, No. 1.
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AU - Kabeer, Basirudeen S.

AU - Lindow, Stephen

AU - Konje, Justin C.

AU - Pukrittayaamee, Sasithon

AU - Utzinger, Juerg

AU - Toufiq, Mohammed

AU - Antoniou, Antonios

AU - Marr, Alexandra K.

AU - Suriyakan, Sangrawee

AU - Kino, Tomoshige

AU - Al Khodor, Souhaila M.

AU - Terranegra, Annalisa

AU - Nosten, François

AU - Paris, Daniel H.

AU - McGready, Rose

AU - Chaussabel, Damien J.

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N2 - Introduction: Preterm birth (PTB) results from heterogeneous influences and is a major contributor to neonatal mortality and morbidity that continues to have adverse effects on infants beyond the neonatal period. This protocol describes the procedures to determine molecular signatures predictive of PTB through high-frequency sampling during pregnancy, at delivery and the postpartum period. Methods and analysis: Four hundred first trimester pregnant women from either Myanmar or Thailand of either Karen or Burman ethnicity, with a viable, singleton pregnancy will be enrolled in this non-interventional, prospective pregnancy birth cohort study and will be followed through to the postpartum period. Fortnightly finger prick capillary blood sampling will allow the monitoring of genome-wide transcript abundance in whole blood. Collection of stool samples and vaginal swabs each trimester, at delivery and postpartum will allow monitoring of intestinal and vaginal microbial composition. In a nested case-control analysis, perturbations of transcript abundance in capillary blood as well as longitudinal changes of the gut, vaginal and oral microbiome will be compared between mothers giving birth to preterm and matched cases giving birth to term neonates. Placenta tissue of preterm and term neonates will be used to determine bacterial colonisation as well as for the establishment of coding and non-coding RNA profiles. In addition, RNA profiles of circulating, non-coding RNA in cord blood serum will be compared with those of maternal peripheral blood serum at time of delivery. Ethics and dissemination: This research protocol that aims to detect perturbations in molecular trajectories preceding adverse pregnancy outcomes was approved by the ethics committee of the Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand (Ethics Reference: TMEC 15-062), the Oxford Tropical Research Ethics Committee (Ethics Reference: OxTREC: 33-15) and the local Tak Province Community Ethics Advisory Board. The results of this cooperative project will be disseminated in multiple publications staggered over time in international peer-reviewed scientific journals.

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