Microbiome in Preterm Birth

NCT04489056 | Unknown DMC

• 1 other identifier: 1668/2020
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The aims of this prospective longitudinal case-control pilot-study are (1) to characterize the changes of the vaginal, uterine and placental microbiome in pregnant women experiencing pPROM with immediate hospitalization and consecutive caesarean section at preterm, in comparison to uneventful term births with elective cesarean section, as well as (2) to evaluate the influence of the maternal on the neonatal microbiome and the early neonatal outcome in pPROM preterm cases, in comparison to uneventful term births. The first aim will be achieved by collecting vaginal and rectal swabs for microbiome analysis in women experiencing pPROM, followed by uterine and placental swabs that are collected during the caesarean section. Control samples will be collected at the same time points from women undergoing elective caesarean section at term. The second aim will be achieved by microbiome analysis of rectal, oral/buccal, and skin swabs taken from newborns that are either born preterm after pPROM, or at term, both by caesarean section.

Conditions

Vaginal Microbiome

Keywords

Vaginal microbiome; Preterm birth; Neonatal microbiome

Outcome Measures

Primary Outcomes (5)

• Changes of the vaginal microbiome after pPROM in comparison to term births

  Abundance measurements (counts) of the amplicon sequence variants (ASVs), as well as ASV sum counts at higher taxonomic levels will be evaluated, to test for significant overlap or differences in microbial community composition in different sample groups. These parameters will be analyzed within each of the study groups, including longitudinal analyses to detect a potential difference from the onset of pPROM to the time of delivery or later (study group), or from pregnancy to the time of delivery or later (control group). In addition, ASVs and ASV sum counts will be compared between the study and control group at predetermined time points. Detection of significantly more abundant amplicon sequence variants between groups will be performed, and adjusted P-values will be calculated using the Benjamini-Hochberg method and differences supported with P- values \<0.05 will be considered significant.

  Till July 2021

• Changes of the rectal microbiome after pPROM in comparison to term births

  Abundance measurements (counts) of the amplicon sequence variants (ASVs), as well as ASV sum counts at higher taxonomic levels will be evaluated, to test for significant overlap or differences in microbial community composition in different sample groups. These parameters will be analyzed within each of the study groups, including longitudinal analyses to detect a potential difference from the onset of pPROM to the time of delivery or later (study group), or from pregnancy to the time of delivery or later (control group). In addition, ASVs and ASV sum counts will be compared between the study and control group at predetermined time points. Detection of significantly more abundant amplicon sequence variants between groups will be performed, and adjusted P-values will be calculated using the Benjamini-Hochberg method and differences supported with P- values \<0.05 will be considered significant.

  Till July 2021

• Changes of the placental microbiome after pPROM in comparison to term births

  Abundance measurements (counts) of the amplicon sequence variants (ASVs), as well as ASV sum counts at higher taxonomic levels will be evaluated, to test for significant overlap or differences in microbial community composition in different sample groups. These parameters will be analyzed within each of the study groups, including longitudinal analyses to detect a potential difference from the onset of pPROM to the time of delivery or later (study group), or from pregnancy to the time of delivery or later (control group). In addition, ASVs and ASV sum counts will be compared between the study and control group at predetermined time points. Detection of significantly more abundant amplicon sequence variants between groups will be performed, and adjusted P-values will be calculated using the Benjamini-Hochberg method and differences supported with P- values \<0.05 will be considered significant.

  Till July 2021

• Changes of the uterine microbiome after pPROM in comparison to term births

  Abundance measurements (counts) of the amplicon sequence variants (ASVs), as well as ASV sum counts at higher taxonomic levels will be evaluated, to test for significant overlap or differences in microbial community composition in different sample groups. These parameters will be analyzed within each of the study groups, including longitudinal analyses to detect a potential difference from the onset of pPROM to the time of delivery or later (study group), or from pregnancy to the time of delivery or later (control group). In addition, ASVs and ASV sum counts will be compared between the study and control group at predetermined time points. Detection of significantly more abundant amplicon sequence variants between groups will be performed, and adjusted P-values will be calculated using the Benjamini-Hochberg method and differences supported with P- values \<0.05 will be considered significant.

  Till July 2021

• Changes of the neonatal microbiome of neonates born after pPROM in comparison to neonates experiencing a term birth

  Abundance measurements (counts) of the amplicon sequence variants (ASVs), as well as ASV sum counts at higher taxonomic levels will be evaluated, to test for significant overlap or differences in microbial community composition in different sample groups. These parameters will be analyzed within each of the study groups, including longitudinal analyses to detect a potential difference from the onset of pPROM to the time of delivery or later (study group), or from pregnancy to the time of delivery or later (control group). In addition, ASVs and ASV sum counts will be compared between the study and control group at predetermined time points. Detection of significantly more abundant amplicon sequence variants between groups will be performed, and adjusted P-values will be calculated using the Benjamini-Hochberg method and differences supported with P- values \<0.05 will be considered significant.

  Till July 2021

Study Arms (2)

Study group

This group will consist of 50 pregnant women, who experienced pPROM between 22+5 and 28+0 gestational weeks, either presenting at the primary study site, or being referred from other hospitals, and delivered at preterm by cesarean section.

Genetic: Swabs for microbiome analysis

Control group

This group will consist of 50 pregnant women, who are scheduled for elective cesarean section at the outpatient department of the primary study site, between a 32+0 and 37+0 gestational weeks, and delivered at term by cesarean section.

Genetic: Swabs for microbiome analysis

Interventions

Swabs for microbiome analysis GENETIC

After informed consent, vaginal swabs will be collected during speculum examination from the lateral vaginal wall and posterior fornix vaginae using a sterile cotton swab combined with an epithelial brush. A rectal swab will be collected by insertion of a sterile swab into the anal sphincter. Intraoperative swabs of the placenta and uterine cavity will be collected during caesarean section under sterile conditions. Neonatal swabs (buccal mucosa and skin) will be collected directly after delivery and in the neonatal period. Stool samples will be taken from the meconium, defined as first stool of the infant and the stool of the newborn in the neonatal period.

Control group; Study group

Eligibility Criteria

• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A total of 100 study participants, meeting all inclusion and non exclusion criteria, will be included, assigned to one of the following groups: Study group: • This group will consist of 50 pregnant women, who experienced pPROM between 22+5 and 28+0 gestational weeks, either presenting at the primary study site, or being referred from other hospitals, and delivered at preterm by cesarean section. Control group: • This group will consist of 50 pregnant women, who are scheduled for elective cesarean section at the outpatient department of the primary study site, between a 32+0 and 37+0 gestational weeks, and delivered at term by cesarean section.

You may qualify if:

• Maternal age ≥18 years at the time of study enrollment
• Singleton pregnancy
• Signed informed consent
• Confirmed preterm premature rupture of membranes (pPROM) or elective cesarean section for term birth (depending on study group)
• Gestational age at the time of pPROM between 22+5 and 28+0 weeks or ≥37+0 gestational weeks at the time of term cesarean section (depending on study group)

You may not qualify if:

• Maternal age \<18 years at the time of study enrollment
• Multiple pregnancy
• Inability to consent to the participation in the study
• Ongoing antibiotic treatment or antibiotic treatment ≤2 weeks before study enrollment
• Vaginal sexual intercourse within 48 hours before study enrollment
• Fresh vaginal bleeding within 48 hours before study enrollment
• Maternal Hepatitis-B or Hepatitis-C infection (i.e., positive on PCR)
• Maternal HIV-infection (i.e., positive on PCR)
• Maternal diabetes mellitus or gestational diabetes

Sponsors & Collaborators

• Medical University of Vienna: lead
• University of Vienna: collaborator

Study Sites (1)

Medical University of Vienna, Dept. of Obstetrics and Gynecology

Vienna, 1090, Austria

RECRUITING

Related Publications (21)

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• Callahan BJ, DiGiulio DB, Goltsman DSA, Sun CL, Costello EK, Jeganathan P, Biggio JR, Wong RJ, Druzin ML, Shaw GM, Stevenson DK, Holmes SP, Relman DA. Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):9966-9971. doi: 10.1073/pnas.1705899114. Epub 2017 Aug 28.

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• Brown RG, Al-Memar M, Marchesi JR, Lee YS, Smith A, Chan D, Lewis H, Kindinger L, Terzidou V, Bourne T, Bennett PR, MacIntyre DA. Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes. Transl Res. 2019 May;207:30-43. doi: 10.1016/j.trsl.2018.12.005. Epub 2018 Dec 27.

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• Stout MJ, Zhou Y, Wylie KM, Tarr PI, Macones GA, Tuuli MG. Early pregnancy vaginal microbiome trends and preterm birth. Am J Obstet Gynecol. 2017 Sep;217(3):356.e1-356.e18. doi: 10.1016/j.ajog.2017.05.030. Epub 2017 May 23.

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• Thorsen J, Brejnrod A, Mortensen M, Rasmussen MA, Stokholm J, Al-Soud WA, Sorensen S, Bisgaard H, Waage J. Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies. Microbiome. 2016 Nov 25;4(1):62. doi: 10.1186/s40168-016-0208-8.

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• Chu DM, Ma J, Prince AL, Antony KM, Seferovic MD, Aagaard KM. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med. 2017 Mar;23(3):314-326. doi: 10.1038/nm.4272. Epub 2017 Jan 23.

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• Huurre A, Kalliomaki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery - effects on gut microbiota and humoral immunity. Neonatology. 2008;93(4):236-40. doi: 10.1159/000111102. Epub 2007 Nov 16.

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  PMID: 25578246 BACKGROUND

• Foessleitner P, Pjevac P, Granser S, Wisgrill L, Pummer L, Eckel F, Seki D, Berry D, Hausmann B, Farr A. The maternal microbiome in pregnancy, delivery, and early-stage development of neonatal microbiome after cesarean section: A prospective longitudinal study. Acta Obstet Gynecol Scand. 2024 May;103(5):832-841. doi: 10.1111/aogs.14773. Epub 2024 Jan 24.

  PMID: 38268221 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Analysis of the maternal vaginal, rectal, placental and uterus microbiome Analysis of the neonatal buccal, skin and stool micro biome

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Alex Farr, MD PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

• Herbert Kiss, MD MBA

  Medical University of Vienna

  STUDY CHAIR

• Angelika Berger, MD MBA

  Medical University of Vienna

  STUDY CHAIR

Central Study Contacts

Philipp Foessleitner, MD BSc

CONTACT

+4314040028190; philipp.foessleitner@meduniwien.ac.at

Nikolaus Keil, MD

CONTACT

+4314040028190; nikolaus.keil@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Alex Farr, MD PhD

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 28, 2020
• Study Start: July 27, 2020
• Primary Completion: July 1, 2021
• Study Completion: December 1, 2021
• Last Updated: September 2, 2020

Record last verified: 2020-09

Locations

AU (1)