<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04489056</url>
  </required_header>
  <id_info>
    <org_study_id>1668/2020</org_study_id>
    <nct_id>NCT04489056</nct_id>
  </id_info>
  <brief_title>Microbiome in Preterm Birth</brief_title>
  <official_title>The Human Microbiome in pPROM, Preterm Birth and the Neonatal Infant: a Prospective Longitudinal Pilot-study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of Vienna</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aims of this prospective longitudinal case-control pilot-study are (1) to characterize&#xD;
      the changes of the vaginal, uterine and placental microbiome in pregnant women experiencing&#xD;
      pPROM with immediate hospitalization and consecutive caesarean section at preterm, in&#xD;
      comparison to uneventful term births with elective cesarean section, as well as (2) to&#xD;
      evaluate the influence of the maternal on the neonatal microbiome and the early neonatal&#xD;
      outcome in pPROM preterm cases, in comparison to uneventful term births.&#xD;
&#xD;
      The first aim will be achieved by collecting vaginal and rectal swabs for microbiome analysis&#xD;
      in women experiencing pPROM, followed by uterine and placental swabs that are collected&#xD;
      during the caesarean section. Control samples will be collected at the same time points from&#xD;
      women undergoing elective caesarean section at term. The second aim will be achieved by&#xD;
      microbiome analysis of rectal, oral/buccal, and skin swabs taken from newborns that are&#xD;
      either born preterm after pPROM, or at term, both by caesarean section.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 100 study participants will be included, assigned to one of the following groups:&#xD;
&#xD;
      Study group:&#xD;
&#xD;
      • This group will consist of 50 pregnant women, who experienced pPROM between 22+5 and 28+0&#xD;
      gestational weeks, either presenting at the primary study site, or being referred from other&#xD;
      hospitals, and delivered at preterm by cesarean section.&#xD;
&#xD;
      Control group:&#xD;
&#xD;
      • This group will consist of 50 pregnant women, who are scheduled for elective cesarean&#xD;
      section at the outpatient department of the primary study site, between a 32+0 and 37+0&#xD;
      gestational weeks, and delivered at term by cesarean section.&#xD;
&#xD;
      Recruitment:&#xD;
&#xD;
      Recruitment of all patients will take place at the Medical University of Vienna, Department&#xD;
      of Obstetrics and Gynecology. Women in the study group will be referred from outside&#xD;
      hospitals or will present for any reason at our department. Verification of pPROM will be&#xD;
      performed by speculum examination and detection of amniotic fluid pooling. In case of unclear&#xD;
      findings, an enzymatic test (e.g., Amnisure®, QUIAGEN Sciences, LLC; Germantown, MD 20874,&#xD;
      USA) will be conducted. Following pPROM verification, women who meet the inclusion criteria&#xD;
      will be offered to participate in the study. Those who experience a spontaneous vaginal&#xD;
      delivery instead of a cesarean section due to any reason, will be considered as drop-out.&#xD;
      Women in the control group will be recruited during their routine presentation for elective&#xD;
      cesarean section (for any reason that does not meet the exclusion criteria of the study) that&#xD;
      will be scheduled at term. Those who experience preterm birth although being scheduled for&#xD;
      elective cesarean at term, will be considered as drop-out. During their consultation at the&#xD;
      outpatient department, these women will be offered to participate in the study.&#xD;
&#xD;
      Sampling:&#xD;
&#xD;
      All swabs will be collected from sub-investigators of this study using a standardized&#xD;
      procedure. For anonymization, only the collection time point, location and ward will be&#xD;
      marked on the swab tubes. After informed consent, vaginal swabs will be collected during&#xD;
      speculum examination from the lateral vaginal wall and posterior fornix vaginae using a&#xD;
      sterile cotton swab combined with an epithelial brush. A rectal swab will be collected by&#xD;
      insertion of a sterile swab into the anal sphincter. Intraoperative swabs of the placenta and&#xD;
      uterine cavity will be collected during caesarean section under sterile conditions. Neonatal&#xD;
      swabs (buccal mucosa and skin) will be collected directly after delivery and in the neonatal&#xD;
      period. Stool samples will be taken from the meconium, defined as first stool of the infant&#xD;
      and the stool of the newborn in the neonatal period. All specimens will immediately be stored&#xD;
      at -80°C after collection. The epithelial brush will be put into RNAlater® RNA stabilization&#xD;
      solution and stored at -80°C.&#xD;
&#xD;
      Microbiome analysis:&#xD;
&#xD;
      Microbiome analysis will be performed at the Joint Microbiome Facility (JMF) of the Medical&#xD;
      University of Vienna and the University of Vienna. Testing will be performed by sub-&#xD;
      investigators at the JMF. The microbial community composition in collected stool swab samples&#xD;
      will be determined by 16S rRNA gene amplicon sequencing. Briefly, DNA will be extracted with&#xD;
      the QIAamp Microbiome Kit or QIAamp DNA Mini Kit (for swab and stool samples, respectively),&#xD;
      followed by 16S rRNA gene amplification and barcoding as previously described. Multiplexed&#xD;
      amplicon samples sequenced on the Illumina MiSeq platform at the JMF. Negative controls&#xD;
      performed during DNA extraction and 16S rRNA gene amplification are routinely included in the&#xD;
      sample processing workflow. The obtained sequence data will be quality-filtered and&#xD;
      demultiplexed, followed by amplicon sequencing variant (ASV) inference with DADA2,16 enabling&#xD;
      analysis at the highest possible taxonomic resolution. Resulting ASV sequences will be&#xD;
      taxonomically classified using SINA with the newest release of the the SILVA SSU rRNA&#xD;
      database. If necessary, contaminants will be removed in silico using the decontam software&#xD;
      package.&#xD;
&#xD;
      Perinatal data:&#xD;
&#xD;
      In addition to swab sampling and analysis, the following perinatal parameters will be&#xD;
      collected, using the PIA Fetal Database, version 5.6.16.917 (GE Viewpoint, Munich, Germany):&#xD;
      Maternal age [number], parity [number], tertiary education [yes/no], ethnicity [category],&#xD;
      relationship status [category], body mass index [number], nicotine abuse [yes/no], history of&#xD;
      pPROM [yes/no], history of PTB [yes/no], preexisting diseases [category], vaginal infection&#xD;
      screening [yes/no], cervical insufficiency [yes/no], preeclampsia [yes/no], bleeding&#xD;
      [yes/no], antenatal steroid prophylaxis [yes/no], ongoing antibiotic treatment [yes/no],&#xD;
      tocolysis [yes/no], magnesium prophylaxis [yes/no], gestational week at delivery [number],&#xD;
      birthweight [number], Apgar score at 1/5/10 minutes [number], umbilical cord arterial pH&#xD;
      [number], transfer to neonatal intensive care unit [yes/no].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">July 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of the vaginal microbiome after pPROM in comparison to term births</measure>
    <time_frame>Till July 2021</time_frame>
    <description>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 &lt;0.05 will be considered significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes of the rectal microbiome after pPROM in comparison to term births</measure>
    <time_frame>Till July 2021</time_frame>
    <description>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 &lt;0.05 will be considered significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes of the placental microbiome after pPROM in comparison to term births</measure>
    <time_frame>Till July 2021</time_frame>
    <description>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 &lt;0.05 will be considered significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes of the uterine microbiome after pPROM in comparison to term births</measure>
    <time_frame>Till July 2021</time_frame>
    <description>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 &lt;0.05 will be considered significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes of the neonatal microbiome of neonates born after pPROM in comparison to neonates experiencing a term birth</measure>
    <time_frame>Till July 2021</time_frame>
    <description>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 &lt;0.05 will be considered significant.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Vaginal Microbiome</condition>
  <arm_group>
    <arm_group_label>Study group</arm_group_label>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Swabs for microbiome analysis</intervention_name>
    <description>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.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Study group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Analysis of the maternal vaginal, rectal, placental and uterus microbiome Analysis of the&#xD;
      neonatal buccal, skin and stool micro biome&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        A total of 100 study participants, meeting all inclusion and non exclusion criteria, will&#xD;
        be included, assigned to one of the following groups:&#xD;
&#xD;
        Study group:&#xD;
&#xD;
        • This group will consist of 50 pregnant women, who experienced pPROM between 22+5 and 28+0&#xD;
        gestational weeks, either presenting at the primary study site, or being referred from&#xD;
        other hospitals, and delivered at preterm by cesarean section.&#xD;
&#xD;
        Control group:&#xD;
&#xD;
        • This group will consist of 50 pregnant women, who are scheduled for elective cesarean&#xD;
        section at the outpatient department of the primary study site, between a 32+0 and 37+0&#xD;
        gestational weeks, and delivered at term by cesarean section.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Maternal age ≥18 years at the time of study enrollment&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Confirmed preterm premature rupture of membranes (pPROM) or elective cesarean section&#xD;
             for term birth (depending on study group)&#xD;
&#xD;
          -  Gestational age at the time of pPROM between 22+5 and 28+0 weeks or ≥37+0 gestational&#xD;
             weeks at the time of term cesarean section (depending on study group)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Maternal age &lt;18 years at the time of study enrollment&#xD;
&#xD;
          -  Multiple pregnancy&#xD;
&#xD;
          -  Inability to consent to the participation in the study&#xD;
&#xD;
          -  Ongoing antibiotic treatment or antibiotic treatment ≤2 weeks before study enrollment&#xD;
&#xD;
          -  Vaginal sexual intercourse within 48 hours before study enrollment&#xD;
&#xD;
          -  Fresh vaginal bleeding within 48 hours before study enrollment&#xD;
&#xD;
          -  Maternal Hepatitis-B or Hepatitis-C infection (i.e., positive on PCR)&#xD;
&#xD;
          -  Maternal HIV-infection (i.e., positive on PCR)&#xD;
&#xD;
          -  Maternal diabetes mellitus or gestational diabetes&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant women</gender_description>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alex Farr, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Vienna</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Herbert Kiss, MD MBA</last_name>
    <role>Study Chair</role>
    <affiliation>Medical University of Vienna</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Angelika Berger, MD MBA</last_name>
    <role>Study Chair</role>
    <affiliation>Medical University of Vienna</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Philipp Foessleitner, MD BSc</last_name>
    <phone>+4314040028190</phone>
    <email>philipp.foessleitner@meduniwien.ac.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nikolaus Keil, MD</last_name>
    <phone>+4314040028190</phone>
    <email>nikolaus.keil@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medical University of Vienna, Dept. of Obstetrics and Gynecology</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Philipp Foessleitner, MD BSc</last_name>
      <phone>+43140400</phone>
      <phone_ext>28220</phone_ext>
      <email>philipp.foessleitner@muv.ac.at</email>
    </contact>
    <contact_backup>
      <last_name>Alex Farr, MD PhD</last_name>
      <phone>+43140400</phone>
      <phone_ext>28220</phone_ext>
      <email>alex.farr@muv.ac.at</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
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  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>September 1, 2020</last_update_submitted>
  <last_update_submitted_qc>September 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Alex Farr, MD PhD</investigator_full_name>
    <investigator_title>Prof. Alex Farr, MD PhD</investigator_title>
  </responsible_party>
  <keyword>Vaginal microbiome</keyword>
  <keyword>Preterm birth</keyword>
  <keyword>Neonatal microbiome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Anonymized data if required and in accordance with data protection regulations</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04489056
org study id: 1668/2020
nct id: NCT04489056
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
A total of 100 study participants 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.

      Recruitment:

      Recruitment of all patients will take place at the Medical University of Vienna, Department
      of Obstetrics and Gynecology. Women in the study group will be referred from outside
      hospitals or will present for any reason at our department. Verification of pPROM will be
      performed by speculum examination and detection of amniotic fluid pooling. In case of unclear
      findings, an enzymatic test (e.g., Amnisure®, QUIAGEN Sciences, LLC; Germantown, MD 20874,
      USA) will be conducted. Following pPROM verification, women who meet the inclusion criteria
      will be offered to participate in the study. Those who experience a spontaneous vaginal
      delivery instead of a cesarean section due to any reason, will be considered as drop-out.
      Women in the control group will be recruited during their routine presentation for elective
      cesarean section (for any reason that does not meet the exclusion criteria of the study) that
      will be scheduled at term. Those who experience preterm birth although being scheduled for
      elective cesarean at term, will be considered as drop-out. During their consultation at the
      outpatient department, these women will be offered to participate in the study.

      Sampling:

      All swabs will be collected from sub-investigators of this study using a standardized
      procedure. For anonymization, only the collection time point, location and ward will be
      marked on the swab tubes. 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. All specimens will immediately be stored
      at -80°C after collection. The epithelial brush will be put into RNAlater® RNA stabilization
      solution and stored at -80°C.

      Microbiome analysis:

      Microbiome analysis will be performed at the Joint Microbiome Facility (JMF) of the Medical
      University of Vienna and the University of Vienna. Testing will be performed by sub-
      investigators at the JMF. The microbial community composition in collected stool swab samples
      will be determined by 16S rRNA gene amplicon sequencing. Briefly, DNA will be extracted with
      the QIAamp Microbiome Kit or QIAamp DNA Mini Kit (for swab and stool samples, respectively),
      followed by 16S rRNA gene amplification and barcoding as previously described. Multiplexed
      amplicon samples sequenced on the Illumina MiSeq platform at the JMF. Negative controls
      performed during DNA extraction and 16S rRNA gene amplification are routinely included in the
      sample processing workflow. The obtained sequence data will be quality-filtered and
      demultiplexed, followed by amplicon sequencing variant (ASV) inference with DADA2,16 enabling
      analysis at the highest possible taxonomic resolution. Resulting ASV sequences will be
      taxonomically classified using SINA with the newest release of the the SILVA SSU rRNA
      database. If necessary, contaminants will be removed in silico using the decontam software
      package.

      Perinatal data:

      In addition to swab sampling and analysis, the following perinatal parameters will be
      collected, using the PIA Fetal Database, version 5.6.16.917 (GE Viewpoint, Munich, Germany):
      Maternal age [number], parity [number], tertiary education [yes/no], ethnicity [category],
      relationship status [category], body mass index [number], nicotine abuse [yes/no], history of
      pPROM [yes/no], history of PTB [yes/no], preexisting diseases [category], vaginal infection
      screening [yes/no], cervical insufficiency [yes/no], preeclampsia [yes/no], bleeding
      [yes/no], antenatal steroid prophylaxis [yes/no], ongoing antibiotic treatment [yes/no],
      tocolysis [yes/no], magnesium prophylaxis [yes/no], gestational week at delivery [number],
      birthweight [number], Apgar score at 1/5/10 minutes [number], umbilical cord arterial pH
      [number], transfer to neonatal intensive care unit [yes/no].
observational model: Case-Control
time perspective: Prospective
measure: Changes of the vaginal microbiome after pPROM in comparison to term births
time frame: Till July 2021
description: 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.
measure: Changes of the rectal microbiome after pPROM in comparison to term births
time frame: Till July 2021
description: 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.
measure: Changes of the placental microbiome after pPROM in comparison to term births
time frame: Till July 2021
description: 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.
measure: Changes of the uterine microbiome after pPROM in comparison to term births
time frame: Till July 2021
description: 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.
measure: Changes of the neonatal microbiome of neonates born after pPROM in comparison to neonates experiencing a term birth
time frame: Till July 2021
description: 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.
arm group label: Study group
description: 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.
arm group label: Control group
description: 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.
intervention type: Genetic
intervention name: Swabs for microbiome analysis
description: 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.
arm group label: Control group
arm group label: Study group
Analysis of the maternal vaginal, rectal, placental and uterus microbiome Analysis of the
      neonatal buccal, skin and stool micro biome
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Pregnant women
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Alex Farr, MD PhD
role: Principal Investigator
affiliation: Medical University of Vienna
last name: Herbert Kiss, MD MBA
role: Study Chair
affiliation: Medical University of Vienna
last name: Angelika Berger, MD MBA
role: Study Chair
affiliation: Medical University of Vienna
last name: Philipp Foessleitner, MD BSc
phone: +4314040028190
email: philipp.foessleitner@meduniwien.ac.at
last name: Nikolaus Keil, MD
phone: +4314040028190
email: nikolaus.keil@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Austria
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responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Alex Farr, MD PhD
investigator title: Prof. Alex Farr, MD PhD
mesh term: Premature Birth
sharing ipd: Undecided
ipd description: Anonymized data if required and in accordance with data protection regulations