Preterm BirthBaBsNCT02392650
Microbiome And Multi'Omics In Preterm Birth: The Bacteria And Birth Study
An observational study of Preterm Birth, run by Baylor College of Medicine at 1 site in United States.
Trial summary
Hominids and hominins serve as remarkable hosts to microbes, and we have co-evolved over the past 4.5 million years as highly plethoric communities. Human-associated microorganisms (the "microbiome") are present in numbers exceeding the quantities of human cells by at least 10-fold beginning in the neonatal period. Read more about this study
- Who is it for?
- Ages 16 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth
- How many people
- 526 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Jun 2025
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 64 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Women who are currently pregnant who are at high risk for preterm birth; Pregnant with one baby (not twins or triplets) and who attend regular prenatal visits. They will spend an extra 20 minutes at 5-6 priority scheduled visits to obtain study samples and complete questionnaires, with the last visit occurring around 6 weeks after delivery.
Who may be able to join
- Gravidae at risk for preterm birth, defined as: History of prior spontaneous preterm birth at 16w0d-36w6d gestational age confirmed by review of medical records. If efforts to retrieve medical records are unsuccessful, eligibility will depend upon the events surrounding the prior birth and birthweight under 2 kg; Documented shortened cervix <2.5 cm by transvaginal ultrasound performed by experienced sonographer at <24 weeks gestational age; Documented and culture-proven complicated lower or upper urinary tract infection defined as a urinary tract infection requiring hospitalization (e.g., pyelonephritis); Documented periodontal disease, treated or untreated; Documented recurrent lower genital infection; Smoking or other chemical dependency that would convey an increased risk of preterm birth; Other clinical concern for high risk of preterm birth (and cleared by PI Dr. Aagaard at BCM or Dr. Saade at UTMB)
- Enrollment at less than or equal to 20 weeks gestation by best obstetrical estimate
- Able to speak English or work with an interpreter
- Cognitively aware enough to be able to participate in the study
- Gravidae with viable pregnancy >10 weeks gestational age
- Willingness to consent to all required aspects of protocol - There will be additional non-required aspects that we will recruit 20% of subjects to participate in. These will be voluntary opt-in aspects
- 16 years of age or older
Who cannot join
- Multifetal gestation at any time during the pregnancy
- Known HIV or Hepatitis C infection
- Known immunosuppressive disease
- Use of any of the following drugs within the last 6 months; Cytokines; Methotrexate or immunosuppressive cytotoxic agents
- History of cancer except for squamous or basal cell carcinomas of the skin or thyroid cancer that have been managed and fully treated.
- Major surgery of the GI tract (including gastric bypass), with the exception of cholecystectomy and appendectomy in the past five years. Any major bowel resection at any time. If conditions arise that require such surgeries during participation in the study, subjects will not be excluded after enrollment. If patient develops need for such surgery after enrollment, they will not be excluded.
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- Documented chronic GI disorders, (e.g., Crohn's diseae)
- Chronic conditions with GI symptoms, (e.g. cystic fibrosis)
- Autism spectrum disorder or significant developmental delay, psychosis, major depressive disorder, or a history of bipolar disorder if there is concern about ability to consent
- Treatment for or suspicion of ever having had toxic shock syndrome.
- Fatal fetal anomaly. Will exclude after enrollment if not previously identified
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Microbiome And Multi'Omics In Preterm Birth: The Bacteria And Birth Study (BaBs)
Hominids and hominins serve as remarkable hosts to microbes, and we have co-evolved over the past 4.5 million years as highly plethoric communities. Human-associated microorganisms (the "microbiome") are present in numbers exceeding the quantities of human cells by at least 10-fold beginning in the neonatal period. The collective genome (the "metagenome") exceeds our human genome in terms of gene content by more than 150-fold. With respect to microbiota and preterm birth, it has generally assumed that the majority of intrauterine infections originate in the lower genital tract, with microbiota ascending into the otherwise sterile intrauterine environment to infect the placenta (preterm birth), fetal membranes (chorioamnionitis), umbilical cord (funisitis), and the fetus (sepsis). However, we and others have recently demonstrated that the vaginal and gut microbiome communities are distinctly structured in pregnancy, and the placenta is in fact not sterile, but rather harbors a low-abundance microbiome which is likely acquired through hematogenous transmission of the oral microbiome.
Based on our prior studies and preliminary data, our central hypothesis is that a distinct and largely commensal resident microbiome in pregnancy renders risk for preterm birth. By utilizing our state-of-the-science technology and analysis tools in a longitudinal case-cohort of preterm birth subjects, we will be able to transform "discovery based" metagenomics and multi'omics science into readily translatable mechanistic studies at a previously unparalleled level.
Read the detailed description
Specific Aim 1. Longitudinal maternal (vaginal, oral, skin, gut), fetal (oral, skin, gut) and placental (basal plate and parenchyma) 16S-based metagenomic profiling with inferred metagenomics will reveal distinct microbial communities in association with preterm birth. Methods: We will enroll 526 at-risk gravidae to yield an approximated 135 preterm births with 401 at-risk term controls. Starting in the first/early second trimester, we will sample multiple body sites (vagina, oral, stool, placenta) at multiple time points (antenatal through delivery), isolate microbial DNA, and perform 16S-based determination of niche-specific microbial communities found in association with preterm birth. With our case-cohort longitudinal design, we will be able to apply our well-developed supervised learning approaches to reveal which taxa contribute to risk of preterm birth, and at what body sites and gestational ages they are predictive of preterm birth.
Specific Aim 2. Whole-genome shotgun (WGS) metagenomics from selected subjects and body sites will enable species identification, generation of microbial gene catalogues, and metabolic reconstructions to determine the structure, function and diversity of the preterm birth microbiome. Methods: To probe metabolic functionality and describe pathogen-related mechanisms, we will analyze changes in total gene content using shotgun metagenomics on a subset of samples. We will build on our functional computational pipelines to fully characterize targeted subjects' metagenomic signatures.
Specific Aim 3. Integrated host genomics, metatranscriptomics and metabonomics data will reveal molecular mechanisms and networks underlying preterm birth in a limited subset of samples. Methods: We will interrogate and integrate our concomitantly acquired clinical metadata, microbial and host gene expression data (RNA-Seq metatranscriptomics), and metabonomics profiling with advanced computational and biostatistical approaches. We will be guided in our choice of subjects by our data from Aims 1 and 2.
- Conditions
- Preterm Birth
- Medical subject headings
- Premature Birth
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterization of Maternal-Fetal microbiome
Longitudinally characterize the maternal, placental, and infant microbiome in a cohort at risk of preterm birth. Not all the women will ultimately deliver preterm; we we will be able to see if there are microbiome changes associated with preterm birth.
Measured: Conception to 4-6 weeks postpartum
Association of maternal microbiome (gut, oral, vaginal, placenta) with preterm birth
Longitudinally characterize the maternal, placental, and infant microbiome in a cohort at risk of preterm birth. Not all the women will ultimately deliver preterm; we we will be able to see if there are microbiome changes associated with preterm birth.
Measured: Conception to 4-6 weeks postpartum
Secondary outcomes (2)
Rate of Preterm Birth
Measure rate of preterm birth <37 and <34 weeks gestation, as defined by best obstetrical estimate of last menstrual period consistent with <24 week sonogram, OR <24 week sonogram with unknown last menstrual period, OR skilled examination and <24 week sonogram
Measured: Conception to date of date of delivery, <37 weeks
Rate of Term Birth
Measure rate of term birth, as defined by best obstetrical estimate of last menstrual period consistent with <24 week sonogram, OR <24 week sonogram with unknown last menstrual period, OR skilled examination and <24 week sonogram
Measured: Conception to date of date of delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2015 (estimated)
- Study startJun 2014
- Primary completionDec 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 526 participants (estimated)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The University of Texas Medical Branch, Galveston
- Responsible party
- Principal investigator, Kjersti Aagaard, Baylor College of Medicine
- Investigators
- Kjersti Aagaard, MD/PhD, Principal investigator, Associate Professor / Vice Chair for Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02392650
- Sponsor's protocol ID
- H-34056
- Acronym
- BaBs
- Status last verified
- May 2023
- First submitted
- 13 Mar 2015
- Last updated
- 11 May 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbiome And Multi'Omics In Preterm Birth: The Bacteria And Birth Study (BaBs)
- ClinicalTrials.gov ID
- NCT02392650
- Acronym / sponsor ID
- BaBs / H-34056
- Conditions
- Preterm Birth
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 526 participants (estimated)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The University of Texas Medical Branch, Galveston
- Study start
- Jun 2014 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 19 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hominids and hominins serve as remarkable hosts to microbes, and we have co-evolved over the past 4.5 million years as highly plethoric communities. Human-associated microorganisms (the "microbiome") are present in numbers exceeding the quantities of human cells by at least 10-fold beginning in the neonatal period. The collective genome (the "metagenome") exceeds our human genome in terms of gene content by more than 150-fold. With respect to microbiota and preterm birth, it has generally assumed that the majority of intrauterine infections originate in the lower genital tract, with microbiota ascending into the otherwise sterile intrauterine environment to infect the placenta (preterm birth), fetal membranes (chorioamnionitis), umbilical cord (funisitis), and the fetus (sepsis). However, we and others have recently demonstrated that the vaginal and gut microbiome communities are distinctly structured in pregnancy, and the placenta is in fact not sterile, but rather harbors a low-abundance microbiome which is likely acquired through hematogenous transmission of the oral microbiome.
Based on our prior studies and preliminary data, our central hypothesis is that a distinct and largely commensal resident microbiome in pregnancy renders risk for preterm birth. By utilizing our state-of-the-science technology and analysis tools in a longitudinal case-cohort of preterm birth subjects, we will be able to transform "discovery based" metagenomics and multi'omics science into readily translatable mechanistic studies at a previously unparalleled level.
Detailed description
Specific Aim 1. Longitudinal maternal (vaginal, oral, skin, gut), fetal (oral, skin, gut) and placental (basal plate and parenchyma) 16S-based metagenomic profiling with inferred metagenomics will reveal distinct microbial communities in association with preterm birth. Methods: We will enroll 526 at-risk gravidae to yield an approximated 135 preterm births with 401 at-risk term controls. Starting in the first/early second trimester, we will sample multiple body sites (vagina, oral, stool, placenta) at multiple time points (antenatal through delivery), isolate microbial DNA, and perform 16S-based determination of niche-specific microbial communities found in association with preterm birth. With our case-cohort longitudinal design, we will be able to apply our well-developed supervised learning approaches to reveal which taxa contribute to risk of preterm birth, and at what body sites and gestational ages they are predictive of preterm birth.
Specific Aim 2. Whole-genome shotgun (WGS) metagenomics from selected subjects and body sites will enable species identification, generation of microbial gene catalogues, and metabolic reconstructions to determine the structure, function and diversity of the preterm birth microbiome. Methods: To probe metabolic functionality and describe pathogen-related mechanisms, we will analyze changes in total gene content using shotgun metagenomics on a subset of samples. We will build on our functional computational pipelines to fully characterize targeted subjects' metagenomic signatures.
Specific Aim 3. Integrated host genomics, metatranscriptomics and metabonomics data will reveal molecular mechanisms and networks underlying preterm birth in a limited subset of samples. Methods: We will interrogate and integrate our concomitantly acquired clinical metadata, microbial and host gene expression data (RNA-Seq metatranscriptomics), and metabonomics profiling with advanced computational and biostatistical approaches. We will be guided in our choice of subjects by our data from Aims 1 and 2.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 10 Years
Who may qualify
- Ages
- 16 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Women who are currently pregnant who are at high risk for preterm birth; Pregnant with one baby (not twins or triplets) and who attend regular prenatal visits. They will spend an extra 20 minutes at 5-6 priority scheduled visits to obtain study samples and complete questionnaires, with the last visit occurring around 6 weeks after delivery.
Key inclusion criteria (7 listed)
- Gravidae at risk for preterm birth, defined as: History of prior spontaneous preterm birth at 16w0d-36w6d gestational age confirmed by review of medical records. If efforts to retrieve medical records are unsuccessful, eligibility will depend upon the events surrounding the prior birth and birthweight under 2 kg; Documented shortened cervix <2.5 cm by transvaginal ultrasound performed by experienced sonographer at <24 weeks gestational age; Documented and culture-proven complicated lower or upper urinary tract infection defined as a urinary tract infection requiring hospitalization (e.g., pyelonephritis); Documented periodontal disease, treated or untreated; Documented recurrent lower genital infection; Smoking or other chemical dependency that would convey an increased risk of preterm birth; Other clinical concern for high risk of preterm birth (and cleared by PI Dr. Aagaard at BCM or Dr. Saade at UTMB)
- Enrollment at less than or equal to 20 weeks gestation by best obstetrical estimate
- Able to speak English or work with an interpreter
- Cognitively aware enough to be able to participate in the study
- Gravidae with viable pregnancy >10 weeks gestational age
Key exclusion criteria (11 listed)
- Multifetal gestation at any time during the pregnancy
- Known HIV or Hepatitis C infection
- Known immunosuppressive disease
- Use of any of the following drugs within the last 6 months; Cytokines; Methotrexate or immunosuppressive cytotoxic agents
- History of cancer except for squamous or basal cell carcinomas of the skin or thyroid cancer that have been managed and fully treated.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Characterization of Maternal-Fetal microbiome
Time frame: Conception to 4-6 weeks postpartum
Longitudinally characterize the maternal, placental, and infant microbiome in a cohort at risk of preterm birth. Not all the women will ultimately deliver preterm; we we will be able to see if there are microbiome changes associated with preterm birth.
Association of maternal microbiome (gut, oral, vaginal, placenta) with preterm birth
Time frame: Conception to 4-6 weeks postpartum
Longitudinally characterize the maternal, placental, and infant microbiome in a cohort at risk of preterm birth. Not all the women will ultimately deliver preterm; we we will be able to see if there are microbiome changes associated with preterm birth.
2 secondary outcomes
Rate of Preterm Birth
Time frame: Conception to date of date of delivery, <37 weeks
Rate of Term Birth
Time frame: Conception to date of date of delivery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kjersti Aagaard, MD/PhD principal investigator
Associate Professor / Vice Chair for Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Preterm Birth, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterization of Maternal-Fetal microbiome (time frame: Conception to 4-6 weeks postpartum). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2023.