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Description and Comparison of Biological Vulnerability in Pre- Versus Full- Term Neonates in Urban Burkina Faso (DenBalo) Days and Weeks of Life

Sponsor
University Ghent (Other)
Overall Status
Recruiting
CT.gov ID
NCT05730569
Collaborator
Institut de Recherche en Sciences de la Santé (IRSS) (Other), Université NAZI BONI (Other), Hasselt University (Other), University of Virginia (Other), University Hospital, Ghent (Other), Cedars-Sinai Medical Center (Other), Sapient Bioanalytics (Other), Stanford University (Other), Centre Muraz (Other), University of Manitoba (Other), Manitoba Interdisciplinary Lactation Center (MILC) (Other), Agence de Formation, de Recherche & d'Expertise en Santé pour l'Afrique (AFRICSanté) (Other)
100
Enrollment
1
Location
10
Anticipated Duration (Months)
10
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the DenBalo study is to apply integrated multi-omics methods to examine the biological mechanisms underlying this vulnerability in preterm neonates in LMICs, with the ultimate goal of identifying targeted interventions to reduce morbidity and mortality in this high-risk population. The evidence generated from this project will ultimately help promote healthy pregnancies and the birth of healthy babies.

To achieve this goal, three research objectives are proposed:

  1. To describe and compare gut microbiota, immune system and breastmilk components in pre- versus full-term neonates in urban Burkina Faso.

  2. To describe and compare the development of the gut microbiota, the immune system and breastmilk components during the first six months of life in pre- versus full-term infants in urban Burkina Faso.

  3. To investigate the relationship between the composition of the gut microbiota, the immune system and breastmilk components during the first six months of life in pre- versus full-term infants in urban Burkina Faso.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    The first days and weeks of life are characterized by a truly impressive cascade of biological processes that drive neonatal growth and development-all of which are crucial to preparing the newborn for life outside the womb.

    First, vaginal delivery exposes neonates to an important natural microbial inoculum from the vaginal microbiota in labor and from the maternal intestinal microbiota at birth. Together, these early colonization events lay the foundation for gut microbiota assembly, inform the arrival of subsequent species through microbial interactions, and dictate infant microbiota maturation. A recent study has shown that a handful of bacteria begin colonizing the infant gut within the first days of life, that gut microbes accumulate gradually over time, and that pioneer strains are retained after a month of life. Whether the gut microbial assembly, maturation, and functional potential differs between pre- versus full-term infants, or is coupled to growth and development, remains unresolved.

    Secondly, the first days and weeks of life represent a time of heightened vulnerability to infectious disease. Neonatal infections account for a tragic 40% of mortality in children under five years of age. This critical time period is increasingly seen as a key determinant in health over the entire lifespan. A recent study using a high-dimensional, unbiased approach to characterize neonatal immune system development reported a dramatic, purposeful trajectory in the first week of life. While much remains to be explored, what is known is that early microbial colonization is vital to optimal host immune development and protection from disease and that, after birth, the most important determinant of infant gut colonization is breastfeeding. The impacts of preterm birth on immune development and function remain enigmatic and the mediating effect of the gut microbiome unknown.

    Thirdly, neonatal nutrition plays a vital role in the two aforementioned processes-because breastfeeding both initiates tropic priming of the newborn gut and transfers numerous immunological factors to the baby. However, few studies have explored the synergy between neonatal microbiome and immunome development, and even fewer through the lens of newborn nutrition. Moreover, virtually zero studies include an integrated characterization of these processes in the preterm neonate. Evidence suggests that, compared to mothers of full-term neonates, the colostrum from mothers of preterm newborns has higher protein and fat content, free amino acids, sodium, and bioactive milk components including HMOs, cytokines, and lactoferrin. But because few studies have evaluated the association between early milk composition and infant growth and development, it is unclear which components are most imperative for a healthy gut microbiota and a robust immune system, particularly in the preterm infant.

    Major advances in systems biology approaches allowing for unbiased, integrated analyses of high-dimensional -omic databases have provided the critical bioinformatic toolkit required to address these questions. Indeed, the ground has never been more fertile for a step-change in commitment to high-impact research on neonatal microbiome and immunome development and the synergy with newborn nutrition.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    100 participants
    Observational Model:
    Case-Control
    Time Perspective:
    Prospective
    Official Title:
    Description and Comparison Biological Vulnerability in Pre- Versus Full- Term Neonates in Urban Burkina Faso (DenBalo): Gut Microbiota, Immune System, and Breastmilk Assembly and Development in the First Days and Weeks of Life
    Actual Study Start Date :
    Jan 9, 2023
    Anticipated Primary Completion Date :
    Nov 9, 2023
    Anticipated Study Completion Date :
    Nov 9, 2023

    Arms and Interventions

    Arm Intervention/Treatment
    Preterm Neonates

    Neonate born between the 34th and 37th week of pregnancy Birth weight ≤2500g and ≥1500g
    Full-Term Neonates

    Neonate born after the 37th week of pregnancy Birth weight >2500g

    Outcome Measures

    Primary Outcome Measures

    1. Change in differential abundances of bacterial genera in the infant gut microbiota [to be assessed at birth and on days 1, 2, 3, 4, 5, 6, 7, 14, 30, 60, 180 of life]

      Shotgun metagenomic sequencing

    Secondary Outcome Measures

    1. Infant gut microbiota α and β diversity [to be assessed at birth and on days 1, 2, 3, 4, 5, 6, 7, 14, 30, 60, 180 of life]

      Shotgun metagenomic sequencing

    2. Infant plasma immunophenotyping [to be assessed at birth and on days 1, 3, 5, 7, 30, 60 of life]

      Flow cytometery

    3. Infant plasma chemokine and cytokine analyses [to be assessed at birth and on days 1, 3, 5, 7, 30, 60 of life]

      Electrochemiluminescence and the MSD V-PLEX Human Biomarker 54-Plex Kit

    4. Maternal breastmilk component* profiling [to be assessed at birth and on days 1, 3, 5, 7, 14, 30, 60 of life]

      *Components include macronutrients, micronutrients, oligosaccharides, growth factors, immunoglobulins, cytokines, metabolites, microbes, and proteins.

    Other Outcome Measures

    1. Differential abundance of bacterial populations of pregnant or lactating woman (PLW) fecal microbiota [to be assessed within 28-30 weeks of gestation, within 33-34 weeks of gestation, on days 7, 14, 30, 60 and 180 of life]

      Shotgun metagenomic sequencing

    2. PLW Infant fecal microbiota α and β diversity [to be assessed within 28-30 weeks of gestation, within 33-34 weeks of gestation, on days 7, 14, 30, 60 and 180 of life]

      Shotgun metagenomic sequencing

    3. PLW fecal enteropathogens [to be assessed within 28-30 weeks of gestation, within 33-34 weeks of gestation, on days 30 and 180 of life]

      TaqMan Array Card (TAC) qPCR to detect 62 infection targets of interest, including viruses, bacteria, protozoa and helminths.

    4. Infant fecal enteropathogens [to be assessed within 28-30 weeks of gestation, within 33-34 weeks of gestation, on days 30 and 180 of life]

      TaqMan Array Card (TAC) qPCR to detect 62 infection targets of interest, including viruses, bacteria, protozoa and helminths.

    5. Maternal plasma immunophenotyping [to be assessed at birth]

      Flow cytometery

    6. Maternal plasma chemokine and cytokine analyses [to be assessed at birth]

      Electrochemiluminescence and the MSD V-PLEX Human Biomarker 54-Plex Kit

    7. Black carbon exposure in umbilical cord arterial blood [to be assessed at birth]

      White-light generation under femtosecond pulsed illumination

    8. Placental DNA adductiomics [to be assessed at birth]

      Hybrid Quadrupole Orbitrap MS (Q-Exactive™) high-resolution mass spectrometry (HRMS)

    9. Relative telomere length (TL) in umbilical cord arterial blood [to be assessed at birth]

      qPCR

    10. Infant untargeted metabolomics on capillary whole blood [to be assessed at birth, on days 1, 3, 5, 7, 14, 30 and 60 of life]

      Modified Agilent RapidFire 360 sample injector coupled to a high-resolution Agilent 6545B liquid chromatography Quadrupole Time-of-Flight (LC/Q-TOF) next-generation rapid liquid chromatography-mass spectrometry (rLC-MS)

    11. Infant untargeted plasma proteomics [to be assessed at birth, on days 1, 3, 5, 7, 14, 30 and 60 of life]

      Harmonized Orbitrap Exploris™ liquid chromatography-mass spectrometry (LC-MS)

    12. Infant multiple mycotoxin profiling on capillary whole blood [to be assessed at birth, on days 7, and 14 of life]

      Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

    13. Maternal untargeted capillary whole blood metabolomics [to be assessed at birth]

      Modified Agilent RapidFire 360 sample injector coupled to a high-resolution Agilent 6545B liquid chromatography Quadrupole Time-of-Flight (LC/Q-TOF) next-generation rapid liquid chromatography-mass spectrometry (rLC-MS)

    14. Maternal untargeted plasma proteomics [to be assessed at birth]

      Harmonized Orbitrap Exploris™ liquid chromatography-mass spectrometry (LC-MS)

    15. Maternal multiple mycotoxin profiling on capillary whole blood [to be assessed at birth]

      Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

    16. PLW shotgun vaginal metagenomics [to be assessed at birth]

      Shotgun metagenomic sequencing

    17. Breastmilk volume intake [to be assessed on days 1, 3, 4, 13 and 14 of life]

      "Dose-to-mother" deuterium oxide dilution

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years to 40 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    INCLUSION CRITERIA

    • Fundal height between 24 and 27 cm

    • Woman living in the health zone of Accart-Ville or Colma 1

    • Woman not planning to give birth or move outside the study area in the first 6 months of the infant's life

    • Gestational age between 27 weeks 1 completed day and 30 weeks 6 days (ultrasound)

    • Monofetal pregnancy without visible malformation

    • Woman agreeing to give her informed consent to participate in the study

    • Woman seen in labor before the rupture of membranes thus allowing vaginal sampling

    • Delivery of a live birth

    • Vaginal birth

    • Absence of severe infectious pathology, severe pneumopathy or respiratory distress in the neonate

    • Neonates who did not receive corticosteroids or antibiotics at birth

    For preterm neonates:

    • Neonate born between the 34th and 37th week of pregnancy

    • Birth weight ≤2500 g and ≥1500 g

    For full-term neonates:

    • Neonate born after the 37th week of pregnancy

    • Birth weight >2500g

    • Possible match with a premature neonate already recruited into the study

    EXCLUSION CRITERIA

    • Fundal height <24 cm or >27 cm

    • Woman living outside the sanitary zone of the Accart-Ville or Colma 1

    • Woman planning to give birth outside the study area or to move from it within the first 6 months of the infants's life

    • Gestational age <27 weeks or ≥31 weeks (ultrasound)

    • Multi-fetal pregnancy

    • Malformation visible on ultrasound

    • Woman seen in labor after rupture of membranes

    • Cesarean delivery

    • Neonate with severe infectious disease, severe pneumopathy or respiratory distress

    • Neonate who received corticosteroids or antibiotics just after birth

    For preterm neonates:

    • Neonate born before the 34th week of pregnancy

    • Birth weight >2500g or <1500g

    For full-term neonates:

    • Birth weight <2500g

    • No matching possible with a premature neonate on the date of birth

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Agence de Formation, de Recherche et d'Expertise en Santé pour l'Afrique (AFRICSanté) Bobo-Dioulasso Burkina Faso

    Sponsors and Collaborators

    • University Ghent
    • Institut de Recherche en Sciences de la Santé (IRSS)
    • Université NAZI BONI
    • Hasselt University
    • University of Virginia
    • University Hospital, Ghent
    • Cedars-Sinai Medical Center
    • Sapient Bioanalytics
    • Stanford University
    • Centre Muraz
    • University of Manitoba
    • Manitoba Interdisciplinary Lactation Center (MILC)
    • Agence de Formation, de Recherche & d'Expertise en Santé pour l'Afrique (AFRICSanté)

    Investigators

    • Principal Investigator: Trenton Dailey-Chwalibóg, M.P.H., Ph.D., University Ghent
    • Principal Investigator: Carl Lachat, M.Eng., Ph.D., University Ghent

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University Ghent
    ClinicalTrials.gov Identifier:
    NCT05730569
    Other Study ID Numbers:
    • DenBalo
    • INV-035474 & INV-036154
    • ONZ-2022-0500
    • 050-2022/CEIRES
    First Posted:
    Feb 16, 2023
    Last Update Posted:
    Feb 21, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University Ghent
    Preterm Birth
    Additional relevant MeSH terms:
    Premature Birth

    Study Results

    No Results Posted as of Feb 21, 2023