Description and Comparison of Biological Vulnerability in Small Vulnerable Newborns Versus Healthy Community Controls in Urban Burkina Faso (DenBalo)

May 29, 2024 updated by: University Ghent

Description and Comparison of Biological Vulnerability in Small Vulnerable Newborns Versus Healthy Community Controls in Urban Burkina Faso (DenBalo): Gut Microbiota, Immune System, and Breastmilk Assembly and Development in the First Days and Weeks of Life

The aim of the DenBalo study is to apply integrated multi-omics methods to examine the biological mechanisms underlying this vulnerability in Small Vulnerable Newborns (SVNs) 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 SVNs versus healthy community controls 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 SVNs versus healthy community controls 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 SVNs versus healthy community controls in urban Burkina Faso.

Study Overview

Status

Recruiting

Conditions

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 SVNs versus healthy, community controls, 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, low birth weight, or small for gestational age 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 SVN. 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 SVN.

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 Type

Observational

Enrollment (Estimated)

140

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Burkina Faso
      • Bobo-Dioulasso, Burkina Faso
        • Recruiting
        • Agence de Formation, de Recherche et d'Expertise en Santé pour l'Afrique (AFRICSanté)
        • Contact:
        • Principal Investigator:
          • Laeticia C Toé, MD, MS
        • Sub-Investigator:
          • Lionel O Ouédraogo, MD, MS
        • Sub-Investigator:
          • Cheick A Ouattara, MD, MS, PhD
        • Sub-Investigator:
          • Moctar Ouédraogo, MS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 40 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population is composed of all pregnant women at the beginning of the third trimester of their pregnancy attending regular antenatal consultations (ANC) at Accart-Ville, Colma 1 or Farakan health centers.

Description

INCLUSION CRITERIA

  • Fundal height between 24 and 27 cm
  • Woman living in the health zone of Accart-Ville, Colma 1 or Farakan
  • 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 24 weeks 0 completed day and 29 weeks 6 days (ultrasound)
  • Monofetal pregnancy without visible malformation
  • Woman agreeing to give her informed consent to participate in the study
  • 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 Small Vulnerable Newborns (SVNs):

  • Low birth weight: <2500g; and/or,
  • Preterm: born between the 34th and 37th week of pregnancy; and/or,
  • Small for Gestational Age: <10 percentile of INTERGROWTH-21st birthweight standards.

For healthy community controls:

  • Neonate born after the 37th week of pregnancy; and,
  • Birth weight >2500g; and,
  • ≥10 percentile of INTERGROWTH-21st birthweight standards; and,
  • Possible match with a SVN 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, Colma 1 or Farakan
  • 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 <24 weeks or ≥30 weeks (ultrasound)
  • Multi-fetal pregnancy
  • Malformation visible on ultrasound
  • Cesarean delivery
  • Neonate with severe infectious disease, severe pneumopathy or respiratory distress
  • Neonate who received corticosteroids or antibiotics just after birth

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Small Vulnerable Newborns
  • Low birth weight: <2500g; and/or,
  • Preterm: born between the 34th and 37th week of pregnancy; and/or,
  • Small for Gestational Age: <10 percentile of INTERGROWTH-21st birthweight standards.
Healthy Community Controls
  • Born after the 37th week of pregnancy; and,
  • Birth weight ≥2500g; and,
  • ≥10 percentile of INTERGROWTH-21st birthweight standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differential abundances of bacterial genera in the infant gut microbiota
Time Frame: to be assessed at on days 3, 7, 14, 30, 60, 180 of life
Shotgun metagenomic sequencing
to be assessed at on days 3, 7, 14, 30, 60, 180 of life

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infant plasma chemokine and cytokine analyses
Time Frame: 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
to be assessed at birth and on days 1, 3, 5, 7, 30, 60 of life
Infant gut microbiota α and β diversity
Time Frame: to be assessed at on days 3, 7, 14, 30, 60, 180 of life
Shotgun metagenomic sequencing
to be assessed at on days 3, 7, 14, 30, 60, 180 of life
Infant plasma immunophenotyping
Time Frame: to be assessed at birth and on days 1, 3, 5, 7, 30, 60 of life
Flow cytometry
to be assessed at birth and on days 1, 3, 5, 7, 30, 60 of life
Maternal breastmilk component* profiling
Time Frame: on days 3, 7, 14, 30, 60 of life
*Components include macronutrients, micronutrients, oligosaccharides, growth factors, immunoglobulins, cytokines, metabolites, microbes, and proteins.
on days 3, 7, 14, 30, 60 of life

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differential abundance of bacterial populations of pregnant or lactating woman (PLW) fecal microbiota
Time Frame: 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
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
PLW Infant fecal microbiota α and β diversity
Time Frame: 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
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
PLW fecal enteropathogens
Time Frame: 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.
to be assessed within 28-30 weeks of gestation, within 33-34 weeks of gestation, on days 30 and 180 of life
Infant fecal enteropathogens
Time Frame: 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.
to be assessed within 28-30 weeks of gestation, within 33-34 weeks of gestation, on days 30 and 180 of life
Maternal plasma chemokine and cytokine analyses
Time Frame: to be assessed at birth
Electrochemiluminescence and the MSD V-PLEX Human Biomarker 54-Plex Kit
to be assessed at birth
Black carbon exposure in umbilical cord arterial blood
Time Frame: to be assessed at birth
White-light generation under femtosecond pulsed illumination
to be assessed at birth
Placental DNA adductiomics
Time Frame: to be assessed at birth
Hybrid Quadrupole Orbitrap MS (Q-Exactive™) high-resolution mass spectrometry (HRMS)
to be assessed at birth
Relative telomere length (TL) in umbilical cord arterial blood
Time Frame: to be assessed at birth
qPCR
to be assessed at birth
Infant untargeted metabolomics on capillary whole blood
Time Frame: 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)
to be assessed at birth, on days 1, 3, 5, 7, 14, 30 and 60 of life
Infant untargeted plasma proteomics
Time Frame: 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)
to be assessed at birth, on days 1, 3, 5, 7, 14, 30 and 60 of life
Infant multiple mycotoxin profiling on capillary whole blood
Time Frame: to be assessed at birth, on days 7, and 14 of life
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
to be assessed at birth, on days 7, and 14 of life
Maternal untargeted capillary whole blood metabolomics
Time Frame: 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)
to be assessed at birth
Maternal untargeted plasma proteomics
Time Frame: to be assessed at birth
Harmonized Orbitrap Exploris™ liquid chromatography-mass spectrometry (LC-MS)
to be assessed at birth
Maternal multiple mycotoxin profiling on capillary whole blood
Time Frame: to be assessed at birth
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
to be assessed at birth
Breastmilk volume intake
Time Frame: to be assessed on days 1, 3, 4, 13 and 14 of life
"Dose-to-mother" deuterium oxide dilution
to be assessed on days 1, 3, 4, 13 and 14 of life
Maternal plasma immunophenotyping
Time Frame: to be assessed at birth
Flow cytometry
to be assessed at birth
PLW shotgun vaginal metagenomics
Time Frame: to be assessed 29-30 weeks of gestation, 33-34 weeks of gestation and at birth
Shotgun metagenomic sequencing
to be assessed 29-30 weeks of gestation, 33-34 weeks of gestation and at birth
Differential abundances of bacterial genera in the infant gut microbiota
Time Frame: to be assessed at birth and on days 1, 2, 4, 5, 6 of life
Shotgun metagenomic sequencing
to be assessed at birth and on days 1, 2, 4, 5, 6 of life
Infant gut microbiota α and β diversity
Time Frame: to be assessed at birth and on days 1, 2, 4, 5, 6 of life
Shotgun metagenomic sequencing
to be assessed at birth and on days 1, 2, 4, 5, 6 of life
Maternal breastmilk component* profiling
Time Frame: to be assessed at birth and on days 1, 3, 5 of life
Shotgun metagenomic sequencing
to be assessed at birth and on days 1, 3, 5 of life
Vaginal cytokines
Time Frame: to be assessed at 29-30 weeks of gestation
Multi-plex assay
to be assessed at 29-30 weeks of gestation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Ghent

Collaborators

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

Investigators

  • Principal Investigator: Trenton Dailey-Chwalibóg, MPH, PhD, University Ghent
  • Principal Investigator: Carl Lachat, MEng, PhD, University Ghent

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 9, 2023

Primary Completion (Estimated)

July 31, 2024

Study Completion (Estimated)

July 31, 2024

Study Registration Dates

First Submitted

January 12, 2023

First Submitted That Met QC Criteria

February 6, 2023

First Posted (Actual)

February 16, 2023

Study Record Updates

Last Update Posted (Actual)

May 31, 2024

Last Update Submitted That Met QC Criteria

May 29, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONZ-2022-0500 (Commission for Medical Ethics (CME), Ghent University (UGent) and Ghent University Hospital (UZGent))
  • INV-035474 & INV-036154 (Other Grant/Funding Number: Bill & Melinda Gates Foundation)
  • 050-2022/CEIRES (Other Identifier: Comité d'Éthique Institutionnel pour la Recherche en Sciences de la Santé)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All the data collected during the DenBalo study will be pseudonymised (i.e., identifable data can still be linked to patient files by means of a code) and the key to the codes will only be accessible to the principal investigators, or his/her representative.

The collected pseudonymised data as well as the collected biological samples can be shared with other (future) researchers for future research projects and studies, exclusively in the context of the same disease/pathology or similar (i.e., in the interest of research on maternal, newborn and child health). This will be done within a strictly legal framework and in compliance with international laws on the protection of personal data.

Only anonymized data will be used in any type of documentation, reports or publications (in the medical scientific literature and/or at medical conferences).

Personal patient data will be stored for at least 25 years after the end of the study.

IPD Sharing Time Frame

Data will be on embargo for a period of 18 months post study implementation.

IPD Sharing Access Criteria

Upon reasonable request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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