Description and Comparison of Biological Vulnerability in Pre- Versus Full-Term Neonates in Urban Burkina Faso

Study Overview
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Brief Summary
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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: To describe and compare gut microbiota, immune system and breastmilk components in pre- versus full-term neonates in urban Burkina Faso. 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. 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.

Detailed Description
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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.

Official Title
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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

Conditions
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Preterm Birth

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Preterm Neonates<br>Neonate born between the 34th and 37th week of pregnancy Birth weight ≤2500g and ≥1500g | |
| Full-Term Neonates<br>Neonate born after the 37th week of pregnancy Birth weight >2500g | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in differential abundances of bacterial genera in the infant gut microbiota | Shotgun metagenomic sequencing | to be assessed at birth and on days 1, 2, 3, 4, 5, 6, 7, 14, 30, 60, 180 of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant gut microbiota α and β diversity | Shotgun metagenomic sequencing | to be assessed at birth and on days 1, 2, 3, 4, 5, 6, 7, 14, 30, 60, 180 of life | 
| Infant plasma immunophenotyping | Flow cytometery | to be assessed at birth and on days 1, 3, 5, 7, 30, 60 of life | 
| Infant plasma chemokine and cytokine analyses | 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 | 
| Maternal breastmilk component* profiling | *Components include macronutrients, micronutrients, oligosaccharides, growth factors, immunoglobulins, cytokines, metabolites, microbes, and proteins. | to be assessed at birth and on days 1, 3, 5, 7, 14, 30, 60 of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm Birth