Clinical trial NCT06787963: Exploring Minor Proteins and Peptides in Human Milk: a Proteomic Analysis Across Lactation Stages
Official title: Quantitative Proteomic Analysis of Minor Whey Proteins and Peptides of Human Milk Across Five Neonatal Groups Classified by Birth Weight During the Three Stages of Lactation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Low Birthweight Infant
Preterm
Very Low Birth Weight Preterms
Keywords: low birth weight
prematurity
gestational age
human milk
bioactive peptides
proteomics
lactation
whey protein
Lead sponsor: Maimónides Biomedical Research Institute of Córdoba
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Reina Sofia de Cordoba
name: Universidad de Granada
name: Universidad de Córdoba
First posted: 2025-01-22
Enrollment: 150
Sex: ALL
Minimum age (years): 0
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Five groups of breastfeeding mothers: Group 1 (n=30) - with neonates of extremely low birth weight; Group 2 (n=30) - with neonates of very low birth weight; Group 3 (n=30) - with neonates of low birth weight; Group 4 (n=30) - with neonates of adequate birth weight; Group 5 (n=30) - with neonates of high birth weight. Additionally, gestational age will be considered to achieve a homogeneous distribution of the groups according to this condition.

Brief summary: Human milk (HM) is the optimal food source for the nutrition, growth, and development of newborns. The protein fraction of HM plays a crucial role in the healthy development of infants. HM contains a wide variety of minor whey proteins and peptides with important bioactive functions, many of which are still unknown. Proteomics allows for the study of biological samples with inherently complex protein mixtures. Proteins are essential for the development of living organisms, both in quantitative and qualitative terms. The combination of proteomic techniques currently enables the study of protein variability and minor peptides in HM across different lactation stages and allows for differential quantification according to gestational age and birth weight. However, studies on the human milk serum proteome during these stages are limited. The aim is to explore the minor whey proteins and peptides in human milk through a longitudinal analysis of five groups of breastfeeding mothers (with 30 extremely low birth weight newborns, 30 very low birth weight newborns, 30 low birth weight newborns, 30 adequate birth weight newborns, and 30 high birth weight newborns). Gestational age will also be considered to ensure homogeneous group distribution according to this condition. HM samples will be collected from each mother during three lactation periods after birth: within the first 48 hours (colostrum), at 5-14 days (transitional milk), and at 100-120 days (mature milk) for the five birth weight groups. In these neonatal/infant groups, minor proteins from whey fraction and peptides will be separated, quantified, and identified using label-free proteomic techniques. This study aims to expand our understanding of the minor proteins and peptides in human milk and their bioactive roles in neonatal health. By examining these components across different birth weight groups and lactation stages, the research will offer insights into how protein and peptide profiles vary by gestational age and birth weight, potentially influencing neonatal development. The findings from this proteomic analysis could not only demonstrate the complexity of human milk composition but also contribute to targeted nutritional support for preterm or low-birth-weight infants, customizing protein supplementation in HM banks and therefore enhancing their growth and developmental outcomes.


Eligibility criteria: Inclusion Criteria:

* Healthy mothers
* With monitored pregnancies within the care area of the Reina Sofía University Hospital in Córdoba
* With newborns expected to be exclusively breastfed until 4 months

Exclusion Criteria:

* Mothers whose newborns have any of the following conditions: congenital malformation, chromosomal abnormality, hypoxia-ischemia, gastroschisis, polycythemia, hypoglycemia, sepsis, blood incompatibility
* Pathological pregnancy, pregnancy by in vitro fertilization, or multiple pregnancies
* With no plan to exclusively breastfeed until 4 months
* Under medical treatment
* Have a drug addiction
* Refuse informed consent
* Have had previous breast surgery
* Live outside the metropolitan area

Primary outcomes:
measure: Minor whey proteins: Lysozyme
timeFrame: Human Milk collection after birth - Time 1: at 48 hours (colostrum),Time 2: at 5-14 days (transitional milk), Time 3: at 100-120 days (mature milk)
measure: Minor whey proteins: Lactoferrin
timeFrame: Human Milk collection after birth - Time 1: at 48 hours (colostrum),Time 2: at 5-14 days (transitional milk), Time 3: at 100-120 days (mature milk)
measure: Minor whey proteins: Bile salt-dependent lipase (BSDL)
timeFrame: Human Milk collection after birth - Time 1: at 48 hours (colostrum),Time 2: at 5-14 days (transitional milk), Time 3: at 100-120 days (mature milk)
measure: Minor whey proteins: Lactoperoxidase
timeFrame: Human Milk collection after birth - Time 1: at 48 hours (colostrum),Time 2: at 5-14 days (transitional milk), Time 3: at 100-120 days (mature milk)
measure: Minor whey proteins: Alpha-1-antitrypsin
timeFrame: Human Milk collection after birth - Time 1: at 48 hours (colostrum),Time 2: at 5-14 days (transitional milk), Time 3: at 100-120 days (mature milk)
measure: Proteome
timeFrame: Human Milk collection after birth - Time 1: at 48 hours (colostrum),Time 2: at 5-14 days (transitional milk), Time 3: at 100-120 days (mature milk)
measure: Free peptides, primarily derived from β-casein
timeFrame: Human Milk collection after birth - Time 1: at 48 hours (colostrum),Time 2: at 5-14 days (transitional milk), Time 3: at 100-120 days (mature milk)
Secondary outcomes:
measure: Muscular ecography
timeFrame: After birth - Time 1: at 48 hours,Time 2: at 5-14 days, Time 3: at 100-120 days
measure: Transfontanellar ecography
timeFrame: After birth - Time 1: at 48 hours,Time 2: at 5-14 days, Time 3: at 100-120 days
Other outcomes:
measure: General information - Mothers
timeFrame: After birth - Time 1: at 48 hours,Time 2: at 5-14 days, Time 3: at 100-120 days (mothers will be asked if any changes have occurred)
measure: General information - Newborns
timeFrame: After birth - Time 1: at 48 hours,Time 2: at 5-14 days, Time 3: at 100-120 days (mothers will be asked if any changes have occurred)
measure: Dietary intake and eating habits
timeFrame: After birth - Time 1: at 48 hours,Time 2: at 5-14 days, Time 3: at 100-120 days
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Córdoba
country: Spain
facility: Maimonides Biomedical Research Institute of Cordoba (IMIBIC)
Study officials:
affiliation: Maimonides Biomedical Research Institute of Cordoba (IMIBIC)
name: José Luis Gómez-Chaparro Moreno, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: