Growth and Microbiome Development in Very Low Birth Weight Infants Fed Primarily Mother's Own Milk vs. Donor Human Milk

February 19, 2024 updated by: Amy Hair, Baylor College of Medicine

Intestinal Microbiota and Short Term Outcomes in Very Low Birth Weight Infants Fed Primarily Donor Human Milk Compared to Infants Fed Primarily Mother's Own Milk

A study to compare growth, development of the intestinal bacterial environment, and other short term outcomes in groups of babies fed primarily their own mother's milk compared to those who receive primarily donor human milk. The investigators hypothesize that infants who receive primarily their own mother's milk will have better growth, a more diverse intestinal bacterial environment, and possibly some improved short term outcomes such as better feeding tolerance and lower rates of infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: Human milk feeding provides numerous benefits to preterm infants due to improvements in gastrointestinal maturation, host defense, infection rates, and improved long-term outcomes in neurodevelopment as well as cardiovascular and metabolic disease. There is accumulating evidence that an exclusive human milk-based diet decreases the rates of necrotizing enterocolitis (NEC) and death, and is associated with better feeding tolerance in very low birth weight (VLBW) infants than a diet of bovine milk-based products. In order to provide VLBW infants the benefits afforded by human milk feeding, the use of donor milk (DM) in neonatal intensive care units (NICU) has increased as many mothers are unable to provide sufficient milk needed for their premature infants. While there have been numerous studies that have favorably compared feeding of mother's own milk (MOM) to formula as well as studies that compare DM to formula, there are relatively few that compare maternal milk to donor milk.

In regard to feeding tolerance and infection prevention, it has been proposed that DM may be less beneficial than MOM due to reduction in biologically active components during pasteurization, including human milk oligosaccharides (HMOs) and other immunological factors, growth factors, and hormones. Finally, alterations in the intestinal microbiota of preterm infants are suspected to contribute to disease states such as NEC, specifically within infants who have decreased microbial diversity. To the investigators knowledge, no studies comparing the intestinal microbiota among infants fed primarily MOM versus those fed primarily DM have been published.

Purpose: To compare growth velocities, time to reach full enteral feeding volume, intestinal microbiota, and short term outcomes (NEC, late-onset sepsis, white matter injury) between infants fed primarily mother's own milk versus pasteurized donor human milk.

Hypothesis: Infants fed primarily (50% or greater) mother's own milk will have increased intestinal microbiome diversity compared to infants fed primarily pasteurized donor human milk.

Design: This prospective cohort study will be conducted in the Level III NICU at Texas Children's Hospital - Pavilion for Women and the Level II NICU at Texas Children's Hospital -- West Tower. Infants less than 1500 g birth weight will be fed exclusively human milk (mother's milk and or donor breast milk) fortified with donor human milk-derived fortifier per the investigators hospital guidelines. Once enteral feeding is established, infants will be categorized into cohorts based on percentage of feeding volume consisting of mother's own milk, including broad categorization of greater than 50% maternal milk versus less than 50%, and possibly tiered analysis of infants who receive less 25% maternal milk, 25-75% maternal milk, and greater than 75% maternal milk.

An enrollment goal of greater than 125 infants including twins and multiples will be targeted for adequate sample size.

Procedure: Infants will be enrolled within 72 hours of birth and started on parenteral nutrition and enteral human milk feedings per standardized feeding protocols and discretion of the attending neonatologist on service. Decisions to decrease or discontinue enteral feedings due to medical instability will be made by the attending neonatologist. Infants will be preferentially fed their own mothers' milk when available. For mothers who are unable to express adequate milk volume for their infants, pooled, pasteurized donor human milk will be offered per established NICU protocol. Feeds will be supplemented with human-milk based fortifier per protocol.

At time of initial consent for the study, mothers will also be asked for consent to obtain a small sample (0.2-0.5 mL) of colostrum or expressed milk produced in the first week of life, as well as weekly milk samples thereafter, in order to analyze bacterial content of milk as it compares to the developing infant microbiome. However, consent for milk collection is not required for the infant's participation in the study. For infants who receive primarily donor milk, weekly samples of the milk they receive may similarly be analyzed for bacterial content.

Infant stool samples will be collected during the first week of life and then at weekly intervals for six weeks for research purposes. The samples will be analyzed via 16S rRNA sequencing to determine diversity of intestinal microbiota. Additional analysis for metabolomics will be considered if lab availability and cost allows.

Once weekly, a research nurse or physician will document growth measurements, including weight, length, and head circumference. Outcome data from the infants' medical records will be recorded, including time to regain birth weight, feeding tolerance as indicated by time required to reach full enteral feeding volumes of 100 ml/kg/day (for hydration) and 130-160 ml/kg/day (final goal volume for nutrition), and rates of NEC, spontaneous intestinal perforation (SIP), late-onset sepsis, and bronchopulmonary dysplasia (BPD). As all preterm infants less than 1000 g birth weight born at TCH-PFW have routinely performed brain MRIs at term gestation or hospital discharge, enrolled infants who fall into this subgroup will have their MRI results reviewed for outcome analysis.

Additional medical record data for collection will include mechanism of delivery (cesarean vs. vaginal), antibiotics received by mother during 2nd and 3rd trimester as well as at time of delivery and while nursing/expressing milk, antibiotics received by baby during hospitalization, length of hospitalization, postmenstrual age at discharge, days NPO, days of parenteral nutrition, percentage of patients with patent ductus arteriosus, and rates of intraventricular hemorrhage, retinopathy of prematurity, and death.

Although there is no long-term follow up currently designed for this study, at time of initial enrollment there will be an optional consent to allow study personnel to access medical records for patients who go on to have neurodevelopmental follow up visits at clinics within the investigators institution. There will also be optional consent for families to be contacted when the infant is approximately 6, 12, 18, and 24 months for developmental follow up. This will allow for possible comparison of neurodevelopmental outcomes at approximately 18-24 months in the subgroup of patients whose mothers consent to these aspects of the study.

No labs will be requested for research purposes. No interventions are part of this protocol.

Study Type

Observational

Enrollment (Actual)

125

Contacts and Locations

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

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine / Texas Children's Hospital

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

No older than 3 days (Child)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Newborn infants less than 1500 g birth weight who are fed primarily either mother's own milk or donor human milk.

Description

Inclusion Criteria:

  • Infants less than 72 hours old and less than 1500 g birth weight, who have reasonable expectation of survival and can adhere to a feeding protocol involving mother's own milk and/or donor milk that will include fortification using Prolacta and potentially human cream.

Exclusion Criteria:

  • Exclusion criteria will include birth weight greater than 1500 g, age > 72 hours old, major congenital anomalies, clinically significant heart disease, abdominal wall defects and/or intestinal atresias, severe perinatal hypoxia, or otherwise less than reasonable expectation of survival through the study period.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Infants fed mother's own milk
Infants fed >50% mother's own milk with enteral feeding.
Other: Observational - no intervention
This study will observe cohorts of infants who are fed primarily either their own mother's milk or donor milk as part of their routine care. No direct intervention is performed as part of the study.
Donor milk fed infants
Infants fed <50% mother's own milk (and thus >50% donor human milk) with enteral feeding.
Other: Observational - no intervention
This study will observe cohorts of infants who are fed primarily either their own mother's milk or donor milk as part of their routine care. No direct intervention is performed as part of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intestinal Microbiome Diversity
Time Frame: 6 weeks
Stool samples during the first 6 weeks of life will be analyzed to compare development of microbial diversity
6 weeks
Hospital Length of Stay
Time Frame: Birth to discharge
Hospital length of stay will be calculated from birth to discharge of infant.
Birth to discharge
Weight Gain
Time Frame: 6-10 weeks
Weight gain will be evaluated weekly throughout the study (defined as g/kg/day)
6-10 weeks
Linear Growth
Time Frame: 6-10 weeks
Linear growth will be measured weekly (defined as cm/week)
6-10 weeks
Head Circumference Growth
Time Frame: 6-10 weeks
Growth in head circumference will be measured weekly (defined as cm/wk)
6-10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Days to Final Enteral Feed Volume
Time Frame: 6-10 weeks
Number of days for infant to reach full enteral feeds.
6-10 weeks
Rates of Necrotizing Enterocolitis (NEC)
Time Frame: 6-10 weeks
the number of patients with a diagnosis of NEC (Stage ≥ IIA) will be collected
6-10 weeks
Rates of Spontaneous Intestinal Perforation (SIP)
Time Frame: 6-10 weeks
the number of patients who develop a spontaneous intestinal perforation will be collected
6-10 weeks
Rates of Late-onset Sepsis
Time Frame: 6-10 weeks
the number of patients with late-onset sepsis will be collected
6-10 weeks

Collaborators and Investigators

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

Sponsor

Baylor College of Medicine

Investigators

  • Principal Investigator: Amy Hair, MD, Baylor College of Medicine - Texas Children's Hospital

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)

July 10, 2015

Primary Completion (Actual)

September 30, 2016

Study Completion (Actual)

October 25, 2018

Study Registration Dates

First Submitted

October 8, 2015

First Submitted That Met QC Criteria

October 9, 2015

First Posted (Estimated)

October 12, 2015

Study Record Updates

Last Update Posted (Estimated)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 19, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-36828

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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