Plain English Summary
Background and study aims
We are carrying out a study of premature infants born before 33 weeks gestation. Our goal is to determine whether a human milk diet works. Necrotizing enterocolitis (NEC) is a serious problem for the premature infant's small intestine. NEC occurs in 7 to 10% of infants with birth weights less than 1.5 kg. Premature infants typically receive cows milk-based products when the mothers own milk (MOM) is not available. Elimination of cow's milk products from the premature infants diet, including cow's milk-based milk fortifiers, has been suggested as a possible way to reduce NEC.
We want to observe the rate of NEC in very premature infants when they receive a diet of exclusively human milk until they reach a minimum of 33 weeks postmenstrual age. The studys findings should help to determine the rate of NEC associated with an entirely human milk diet.
Who can participate?
The study aims to recruit all premature infants born before 33 weeks gestation admitted to a single neonatal intensive care unit during a 30-month period.
What does the study involve?
Mothers of infants admitted to a neonatal intensive care unit (NICU) was encouraged to provide milk for their infants. Until infants were ready for milk feedings, they received nutrition intravenously. Milk production requires the mother to use electric pumps and hands on the breast to express their milk. Lactation consultants provide mothers with training and supplies. The MOM was refrigerated or frozen until it was used for feeding. In case they were unable to supply enough MOM, mothers were offered pasteurized donor human milk (DHM) from a milk bank as an alternative to cows milk formula. Mothers provided written consent in order to receive DHM. In the event that a fortifier of MOM or DHM was recommended, a DHM-based fortifier was provided. After 33 weeks, routine feeding practices permit artificial milk products when MOM was not available. At the end of the study we will evaluate the group for the appearance of NEC in relation to the diet provided.
What are the possible benefits and risks of participating?
The risk of NEC associated with an EHM diet is unknown; The EHM diet is the diet recommended by the American Academy of Pediatrics (AAP) for premature infants: MOM is the first choice, DHM is the second choice and formula is the last choice. DHM and DHM-based milk fortifier are expensive and they are nutritional products. Participating infants benefit from receipt of DHM products which are expensive and nutritional. The hospital pays for these products. The risk of using MOM includes infections or medications acquired by the infant from its mothers milk. If necessary, DHM can be substituted for MOM, which is a potential benefit to the infant. The potential risk of the EHM diet leading to slower growth (compared to formula) which is balanced by providing DHM-based fortifier. The potential risks of a formula diet include an increased rate of NEC, excessive weight gain leading to obesity, and poorer developmental outcome at later ages. The balance of the multiple risks and benefits are not clear.
Where is the study run?
The study site is at the Deaconess-Womens Hospital, located in Newburgh, IN, USA.
What is the study period?
July 2010 through December 2012.
Who is funding the study?
The Deaconess-Womens Hospital.
Who is the main contact?
Dr Kenneth Herrmann
Kenneth.Herrmann@deaconess.com
Trial website
Contact information
Type
Scientific
Primary contact
Dr Kenneth Herrmann
ORCID ID
Contact details
4199 Gateway Boulevard
Suite 3990
Newburgh
47630
United States of America
+1-812-842-4259
kenneth.herrmann@deaconess.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Necrotizing enterocolitis and exclusively human milk feeding through 33 weeks postmenstrual age: single arm-cohort prospective trial
Acronym
Study hypothesis
A portion of the incidence of necrotizing enterocolitis (NEC) is associated with bovine-based artificial milk feeding provided before 33 weeks postmenstrual age (PMA).
Ethics approval
Studies evaluating the safety of nutrition products are exempt from institutional review approval. Mothers own milk and DHM are not regulated by the FDA. Investigators are not permitted to determine their own exemption status; The Research Institute of Deaconess Clinic performs the exemption status determination: (http://www.deaconess.com/DeaconessClinic/Clinical-Research.aspx).
Study design
Single arm-cohort prospective trial
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
http://www.deaconess.com/milkdonor
Condition
Risk of necrotizing enterocolitis (NEC) associated with a diet entirely of human milk.
Intervention
Premature infants receive an entirely human milk diet from birth through 33 weeks postmenstrual age
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
The occurrence of necrotizing enterocolitis (NEC) greater or equal to Bell's stage II. This is an event that has a dramatic onset. The onset is recorded in the EMR as a date. Retrospectively, the chronological day of onset (date of onset minus the date of birth) is determined. Similarly, the Postmenstrual Age (PMA) at onset (gestational age plus the chronological age) is also retrospectively determined.
Secondary outcome measures
Assessed after completions includes:
1. Duration of parenteral nutrition (TPN): PN orders are written daily, beginning at the time of birth. PN is determined to stop on the day that no new parenteral orders are written. The duration is calculated retrospectively by PMA for the day PN stops: (gestational age plus the chronological age).
2. Duration of NICU hospitalization (postmenstrual age at discharge): The duration of hospital stay ends on the date the infant leaves the hospital and goes home with its parents. The duration is calculated retrospectively by PMA for the day the infant goes home: (gestational age plus the chronological age).
3. Markers of milk feeding intolerance: Enteral feeding tolerance is measured retrospectively, based on the feeding provided on the day the infant is discharged to the parents. Feeding categories include: breast milk; bovine based artificial milk with intact proteins; bovine based artificial milk with hydrolyzed proteins; amino-acid based artificial milk. (Intolerance of feeding occurs when bovine based artificial milk with hydrolyzed proteins or an amino-acid based artificial milk is prescribed on the day of discharge to the parents).
Enteral feeding is measured retrospectively, determined by the use of a medication (metoclopramide), used at any duration of time for any reason prior to discharge to the parents. (Intolerance of feeding is suspected if metoclopramide is used on any day).
Overall trial start date
01/07/2010
Overall trial end date
31/12/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
All infants admitted to a single neonatal intensive care unit (NICU) from July 1, 2010 through December 31, 2012, and born before 33 weeks gestation
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
All infants in a 30 month period, born before 33 weeks gestation
Participant exclusion criteria
All infants admitted to the neonatal intensive care unit (NICU) in the study period are evaluated. Infants of parents that do not provide mother's own milk and also do not consent for donor human milk are excluded in the analysis of human milk-fed infants.
Recruitment start date
01/07/2010
Recruitment end date
31/12/2012
Locations
Countries of recruitment
United States of America
Trial participating centre
4199 Gateway Boulevard
Newburgh
47630
United States of America
Sponsor information
Organisation
The Deaconess Women's Hospital (USA)
Sponsor details
4199 Gateway Boulevard
Newburgh
47630
United States of America
+1-812-842-4259
Kenneth.Herrmann@deaconess.com
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Deaconess-Women's Hospital (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Australian Research Council (DP11110103125) (Australia)
Alternative name(s)
ARC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Australia
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24588561