Condition category
Digestive System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

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 cow’s milk-based products when the mother’s own milk (MOM) is not available. Elimination of cow's milk products from the premature infant’s 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 study’s 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 cow’s 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 mother’s 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-Women’s Hospital, located in Newburgh, IN, USA.

What is the study period?
July 2010 through December 2012.

Who is funding the study?
The Deaconess-Women’s Hospital.

Who is the main contact?
Dr Kenneth Herrmann

Trial website

Contact information



Primary contact

Dr Kenneth Herrmann


Contact details

4199 Gateway Boulevard
Suite 3990
United States of America

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Necrotizing enterocolitis and exclusively human milk feeding through 33 weeks postmenstrual age: single arm-cohort prospective trial


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. Mother’s 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: (

Study design

Single arm-cohort prospective trial

Primary study design


Secondary study design

Cohort study

Trial setting


Trial type


Patient information sheet


Risk of necrotizing enterocolitis (NEC) associated with a diet entirely of human milk.


Premature infants receive an entirely human milk diet from birth through 33 weeks postmenstrual age

Intervention type



Not Applicable

Drug names

Primary outcome measures

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


Overall trial end date


Reason abandoned


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


Age group




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


Recruitment end date



Countries of recruitment

United States of America

Trial participating centre

4199 Gateway Boulevard
United States of America

Sponsor information


The Deaconess Women's Hospital (USA)

Sponsor details

4199 Gateway Boulevard
United States of America

Sponsor type

Hospital/treatment centre



Funder type

Hospital/treatment centre

Funder name

Deaconess-Women's Hospital (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Australian Research Council (DP11110103125) (Australia)

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government



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

Results - basic reporting

Publication summary

2014 results in:

Publication citations

Additional files

Editorial Notes