Breast MilkNCT03324126
Individualized Fortification of Breast Milk
An observational study of Breast Milk and Premature Infant, run by Ozgul Bulut.
Trial summary
Objectives: To compare the effects of two different methods of individualized protein fortification of breast milk on the early growth of VLBW preterm infants. Design: VLBW preterm infants ≤ 32 weeks of gestational age were included in the study and randomized into two groups according to the method of breast milk… Read more about this study
- Who is it for?
- Ages 25 to 32 weeks
- Conditions the study is for
- Breast Milk, Premature Infant
- How many people
- 32 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2013to 28 Feb 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 32 weeks
- All sexes
- No healthy volunteers
- Child
Study population: Very-low-birth-weight preterm infants ≤ 32 weeks of gestational age were included in the study and randomized into two groups according to the method of breast milk fortification.
Who may be able to join
- Very-low-birth-weight preterm infants ≤ 32 weeks of gestational age who were fed exclusively fortified breast milk.
Who cannot join
- The exclusion criteria were any congenital abnormality, a metabolic disease, necrotizing enterocolitis, bronchopulmonary dysplasia, and feeding with formula or formula plus breast milk.
About this study
Official title: Effects of Targeted Versus Adjustable Protein Fortification of Breast Milk on Early Growth in Very-low-birth-weight Preterm Infants: A Randomized Clinical Trial
Objectives: To compare the effects of two different methods of individualized protein fortification of breast milk on the early growth of VLBW preterm infants.
Design: VLBW preterm infants ≤ 32 weeks of gestational age were included in the study and randomized into two groups according to the method of breast milk fortification. In the targeted protein fortification group, breast milk samples were analyzed daily via mid-infrared spectroscopy and additional protein was provided to maintain an intake of 4.5 g/kg/day. In the adjustable protein fortification group, blood urea nitrogen (BUN) levels were monitored weekly, and if the level was < 5 mg/dL, the amount of protein fortification was gradually increased to an "estimated" maximum level of 4.5 g/kg/day, as per the policy of neonatal intensive care unit. The cumulative amounts of protein, energy, fat, and carbohydrate given to infants prior to study commencement and during the study period were calculated. Anthropometric measurements were performed in both groups weekly for 4 weeks to compare their growth, and blood data including pH, base deficit, and urea, creatinine, and albumin levels were collected.
Read the detailed description
Optimal feeding during the early neonatal period is critical because inadequate nutrition, especially of very-low-birth-weight (VLBW) preterm infants, causes growth restrictions and has negative effects on neurocognitive development (1-5).
Although breast milk is the first choice for nutrition of preterm infants (6, 7), it falls short of meeting all of the nutritional needs of VLBW infants unless fortified (8-10). Therefore, standard fortification (addition of a fixed amount of a commercial fortifier to breast milk) has become a commonly used method in neonatal intensive care units (NICUs) (11, 12). Standard fortification is performed based on assumptions made about the protein level in breast milk. However, protein levels show inter- and intra-individual variation, and the assumed levels in the milk of the mothers of preterm infants (2.1-2.4 g/100 kcal) is reduced to <1.5 g/100 kcal after the 14th day of lactation (10, 13-17). The protein content of commercial fortifiers ranges from 0.7 to 1.1 g/100 mL, and they thus can only increase the amount of protein in breast milk to 3.25 g/100 kcal. Therefore, the standard fortification method fails to meet the daily protein need of 3.5-4.5 g/kg/day of VLBW infants that is recommended by the European Society for Pediatric Gastroenterology Hepatology and Nutrition (18, 19).
Individualized fortification is another method recommended for optimizing breast milk fortification, and it is considered the best solution for addressing the protein deficiencies of VLBW preterm infants (10, 12). There are two valid methods of individualized fortification: "targeted fortification" based on analyses of breast milk proteins, and "adjustable fortification" based on the blood urea nitrogen (BUN) - reflected metabolic response of infants (10, 12). Despite these developments, there is still no consensus on the optimum fortification method; many different protocols are applied in NICUs worldwide (20, 21).
To the best of the investigators knowledge, no study has yet compared these two individualized fortification methods for nutrition of preterm infants. Therefore, the investigators compared the effects of targeted and adjustable protein fortification on the early growth of breastfed VLBW preterm infants.
- Conditions
- Breast Milk, Premature Infant
- Keywords
- Preterm infants, very low birth weight, breast milk, individualized fortification, targeted protein fortification, adjustable protein fortification, growth
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Targeted fortification | In the targeted protein fortification group, breast milk samples were analyzed daily via mid-infrared spectroscopy and additional protein was provided to maintain an intake of 4.5 g/kg/day. | |
| Adjustable fortification | In the adjustable protein fortification group, blood urea nitrogen (BUN) levels were monitored weekly, and if the level was < 5 mg/dL, the amount of protein fortification was gradually increased to an "estimated" maximum level of 4.5 g/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight gain
The mean of weight gain (g/kg/day)
Measured: 4 weeks
Head circumference
The mean of head circumference (mm/week)
Measured: 4 weeks
Length
The mean of length (mm/week)
Measured: 4 weeks
Secondary outcomes (8)
Blood Urea Nitrogen (BUN)
The mean of BUN (mg/dL)
Measured: 4 weeks
Albumin
The mean of albumin (g/dL)
Measured: 4 weeks
Base deficit
The mean of base deficit (mEq/L)
Measured: 4 weeks
Protein content
The mean of total daily intake of protein (g/kg/day)
Measured: 4 weeks
Calorie intake
The mean of total daily intake of calorie (kcal/kg/day)
Measured: 4 weeks
Carbonhydrate content
The mean of total daily intake of carbohydrate (g/kg/day)
Measured: 4 weeks
Lipid content
The mean of total daily intake of lipid (g/kg/day)
Measured: 4 weeks
Protein/Energy Ratio
The mean of total daily intake of Protein\Energy Ratio
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study start1 Sep 2013
- Primary completion1 Dec 2013
- Study completion28 Feb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast MilkStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ozgul Bulut
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ozgul Bulut, Istanbul University
- Investigators
- Zeynep Ince, Prof., Study director, Istanbul University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03324126
- Sponsor's protocol ID
- 35496
- Status last verified
- Oct 2017
- First submitted
- 30 Sep 2017
- Last updated
- 27 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: I'm not currently clear about sharing IPD. I will consider this at a later stage.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Targeted Versus Adjustable Protein Fortification of Breast Milk on Early Growth in Very-low-birth-weight Preterm Infants: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03324126
- Acronym / sponsor ID
- 35496
- Conditions
- Breast Milk, Premature Infant
- Keywords
- Preterm infants, very low birth weight, breast milk, individualized fortification, targeted protein fortification, adjustable protein fortification, growth
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Ozgul BulutUniversity, hospital or other
- Study start
- 1 Sep 2013 (actual)
- Primary completion
- 1 Dec 2013 (actual)
- Study completion
- 28 Feb 2014 (actual)
- First posted
- 27 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives: To compare the effects of two different methods of individualized protein fortification of breast milk on the early growth of VLBW preterm infants.
Design: VLBW preterm infants ≤ 32 weeks of gestational age were included in the study and randomized into two groups according to the method of breast milk fortification. In the targeted protein fortification group, breast milk samples were analyzed daily via mid-infrared spectroscopy and additional protein was provided to maintain an intake of 4.5 g/kg/day. In the adjustable protein fortification group, blood urea nitrogen (BUN) levels were monitored weekly, and if the level was < 5 mg/dL, the amount of protein fortification was gradually increased to an "estimated" maximum level of 4.5 g/kg/day, as per the policy of neonatal intensive care unit. The cumulative amounts of protein, energy, fat, and carbohydrate given to infants prior to study commencement and during the study period were calculated. Anthropometric measurements were performed in both groups weekly for 4 weeks to compare their growth, and blood data including pH, base deficit, and urea, creatinine, and albumin levels were collected.
Detailed description
Optimal feeding during the early neonatal period is critical because inadequate nutrition, especially of very-low-birth-weight (VLBW) preterm infants, causes growth restrictions and has negative effects on neurocognitive development (1-5).
Although breast milk is the first choice for nutrition of preterm infants (6, 7), it falls short of meeting all of the nutritional needs of VLBW infants unless fortified (8-10). Therefore, standard fortification (addition of a fixed amount of a commercial fortifier to breast milk) has become a commonly used method in neonatal intensive care units (NICUs) (11, 12). Standard fortification is performed based on assumptions made about the protein level in breast milk. However, protein levels show inter- and intra-individual variation, and the assumed levels in the milk of the mothers of preterm infants (2.1-2.4 g/100 kcal) is reduced to <1.5 g/100 kcal after the 14th day of lactation (10, 13-17). The protein content of commercial fortifiers ranges from 0.7 to 1.1 g/100 mL, and they thus can only increase the amount of protein in breast milk to 3.25 g/100 kcal. Therefore, the standard fortification method fails to meet the daily protein need of 3.5-4.5 g/kg/day of VLBW infants that is recommended by the European Society for Pediatric Gastroenterology Hepatology and Nutrition (18, 19).
Individualized fortification is another method recommended for optimizing breast milk fortification, and it is considered the best solution for addressing the protein deficiencies of VLBW preterm infants (10, 12). There are two valid methods of individualized fortification: "targeted fortification" based on analyses of breast milk proteins, and "adjustable fortification" based on the blood urea nitrogen (BUN) - reflected metabolic response of infants (10, 12). Despite these developments, there is still no consensus on the optimum fortification method; many different protocols are applied in NICUs worldwide (20, 21).
To the best of the investigators knowledge, no study has yet compared these two individualized fortification methods for nutrition of preterm infants. Therefore, the investigators compared the effects of targeted and adjustable protein fortification on the early growth of breastfed VLBW preterm infants.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Targeted fortification | – | –In the targeted protein fortification group, breast milk samples were analyzed daily via mid-infrared spectroscopy and additional protein was provided to maintain an intake of 4.5 g/kg/day. |
| Adjustable fortification | – | –In the adjustable protein fortification group, blood urea nitrogen (BUN) levels were monitored weekly, and if the level was < 5 mg/dL, the amount of protein fortification was gradually increased to an "estimated" maximum level of 4.5 g/kg/day |
Who may qualify
- Ages
- 25 to 32 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Very-low-birth-weight preterm infants ≤ 32 weeks of gestational age were included in the study and randomized into two groups according to the method of breast milk fortification.
Key inclusion criteria (1 listed)
- Very-low-birth-weight preterm infants ≤ 32 weeks of gestational age who were fed exclusively fortified breast milk.
Key exclusion criteria (1 listed)
- The exclusion criteria were any congenital abnormality, a metabolic disease, necrotizing enterocolitis, bronchopulmonary dysplasia, and feeding with formula or formula plus breast milk.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Weight gain
Time frame: 4 weeks
The mean of weight gain (g/kg/day)
Head circumference
Time frame: 4 weeks
The mean of head circumference (mm/week)
Length
Time frame: 4 weeks
The mean of length (mm/week)
8 secondary outcomes
Blood Urea Nitrogen (BUN)
Time frame: 4 weeks
Albumin
Time frame: 4 weeks
Base deficit
Time frame: 4 weeks
Protein content
Time frame: 4 weeks
Calorie intake
Time frame: 4 weeks
Carbonhydrate content
Time frame: 4 weeks
Lipid content
Time frame: 4 weeks
Protein/Energy Ratio
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
- Individual participant dataSharing planned: Undecided. I'm not currently clear about sharing IPD. I will consider this at a later stage.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zeynep Ince, Prof. study director
Istanbul University
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Milk and Premature Infant, run by Ozgul Bulut.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight gain (time frame: 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.