Individualized Fortification of Breast Milk

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.

Study Overview

• Status: Completed
• Conditions: Premature Infant; Breast Milk

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 Type: Observational
• Enrollment (Actual): 32

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

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.

Description

Inclusion Criteria:

- Very-low-birth-weight preterm infants ≤ 32 weeks of gestational age who were fed exclusively fortified breast milk.

Exclusion Criteria:

• The exclusion criteria were any congenital abnormality, a metabolic disease, necrotizing enterocolitis, bronchopulmonary dysplasia, and feeding with formula or formula plus breast milk.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight gain	The mean of weight gain (g/kg/day)	4 weeks
Head circumference	The mean of head circumference (mm/week)	4 weeks
Length	The mean of length (mm/week)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Urea Nitrogen (BUN)	The mean of BUN (mg/dL)	4 weeks
Albumin	The mean of albumin (g/dL)	4 weeks
Base deficit	The mean of base deficit (mEq/L)	4 weeks
Protein content	The mean of total daily intake of protein (g/kg/day)	4 weeks
Calorie intake	The mean of total daily intake of calorie (kcal/kg/day)	4 weeks
Carbonhydrate content	The mean of total daily intake of carbohydrate (g/kg/day)	4 weeks
Lipid content	The mean of total daily intake of lipid (g/kg/day)	4 weeks
Protein/Energy Ratio	The mean of total daily intake of Protein\Energy Ratio	4 weeks

Collaborators and Investigators

• Sponsor: Ozgul Bulut
• Investigators: Study Director: Zeynep Ince, Prof., Istanbul University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): February 28, 2014

Study Registration Dates

• First Submitted: September 30, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: growth; breast milk; Preterm infants; very low birth weight; individualized fortification; targeted protein fortification; adjustable protein fortification
• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 35496

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: I'm not currently clear about sharing IPD. I will consider this at a later stage.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No