Targeted Breast Milk Fortification for Very Low Birth Weight Infants in the NICU

Targeted Fortification of Human Breast Milk and Adjustment of TPN for Very Low Birth Weight Infants to Optimize Growth and Nutrition Using the Miris Mid-infrared Human Milk Analyzer

This study evaluates the effectiveness of individualized human milk fortification for very low birth weight (<1500 g) babies in the NICU (Neonatal Intensive Care Unit) to optimize their growth. Breast milk analysis will occur on a weekly basis using the Miris Human Milk Analyzer. In the Control group, participants will receive standard TPN (total parenteral nutrition) and lipids and breast milk fortification according to MetroHealth's NICU guidelines. The Intervention group will receive TPN and lipids optimized depending on the results of breast milk analysis, followed by additional individualized fortification using additional microlipids and/or liquid protein to achieve the goal of 4g protein/kg/day and 100-130 kcal/kg/day.

Study Overview

• Status: Terminated
• Conditions: Human Milk; Breast Milk; Neonate
• Intervention / Treatment: Dietary supplement: Targeted Fortification; Device: The Miris Human Milk Analyzer

Detailed Description

Human milk has a variety of benefits for neonates, especially premature neonates, including a decreased risk of for necrotizing enterocolitis, sudden infant death syndrome (SIDS), respiratory syncytial virus (RSV) bronchiolitis, respiratory infections, and many other childhood conditions. There is variability in macronutrient and caloric content of breast milk between mothers, making it difficult to accurately quantify the nutritional content the breast milk is providing. The protein content varies by postnatal age, and the fat content varies temporally during a feed. Currently calculations use a standard value for caloric density and macronutrient content of breast milk, which is a reported average, but not necessarily specific to each individual mother. Human milk analysis has been used to address this variability. The Miris Human Milk Analyzer (HMA) is a mid-infrared analyzer and has been evaluated in many studies. It measures the macronutrient content of breast milk, providing values for protein, fat, carbohydrates, and calculated calories. By having this information available, the fortification added to breast milk can be tailored specifically to each mother's breast milk composition to meet each neonate's nutritional needs, and optimize growth.This will be a prospective randomized control study of preterm infants less than 1500 grams [very low birth weight (VLBW)] receiving human milk (maternal or donor) will be included. The control group will receive adjustment of total parenteral nutrition (TPN) per NICU guidelines as enteral feedings are advanced followed by standard fortification of human milk. The intervention group will have TPN (protein and lipids) adjusted based on analysis of human milk as feedings are advanced to provide goal 4g/kg/day of protein and 100-130 kcal/kg/day followed by targeted fortification of breast milk based on human milk analysis to continue to provide 4 g/kg/day of protein and 100-130 kcal/kg/day for once full feeds are achieved. The primary aim of this study is to evaluate the growth, anthropometric measurements, and body composition, to see if targeted fortification improves neonatal growth. By optimizing neonatal growth and nutrition there is potential to also have an impact on other morbidities and long term neurodevelopmental outcomes.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Premature infants <1500 g
• Mother consenting to provide breast milk or use of donor breast milk

Exclusion Criteria:

• Infants with major congenital malformations
• Infants with medical conditions precluding them from having breast milk
• Mothers with medical conditions that preclude them form providing breast milk
• Insufficient breast milk supply
• Refusal of donor breast milk
• Mother is non-English speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group (standard fortification); Breast milk will be fortified standard with Similac Human Milk Fortifier 1 packet: 50 ml breast milk at 50ml/kg/day enteral feeds, then 1 packet:25 ml breast milk at 75 ml/kg/day. As feedings are advanced to goal of 150 ml/kg/day, the TPN and SMOF lipids (Fat Emulsion Comprised of Soy Oil, Medium Chain Triglycerides, Olive Oil, and Fish Oil) will be decreased per standard management and NICU guidelines.
Experimental: Intervention group (targeted fortification); Breast milk will be fortified standard with Similac Human Milk Fortifier 1 packet: 50 ml breast milk at 50ml/kg/day enteral feeds, then 1 packet:25 ml breast milk at 75 ml/kg/day. During this time, as the volume decreases, the TPN and SMOF lipids will be optimized to provide a goal of 4 g/kg/day of protein, and 100-130kcal/kg/day. At 100 ml/kg/day of enteral feeds additional liquid protein and/or microlipids will be added to the breast milk to provide goal of 4 g/kg/day of protein and 100-130 kcal/kg/day. This will be determined by analysis of the milk and reported composition. They will continue targeted fortification for 4 weeks after achieving full feeds of 150 ml/kg/day. Breast milk analysis will occur on a weekly basis immediately after birth for all infants enrolled in the study.	Dietary supplement: Targeted Fortification; The TPN and SMOF lipids will be optimized to provide a goal of 4 g/kg/day of protein, and 100-130kcal/kg/day. At 100 ml/kg/day of enteral feeds additional liquid protein and/or microlipids will be added to the breast milk to provide goal of 4 g/kg/day of protein and 100-130 kcal/kg/day. This will be determined by analysis of the milk and reported composition. They will continue targeted fortification for 4 weeks after achieving full feeds of 150 ml/kg/day.; Device: The Miris Human Milk Analyzer; The Miris human milk analyzer is a mid infrared that reports the amount of energy absorbed at each wavelength. The amount of fat (grams), lactose (grams), total protein (grams), true protein (grams), and energy (kcal) per 100 ml will be reported.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Composition	Body composition will be measured by air displacement plethysmography (PEAPod). As standardized assessment of body composition is relatively new in the preterm infant population, we are using clinical judgment to determine that a difference in fat free mass z-score (from data from Norris T, 2019) of 0.5 is clinically significant.	4 weeks after baby reaches full feeds (150 mL/kg/day) or at NICU discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Gain Velocity	Weight gain velocity, measured in grams/kg/day	From enrollment in study to 4 weeks after full feeds (150 mL/kg/day) or at NICU discharge.
Weight Gain	Daily weight will be obtained, measured in grams	From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Linear Growth	Weekly measurements of length will be obtained throughout the study, measured in centimeters	From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Head Circumference Growth	Weekly measurements of head circumference will be obtained throughout the study, measured in centimeters	From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Body Composition	Mid upper arm circumference (cm) or skinfold thickness (mm) will be measured weekly throughout the study and combined with length to calculate the body composition	From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.

Collaborators and Investigators

• Sponsor: MetroHealth Medical Center
• Investigators: Principal Investigator: Sharon Groh-Wargo, PhD, RDN, MetroHealth Medical Center

Publications and helpful links

General Publications

• Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012 Mar;129(3):e827-41. doi: 10.1542/peds.2011-3552. Epub 2012 Feb 27.
• Martin CR, Ling PR, Blackburn GL. Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. Nutrients. 2016 May 11;8(5):279. doi: 10.3390/nu8050279.
• Fusch G, Kwan C, Kotrri G, Fusch C. "Bed Side" Human Milk Analysis in the Neonatal Intensive Care Unit: A Systematic Review. Clin Perinatol. 2017 Mar;44(1):209-267. doi: 10.1016/j.clp.2016.11.001. Epub 2016 Dec 29.
• Tudehope DI. Human milk and the nutritional needs of preterm infants. J Pediatr. 2013 Mar;162(3 Suppl):S17-25. doi: 10.1016/j.jpeds.2012.11.049.

Helpful Links

• Miris HMA, Human Milk Analyzer website

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 18, 2019

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Targeted Fortification; Human Milk Analysis; Neonatal Nutrition
• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 19-00200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No