Breast Milk, Human Milk, Neonate
Conditions
Keywords
Targeted Fortification, Human Milk Analysis, Neonatal Nutrition
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTTargeted 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.
DEVICEThe 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.
Sponsors
MetroHealth Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
After randomization, the groups will not be blinded to the investigators or caregivers.
Intervention model description
This study will be a randomized control trial with 2 arms: control group (standard fortification) or intervention group (targeted fortification) in a 1:1 allocation ratio. Allocation group will be stratified to four groups according to birth weight: \<750g, 751-1000g, 1001-1250g, 1251-1500g. This stratification is based upon our NICU feeding guideline, and will ensure that enrolled infants will receive comparable nutrition progression (e.g. NPO (nil per os) days, days of trophic feeds) throughout the study period. The allocation will be concealed in a sequentially numbered, opaque, sealed envelope, that will be opened after consent is obtained.
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body Composition | 4 weeks after baby reaches full feeds (150 mL/kg/day) or at NICU discharge | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight Gain Velocity | From enrollment in study to 4 weeks after full feeds (150 mL/kg/day) or at NICU discharge. | Weight gain velocity, measured in grams/kg/day |
| Weight Gain | From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge. | Daily weight will be obtained, measured in grams |
| Linear Growth | From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge. | Weekly measurements of length will be obtained throughout the study, measured in centimeters |
| Head Circumference Growth | From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge. | Weekly measurements of head circumference will be obtained throughout the study, measured in centimeters |
| Body Composition | From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge. | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 2 |
| 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.
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. | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study discontinued with onset of COVID-19 pandemic | 2 | 1 |
Baseline characteristics
| Characteristic | Intervention Group (Targeted Fortification) | Total | Control Group (Standard Fortification) |
|---|---|---|---|
| Age, Continuous | 29 weeks | 28.8 weeks | 28.5 weeks |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 1 participants | 3 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 4 weeks after baby reaches full feeds (150 mL/kg/day) or at NICU discharge
Population: Study discontinued due to onset of COVID pandemic. No data were collected for this Outcome Measure.
Secondary
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
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Population: Study discontinued due to onset of COVID pandemic. No data were collected for this Outcome Measure.
Secondary
Head Circumference Growth
Weekly measurements of head circumference will be obtained throughout the study, measured in centimeters
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Population: Study discontinued due to onset of COVID pandemic. No data were collected this Outcome Measure.
Secondary
Linear Growth
Weekly measurements of length will be obtained throughout the study, measured in centimeters
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Population: Study discontinued due to onset of COVID pandemic. No data were collected for this Outcome Measure.
Secondary
Weight Gain
Daily weight will be obtained, measured in grams
Time frame: From enrollment in study to 4 weeks at full feeds (150 mL/kg/day) or at NICU discharge.
Population: Study discontinued due to onset of COVID pandemic. No data were collected for this Outcome Measure.
Secondary
Weight Gain Velocity
Weight gain velocity, measured in grams/kg/day
Time frame: From enrollment in study to 4 weeks after full feeds (150 mL/kg/day) or at NICU discharge.
Population: Study discontinued due to onset of COVID pandemic. No data were collected for this Outcome Measure.