Clinical trial NCT04809350: Human Milk Fortification With Adjustable Versus Targeted Method
Official title: Effect of Adjustable Versus Targeted Human Milk Fortification on Weight Gain in Preterm Infants With Birth Weight <1250 g: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Growth Failure
Keywords: Human milk
Fortification
Preterm infants
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2021-03-22
Enrollment: 52
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Research question: Do preterm infants born \<1250 g achieve better weight gain with targeted fortification compared with the adjustable fortification of human milk?

Hypothesis: Targeted fortification of human milk results in better weight gain in infants with birth weight \<1250 gr when compared to the adjustable fortification.

Study design: Open-label, pragmatic, parallel randomized controlled trial in appropriate for gestational age infants with birth weight \<1250 g.

Detailed description: Human milk is the ideal diet for neonates. However, it does not provide enough energy, protein, and sodium to meet the nutritional requirements of very preterm infants. Postnatal growth failure is common despite the current use of human milk fortifiers. The main human milk fortification methods include:

1. standard HM fortification (SF) which assumes an average composition of breast milk and adds fortifiers in a fixed dosage. It does not account for variations of nutrient content in human milk
2. Individualized human milk fortification which encompasses two methods:

   1. Adjustable HM fortification (AF): Protein supplementation is provided in addition to SF according to blood urea nitrogen (BUN) concentration which reflects the infant's metabolic response to protein intake. However, there are clinical scenarios in which the BUN levels are not a reliable marker of protein intake, such as acute kidney injury.
   2. Targeted HM fortification (TF): Based on routine analyses of HM that are used to adjust fortification to meet the recommended requirements for infants. It does not take into consideration that the requirements of infants may vary.

SF has frequently failed to achieve appropriate weight gain, while individualized (AF or TF) fortification seems to have better performance. However, the evidence to support one method over the other is lacking.

The objective of the study is to compare weekly average weight gain between preterm infants on AF versus TF.

Once the written consent is obtained, the infant will be randomized to AF or TF. The sequence code will be kept in sequential numbered sealed envelopes. Infants from multiple births will be included as 1 unit and randomized to the same arm of the study.

For patients allocated to the TF group, breast milk will be analyzed twice weekly for energy, protein, and sodium contents. The daily protein, fat, and sodium intakes will be then calculated and optimized to meet the recommended dietary reference intake (DRI) for preterm infants with birth weight \<1250 g.

For patients allocated to the AF group, weekly BUN measurements will be performed. Based on BUN concentrations, the liquid protein will be added to achieve the targeted BUN level. Additional calories will be added using formula if growth is suboptimal or DRI is not met based on the assumed human milk content for protein and energy.

The intervention will last 4-8 weeks. For all patients, the day the first BUN concentration and milk analyses are done will be day 1 of intervention. The following measurements will be performed on days 7-8, 14-16, 21-23, and 28-30 of intervention: Weight (grams), length and head circumference (centimeters), BUN and sodium concentrations.

Data on maternal and neonatal characteristics will be collected from their electronic and physical charts.

Eligibility criteria: Inclusion Criteria:

* Infants with birth weight \<1250 g born at Foothills Medical Centre.
* Appropriate for gestational age (AGA) (according to Fenton's Charts).

Exclusion Criteria:

* Abnormal Newborn Metabolic Screen
* Major congenital anomalies intervention.
* Patients who develop NEC prior to enrollment.
* Patients with confirmed congenital Toxoplasmosis, Syphilis, Rubella, Cytomegalovirus, Herpes simplex virus, Varicella and/or Zika (TORCH infections).
* Patients receiving systemic steroids.
* Patients with acute kidney injury (AKI).

Primary outcomes:
measure: Average weight gain in infants on Adjustable versus Targeted human milk fortification
timeFrame: Weekly for 8 weeks
Secondary outcomes:
measure: Anthropometrics in infants on Adjustable versus Targeted human milk fortification
timeFrame: Weekly for 8 weeks
measure: BUN concentration in infants on Adjustable versus Targeted human milk fortification
timeFrame: Weekly for 4 weeks
measure: Incidence of extra uterine growth restriction
timeFrame: At 36 weeks CA
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
Study officials:
affiliation: University of Calgary
name: Belal Alshaikh, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: