Effect of Hindmilk on Growth Velocity of Very Preterm Infants

Research question: Does feeding hindmilk improve weight gain in very preterm infants with poor growth velocity?

Hypothesis: In very preterm infants (born less than 32 weeks gestation) with poor postnatal growth velocity (<15 g/kg/day), feeding hindmilk would improve average weight gain by at least 4 g/kg per day.

Study design: This will be a prospective cohort study in very preterm infants admitted to the Neonatal Intensive Care Unit (NICU) at Foothills Medical Centre

Study Overview

• Status: Recruiting
• Conditions: Weight Gain
• Intervention / Treatment: Dietary supplement: Hindmilk

Detailed Description

Extra-uterine growth restriction (EUGR) is one of the most common findings among very preterm infants at discharge from neonatal intensive care units. EUGR is associated with major morbidities such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and impaired neurodevelopment. EUGR is caused by slow postnatal growth and largely results from energy and protein deficits. These deficits occur despite the current fortifications of human milk. Hindmilk, the milk at the end of a breast pumping session, has higher fat and energy content compared to the composite milk. Feeding hindmilk can be a natural and innovative way to provide additional calories for very preterm infant. Hindmilk is rich in some fatty acids that are currently under investigation to prevent BPD and ROP and improve neurodevelopment. The aim of this study is to assess growth benefits of feeding hindmilk and to explore whether it can improve fatty acids profile in very preterm infants.

Dietitians (RD) and Lactation Consultant (LC) will screen and identify eligible mother-infant pairs. Once mother's consent obtained, LC will hand out the "hindmilk information sheet" and teach the mother how to separate her milk. A sample (10 ml) of composite pumped fresh milk will be collected and placed in the fridge. These samples will be sent for analysis within 24 hours of collection to minimize any changes to contents. Samples for Erythrocyte membrane fatty acid (FA) profile will be collected on dried blood spot (30-100 µL). These samples will be collected within 72 hours of the consent. It will be coordinated with blood tests ordered by the clinical team within that period. Dried blood spots are stable in room temperature for 28 days however we will store them in the -80̊ C freezer within 72 hours of collection. Another milk sample, hindmilk this time, will be sent for testing within 24-48 hour of starting hindmilk. This is to ensure that assessment of milk contents is performed in the same mother's lactation stage. The second dried blood spot will be drawn after 2-4 weeks of starting hindmilk. The 2-4 weeks period is to allow timing with other blood work-ups. In General, blood glucose is done every 2-3 days in babies with poor growth and growth laboratory testing is normally done every 2-3 weeks.

Data on fluid volumes, feeds, macronutrients intakes and any change in nutrition plan will be collected from electronic dietitian's notes. Dietitians will ensure proper and detailed documentation of nutritional information. Average weight gain (in gram/kg per day) is calculated as mentioned before. Average weight gain will be compared initially between the week before and the week after starting hindmilk. The day that hindmilk started will be used to identify the start point however it will not be used in either the pre- or the post-hindmilk calculation. Clinical team will be encouraged to not order other changes to the nutrition plan for the first week after starting hindmilk. Daily weight, weekly length and head circumference will be collected from the electronic charts. Furthermore, weight, length and head circumference at completed gestational week will be used to calculate Z scores using Fenton Z scores calculator.

Data on maternal and neonatal characteristics will be collected from their electronic and physical charts. Composite milk, foremilk and hindmilk volumes will be collected from the collection sheet that has been already used in our NICU.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Belal Alshaikh, MD, MSc; Phone Number: 403-955-2320; Email: belal.alshaikh@ahs.ca
• Study Contact Backup: Name: Zainab Towage, MD; Email: zainab.towage@ahs.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N2T9
      • Recruiting
      • Foothills Medical Centre
      • Contact: Belal Alshaikh, MD, MSc; Phone Number: 403-955-2320; Email: belal.alshaikh@ahs.ca
      • Contact: Zainab Towage, MD; Email: zainab.towage@ahs.ca
      • Principal Investigator: Belal Alshaikh, MD, MSc
      • Sub-Investigator: Zainab Towage, MD
      • Sub-Investigator: Kamran Yusuf, MD
      • Sub-Investigator: Wissam Alburaki, MD
      • Sub-Investigator: Christel Major, RN, LC
      • Sub-Investigator: JillMarie Spence, RD
      • Sub-Investigator: Jannette Festival, RN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Very preterm infant ( <32 weeks at birth)
• On full enteral feeds for more than 2 weeks (full feed is defined at the time of reaching 120 ml/kg/day with no parenteral nutrition used)
• Poor weight gain (<15 g/kg per day) despite optimization of energy and protein intakes by RDs (calories intake: 125-135 Kcal/kg per day and protein: 4-4.5 g/kg per day)
• Mothers have enough milk supply (>150% of infant's daily needs)

Exclusion Criteria

• Congenital anomalies
• Small for gestational age infants (< 10th percentile) at birth

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hindmilk; Hindmilk, the milk at the end of a breast pumping session, has higher fat and energy content compared to the composite milk.	Dietary supplement: Hindmilk; Mother will be taught to separate her milk and infant will receive only hindmilk for feeds

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Weight Gain	Difference in weight gain the week before hindmilk and the week after	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of feeding hindmilk on anthropometrics	Compared to published rates in NICUs	At 36 weeks post menstrual age and/or discharge (up to 13 weeks)
Effect of feeding hindmilk on body mass index	Compared to published rates in NICUs	At 36 weeks post menstrual age and/or discharge (up to 13 weeks)
Incidence of extra uterine growth restriction	Defined as wight less than 10th percentile. Compared to published rates in NICUs	At 36 weeks post menstrual age and/or discharge (up to 13 weeks)
Incidence of bronchopulmonary dysplasia and retinopathy of prematurity	BPD will be defined according to Child Health and Human Development as the requirement for positive pressure support (CPAP or high flow nasal cannula ≥ 1 liter per minute (LPM)), or oxygen dependency at 36 corrected gestational age. ROP will be defined according to the international classification1 or requiring treatment. Compared to published rates in NICUs	At 36 weeks post menstrual age and/or discharge (up to 13 weeks)
Correlation between human milk content (fat, protein and energy) and weight gain	Linear regression analysis will be used to correct for any confounding factors	Within 4 weeks of enrollment
Effect of hindmilk on erythrocyte membranes fatty acids profile.	Comparison between sample taken at 24 hours and sample at week 2-4 after hindmilk	Within 4 weeks of enrollment
Changes in mother's milk volumes after feeding hindmilk.	Monitor the milk output of mothers throughout the study	Until 36 weeks post menstrual age and/or discharge (up to 13 weeks)

Collaborators and Investigators

• Sponsor: Belal Alshaikh

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 22, 2019
• Primary Completion (ANTICIPATED): December 30, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: August 14, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (ACTUAL): August 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: preterm infants; hindmilk
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain
• Other Study ID Numbers: REB18-0195

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: No