Human Milk Oligosaccharides (HMOs) Post-market Study on Infants (NEHMO)

Growth and Feeding Tolerance of Infants Consuming a Formula Supplemented With Human Milk Oligosaccharides (HMOs): An Uncontrolled, Open-label, Prospective Study

Human milk oligosaccharides (HMOs) represent the third largest solid component of breast milk. Technology advancements made it possible to supplement infant formulas with HMOs (2'FL, LNnT). Two published RCTs have demonstrated that infant formulas supplemented with 2'FL or 2'FL+LNnT are safe, well-tolerated, support normal grow, and may support healthy GI function and confer immune benefits. The performance of HMOs-supplemented formulas assessed in a real-world setting is complementary to previously conducted RCTs conducted in highly controlled clinical settings. Main objectives will be to monitor the safety & tolerance of HMOs-supplemented formulas in larger and diverse infant populations; to assess the performance of HMOs-supplemented formulas in mixed-fed infants, a population that was not studied in previous RCTs but likely represents a relatively common feeding regimen. Finally, considering the potential health/immune benefits of HMOs, it is also important explore the incidences of illnesses (i.e., respiratory illnesses, GI illnesses, and fever) associated with consuming HMOs-supplemented formulas and compare with breastfed infants data.

Study Overview

• Status: Completed
• Conditions: Growth; Tolerance; Adverse Event; Disorder of Intestine; Disorder Lung
• Intervention / Treatment: Other: HMO-supplemented infant formula

Detailed Description

Objectives:

The main objective of this study is to document the growth and feeding tolerance of healthy term infants consuming an infant formula supplemented with HMOs for 8 weeks (56 days), in a real-world setting.

Main endpoints:

1. Growth documented via monitoring the anthropometric parameters including weight, length, head circumference, BMI and their corresponding z-scores (i.e., z-scores for weight-for-age, length-for-age, weight-for-length, head circumference-for-age, and BMI-for-age) calculated using the 2006 WHO Growth Standards
2. Feeding tolerance assessed via monitoring parent-reported overall GI symptom burden measured by the Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score (13-item summary score)

Additional objectives:

To describe the following outcomes in infants fed an infant formula supplemented with HMOs:

1. Formula acceptability
2. Despite there are no expected safety concerns, standard Adverse Events (AEs) monitoring will be implemented during the study

Additional endpoints:

1. Formula acceptability assessed by the Study Formula Satisfaction Questionnaire

2. Reported AEs and Serious Adverse Events (SAEs) including type, incidence, severity, seriousness and relation to study formula consumption as well as concomitant medications and non-pharmacological treatments.

   • Select morbidities of interest (i.e., respiratory illnesses, GI illnesses, and fever) will be collected as part of AE reporting and specific corresponding AE guidance forms will be used to standardize reporting of such AEs

Trial design:

Uncontrolled, single arm, open-label, prospective study in infants (enrolled at postnatal age 7 days to 2 months) fed the study formula for 8 weeks (56 days)

A group of exclusively breastfed infants (BF) will serve as a reference group in parallel to the study arm. For the BF group, Infants must have been exclusively consuming breast milk since birth, and their parent(s) must have made the decision to continue exclusively breastfeeding until at least 4 month of age

Trial population:

Healthy, male and female, term infants, 7 days postnatal age to 2 months of age at the enrollment

Treatment duration:

Total study participation/intervention up to approximately 8 weeks

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08028
    • Universitary Hospital Quirón-Dexeus
  • Madrid, Spain, 28034
    • Ruber Internacional Clinic
  • Sevilla, Spain
    • Hispalense Group
  • Valencia, Spain, 46021
    • Casa de la Salud, Hospital
  • Canarias
    • Las Palmas De Gran Canaria, Canarias, Spain, 35005
      • Vitha Santa Catalina Hospital
  • Galicia
    • Coruña, Galicia, Spain, 15011
      • Hospital Maternal MH Belén

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s) have been informed of all pertinent aspects of the study
2. Parent(s) are willing and able to fulfill the requirements of the study protocol
3. Healthy full term (37-42 weeks gestation) infant
4. Be between post-natal age (Date of Birth = Day 0) 7 days to 2 months
5. Parent(s) must have independently elected, before enrollment, to formula feed

Exclusion Criteria:

1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s) have been informed of all pertinent aspects of the study
2. Parent(s) are willing and able to fulfill the requirements of the study protocol
3. Healthy full term (37-42 weeks gestation) infant
4. Be between post-natal age (Date of Birth = Day 0) 7 days to 2 months
5. Infants must have been exclusively consuming breast milk since birth, and their parent(s) must have made the decision to continue exclusively breastfeeding until at least 4 month of age

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Formula-fed infants; Infants fed exclusively with experimental formula	Other: HMO-supplemented infant formula; Starter Infant Formula supplemented with 1.5g/L of Human Milk Oligosaccharides
Experimental: Mixed-fed infants; Infants receiving breastmilk and experimental formula	Other: HMO-supplemented infant formula; Starter Infant Formula supplemented with 1.5g/L of Human Milk Oligosaccharides
No Intervention: Breast-fed infants; Reference group of exclusively breastfed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
World Health Organization (WHO) based weight-for-age z-scores	Weight-for-age z-scores using WHO growth standards	8 weeks (study end)
World Health Organization (WHO) based length-for-age z-scores	Length-for-age z-scores using WHO growth standards	8 weeks (study end)
World Health Organization (WHO) weight-for-length z-scores	Weight-for-length z-scores using WHO growth standards	8 weeks (study end)
World Health Organization (WHO) head-circumference-for-age z-scores	head-circumference-for-age z-scores using WHO growth standards	8 weeks (study end)
World Health Organization (WHO) based body-mass-index (BMI)-for-age z-scores	Weight and height will be combined to calculate BMI in kg/m^2, then BMI-for-age z-scores will be derived using WHO growth standards	8 weeks (study end)
Feeding tolerance	The Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score will be used to assess GI distress. This is a validated 13-item questionnaire where each item is scored on a scale of 1 to 5 with higher values indicating greater GI distress. A composite IGSQ score is derived from summing the individual scores with a possible range of 13 to 65 where higher values indicate greater GI distress and values ≤23 indicate no digestive distress.	4 weeks (study midpoint)
Feeding tolerance	The Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score will be used to assess GI distress. This is a validated 13-item questionnaire where each item is scored on a scale of 1 to 5 with higher values indicating greater GI distress. A composite IGSQ score is derived from summing the individual scores with a possible range of 13 to 65 where higher values indicate greater GI distress and values ≤23 indicate no digestive distress.	8 weeks (study end)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Formula acceptability	Study Formula Satisfaction Questionnaire	4 weeks (study midpoint), 8 weeks (study end)
Standard adverse events (AEs) reporting for safety assessment	Reported adverse events (AEs) and Serious Adverse Events (SAEs) include type, incidence, severity, seriousness and relation to feeding	From the time the informed consent form has been signed at enrollment infant age less than 7 days to 2 months through the 8 weeks of intervention
Weight	Weight measurements in grams	8 weeks (study end)
Length	Length measurements in centimeters	8 weeks (study end)
Head circumference	Head circumference measurements in centimeters	8 weeks (study end)
Body-mass-index (BMI)	Weight and height will be combined to report BMI in kg/m^2	8 weeks (study end)

Collaborators and Investigators

• Sponsor: Nestlé
• Collaborators: Puerta de Hierro University Hospital; University of Navarrra Hospital (Clinica Universitaria); Grupo Pulso; Casa de la Salud Hospital; Vitha Santa Catalina Hospital; Quirón-Dexeus Universitary Hospital; Hospital Ruber Internacional; Grupo Hispalense de Pediatría Hospital; MH Belén Maternal Hospital

Publications and helpful links

General Publications

• Storm HM, Shepard J, Czerkies LM, Kineman B, Cohen SS, Reichert H, Carvalho R. 2'-Fucosyllactose Is Well Tolerated in a 100% Whey, Partially Hydrolyzed Infant Formula With Bifidobacterium lactis: A Randomized Controlled Trial. Glob Pediatr Health. 2019 Mar 15;6:2333794X19833995. doi: 10.1177/2333794X19833995. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Growth; Tolerance; Respiratory infection; Adverse Event; Gastrointestinal disorder; Gastrointestinal infection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Disease; Intestinal Diseases
• Other Study ID Numbers: 1806INF - Spain

Drug and device information, study documents

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