Optimizing Nutrition and Milk (Opti-NuM) Project (Opti-NuM)

Improving Growth and Neurodevelopment of Very Low Birth Weight Infants Through Precision Nutrition: the Optimizing Nutrition and Milk (Opti-NuM) Project

Early nutrition critically influences growth, neurodevelopment and morbidity among infants born of very low birth weight (VLBW), but current one-size-fits-all feeding regimes do not optimally support these vulnerable infants. There is increasing interest in "precision nutrition" approaches, but it is unclear which Human Milk (HM) components require personalized adjustment of doses. Previous efforts have focused on macronutrients, but HM also contains essential micronutrients as well as non-nutrient bioactive components that shape the gut microbiome. Further, it is unclear if or how parental factors (e.g. body mass index, diet) and infant factors (e.g. genetics, gut microbiota, sex, acuity) influence relationships between early nutrition and growth, neurodevelopment and morbidity. Understanding these complex relationships is paramount to developing effective personalized HM feeding strategies for VLBW infants. This is the overarching goal of the proposed Optimizing Nutrition and Milk (Opti-NuM) Project.

The Opti-NuM Project brings together two established research platforms with complementary expertise and resources: 1) the MaxiMoM Program* with its clinically embedded translational neonatal feeding trial network in Toronto (Dr. Deborah O'Connor, Dr. Sharon Unger) and 2) the International Milk Composition (IMiC) Consortium, a world-renowned multidisciplinary network of HM researchers and data scientists collaborating to understand how the myriad of HM components contribute "as a whole" to infant growth and development, using systems biology and machine learning approaches. Members of the IMiC Corsortium that will work with on this study are located at the University of Manitoba (Dr. Meghan Azad), University of California (Dr. Lars Bode) and Stanford (Dr. Nima Aghaeepour).

Study Overview

• Status: Recruiting
• Conditions: Growth & Development; Human Milk Nutrition; Very Low Birth Weight Baby; Human Milk Feeding; Nutritional Requirements; Human Milk Microbiome; Human Milk Fortification; Early Nutrition and the Preterm Infant
• Intervention / Treatment: Other: Opti-NuM is an observational secondary use of data/samples study, the investigators will analyze information and specimens from the MaxiMoM platform RCTs. No interventions form part of this study.

Detailed Description

Observational study mode:

The Opti-NuM Project is a retrospective secondary data/sample use study.

Time perspective:

Secondary use data and biospecimens accruing from the 2 completed studies DoMINO and OptiMOM (NCT02137473) and 1 ongoing RCT MaxiMoM (NCT05308134) are included in this project.

Sampling method:

This project is a secondary use of data/samples, from a cohort consisting of participants of the MaxiMoM Platform RCTs.

• Study Type: Observational
• Enrollment (Estimated): 1100

Contacts and Locations

• Study Contact: Name: Dubraiicka Pichardo, MSc; Phone Number: 305777 416-813-7654; Email: dubraiicka.pichardo@sickkids.ca
• Study Contact Backup: Name: Aneta Plaga, BSc; Phone Number: 416-978-2422; Email: aneta.plaga@utoronto.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Active, not recruiting
      • University of Manitoba
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Dubraiicka Pichardo, MSc; Phone Number: 305777 416-813-7654; Email: dubraiicka.pichardo@sickkids.ca
      • Contact: Eugene Ng, MD, FRCPC; Phone Number: 87781 416-480-6100; Email: eugene.ng@sunnybrook.ca
      • Contact: Eugene Ng, MD, FRCPC, FAAP
    • Toronto, Ontario, Canada, M5G 1X5
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Sharon L Unger, MD; Phone Number: 416-586-8593; Email: Sharon.Unger@sinaihealth.ca
      • Contact: Dubraiicka Pichardo, MSc; Phone Number: 305777 4168137654; Email: dubraiicka.pichardo@sickkids.ca
      • Contact: Sharon L Unger, MD
    • Toronto, Ontario, Canada, M5G 0A4
      • Active, not recruiting
      • The Hospital for Sick Children
• United States
  • California
    • Palo Alto, California, United States, 94304-1212
      • Active, not recruiting
      • Stanford University
    • San Diego, California, United States, 92093-0715
      • Active, not recruiting
      • University of California - San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Very Low Birth Weight infants

Description

Inclusion Criteria:

• Secondary data and biospecimens from participants of the MaxiMoM Platform RCTs

Exclusion Criteria:

• Data and biospecimens from infants who are not enrolled in the three trials are eligible for this project.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants of the MaxiMoM Platform Trials; Secondary data use and biospecimens from participants of the MaxiMoM Platform Trials are infants born 1500g or less (infant weight), born in the Greater Toronto Area.	Other: Opti-NuM is an observational secondary use of data/samples study, the investigators will analyze information and specimens from the MaxiMoM platform RCTs. No interventions form part of this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive composite score on the Bayley Scales of Infant and Toddler Development.	Our primary outcome is the cognitive composite score on the Bayley Scales of Infant and Toddler Development collected from the medical record or by home-visit by our research staff. The Bayley is the most widely used instrument globally by clinicians and researchers to assess developmental functioning of infants, toddlers and young children across cognitive, language (receptive, expressive) and motor (fine, gross) domains. Cognitive, language and motor composite scores will be standardized to a mean of 100 with a standard deviation of 15. The range on the composite Bayle Scores is from less than 0.1 to more than 99.9 percentile. A score lower than the 10th percentile indicates developmental delay.	At 18-24 months CA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Language composite score from the Bayley Scales of Infant and Toddler Development	Language composite score from the Bayley Scales of Infant and Toddler Development. The range on the composite Bayle Scores is from less than 0.1 to more than 99.9 percentile. A score lower than the 10th percentile indicates developmental delay.	At 18-24 months CA
Motor composite score from the Bayley Scales of Infant and Toddler Development	Motor composite score from the Bayley Scales of Infant and Toddler Development. The range on the composite Bayle Scores is from less than 0.1 to more than 99.9 percentile. A score lower than the 10th percentile indicates developmental delay.	At 18-24 months CA
Weight (g)	Weight gains serve as early indicators of the effectiveness of early nutrition and are on the causal pathway to neurodevelopment. Daily weights are prospectively extracted from medical records.	Initial hospitalization, approximately 50 days; at 4 months and 18-24 months CA clinic visit.
Length (cm)	Length gains serve as early indicators of the effectiveness of early nutrition and are on the causal pathway to neurodevelopment. Weekly length is determined by research staff using length boards and standardized procedures.	Initial hospitalization, approximately 50 days; at 4 months and 18-24 months CA clinic visit.
Head circumference (cm)	Head circumference (HC) gains serve as early indicators of the effectiveness of early nutrition and are on the causal pathway to neurodevelopment. Weekly HC measurements are determined by research staff using non-stretchable tape measures and standardized procedures.	Initial hospitalization, approximately 50 days; at 4 months and 18-24 months CA clinic visit.
Serious morbidities	Serious morbidities including late-onset sepsis (>day 5, positive blood or cerebrospinal fluid culture), NEC (Bell stage ≥II), chronic lung disease (respiratory support at 36 weeks) and retinopathy of prematurity requiring treatment are collected prospectively from the medical chart.	During hospital stay, an average of 60 days.

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: University of Manitoba; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Sunnybrook Health Sciences Centre; University of California, San Diego; Stanford University; University of Toronto; Mount Sinai Hospital, Canada
• Investigators: Principal Investigator: Deborah L O'Connor, PhD, RN, The Hospital for Sick Children

Publications and helpful links

General Publications

• O'Connor DL, Kiss A, Tomlinson C, Bando N, Bayliss A, Campbell DM, Daneman A, Francis J, Kotsopoulos K, Shah PS, Vaz S, Williams B, Unger S; OptiMoM Feeding Group. Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial. Am J Clin Nutr. 2018 Jul 1;108(1):108-116. doi: 10.1093/ajcn/nqy067. Erratum In: Am J Clin Nutr. 2019 Aug 1;110(2):529. doi: 10.1093/ajcn/nqz091. Am J Clin Nutr. 2020 May 1;111(5):1112. doi: 10.1093/ajcn/nqaa042.
• O'Connor DL, Gibbins S, Kiss A, Bando N, Brennan-Donnan J, Ng E, Campbell DM, Vaz S, Fusch C, Asztalos E, Church P, Kelly E, Ly L, Daneman A, Unger S; GTA DoMINO Feeding Group. Effect of Supplemental Donor Human Milk Compared With Preterm Formula on Neurodevelopment of Very Low-Birth-Weight Infants at 18 Months: A Randomized Clinical Trial. JAMA. 2016 Nov 8;316(18):1897-1905. doi: 10.1001/jama.2016.16144.

Helpful Links

• MaxiMoM Research Platform

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Very Low Birth Weight Infants; Early nutrition and the preterm infant; Human milk feeding
• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: 4842 (Duke legacy protocol number); 5R01HD111018-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data transfer will take place via Secure File Transfer Protocol (SFTP). Sub-agreements which cover data and sample sharing and confidentiality is in place.
• IPD Sharing Time Frame: December 2024 to December 2027

IPD Sharing Access Criteria

During the Opti-NuM project the following institutions will be involved in data and sample analysis as indicated. Data sharing will take place through SFTP, bio specimens will be shipped for analyses.

• The Hospital for Sick Children (Lead, Deborah O'Connor PhD RD): Both data and sample analysis
• The University of Toronto (Lead, Deborah O'Connor PhD RD): Both data and sample analysis
• The University of Manitoba (Lead, Meghan Azad PhD): Data analysis; No sample analysis
• Stanford University (Lead, Nima Aghaeepour PhD): Data analysis; No sample analysis
• University of California (Lead, Lars Bode PhD): Oligosaccharide analysis of human milk samples only. No data provided to this site.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

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