Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia (MOBYDIck)

Maternal Omega-3 Supplementation to Reduce BronchopulmonarY Dysplasia in Very Preterm Infants (MOBYDIck Trial)

The aim of this randomized controlled trial is to determine whether docosahexaenoic acid (or DHA, an omega-3 lipid) supplementation in lactating mothers providing breast-milk to their infant born below 29 0/7 weeks of gestational age (GA) improves BPD-free survival at 36 weeks post-menstrual age (PMA). Half of participants will receive docosahexaenoic acid (DHA), an omega-3 lipid, while the other half will receive a placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Child Development; Bronchopulmonary Dysplasia; Neonatal and Perinatal Conditions
• Intervention / Treatment: Dietary supplement: DHA-rich algal oil; Combination product: Placebo

Detailed Description

Every year in Canada, 1500 babies who are born early (prematurely) develop a serious lung disease called bronchopulmonary dysplasia (BPD). BPD causes major health problems in these infants, especially in their early childhood. In most situations, breast-milk is the ideal source of nutrition for growth and development of premature babies. However, diets of Canadian mothers are generally deficient in omega-3 lipids (essential fats), resulting in lower protection from these omega-3 lipids in mother's milk-fed infants. Previous research has shown that giving DHA to mothers of premature babies is safe both for the mother and for their baby, and is an efficient way of helping babies meet their dietary requirements from breast-milk. Furthermore, this previous research also suggests that this intervention may reduce the risk of BPD in premature babies receiving breast-milk.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
    • Edmonton, Alberta, Canada, T5H 3V9
      • Royal Alexander Hospital
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Royal Columbian Hospital
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's and Women's Health Centre of British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Victoria General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St Boniface General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Science Centre
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center, Glen Site, Montreal Children's Hospital
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Centre
    • Québec, Quebec, Canada, G1V 4G2
      • CHU de Québec-Université Laval, Centre Mère Enfant Soleil du CHUL
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age more than or equal to 16 years
2. Pre-term delivery (230/7- 286/7 weeks gestation)
3. No contraindication to breastfeeding
4. Subject intends to provide own breast milk to infant
5. Randomization before or at 72 hours post delivery

Exclusion Criteria:

MOTHERS

1. Mother is taking > 250 mg of daily DHA supplementation for last 3 months
2. Mother who is currently enrolled or has participated in another clinical trial in which she had received an investigational drug or intervention within 3 months of the date of randomization (unless approved by the Trial Coordinating Centre)
3. Inability to comprehend and comply with study requirements
4. Participation in this study in a previous pregnancy

INFANTS

1. Significant congenital malformations in the infant (or one of the infants in case of multiple pregnancy)
2. Infant (or one of the infants in case of multiple pregnancy) who is currently enrolled in another clinical trial (unless approved by the Trial Coordinating Centre)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DHA-rich algal oil; 1200mg DHA per day	Dietary supplement: DHA-rich algal oil; Mothers will receive a DHA-rich algal oil treatment (400 mg DHA per capsule) three times a day before meals from randomization (<72 hours post-delivery) until the infant reaches 36 weeks PMA.; Other Names: DHA group
Placebo Comparator: Placebo; No supplementation in DHA	Combination product: Placebo; Mothers will receive a placebo capsule three times a day before meals from randomization (<72 hours post-delivery) until the infant reaches 36 weeks PMA.; Other Names: Placebo group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BPD-free survival	Defined as (1- combined rate of mortality and BPD in survivors). Mortality is defined as death from any cause between randomization and 36 weeks PMA. Physiological BPD is defined as the need for oxygen and/or ventilation at 36 weeks	at 36 weeks PMA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality is defined as death from any cause.	until 36 weeks PMA
Bronchopulmonary Dysplasia (BPD)	Physiological BPD is defined as the need for oxygen and/or ventilation at 36 weeks	at 36 weeks PMA
Mild, moderate and severe BPD	Defined according to the severity-based National Institute of Child Health & Development (NICHD) criteria	at 36 weeks PMA
Necrotizing enterocolitis stage 2 or greater	According to Bell criteria	until first discharge home or 40 weeks PMA
Any intraventricular hemorrhage and severe grade III or IV	According to Papile's classification; Screening is performed as routine care;	from randomization until discharge home or 40 weeks PMA
Periventricular leucomalacia	Screening is performed as routine care	until discharge home or 40 weeks PMA
Sepsis	Defined as culture-positive (blood or cerebrospinal fluid) and/or clinical infection (with antibiotics ≥5 days)	until discharge home or 40 weeks PMA
Retinopathy of prematurity (any or threshold)	According to the assessment by ophthalmologist, collected in the medical chart	until first discharge home or 40 weeks PMA
Patent ductus arterious	Requiring surgical ligation	until first discharge home or 40 weeks PMA
Significant cholestasis	Defined as conjugated serum bilirubin ≥34 µmol/L	until first discharge home or 36 weeks PMA
Child anthropometry	Weight, length and cranial circumference as routinely measured and collected in the chart	until first discharge home or 36 weeks PMA
Neuro-development	Defined as mean cognitive, language and motor composite scores of the Bayley Scale of Infant and Toddler Development's third edition (Bayley-III)	at 18-22 months corrected age (CA)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supplemental Oxygen	Defined as need for supplemental oxygen (mL/min flow or FiO2)	at 36 weeks PMA
Duration of supplemental oxygen or respiratory support	Defined as cumulative days on supplemental oxygen or respiratory support	until first discharge home or 36 weeks PMA
Hospitalization duration	Defined as number of days in hospital	until first discharge home or 40 weeks PMA
Cerebral palsy	will be ascertained using standard definitions and severity classified using the Gross Motor Function Classification System	at 18-22 months CA
Child anthropometry	Weight, length and cranial circumference	at 18-22 months CA
Deafness	Hearing tests will be performed by audiologists according to standard practice	until 18-22 months CA
Blindness (yes/no), visual acuity +/- strabismus	According to ophthalmologist or orthoptist examination	until 18-22 months CA
Death since 40weeks	Any cause	from first discharge or 40 weeks PMA until 18-22 months CA
Number of hospital readmissions	Assessment by standardized interview	From first discharge until 18-22 months CA
Respiratory morbidities	Physical examination will be performed by a pediatrician and a standardized general health questionnaire (including respiratory health outcomes) will be completed. Respiratory health outcomes will include respiratory symptoms, hospital admissions for respiratory deteriorations, use of inhaled therapies.	until 18-22 months CA
Maternal Satisfaction	Assessment by a questionnaire	at 36 weeks PMA
Maternal significant episodes of bleeding requiring treatment or hospitalization until 4 weeks post intervention	Assessment by standardized interview	from date of randomization up to 40 weeks PMA
Acceptability of a study at 8 years of age involving brain magnetic resonance imaging (MRI)	Semistructured interviews framed using the theoretical domains framework will be conducted to identify potential barriers and facilitators that may influence participation in a follow-up study with brain MRI at 8 years of age. A subsample of n=194 children will be eligible to participate if they have not died or withdrawn from the trial and if they were born and enrolled at the following centres: CHU de Québec-Université Laval; Centre Hospitalier Universitaire de Sherbrooke, CHUS; CHU Sainte-Justine; Jewish General Centre; McGill University Health Center, Glen Site, Montreal Children's Hospital	at 60 months CA
Child health-related quality of life	Assessed by the Pediatric Quality of Life Inventory (PedsQL). A subsample of n=194 children will be eligible to participate if they have not died or withdrawn from the trial and if they were born and enrolled at the following centres: CHU de Québec-Université Laval; Centre Hospitalier Universitaire de Sherbrooke, CHUS; CHU Sainte-Justine; Jewish General Centre; McGill University Health Center, Glen Site, Montreal Children's Hospital	at 60 months CA
Behavioral problems	Assessed by the Total Difficulties scores, Externalizing and Internalizing scores of the Strengths and Difficulties Questionnaire. A subsample of n=194 children will be eligible to participate if they have not died or withdrawn from the trial and if they were born and enrolled at the following centres: CHU de Québec-Université Laval; Centre Hospitalier Universitaire de Sherbrooke, CHUS; CHU Sainte-Justine; Jewish General Centre; McGill University Health Center, Glen Site, Montreal Children's Hospital	at 60 months CA
Executive function	Assessed by the Global executive composite score of the Behavior Rating Inventory of Executive Function - Preschool. A subsample of n=194 children will be eligible to participate if they have not died or withdrawn from the trial and if they were born and enrolled at the following centres: CHU de Québec-Université Laval; Centre Hospitalier Universitaire de Sherbrooke, CHUS; CHU Sainte-Justine; Jewish General Centre; McGill University Health Center, Glen Site, Montreal Children's Hospital	at 60 months CA
Global developmental delay	Assessed by the 5 developmental areas of the Ages and Stages Questionnaire. A subsample of n=194 children will be eligible to participate if they have not died or withdrawn from the trial and if they were born and enrolled at the following centres: CHU de Québec-Université Laval; Centre Hospitalier Universitaire de Sherbrooke, CHUS; CHU Sainte-Justine; Jewish General Centre; McGill University Health Center, Glen Site, Montreal Children's Hospital	at 60 months CA
Exposure and impact of the COVID-19 pandemic	Impact on the home environment, quality of life, development and behavioral and executive functioning. A subsample of n=194 children will be eligible to participate if they have not died or withdrawn from the trial and if they were born and enrolled at the following centres: CHU de Québec-Université Laval; Centre Hospitalier Universitaire de Sherbrooke, CHUS; CHU Sainte-Justine; Jewish General Centre; McGill University Health Center, Glen Site, Montreal Children's Hospital	at 60 months CA

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Collaborators: Canadian Institutes of Health Research (CIHR); Laval University
• Investigators: Principal Investigator: Isabelle Marc, MD, PhD, CHU de Québec, Université Laval; Principal Investigator: Pascal Lavoie, MD, PhD, Children's and Women's Health Centre of BC, University of British Columbia; Principal Investigator: Benoît Mâsse, PhD, CHU Sainte-Justine, Université de Montreal; Principal Investigator: Thierry Lacaze, MD, PhD, Children's Hospital of Eastern Ontario, University of Ottawa; Principal Investigator: Anne-Monique Nuyt, MD, PhD, CHU Sainte-Justine, Université de Montreal; Principal Investigator: William Fraser, MD, MSc, Universite de Sherbrooke

Publications and helpful links

General Publications

• Fougere H, Bilodeau JF, Lavoie PM, Mohamed I, Rudkowska I, Pronovost E, Simonyan D, Berthiaume L, Guillot M, Piedboeuf B, Julien P, Marc I. Docosahexaenoic acid-rich algae oil supplementation on breast milk fatty acid profile of mothers who delivered prematurely: a randomized clinical trial. Sci Rep. 2021 Nov 2;11(1):21492. doi: 10.1038/s41598-021-01017-8.
• Ndiaye ABKT, Mohamed I, Pronovost E, Angoa G, Piedboeuf B, Lemyre B, Afifi J, Qureshi M, Series T, Guillot M, Simonyan D, Yusuf K, Lavoie PM, Fraser WD, Masse B, Nuyt AM, Lacaze-Masmonteil T, Marc I. Use of SMOF lipid emulsion in very preterm infants does not affect the incidence of bronchopulmonary dysplasia-free survival. JPEN J Parenter Enteral Nutr. 2022 Nov;46(8):1892-1902. doi: 10.1002/jpen.2380. Epub 2022 May 8.
• Angoa G, Pronovost E, Ndiaye ABKT, Lavoie PM, Lemyre B, Mohamed I, Simonyan D, Qureshi M, Afifi J, Yusuf K, Series T, Guillot M, Piedboeuf B, Fraser WD, Nuyt AM, Masse B, Lacaze-Masmonteil T, Marc I. Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial. Neonatology. 2022;119(3):377-385. doi: 10.1159/000524147. Epub 2022 Apr 12.
• Guillot M, Synnes A, Pronovost E, Qureshi M, Daboval T, Caouette G, Olivier F, Bartholomew J, Mohamed I, Masse E, Afifi J, Hendson L, Lemyre B, Luu TM, Strueby L, Cieslak Z, Yusuf K, Pelligra G, Ducruet T, Ndiaye ABKT, Angoa G, Series T, Piedboeuf B, Nuyt AM, Fraser W, Masse B, Lacaze-Masmonteil T, Lavoie PM, Marc I. Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children. Pediatrics. 2022 Jul 1;150(1):e2021055819. doi: 10.1542/peds.2021-055819.
• Guillot M, Robitaille CA, Turner L, Pronovost E, Caouette G, Matte-Gagne C, Olivier F, Bartholomew J, Masse E, Morin A, Mohamed I, Marc I. Effects of maternal docosahexaenoic acid supplementation on brain development and neurodevelopmental outcomes of breastfed preterm neonates: protocol for a follow-up at preschool age of a randomised clinical trial (MOBYDIckPS). BMJ Open. 2022 May 4;12(5):e057482. doi: 10.1136/bmjopen-2021-057482.
• Marc I, Piedboeuf B, Lacaze-Masmonteil T, Fraser W, Masse B, Mohamed I, Qureshi M, Afifi J, Lemyre B, Caouette G, Bartholomew J, Nuyt AM, Julien P, Synnes A, Lucas M, Perreault T, Strueby L, Cieslak Z, Yusuf K, Pelligra G, Masse E, Larsen B, de Cabo C, Ruth C, Khurshid F, Lavoie PM. Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial. JAMA. 2020 Jul 14;324(2):157-167. doi: 10.1001/jama.2020.8896.
• Fougere H, Greffard K, Guillot M, Rudkowska I, Pronovost E, Simonyan D, Marc I, Bilodeau JF. Docosahexaenoic acid-rich algae oil supplementation in mothers of preterm infants is associated with a modification in breast milk oxylipins profile. Lipids Health Dis. 2023 Jul 14;22(1):103. doi: 10.1186/s12944-023-01870-8.
• Series T, Guillot M, Angoa G, Pronovost E, Ndiaye ABKT, Mohamed I, Simonyan D, Lavoie PM, Synnes A, Marc I; MOBYDIck trial group. Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm? J Pediatr. 2023 Sep;260:113531. doi: 10.1016/j.jpeds.2023.113531. Epub 2023 Jun 1.
• Marc I, Julien P, Lavoie PM. Maternal Docosahexaenoic Acid Supplementation and Bronchopulmonary Dysplasia in Infants-Reply. JAMA. 2020 Nov 24;324(20):2105. doi: 10.1001/jama.2020.19410. No abstract available.
• Paquet SP, Pronovost E, Simonyan D, Caouette G, Matte-Gagne C, Olivier F, Bartholomew J, Morin A, Mohamed I, Marc I, Guillot M. Maternal high-dose docosahexaenoic acid supplementation and neurodevelopment at 5 Years of preterm children. Clin Nutr ESPEN. 2024 Dec;64:253-262. doi: 10.1016/j.clnesp.2024.09.029. Epub 2024 Oct 11.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2015
• Primary Completion (Actual): April 25, 2019
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 19, 2015
• First Submitted That Met QC Criteria: February 19, 2015
• First Posted (Estimated): February 25, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Breastfeeding; Omega-3 Fatty Acids; Neonatal Prematurity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia
• Other Study ID Numbers: 2015-2144, B14-09-2144-21; MOP-136964 (Other Grant/Funding Number: Canadian Institutes of Health Research (CIHR))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO