Clinical trial NCT02371460: Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia
Official title: Maternal Omega-3 Supplementation to Reduce BronchopulmonarY Dysplasia in Very Preterm Infants (MOBYDIck Trial)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia
Child Development
Neonatal and Perinatal Conditions
Keywords: Neonatal Prematurity
Omega-3 Fatty Acids
Breastfeeding
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Laval University
First posted: 2015-02-25
Enrollment: 800
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: BPD-free survival
timeFrame: at 36 weeks PMA
Secondary outcomes:
measure: Mortality
timeFrame: until 36 weeks PMA
measure: Bronchopulmonary Dysplasia (BPD)
timeFrame: at 36 weeks PMA
measure: Mild, moderate and severe BPD
timeFrame: at 36 weeks PMA
measure: Necrotizing enterocolitis stage 2 or greater
timeFrame: until first discharge home or 40 weeks PMA
measure: Any intraventricular hemorrhage and severe grade III or IV
timeFrame: from randomization until discharge home or 40 weeks PMA
measure: Periventricular leucomalacia
timeFrame: until discharge home or 40 weeks PMA
measure: Sepsis
timeFrame: until discharge home or 40 weeks PMA
measure: Retinopathy of prematurity (any or threshold)
timeFrame: until first discharge home or 40 weeks PMA
measure: Patent ductus arterious
timeFrame: until first discharge home or 40 weeks PMA
measure: Significant cholestasis
timeFrame: until first discharge home or 36 weeks PMA
measure: Child anthropometry
timeFrame: until first discharge home or 36 weeks PMA
measure: Neuro-development
timeFrame: at 18-22 months corrected age (CA)
Other outcomes:
measure: Supplemental Oxygen
timeFrame: at 36 weeks PMA
measure: Duration of supplemental oxygen or respiratory support
timeFrame: until first discharge home or 36 weeks PMA
measure: Hospitalization duration
timeFrame: until first discharge home or 40 weeks PMA
measure: Cerebral palsy
timeFrame: at 18-22 months CA
measure: Child anthropometry
timeFrame: at 18-22 months CA
measure: Deafness
timeFrame: until 18-22 months CA
measure: Blindness (yes/no), visual acuity +/- strabismus
timeFrame: until 18-22 months CA
measure: Death since 40weeks
timeFrame: from first discharge or 40 weeks PMA until 18-22 months CA
measure: Number of hospital readmissions
timeFrame: From first discharge until 18-22 months CA
measure: Respiratory morbidities
timeFrame: until 18-22 months CA
measure: Maternal Satisfaction
timeFrame: at 36 weeks PMA
measure: Maternal significant episodes of bleeding requiring treatment or hospitalization until 4 weeks post intervention
timeFrame: from date of randomization up to 40 weeks PMA
measure: Acceptability of a study at 8 years of age involving brain magnetic resonance imaging (MRI)
timeFrame: at 60 months CA
measure: Child health-related quality of life
timeFrame: at 60 months CA
measure: Behavioral problems
timeFrame: at 60 months CA
measure: Executive function
timeFrame: at 60 months CA
measure: Global developmental delay
timeFrame: at 60 months CA
measure: Exposure and impact of the COVID-19 pandemic
timeFrame: at 60 months CA
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexander Hospital
state: Alberta
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Children's and Women's Health Centre of British Columbia
state: British Columbia
city: Victoria
country: Canada
facility: Victoria General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St Boniface General Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston Health Science Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center, Glen Site, Montreal Children's Hospital
state: Quebec
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Centre
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec-Université Laval, Centre Mère Enfant Soleil du CHUL
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: CHU de Québec, Université Laval
name: Isabelle Marc, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's and Women's Health Centre of BC, University of British Columbia
name: Pascal Lavoie, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Sainte-Justine, Université de Montreal
name: Benoît Mâsse, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Eastern Ontario, University of Ottawa
name: Thierry Lacaze, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Sainte-Justine, Université de Montreal
name: Anne-Monique Nuyt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Université de Sherbrooke
name: William Fraser, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.