Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia

Child Development Clinical Trial

— MOBYDIck  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02371460
• Other study ID #: 2015-2144, B14-09-2144-21
• Secondary ID: MOP-136964
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 23, 2015
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: CHU de Quebec-Universite Laval
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 800
• Est. completion date: March 2025
• Est. primary completion date: April 25, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Child Development
• Neonatal and Perinatal Conditions

Intervention

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.

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.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Royal Alexander Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Kingston Health Science Centre	Kingston	Ontario
Canada	McGill University Health Center, Glen Site, Montreal Children's Hospital	Montreal	Quebec
Canada	CHU Sainte-Justine	Montréal	Quebec
Canada	Jewish General Centre	Montréal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	CHU de Québec-Université Laval, Centre Mère Enfant Soleil du CHUL	Québec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Children's and Women's Health Centre of British Columbia	Vancouver	British Columbia
Canada	Victoria General Hospital	Victoria	British Columbia
Canada	Health Sciences Centre	Winnipeg	Manitoba
Canada	St Boniface General Hospital	Winnipeg	Manitoba

Sponsors (3)

Lead Sponsor	Collaborator
CHU de Quebec-Universite Laval	Canadian Institutes of Health Research (CIHR), Laval University

Country where clinical trial is conducted

Canada, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Supplemental Oxygen	Defined as need for supplemental oxygen (mL/min flow or FiO2)	at 36 weeks PMA
Other	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
Other	Hospitalization duration	Defined as number of days in hospital	until first discharge home or 40 weeks PMA
Other	Cerebral palsy	will be ascertained using standard definitions and severity classified using the Gross Motor Function Classification System	at 18-22 months CA
Other	Child anthropometry	Weight, length and cranial circumference	at 18-22 months CA
Other	Deafness	Hearing tests will be performed by audiologists according to standard practice	until 18-22 months CA
Other	Blindness (yes/no), visual acuity +/- strabismus	According to ophthalmologist or orthoptist examination	until 18-22 months CA
Other	Death since 40weeks	Any cause	from first discharge or 40 weeks PMA until 18-22 months CA
Other	Number of hospital readmissions	Assessment by standardized interview	From first discharge until 18-22 months CA
Other	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
Other	Maternal Satisfaction	Assessment by a questionnaire	at 36 weeks PMA
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	Mortality	Mortality is defined as death from any cause.	until 36 weeks PMA
Secondary	Bronchopulmonary Dysplasia (BPD)	Physiological BPD is defined as the need for oxygen and/or ventilation at 36 weeks	at 36 weeks PMA
Secondary	Mild, moderate and severe BPD	Defined according to the severity-based National Institute of Child Health & Development (NICHD) criteria	at 36 weeks PMA
Secondary	Necrotizing enterocolitis stage 2 or greater	According to Bell criteria	until first discharge home or 40 weeks PMA
Secondary	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
Secondary	Periventricular leucomalacia	Screening is performed as routine care	until discharge home or 40 weeks PMA
Secondary	Sepsis	Defined as culture-positive (blood or cerebrospinal fluid) and/or clinical infection (with antibiotics =5 days)	until discharge home or 40 weeks PMA
Secondary	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
Secondary	Patent ductus arterious	Requiring surgical ligation	until first discharge home or 40 weeks PMA
Secondary	Significant cholestasis	Defined as conjugated serum bilirubin =34 µmol/L	until first discharge home or 36 weeks PMA
Secondary	Child anthropometry	Weight, length and cranial circumference as routinely measured and collected in the chart	until first discharge home or 36 weeks PMA
Secondary	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)