Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001078347
Ethics application status
Approved
Date submitted
20/07/2017
Date registered
25/07/2017
Date last updated
17/01/2023
Date data sharing statement initially provided
17/01/2023
Date results information initially provided
17/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Fish oil in pregnancy for a healthy start to life for the children of overweight mothers
Scientific title
Double-blind RCT of fish oil supplementation in pregnancy and lactation to improve metabolic health in the children of mothers with overweight or obesity
Secondary ID [1] 292470 0
None
Universal Trial Number (UTN)
U1111-1199-5860
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Maternal obesity 304095 0
Childhood obesity 304096 0
Metabolic dysfunction in childhood 304097 0
Condition category
Condition code
Metabolic and Endocrine 303432 303432 0 0
Other metabolic disorders
Diet and Nutrition 303457 303457 0 0
Obesity
Reproductive Health and Childbirth 303479 303479 0 0
Antenatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
6 x 1g capsules of n-3 PUFA rich fish oil will be taken on each day of pregnancy and for 3 months during the breastfeeding period. Note that if the mother chooses to stop breastfeeding then supplementation will stop early, this will be at birth if the mother decides not to breastfeed at all. Compliance will be assessed by return of unused capsules, and secondarily by measurement of n-3 PUFA levels in maternal red blood cells. Note that the expected concentration of n-3 PUFAs in this oil is 33% EPA/22% DHA, but this will be independently verified. The expected dose of n-3 PUFAs (EPA and DHA) is 3g/day.
Intervention code [1] 298655 0
Treatment: Other
Intervention code [2] 298671 0
Prevention
Comparator / control treatment
6 grams of olive oil taken in capsules on each day of pregnancy and for 3 months during the breastfeeding period (if the mother chooses to breastfeed)
Control group
Placebo

Outcomes
Primary outcome [1] 302811 0
Whole body percentage body fat (excluding head), as measured by dual x-ray absorptiometry (DXA) scan (in the offspring)
Timepoint [1] 302811 0
2 weeks of age
Secondary outcome [1] 337124 0
Birth Weight, measured in the delivery room using an infant scale
Timepoint [1] 337124 0
At birth
Secondary outcome [2] 337127 0
Whole body percentage body fat (excluding head), as measured by dual x-ray absorptiometry (DXA) scan (in the offspring)
Timepoint [2] 337127 0
at 3 months of age
Secondary outcome [3] 337128 0
Calculated from insulin and glucose measured from a fasting blood sample.
Timepoint [3] 337128 0
3 months of age
Secondary outcome [4] 337129 0
Weight measured using an infant scale
Timepoint [4] 337129 0
2 weeks, 3 months and 12 months of age
Secondary outcome [5] 337130 0
HOMA-IR calculated from maternal fasting insulin and glucose concentration
Timepoint [5] 337130 0
At 30 weeks of pregnancy
Secondary outcome [6] 337177 0
Ponderal index in the offspring calculated from length and weight
Timepoint [6] 337177 0
2 weeks, 3 months and 12 months of age
Secondary outcome [7] 337178 0
Insulin sensitivity as determined by a modified IVGTT with minimal modelling (offspring)
Timepoint [7] 337178 0
4-7 years of age
Secondary outcome [8] 417592 0
Hair cortisol measurement
Timepoint [8] 417592 0
2 weeks of infant age
Secondary outcome [9] 417593 0
Stool sample from infant for microbiome analysis
Timepoint [9] 417593 0
2 weeks of age
Secondary outcome [10] 417594 0
Whole body percentage body fat of the infant measured by bioimpedance spectroscopy analysis
Timepoint [10] 417594 0
12 months
Secondary outcome [11] 417595 0
Complementary food frequency questionnaire to assess infant feeding patterns
Timepoint [11] 417595 0
12 months
Secondary outcome [12] 417596 0
HOMA-IR calculated from glucose and insulin concentration in umbilical cord blood, sample taken by the lead maternal carer at birth.
Timepoint [12] 417596 0
Birth
Secondary outcome [13] 417597 0
Maternal body mass index calculated from height and weight (weight measured using a Wedderburn digital scale, height measured using a Harpenden stadiometer)
Timepoint [13] 417597 0
30 weeks of gestation, 2 weeks after birth and 3 months after birth.
Secondary outcome [14] 417598 0
Maternal blood pressure (sitting), systolic and diastolic. It will be measured using an automatic oscillometric sphygmomanometer.
Timepoint [14] 417598 0
30 weeks of pregnancy as well as 2 weeks and 3 months
Secondary outcome [15] 417599 0
Dietary PUFA intake using the New Zealand PUFA semi-quantitative food frequency questionnaire (for the mother)
Timepoint [15] 417599 0
30 weeks of pregnancy, 2 weeks and 3 months of infant age.
Secondary outcome [16] 417600 0
Edinburgh Postnatal Depression Scale (for the mother)
Timepoint [16] 417600 0
30 weeks of gestation, 2 weeks, 3 months and 12 months of infant age
Secondary outcome [17] 417601 0
International Physical Activity Questionnaire Long Form (for the mother)
Timepoint [17] 417601 0
30 weeks of gestation, 2 weeks and 3 months of infant age.
Secondary outcome [18] 417602 0
SF12 Health Related Quality of Life questionnaire (for the mother)
Timepoint [18] 417602 0
30 weeks of gestation, 2 weeks and 3 months of infant age.
Secondary outcome [19] 417603 0
Breast milk analysis for EPA + DHA concentration (a composite outcome)
Timepoint [19] 417603 0
2 weeks and 3 months of infant age.
Secondary outcome [20] 417604 0
Birth Length, measured using a paper tape measure.
Timepoint [20] 417604 0
At birth
Secondary outcome [21] 417605 0
Birth Head Circumference, measured using a paper tape measure
Timepoint [21] 417605 0
At birth
Secondary outcome [22] 417606 0
Birth Body Mass Index Calculated from Birth Length and Weight. Birth length and weight will be extracted from the infant Well Child Book, or the Birth discharge summary. Both will have been measured by the health staff involved in the routine initial care/assessment of the child, e.g. the midwife, hospital nurse, or paediatric doctor. It is expected that length will have been measured supine using a paper tape measure, while weight will be assessed using digital scales.
Timepoint [22] 417606 0
At Birth
Secondary outcome [23] 417607 0
Infant triglyceride concentration measured in fasting blood
Timepoint [23] 417607 0
3 months of infant age
Secondary outcome [24] 417608 0
Infant length measured using a lying neonatometer (at 2 weeks and 3 months) and a lying infantometer (at 12 months) of age.
Timepoint [24] 417608 0
2 weeks, 3 months, 12 months of infant age
Secondary outcome [25] 417609 0
Infant head circumference measured using a paper tape measure
Timepoint [25] 417609 0
2 weeks, 3 months, 12 months of infant age
Secondary outcome [26] 417610 0
Abdominal circumference measured using a paper tape measure
Timepoint [26] 417610 0
2 weeks, 3 months, 12 months of infant age
Secondary outcome [27] 417611 0
Infant body mass index calculated from length and weight.
Length will be measured using a neonatometer or infant stadiometer. Weight will be measured using digital scales.
Timepoint [27] 417611 0
2 weeks, 3 months and 12 months of infant age
Secondary outcome [28] 417612 0
Chest circumference measured using a paper tapemeasure
Timepoint [28] 417612 0
12 months of infant age
Secondary outcome [29] 417613 0
Mid-arm circumference measured using a paper tape measure
Timepoint [29] 417613 0
12 months of age
Secondary outcome [30] 417614 0
Triceps skinfold thickness measured using a Holtain skin fold caliper
Timepoint [30] 417614 0
12 months of infant age
Secondary outcome [31] 417615 0
Subscapular skinfold thickness measured using a Holtain skin fold caliper.
Timepoint [31] 417615 0
12 months of age
Secondary outcome [32] 417616 0
Maternal fasting glucose concentration
Timepoint [32] 417616 0
30 weeks of pregnancy
Secondary outcome [33] 417617 0
maternal fasting insulin concentration
Timepoint [33] 417617 0
30 weeks of pregnancy
Secondary outcome [34] 417618 0
maternal fasting triglyceride concentration
Timepoint [34] 417618 0
30 weeks of pregnancy
Secondary outcome [35] 417619 0
Maternal HbA1c from blood
Timepoint [35] 417619 0
30 weeks of pregnancy
Secondary outcome [36] 417620 0
omega-3 index measured from maternal red blood cells
Timepoint [36] 417620 0
30 weeks of pregnancy
Secondary outcome [37] 417621 0
Umbilical cord blood omega-3 index from red blood cells. This will be measured in a cord blood sample taken by the lead maternal carer at the time of birth.
Timepoint [37] 417621 0
Birth
Secondary outcome [38] 417622 0
Umbilical cord blood c-peptide concentration. Measured from a cord blood sample taken by the lead maternal carer at birth.
Timepoint [38] 417622 0
Birth

Eligibility
Key inclusion criteria
Pregnant women, with BMI >=25, singleton pregnancy, between 12-20 weeks of gestation
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Current use of tobacco or nicotine, illicit drugs or medications that influence blood pressure, lipid metabolism or insulin sensitivity. Having diabetes mellitus or chronic illnesses such as autoimmune disease or malignancy.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will involve contacting the holder of the allocation schedule who is not involved in recruitment, carrying out or analyzing the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
A previous update stated "Women who develop gestational diabetes will exit the study at the time of diagnosis of GDM and will not have any further assessments of themselves or their baby". This has been reversed. Women who develop gestational diabetes will not exit the study. Their babies will still receive all assessments and be included in the final analysis
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Treatment evaluation will be based on intention to treat. General linear regression models will be used to evaluate the treatment effect on the primary outcome and other offspring measures between the two treatment groups, adjusting for maternal age, BMI and parity at study entry, gestational age at birth, and offspring sex and age. Statistical analyses will be performed in SAS v9.4 (SAS Institute Inc., Cary, NC, USA). Statistical tests will be two-tailed and significance maintained at 5%, without adjustment for multiple testing. Missing data will be imputed for analysis of the primary outcome. Secondary analyses of data for which there are multiple measures over time e.g infant auxology and body composition, will use linear mixed models based on repeated measures.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/03/2018
Actual
29/03/2018
Date of last participant enrolment
Anticipated
1/10/2018
Actual
2/02/2020
Date of last data collection
Anticipated
1/04/2026
Actual
Sample size
Target
160
Accrual to date
Final
129
Recruitment outside Australia
Country [1] 9067 0
New Zealand
State/province [1] 9067 0
Auckland

Funding & Sponsors
Funding source category [1] 297036 0
Government body
Name [1] 297036 0
A Better Start National Science Challenge, Funded by the Ministry of Business, Innovation and Employment
Country [1] 297036 0
New Zealand
Funding source category [2] 297041 0
Charities/Societies/Foundations
Name [2] 297041 0
Cure Kids
Country [2] 297041 0
New Zealand
Funding source category [3] 297042 0
Government body
Name [3] 297042 0
Health Research Council
Country [3] 297042 0
New Zealand
Primary sponsor type
University
Name
Liggins Institute, University of Auckland
Address
Private bag 92019
Victoria Street West
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 296040 0
None
Name [1] 296040 0
None
Address [1] 296040 0
None
Country [1] 296040 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298221 0
Health and Disability Ethics Committees (New Zealand)
Ethics committee address [1] 298221 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 298221 0
New Zealand
Date submitted for ethics approval [1] 298221 0
01/08/2017
Approval date [1] 298221 0
03/10/2017
Ethics approval number [1] 298221 0

Summary
Brief summary
In New Zealand the majority of men (71%) and women (60%) are now overweight or obese. Obesity leads to cardiovascular disease, type 2 diabetes and some cancers, which are among the world’s greatest health problems. Within NZ, Maori, Pasifika and those who are poorer are more greatly affected.

Most women of reproductive age are also overweight or obese (60%). This is important as the offspring of women who are obese have alterations in the way their metabolism works that increase the chance that they will be a large baby, become overweight and eventually develop diabetes and cardiovascular disease. When these babies are born, they are already at a health disadvantage. The underlying problem is that insulin, the hormone that controls blood sugar works less well in their bodies.

I have shown in rats, that supplementing obese mothers with fish oil can prevent the offspring from developing problems with insulin action as they age. If this treatment had the same effect in humans, pregnant women could use it to reduce their unborn child’s lifetime risk of disease. This is a treatment that is already easily available in stores, so that it would be easy for women to take up.

We will enrol women into a clinical trial where they are randomised to take either fish oil, or a placebo (capsules with ordinary olive oil) on every day of pregnancy and the first 3 months of breastfeeding. When the baby is born we will measure its body fat using a special scan (at two weeks of age). We will reassess the baby again at 3 months and 12 months of age. We will keep in contact over time, and when the child is 4-7 years old we will perform a detailed assessment of the child’s metabolism, including assessing insulin action.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76386 0
Dr Benjamin Albert
Address 76386 0
Liggins Institute, University of Auckland
Private Bag 92019
Victoria Street West
Auckland 1142
Country 76386 0
New Zealand
Phone 76386 0
+64 9 923 6691
Fax 76386 0
+64 9 373 8763
Email 76386 0
[email protected]
Contact person for public queries
Name 76387 0
Dr Benjamin Albert
Address 76387 0
Liggins Institute, University of Auckland
Private Bag 92019
Victoria Street West
Auckland 1142
Country 76387 0
New Zealand
Phone 76387 0
+64 9 923 6691
Fax 76387 0
+64 9 373 8763
Email 76387 0
[email protected]
Contact person for scientific queries
Name 76388 0
Dr Benjamin Albert
Address 76388 0
Liggins Institute, University of Auckland
Private Bag 92019
Victoria Street West
Auckland 1142
Country 76388 0
New Zealand
Phone 76388 0
+64 9 923 6691
Fax 76388 0
+64 9 373 8763
Email 76388 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The written consent form approved by the HDEC ethics committee and signed by all participants did not grant permission to publish individual participant data. Permission was granted for anonymised group analyses, which will be published in scientific journals


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18063Study protocolSatokar VV, Cutfield WS, Derraik JG, Harwood M, Okasene-Gafa K, Beck K, Cameron-Smith D, O’Sullivan JM, Sundborn G, Pundir S, Mason RP. Double-blind RCT of fish oil supplementation in pregnancy and lactation to improve the metabolic health in children of mothers with overweight or obesity during pregnancy: study protocol. BMJ open. 2020 Dec 1;10(12):e041015.https://bmjopen.bmj.com/content/10/12/e041015.abstract  373332-(Uploaded-13-01-2023-08-19-37)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFish oil supplementation during pregnancy and postpartum in mothers with overweight and obesity to improve body composition and metabolic health during infancy: A double-blind randomized controlled trial.2023https://dx.doi.org/10.1016/j.ajcnut.2023.02.007
EmbaseDouble-blind RCT of fish oil supplementation in pregnancy and lactation to improve the metabolic health in children of mothers with overweight or obesity during pregnancy: Study protocol.2020https://dx.doi.org/10.1136/bmjopen-2020-041015
N.B. These documents automatically identified may not have been verified by the study sponsor.