Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001250820
Ethics application status
Approved
Date submitted
3/08/2021
Date registered
15/09/2021
Date last updated
12/01/2023
Date data sharing statement initially provided
15/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of boosting breastmilk supply on maternal and infant health
Scientific title
Effect of evidence-based methods and measurement on breastfeeding duration and infant health.
Secondary ID [1] 305110 0
None
Universal Trial Number (UTN)
U1111-1267-7871
Trial acronym
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Low breastmilk production 322764 0
Overweight 322765 0
Obesity 322766 0
Diabetes Mellitus 322767 0
Gestational diabetes mellitus 322768 0
Polycystic Ovary Syndrome 322769 0
Intrauterine Growth Restriction 322771 0
Pre-eclampsia 322772 0
Hypertension 322773 0
Condition category
Condition code
Reproductive Health and Childbirth 320348 320348 0 0
Breast feeding
Reproductive Health and Childbirth 320349 320349 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 320350 320350 0 0
Fetal medicine and complications of pregnancy
Metabolic and Endocrine 320351 320351 0 0
Diabetes
Mental Health 320353 320353 0 0
Studies of normal psychology, cognitive function and behaviour
Metabolic and Endocrine 320356 320356 0 0
Other endocrine disorders
Reproductive Health and Childbirth 320521 320521 0 0
Antenatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention study protocol includes:
- Antenatal breastfeeding education to ensure frequent breastmilk removal postnatally to improve breastmilk production outcomes (De Carvalho, et al., 1982; Yamauchi & Yamanouchi, 1990). Individual education will be provided in late pregnancy (36 weeks onwards) by a current International Board Certified Lactation Consultant with over 10 years experience. It will be conducted during a routine 60 minute antenatal appointment at one of the four One for Women rooms in suburban Perth . Breastmilk removal will be promoted within 2 hours of birth and at least 8 times in 24 hours in the first two weeks postpartum. i.e. every 2 - 4 hours, no more than one 5 hour interval.
- If a participant is unable to directly breastfeed due to maternal or infant health issues or separation (neonatal nursery admission, mother very unwell, nipple pain, baby unable to latch or not feeding well) breastfeeds are to be replaced or supplemented with breast expression using a hospital grade pump. Participants in the intervention arm will be loaned a Medela Symphony pump, a hospital grade electric pump, in late pregnancy (i.e. from 36 weeks gestation ). This is to provide ease of access to a hospital grade pump if required after birth. It will be given at a One for Women antenatal appointment by either the attending Midwife, General Practitioner Obstetrician (GPO) or by the researcher an IBCLC. Detailed instructions via a hand-out will be given to participants with the pump, including when to use, how to use and how to clean the pump as well as on breastmilk storage and use. Any questions will be addressed at this time in addition participants will be given the contact e-mail address of the researcher (an IBCLC) to answer any further queries.
- Participants in the intervention arm will receive phone support every 3 - 4 days for 3 weeks postpartum as evidence concludes that phone calls improve perceived quality of postnatal care (Dennis & Kingston, 2008). The phone calls will be provided by a current International Board Certified Lactation Consultant (IBCLC) with over 10 years experience in the field of lactation. These will be personalised to address any particular concerns or challenges the participant is experiencing and provide consistent evidence based advice. The phone calls will not have time constraints applied and each call may take up to 30 to 60 minutes.
Intervention adherence will be assessed by participant data logging.

De Carvalho, M., Robertson, S., Merkatz, R., & Klaus, M. (1982). Milk intake and frequency of feeding in breast fed infants. Early Human Development, 7(2), 155-163.

Dennis, C., & Kingston, D. (2008). A systematic review of telephone support for women during pregnancy and the early postpartum period. Journal Obstetric Gynecological Neonatal Nursing, 37(3), 301-314.

Yamauchi, Y., & Yamanouchi, I. (1990). Breast-feeding frequency during the first 24 hours after birth in full-term neonates. Pediatrics, 86(2), 171–175.
Intervention code [1] 321109 0
Prevention
Intervention code [2] 321112 0
Treatment: Other
Comparator / control treatment
The control arm of the study will receive standard care this includes, antenatal breastfeeding education to ensure frequent breastmilk removal postnatally to improve breastmilk production outcomes (De Carvalho, et al., 1982; Yamauchi & Yamanouchi, 1990). Individual education will be provided in late pregnancy (36 weeks onwards) by a current International Board Certified Lactation Consultant with over 10 years experience. It will be conducted during a routine 60 minute antenatal appointment at one of the four One for Women rooms in suburban Perth . Breastmilk removal will be promoted within 2 hours of birth and at least 8 times in 24 hours in the first two weeks postpartum. i.e. every 2 - 4 hours, no more than one 5 hour interval.

The control arm participants will not be loaned a breast pump and will not receive regular phone support from an a current International Board Certified Lactation Consultant (IBCLC).

De Carvalho, M., Robertson, S., Merkatz, R., & Klaus, M. (1982). Milk intake and frequency of feeding in breast fed infants. Early Human Development, 7(2), 155-163.

Yamauchi, Y., & Yamanouchi, I. (1990). Breast-feeding frequency during the first 24 hours after birth in full-term neonates. Pediatrics, 86(2), 171–175.
Control group
Active

Outcomes
Primary outcome [1] 328203 0
Breastmilk production
Breastmilk production will be measured by using the test weigh method which is a well validated, established and published method developed and routinely utilised by the Hartmann Geddes Research Group at the University of Western Australia (UWA). Electronic scales (Baby Weigh scale, Medela AG, Switzerland, sensitive to 2 g) will be used. The participant will weigh the infant before and after each feed over a 24-hour period and the difference in grams is equivalent to millilitres of milk fed/removed. Data of each feed will be entered by the participants into the online clinical trials data platform Research Electronic Data Capture (REDcap) system. In addition to breastfeeds, breast expressions and bottle feeds (breastmilk/formula) will be recorded. Subsequent calculations of key variables will include feed frequency and duration, 24 hour volume fed by breast/bottle, 24 hour volume expressed, total 24 hour production.
Timepoint [1] 328203 0
2 weeks postpartum, 6 weeks postpartum (primary endpoint)
Secondary outcome [1] 398009 0
Breastmilk feeding patterns - composite of exclusivity and duration of breastmilk feeding (defined as the process of feeding a mothers breastmilk to her infant, either directly from the breast or by expressing the milk from the breast and bottle-feeding it to the infant).
In the first two postpartum weeks data will be collected from participant recordings of feeding patterns in the first using either a study specific daily feeding diary provided by the researchers or an application of the participants own choice. Data will also be collected at 2 weeks using information provided by an online study specific questionnaire administered by clinical trials data platform Research Electronic Data Capture (REDcap) system and from the 24 hour production study conducted at 2 weeks.
At 6 weeks data will be collected using information provided by an online study specific questionnaire administered by clinical trials data platform Research Electronic Data Capture (REDcap) system and from a 6 week 24 hour production study.
At 12, 24 and 52 weeks data will be collected using information provided by an online study specific questionnaire administered by clinical trials data platform Research Electronic Data Capture (REDcap) system.
Timepoint [1] 398009 0
2, 6, 12, 24, 52 weeks weeks postpartum.
Secondary outcome [2] 398022 0
Infant health - composite of incidence and duration of acute infant infections and allergies
Using data collected from an online study specific participant questionnaires via clinical trials data platform Research Electronic Data Capture (REDcap) system at 2, 6, 12, 24 and 52 weeks the relationships between breastfeeding duration and infant health will be explored. Any infant illness will be documented including symptoms, duration and medications taken for the condition.
Timepoint [2] 398022 0
2, 6, 12, 24, 52 weeks of infant life
Secondary outcome [3] 398023 0
Infant growth parameters - a composite of infant head circumference, weight and length.
Infant anthropometric data will be collected from the participants online via clinical trials data platform Research Electronic Data Capture (REDcap) system by study specific questionnaires at 2, 6, 12, 24 and 52 weeks. These anthropometric measurements will be compared to normal developmental milestones.
Timepoint [3] 398023 0
2, 6, 12, 24, 52 weeks of infant life
Secondary outcome [4] 398027 0
Maternal physical wellbeing will be assessed.
Data will be collected using an online study specific participant questionnaire administered by clinical trials data platform Research Electronic Data Capture (REDcap) system. Any maternal illness will be documented including symptoms, duration and medications taken for the condition.
Timepoint [4] 398027 0
At late pregnancy (from 36 weeks), then at 2, 6, 12, 24 and 52 weeks postpartum.
Secondary outcome [5] 398036 0
Maternal emotional wellbeing will be assessed using a combination of well-being surveys.
Data will be collected through validated maternal well-being questionnaires that will be administered via clinical trials data platform Research Electronic Data Capture (REDcap) system and each take less than 15 minutes to complete. These include:
- The Wellbeing survey
- The Perceived Stress Scale
- The McMaster Family Assessment Device
- The Mental Health Continuum - Short form
- The Infant Sleep Survey (applicable only in the postpartum period)
Timepoint [5] 398036 0
At late pregnancy (from 36 weeks), then at 2, 6, 12, 24 and 52 weeks postpartum.
Secondary outcome [6] 398802 0
Breastmilk composition will be analysed.
The initial breastmilk components to be examined will include lactose, casein, protein, citrate, potassium, sodium and zinc.
Breastmilk samples of 5 ml will be collected from each breast for composition analysis.
Timepoint [6] 398802 0
1,2 and 6 weeks postpartum
Secondary outcome [7] 398803 0
Breastmilk composition will be analysed.
Subject to additional research funding there may be further analysis of milk composition. The breastmilk components to be measured are the hormones, insulin, leptin and adiponectin.
Breastmilk samples of 5 ml will be collected from each breast for composition analysis.
Timepoint [7] 398803 0
1,2 and 6 weeks postpartum
Secondary outcome [8] 398804 0
Breastmilk composition will be analysed.
Subject to additional research funding there may be further analysis of milk composition. The breastmilk components to be measured are the immune proteins, lactoferrin, lysozyme, Secretory IgA by diagnostic assay ELISA (Enzyme linked immunosorbent assay).
Breastmilk samples of 5 ml will be collected from each breast for composition analysis.
Timepoint [8] 398804 0
1,2 and 6 weeks postpartum
Secondary outcome [9] 398805 0
Breastmilk composition will be analysed.
Subject to additional research funding there may be further analysis of milk composition. The breastmilk microbiome will be examined using 16S rRNA long amplicon sequencing.
Breastmilk samples of 5 ml will be collected from each breast for composition analysis.

Timepoint [9] 398805 0
1,2 and 6 weeks postpartum
Secondary outcome [10] 400115 0
Assess adequacy of breast milk removal from the breast.
During the breastmilk production study a small milk sample (<1ml) will be collected from each breast immediately before and after each breastfeed or expression for measurement of the cream content of the milk.

Timepoint [10] 400115 0
2 and 6 weeks postpartum.

Eligibility
Key inclusion criteria
To be eligible for the study participants must satisfy at least one or a combination of the following conditions.
- overweight defined by pre-pregnancy BMI 25 - 29.9
- obesity defined by pre-pregnancy BMI greater than or equal to 30
- pre-existing diabetes mellitus
- gestational diabetes mellitus (GDM)
- polycystic ovarian syndrome (PCOS)
- intrauterine growth restriction (IUGR)
- pregnancy induced hypertension
- preeclampsia
- previous history of low unexplained breastmilk supply

In addition participants must
- sign the RCT consent form
- be willing and able to comply with all study requirements, including intention to breastfeed for at least 6 months, timing and nature of required data collection and follow-up of mother and baby for 12 month period.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- preterm birth defined as births less than 37 completed weeks gestation
- infant syndromes or diseases that impact feeding
- previous breast surgery, including augmentation, reduction, breast lifts, nipple piercings and history of previous abscess requiring surgery/aspiration
- breast hypoplasia
- pituitary disorders
- contraindications to breastfeeding eg. HIV or mental health disorders where the participant is prescribed medication incompatible with breastfeeding
- multiple pregnancy (twins or more)
- non-English speaking women and those living outside the metropolitan area will not be recruited.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
180 women at high risk for low milk production will be recruited. 90 will be allocated to standard care and 90 will be allocated to the intervention. The sample size was calculated using the assumption that the researchers are looking for an increase in milk production like that of domperidone a medication used to increase milk production (based on a clinically meaningful difference of 100ml which is like an actual observed difference of 109ml) in the intervention group compared to the standard care group (Grzeskowiak et al., 2018).

Statistical analysis plan:
The primary outcomes will be assessed using a t-test to compare 24 hour milk productions of the control and intervention groups at 2 and 6 weeks postpartum. Milk production will be extracted from Redcap for analyses. The reference range for normal milk production is 788ml +/- 169ml /24hr and low milk supply will be defined as < 600ml/24hr both based on published data (Kent et al., 2006). In addition, the incidence and duration of “exclusive” (only the mother’s own breastmilk with no other foods or fluids) and “partial” breastmilk feeding (mother’s own breastmilk with other foods or fluids) over the first 12 months will be reported along with details of acute infant infections. Analysis of 24-hour milk production and the incidence of low supply will be examined for association with the nutritional and non-nutritional components of breastmilk using regression and logistic regression. Breastmilk samples will be analysed to determine if detectable changes in composition or certain bacterial profiles are associated with lower milk productions and breastfeeding duration and exclusivity .
If numbers allow regression will also be used to examine the impact on milk production of each condition (potentially this will include; obesity, hypothyroidism, polycystic ovarian syndrome along with pregnancy complications including gestational diabetes mellitus, pregnancy induced hypertension, preeclampsia and intrauterine growth restriction. All regression and logistic regression models may be run with and without cofounders relating to well-being. Analyses will be conducted in R (a statistical software program ) by a biostatistician.
Percentage of Available Milk Removed (PAMR) will be calculated during the 24 hour milk profiles by collecting a small milk sample (<1ml) from each breast immediately before and after each breastfeed or expression. Milk transfer volume alone does not accurately reflect the degree of breast emptying because the degree of breast fullness varies between feeds. Milk fat content is related to the degree of fullness of the breast and so a quadratic equation can be used to estimate the percentage of available milk removed (PAMR) for individual women using milk fat concentrations calculated from milk samples collected pre- and post-breastfeed and/or pumping over a 24 hour period (Daly et al, 1993).


Daly, S., Di Rosso, A., Owens, R., & Hartmann, P. (1993). Degree of breast emptying explains changes in the fat content, but not fatty acid composition of human milk. Experimental Physiology, 78, 741 - 755.

Grzeskowiak, L., Smithers, L., Amir, L., & Grivella, R. (2018). Domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants: a systematic review and meta-analysis. BJOG, 125(11),1371-1378.

Kent, J., Mitoulas, L., Cregan, M., Ramsay, D., Doherty, D., & Hartmann, P. (2006). Volume and Frequency of Breastfeeding and Fat Content of Breastmilk Throughout the Day. Pediatrics 117 :e387 - 395.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/09/2021
Actual
18/11/2021
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
31/01/2025
Actual
Sample size
Target
180
Accrual to date
50
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment postcode(s) [1] 39276 0
6021 - Balcatta
Recruitment postcode(s) [2] 34650 0
6027 - Joondalup
Recruitment postcode(s) [3] 34649 0
6050 - Mount Lawley
Recruitment postcode(s) [4] 34648 0
6056 - Midland
Recruitment postcode(s) [5] 34651 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 309114 0
Charities/Societies/Foundations
Name [1] 309114 0
Telethon
Country [1] 309114 0
Australia
Primary sponsor type
University
Name
The University of Western Australia - School of Molecular Sciences
Address
The University of Western Australia
M551 35 Stirling Highway
Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 310065 0
None
Name [1] 310065 0
Address [1] 310065 0
Country [1] 310065 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308983 0
The University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 308983 0
The University of Western Australia
35 Stirling Highway
Crawley WA 6009
Ethics committee country [1] 308983 0
Australia
Date submitted for ethics approval [1] 308983 0
07/07/2021
Approval date [1] 308983 0
09/11/2021
Ethics approval number [1] 308983 0
Ref: 2021/ET000356

Summary
Brief summary
The primary purpose of the study is to determine whether frequent milk removal and phone support across the first three weeks after birth improves both breastfeeding outcomes and maternal fetal health outcomes for women at high risk of low milk production.

The study is a randomised control trial (RCT) with 180 participants.

Women who are antenatally identified as being at high risk for lactation difficulties will be eligible for the trial. They may have one or a combination of the following health factors, overweight or obesity defined by pre-pregnancy BMI, pre-existing diabetes mellitus, gestational diabetes mellitus (GDM), polycystic ovarian syndrome (PCOS), intrauterine growth restriction (IUGR), pregnancy induced hypertension, preeclampsia and previous history of low unexplained breastmilk supply,

The intervention arm (n=90) will receive individual education about frequent feeding and removal of milk from the breast after birth, provision of an electric hospital grade pump in late pregnancy for ease of access post birth and postpartum phone support from an IBCLC every days 3- 4 days for 3 weeks.

In contrast, the control arm (n=90) will only receive individual education about frequent feeding and removal of milk from the breast after birth.

The primary outcome of the trial is 24 hour milk production at 2 and 6 weeks postpartum.

Other data to be compared between the two groups over the 12 months are:
- Exclusivity and duration of breastmilk feeding
- Incidence and duration of acute infant infections
- Anthropometric data on the infants
- Maternal physical and emotional health

The study will also investigate changes in breastmilk composition associated with low breastmilk production at 1, 2 and 6 weeks.

The study hypothesis is that women who are provided with regular telephone support to regularly remove milk through breastfeeding +/- pumping during the first 3 postnatal weeks, and are loaned an electric hospital grade breast pump, will have a higher milk production volume at 2 weeks and 6 weeks postpartum than those who do not receive regular telephone support and an electric hospital grade breast pump.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112550 0
Prof Donna Geddes
Address 112550 0
School of Molecular Sciences.
The University of Western Australia
M310, 35 Stirling Highway
Crawley WA 6009
Country 112550 0
Australia
Phone 112550 0
+61 8 64887006
Fax 112550 0
Email 112550 0
[email protected]
Contact person for public queries
Name 112551 0
Sharon Perrella
Address 112551 0
School of Molecular Sciences.
The University of Western Australia
M310, 35 Stirling Highway
Crawley WA 6009
Country 112551 0
Australia
Phone 112551 0
+61 8 64881208
Fax 112551 0
Email 112551 0
[email protected]
Contact person for scientific queries
Name 112552 0
Sharon Perrella
Address 112552 0
School of Molecular Sciences.
The University of Western Australia
M310, 35 Stirling Highway
Crawley WA 6009
Country 112552 0
Australia
Phone 112552 0
+61 8 64881208
Fax 112552 0
Email 112552 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after deidentification.
When will data be available (start and end dates)?
Beginning 3 months following main results publication. No end date determined.
Available to whom?
To researchers who provide a methodologically sound proposal and on case-by-case basis at the discretion of the primary sponsor.
Available for what types of analyses?
For individual participant data meta-analysis.
How or where can data be obtained?
Access subject to approvals by principal investigator ([email protected]).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12532Study protocol  [email protected]
12534Informed consent form  [email protected]
12535Ethical approval  [email protected]



Results publications and other study-related documents

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