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Trial registered on ANZCTR


Registration number
ACTRN12617001047381
Ethics application status
Approved
Date submitted
5/07/2017
Date registered
18/07/2017
Date last updated
18/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring changes in breast milk composition as markers of mastitis in mothers of preterm infants
Scientific title
Exploring changes in breast milk composition as markers of mastitis in mothers of preterm infants
Secondary ID [1] 292225 0
Nil
Universal Trial Number (UTN)
U1111-1198-8645
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lactational mastitis 303723 0
Secretory activation 303724 0
Condition category
Condition code
Reproductive Health and Childbirth 303096 303096 0 0
Breast feeding
Infection 303097 303097 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Mastitis is an inflammatory condition of the lactating breast that may have insidious onset and can present with or without infection. It is associated with raised breast milk sodium concentrations and elevated sodium:potassium ratios. This study will examine relationships between breast milk sodium (Na) and potassium (K) concentrations and calculated Na:K ratios (as determined through bedside monitoring devices) and symptoms of mastitis in mothers of hospitalised preterm infants.
Monitoring of breast milk Na and K concentrations and ratios, breast health and milk production will be performed on postnatal days 2, 4, 6, 8, 10 and then every 3 days until discharge / transfer from the study hospital. (The average length of stay for the study population is estimated to be 3 weeks).
Microbiological testing of milk samples will be performed on days 6, 13, then every 6 days until discharge / transfer from the study hospital.
In the event that a participant develops signs of mastitis, milk Na and K concentrations and ratios, breast health symptoms and milk production will be measured daily until 48 hours post resolution of symptoms. A milk sample will be collected for microbiological analysis on the day of onset of symptoms.
Intervention code [1] 298387 0
Diagnosis / Prognosis
Intervention code [2] 298388 0
Early Detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302478 0
Breast milk Na concentrations.
A handheld device (L'Aqua Twin Compact Na Meter, Horiba Scientific) will be used to measure Na concentrations in duplicate using a 0.2 mL milk sample from each breast..
Timepoint [1] 302478 0
Postnatal days 2, 4, 6, 8, 10, 13 and every 3 days thereafter until infant discharge/transfer from the neonatal nurseries of the study hospital.
During an episode of suspected mastitis, Na concentrations will be measured daily from day of onset until 48 hours post resolution of symptoms.
Primary outcome [2] 302479 0
Breast milk K concentrations.
A handheld device (L'Aqua Twin Compact Na Meter, Horiba Scientific) will be used to measure K concentrations in duplicate using a 0.2 mL milk sample from each breast..
Timepoint [2] 302479 0
Postnatal days 2, 4, 6, 8, 10, 13 and every 3 days thereafter until infant discharge/transfer from the neonatal nurseries of the study hospital.
During an episode of suspected mastitis, K concentrations will be measured daily from day of onset until 48 hours post resolution of symptoms.
Primary outcome [3] 302480 0
Breast milk sodium-potassium (Na:K) ratios. These will be calculated from measured milk sodium and potassium concentrations for each breast.
Timepoint [3] 302480 0
Postnatal days 2, 4, 6, 8, 10, 13 and every 3 days thereafter until infant discharge/transfer from the neonatal nurseries of the study hospital.
During an episode of suspected mastitis, Na:K ratios will be measured daily from day of onset until 48 hours post resolution of symptoms.
Secondary outcome [1] 336135 0
Presence and abundance of bacterial species will be determined through microbiological culture of 2mL breast milk sample from each breast.
Timepoint [1] 336135 0
Postnatal days 8, 13 and then every 6 days thereafter until discharge/transfer from the neonatal nurseries of the study hospital.
On the day of onset of symptoms of mastitis, breast milk samples will be collected for microbiological culture.
Secondary outcome [2] 336137 0
Breast health will be assessed to assist in identifying mastitis using a questionnaire that screens for local and systemic symptoms. The Breast Health Questionnaire was designed specifically for this study, based on the work of Dr Catherine Fetherston.
FETHERSTON, C. 2003. Relationships between clinical descriptors and changes in the physiology of the lactating breast before, during and after non-inflammatory and inflammatory breast disorders. Thesis (Ph.D.)--University of Western Australia, 2004.
Timepoint [2] 336137 0
Postnatal days 2, 4,6, 8, 10, 13 and then every 3 days thereafter until discharge/transfer from the neonatal nurseries of the study hospital.
During an episode of suspected mastitis, the breast health questionnaire will be completed daily from onset until 48 hours post resolution of symptoms.
Secondary outcome [3] 336138 0
24hr milk production volume. Participants are exclusively or predominantly expressing their breast milk. Maternal records of expression volumes over a 24hr period will be documented to assess for secretory activation and effects of mastitis..
Timepoint [3] 336138 0
Postnatal days 2, 4,6, 8, 10, 13 and then every 3 days thereafter until discharge/transfer from the neonatal nurseries of the study hospital.
During an episode of suspected mastitis, 24hr breast milk expression volumes will be collected daily from onset until 48 hours post resolution of symptoms.
Secondary outcome [4] 336708 0
Incidence rate of mastitis in the first 8 postnatal weeks.
Timepoint [4] 336708 0
Occurrence of mastitis will be recorded during infant admission to neonatal nursery at study hospital. Maternal reports of mastitis and its treatment post discharge from the study hospital will be recorded at follow up with phone calls at 4 and 8 weeks postnatal.
Secondary outcome [5] 336709 0
Breastfeeding duration to 8 weeks postnatal
Timepoint [5] 336709 0
Breastfeeding status and where applicable, date of weaning, will be recorded at follow up phone calls at 4 and 8 weeks postnatal.

Eligibility
Key inclusion criteria
English speaking mothers of preterm infants born at 29-34 weeks gestation who are expressing breast milk for their hospitalised infants.
Minimum age
18 Years
Maximum age
60 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Mothers who require hospitalisation beyond routine postnatal care.
Mothers with complex health issues that prevent regular breast expression and/or daily visiting at study hospital.
Mothers that require the use of an interpreter to receive study information and provide informed consent.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The primary aim of this study is to determine whether elevated Na:K ratios measured at point of care are associated with mastitis in mothers of hospitalised preterm infants. Relationships between elevated Na:K ratios and breast symptoms, positive microbiology culture and acute reductions in 24hr milk production volume of the affected breast/s will be examined.
If the expected incidence of mastitis is 20% over the first 8 weeks with a roughly uniform rate of occurrence, then it is expected that there would 4.5 cases of mastitis or elevated Na:K ratio in 2.5-3 weeks (estimated average length of stay prior to transfer/discharge from study hospital for infants born 29-34 weeks gestation prior to transfer/discharge).
Using a mixed binomial model with repeated measurements of Na:K ratio over an average of 2.5-3 weeks and separate evaluations of breast symptoms, microbiological culture and reductions in 24 hour milk production, it is estimated that 62 participants are required to ensure that there is a 95% chance of seeing at least 2 cases of elevated Na:K ratio, as calculated using a simulation model with a=0.05 to a power of 95%.
A secondary aim of the study is to observe the incidence of mastitis in mothers of preterm infants. Recruitment of 65 participants will allow estimation of the true incidence (within 95% CI) in this population, based on an estimate of approximately 20% of mothers developing mastitis over 8 postnatal weeks (Cullinane et al 2015).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 8399 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 16471 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 296765 0
University
Name [1] 296765 0
The University of Western Australia
Address [1] 296765 0
M310, 35 Stirling Highway
Crawley WA 6009
Country [1] 296765 0
Australia
Primary sponsor type
Individual
Name
A/Prof Donna Geddes
Address
The University of Western Australia
M310, 35 Stirling Highway
Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 295753 0
Individual
Name [1] 295753 0
Prof Karen Simmer
Address [1] 295753 0
Neonatology Clinical Care Unit
Kind Edward Memorial Hospital
374 Bagot Road
Subiaco WA 6008
Country [1] 295753 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297993 0
Human Research Ethics Committee, Women and Newborn Health Service
Ethics committee address [1] 297993 0
King Edward Memorial Hospital
374 Bagot Road
Subiaco WA 6008
Ethics committee country [1] 297993 0
Australia
Date submitted for ethics approval [1] 297993 0
02/02/2017
Approval date [1] 297993 0
14/06/2017
Ethics approval number [1] 297993 0

Summary
Brief summary
Background: Mastitis is a common inflammatory complication of lactation that may progress to infection. The onset may be insidious or sudden, and it impacts maternal wellbeing through breast pain, fever and flu like symptoms. Mastitis may progress to abscess, and potentially impacts the health of the preterm infant through reduced milk production and possible transmission of infection. Mothers of hospitalised preterm infants are at increased risk of mastitis due to a number of predisposing factors including use of a breast pump, poor health of the mother and/or infant, and exposure to pathogens within the hospital environment.
Early detection and treatment of mastitis is critical to limiting its severity, with microbiological culture of milk recommended for hospital acquired cases. While an elevated milk sodium:potassium (Na:K) ratio is considered a marker of mastitis there are currently no clinical tests to confirm its onset. Mothers of hospitalised infants are typically required to access community based medical care for suspected mastitis. This can be difficult as they are typically dependent on others for transport after a caesarean birth, and insidious symptoms can be overlooked. Point of care (POC) screening of breast milk for elevated Na:K may offer a clinical tool for early detection of mastitis and therefore timely management, thus minimising the impact on the mother and infant.
Objectives:
To determine whether milk Na:K >1.0 ratios measured at POC are associated with mastitis in mothers of preterm infants.
To determine the incidence of mastitis in a sample of mothers who are expressing milk for their hospitalised preterm infants.
To determine whether acute reductions in 24-hour milk production volumes are associated with markers of mastitis.

Trial Plan: An observational study of 65 mothers of preterm infants will be carried out. Breast milk Na and K concentrations will be measured at POC and Na:K calculated every second day from day 2 to day 10, and then every 3rd day until infant discharge from the neonatal nurseries of the study hospital. In the event of suspected mastitis, Na and K monitoring will occur daily from onset to 48 hours post resolution of symptoms. Microbiological cultures of milk samples will be performed on day 8, day 13 and every 6 days until infant discharge, and at the onset of mastitis. Breast symptoms and milk production volumes will be recorded at each sampling time point. Incidence of mastitis and breastfeeding outcomes will be tracked to 8 weeks postnatal
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75682 0
A/Prof Donna Geddes
Address 75682 0
The University of Western Australia
M310, 35 Stirling Highway
Crawley WA 6009
Country 75682 0
Australia
Phone 75682 0
+61 8 6488 2988
Fax 75682 0
+61 8 6488 7086
Email 75682 0
donna.geddes@uwa.edu.au
Contact person for public queries
Name 75683 0
Dr Sharon Perrella
Address 75683 0
The University of Western Australia
M310, 35 Stirling Highway
Crawley WA 6009
Country 75683 0
Australia
Phone 75683 0
+61 8 6488 4467
Fax 75683 0
+61 8 6488 7086
Email 75683 0
sharon.perrella@uwa.edu.au
Contact person for scientific queries
Name 75684 0
Dr Sharon Perrella
Address 75684 0
The University of Western Australia
M310, 35 Stirling Highway
Crawley WA 6009
Country 75684 0
Australia
Phone 75684 0
+61 8 6488 4467
Fax 75684 0
+61 8 6488 7086
Email 75684 0
sharon.perrella@uwa.edu.au

No information has been provided regarding IPD availability
Summary results
No Results