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Trial registered on ANZCTR


Registration number
ACTRN12615000245594
Ethics application status
Approved
Date submitted
14/02/2015
Date registered
18/03/2015
Date last updated
13/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Development of Breastfeeding Skills in Preterm Infants
Scientific title
Preterm Infants’ Use of Vacuum Triggered and Conventional Bottle-Feeding Teats and the Effect on Breastfeeding Efficacy (total mL transfer) and Efficiency (mL/min).
Secondary ID [1] 286172 0
Nil
Universal Trial Number (UTN)
U1111-1167-2041
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Development of oral feeding skills in preterm infants. 294192 0
Condition category
Condition code
Oral and Gastrointestinal 294514 294514 0 0
Normal oral and gastrointestinal development and function
Reproductive Health and Childbirth 294717 294717 0 0
Breast feeding
Reproductive Health and Childbirth 294718 294718 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For oral feeds where the breastfeeding mother is not available, bottle feeds will be offered using differing bottle-feeding teats according to infant allocation.
Experimental group: a vacuum triggered bottle-feeding teat (Calmita starter or advanced, Medela AG) will be used throughout the infant’s stay in the study site’s neonatal nurseries. Experimental group infants will use the Calmita starter teat (lower vacuum threshold), and will change to the advanced teat (higher vacuum threshold) upon demonstrating the ability to suck a full feed with the starter teat.
Adherence to use of the experimental teat will be monitored by research and nominated clinical staff on at least 4 days per week.
Intervention code [1] 291178 0
Treatment: Devices
Comparator / control treatment
Control (comparator) group: a conventional bottle-feeding teat (Havenhall PTB700 slow flow teat) will be used throughout the infant’s stay in the study site’s neonatal nurseries.
Control group
Active

Outcomes
Primary outcome [1] 294294 0
Primary Outcome 1: The total volume (mL) transferred at monitored breastfeeds
Electronic scales (BabyWeigh Scale, Medela AG, Switzerland, sensitive to 2g) will be used to weigh infants before and after monitored feeds. The amount of milk consumed is calculated as the difference between the pre-feed and post-feed infant weights, and 1g ˜ 1mL.
Timepoint [1] 294294 0
Timepoints: 33, 34, 35 weeks and term corrected gestational age (CGA).
33/40 CGA: 1 breastfeed
34/30 CGA: 2 breastfeeds (full and empty breast)
35/40 CGA: 1-2 breastfeeds (with and without nipple shield)
Term CGA: 1 breastfeed
Secondary outcome [1] 312971 0
Secondary Outcome 1: Feed efficiency (mL/min) for monitored breastfeeds and bottle-feeds
Feed efficiency (g/minute) is calculated as the amount of milk consumed during the feed (g) divided by the duration of the feed (minutes) and reported as mL/min.
Timepoint [1] 312971 0
Timepoints: 33, 34, 35 weeks and term CGA
One bottle-feed will be monitored at 33/40 CGA (if bottles already introduced), 34 and 35/40 One breastfeed will be monitored at 33, 34, 35/40 and term CGA
Secondary outcome [2] 312975 0
Secondary Outcome 2; Mean, peak and baseline intraoral vacuum for monitored breastfeeds and bottle-feeds
Intra-oral vacuum (relative to atmospheric pressure, mmHg) will be measured via a small Silastic tube (SNS, Medela AG, Switzerland) attached to a pressure transducer (Cobe Laboratories, Frenchs Forest, NSW, Australia) taped alongside and terminating just past the nipple or teat tip (2mm). The pressure transducer will be connected to a bridge amp (AD Instruments, Castle Hill, NSW, Australia) via an interconnect cable (Cobe Laboratories). The output of the pressure transducer and ultrasound images will be channeled to a Power Lab (AD Instruments, Castle Hill, NSW, Australia) and simultaneous recordings made using the software package Chart v4.5 (AD Instruments) on a laptop computer.
Timepoint [2] 312975 0
Timepoints: 33, 34, 35 weeks and term CGA
One bottle-feed will be monitored at 33/40 CGA (if bottles already introduced), 34 and 35/40 One breastfeed will be monitored at 33, 34, 35/40 and term CGA
Secondary outcome [3] 312976 0
Secondary Outcome 3: Total suck duration (mins) for monitored breastfeeds and bottle-feeds.
Output from pressure transducer and ultrasound imaging (as described above) will be used to measure suck duration.
Timepoint [3] 312976 0
Timepoints: 33, 34, 35 weeks and term CGA
One bottle-feed will be monitored at 33, 34 and 35/40 CGA
33/40 CGA: 1 breastfeed
34/30 CGA: 2 breastfeeds (full and empty breast)
35/40 CGA: 1-2 breastfeeds (with and without nipple shield)
Term CGA: 1 breastfeed
Secondary outcome [4] 312977 0
Secondary Outcome 4: Total suck bursts for monitored breastfeeds and bottle feeds
Output from pressure transducer and ultrasound imaging (as described above) will be used to measure suck bursts.
Timepoint [4] 312977 0
Timepoints: 33, 34, 35 weeks and term CGA
One bottle-feed will be monitored at 33, 34 and 35/40 CGA
33/40 CGA: 1 breastfeed
34/30 CGA: 2 breastfeeds (full and empty breast)
35/40 CGA: 1-2 breastfeeds (with and without nipple shield)
Term CGA: 1 breastfeed
Secondary outcome [5] 312978 0
Secondary Outcome 5: Preterm Infant Breastfeeding Behavior Scale (PIBBS)1 score for monitored breastfeeds

The PIBBS rates aspects of breastfeeding such as rooting, attachment, sucking and swallowing using a six item scale, with higher scores indicating greater competence.
1. Nyqvist, K.H., et al., Development of the Preterm Infant Breastfeeding Behavior Scale (PIBBS): a study of nurse-mother agreement. Journal of Human Lactation 1996. 12: p. 207-19.
Timepoint [5] 312978 0
Timepoints: 33, 34, 35 weeks and term CGA
33/40 CGA: 1 breastfeed
34/30 CGA: 2 breastfeeds (full and empty breast)
35/40 CGA: 1-2 breastfeeds (with and without nipple shield)
Term CGA: 1 breastfeed
Secondary outcome [6] 312979 0
Secondary Outcome 6: Volume transferred from a full breast (expressed >3hr prior to feed) and from an empty breast (expressed <1hr prior to feed)
Estimation of Degree of Breast Fullness Breastmilk fat concentrations increase as the volume of milk available within the breast reduces. Changes in breastmilk fat concentration over the course of a breastfeed or expression provide an indication of fullness, and when pre/post samples are collected over a 24hr period, estimation of the degree of fullness can be made. A small milk sample (<1.0mL) will be taken before and after monitored breastfeeds, and mothers will have the option of collecting pre/post samples over a 24hr period. The measurement of fat concentrations of samples will provide a more sensitive estimation of breast fullness.
Timepoint [6] 312979 0
Timepoint: 34 weeks CGA
Secondary outcome [7] 312980 0
Secondary Outcome 7: Volume transferred when breastfeeding with and without a nipple shield
Electronic scales (BabyWeigh Scale, Medela AG, Switzerland, sensitive to 2g) will be used to weigh infants before and after monitored feeds. The amount of milk consumed is calculated as the difference between the pre-feed and post-feed infant weights, and 1g ˜ 1mL.

Timepoint [7] 312980 0
Timepoint: 35 weeks CGA
Secondary outcome [8] 312981 0
Secondary Outcome 8; Incidence of bradycardia for monitored breastfeeds and bottle-feeds

Bradycardic episodes will be recorded from cardiac monitors or pulse oximeters that are routinely used in the neonatal nursery setting.
Timepoint [8] 312981 0
Timepoints: 33, 34, 35 weeks CGA
One bottle-feed will be monitored at 33, 34 and 35/40 CGA
33/40 CGA: 1 breastfeed
34/30 CGA: 2 breastfeeds (full and empty breast)
35/40 CGA: 1-2 breastfeeds (with and without nipple shield)
Secondary outcome [9] 312982 0
Secondary Outcome 9; Incidence of O2 desaturation for monitored breastfeeds and bottle-feeds

Desaturation episodes will be recorded from pulse oximeters that are routinely used in the neonatal nursery setting.
Timepoint [9] 312982 0
Timepoints: 33, 34, 35 weeks CGA
One bottle-feed will be monitored at 33, 34 and 35/40 CGA
33/40 CGA: 1 breastfeed
34/30 CGA: 2 breastfeeds (full and empty breast)
35/40 CGA: 1-2 breastfeeds (with and without nipple shield)
Secondary outcome [10] 312983 0
Secondary Outcome 10: Timing of achievement of full oral feeding.
Full oral feeding is defined as the ability to ingest all feeds orally ie. through breastfeeding or feeding from a bottle without the requirement for parenteral nutrition or top up feeds via an intra-gastric tube.
Timepoint [10] 312983 0
Timepoint: NA (monitored to 12 weeks corrected postnatal age)
Secondary outcome [11] 312984 0
Secondary Outcome 11: Timing of achievement of full breastfeeding.
Full breastfeeding is defined as the ability to ingest all feeds at the breast over a 24hr period ie. top up / supplementary feeds from a bottle are not required.
Timepoint [11] 312984 0
Timepoint: NA (monitored to 12 weeks corrected postnatal age)
Secondary outcome [12] 312985 0
Secondary Outcome 12: Duration of breastfeeding
Duration of any breastfeeding is the measured outcome, however we will also record exclusivity of breastfeeding.
Timepoint [12] 312985 0
Timepoint: NA (monitored to 12 weeks corrected postnatal age)

Eligibility
Key inclusion criteria
Medically stable preterm infants born 24 – 33 weeks, and mothers with an intention to breastfeed that have a total daily breastmilk expression volume of at least 300 mL/24hr.
Minimum age
No limit
Maximum age
4 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Mothers with a history of breast surgery, infants receiving CPAP or mechanical ventilation at 34 weeks CGA, acute illness and/or infection and congenital disease or malformation.

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)
Random allocation achieved through the use of sequentially numbered opaque envelopes that have been prepared by a statistician who is not involved in recruitment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random allocation in blocks to either a control group (conventional teat) or an intervention group (vacuum controlled teat).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculation: The primary outcome measure for this study is the total volume transferred during a breastfeed. Meier reported average transfer volumes of 18.4mL +/- 13.2 and 3.9mL +/- 7.0 with and without nipple shield, respectively (Meier et al, 2000). Samples sizes required to detect a clinically relevant effect of 5mL difference between feeds with full and empty breasts were calculated separately for these two conditions. The more conservative calculation is that the study would need 24 infants in each treatment group to have 80% power (Type I error rate a=0.05) of detecting a difference this large. Allowing for a possible dropout rate of 20%, as was observed in a similar study, 30 infants per group will need to be recruited at 33 weeks CGA. The sample size was calculated as if the data will be analysed using an independent samples t-test. Actual analyses will be more powerful, and thus will have power to detect smaller differences.
Using this sample size, an independent samples t test would have the power to detect differences in secondary outcomes equivalent to 0.83 * SD. This is equivalent to differences of approximately 3.9 min total sucking duration, and 12 suck bursts per feed. As with the primary outcome, use of covariate data, repeated measurements and more powerful analytic techniques increase the likelihood of detecting smaller differences than those determined here.

Data analysis: Data will be analysed on an intention to treat basis using R 2.15 or later versions (The R Core Team) with nlme, lattice and multcomp packages for linear mixed models, graphical exploration and general linear hypothesis tests, respectively. To monitor both safety and efficacy, interim analysis will be performed when complete data is available for 15 infants in each group, with p values set to p=0.029 for both interim and final analyses as per Pocock (p372).
For the monitored breastfeeds, differences in milk transfer volume as well as measured sucking, physiological, and feeding variables, linear mixed effects modelling will be used, with grouping for the random effects at the participant level. Use of nipple shield (yes/no), breast fullness (full/empty) and relevant demographic variables will be considered as predictive factors.

Meier, P.P., et al., Nipple shields for preterm infants: effect on milk transfer and duration of breastfeeding. J Hum Lact, 2000. 16(2): p. 106-14; quiz 129-31.
The R Core Team, R: A language and environment for statistical computing, in Foundation for Statistical Computing. 2008: Vienna, Austria.
Piantadosi, S., Clinical trials: a methodological perspective. Wiley Series in Probability and Statistics, ed. W.A. Shewhart and S.S. Wilks2005, Hoboken: John Wiley & Sons, Inc.

Recruitment
Recruitment status
Completed
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] 3448 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 9218 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 290742 0
Charities/Societies/Foundations
Name [1] 290742 0
Telethon
(administered by Women & Infant’s Research Foundation)
Address [1] 290742 0
50 Hasler Road
Osborne Park WA 6017
Country [1] 290742 0
Australia
Funding source category [2] 290743 0
University
Name [2] 290743 0
Centre for Neonatal Research and Education
The University of Western Australia
Address [2] 290743 0
The University of Western Australia
M551, 35 Stirling Highway
Crawley WA 6009
AUSTRALIA
Country [2] 290743 0
Australia
Primary sponsor type
University
Name
Centre for Neonatal Research and Education, The University of Western Australia
Address
The University of Western Australia
M551, 35 Stirling Highway
Crawley WA 6009
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 289430 0
Individual
Name [1] 289430 0
A/Prof Donna Geddes
Address [1] 289430 0
School of Chemistry and Biochemistry
The University of Western Australia (M310)
35 Stirling Highway
Crawley WA 6009
Country [1] 289430 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292377 0
Human Research Ethics Committee, Women and Newborn Health Service
Ethics committee address [1] 292377 0
Human Research Ethics Committee (KEMH)
Clinical Ethics Service
Princess Margaret Hospital for Children
Roberts Road
Subiaco WA 6008

Ethics committee country [1] 292377 0
Australia
Date submitted for ethics approval [1] 292377 0
03/12/2014
Approval date [1] 292377 0
13/02/2015
Ethics approval number [1] 292377 0
Approval ID: 2012125EW
Ethics committee name [2] 298183 0
Human Research Ethics Committee
Ethics committee address [2] 298183 0
The University of Western Australia
35 Stirling Highway
Crawley WA 6009
Ethics committee country [2] 298183 0
Australia
Date submitted for ethics approval [2] 298183 0
01/04/2015
Approval date [2] 298183 0
14/04/2015
Ethics approval number [2] 298183 0
RA/4/1/7489

Summary
Brief summary
This study aims to investigate the development of preterm breastfeeding skills and the impact of bottle-feeding teats, nipple shields and degree of breast fullness on the achievement of full oral feeding. As mothers are unable to be in the neonatal nursery for all of their infant’s suck feeds, bottle feeds are required occasionally. There is evidence that an intraoral vacuum-triggered teat (Calmita, Medela AG) encourages a sucking action similar to breastfeeding and reduces the length of hospital stay and formula use at discharge compared to a conventional teat. We wish to examine the effects of different teats and breastfeeding support on feeding outcomes.
Objectives:
1. To track over time the maturation of intraoral vacuum, coordination of sucking, swallowing and breathing, and maintenance of a normal heart rate and oxygen saturation during feeding, and to determine if this is related to increased breastfeeding effectiveness and efficiency.
2. To explore the effect of the amount of milk available in the breast on the volume of milk transferred during breastfeeding at 34 weeks corrected gestational age (CGA).
3. To explore the use of a nipple shield on the volume of milk transferred at 35 weeks CGA.
4. To compare suck-swallow-breathe coordination during breastfeeding with that during bottle feeding with Calmita, and bottle-feeding with a conventional teat.
5. To determine the effect of a vacuum triggered teat on timing of achievement of full breastfeeding and on breastfeeding duration
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54922 0
Prof Karen Simmer
Address 54922 0
Centre for Neonatal Research and Education
The University of Western Australia
M551, 35 Stirling Highway
Crawley WA 6009
Country 54922 0
Australia
Phone 54922 0
+61 8 9340 1262
Fax 54922 0
+61 8 9340 1266
Email 54922 0
Karen.Simmer@uwa.edu.au
Contact person for public queries
Name 54923 0
Dr Sharon Perrella
Address 54923 0
School of Molecular Sciences, The University of Western Australia
M310, 35 Stirling Highway, Crawley WA 6009
Country 54923 0
Australia
Phone 54923 0
+61 8 6488 4467
Fax 54923 0
+61 8 6488 7086
Email 54923 0
Sharon.Perrella@uwa.edu.au
Contact person for scientific queries
Name 54924 0
Dr Sharon Perrella
Address 54924 0
School of Molecular Sciences, The University of Western Australia,
M310, 35 Stirling Highway, Crawley WA 6009
Country 54924 0
Australia
Phone 54924 0
+61 8 6488 4467
Fax 54924 0
+61 8 6488 7086
Email 54924 0
Sharon.Perrella@uwa.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary