Partnering With Parents for Pumping Success: Feasibility of Personalized Lactation Support Utilizing Point-of-Care Human Milk Biomarkers
Phase: NA
Conditions: Breastfeeding, Preterm Birth, Breast Pumping, Lactation; Insufficient, Partial
Sponsor: The Hospital for Sick Children

SALT Protocol  
Version 5 June 2023 
 
i 
Partnering with Parents for Pumping Success: Feasibility of Personalized Lactation Support Utilizing 
Point-of-Care Human Milk Biomarkers 
(short title: Sodium Awareness in Lactation Trial [SALT]) 
Principal Investigator:  
Samantha Anthony SW PhD 
PGCRL 
Room 6.9710, 666 Bay St., Toronto, M5G 0A4 
Samantha.anthony@sickkids.ca 
416-813-7654 x 303126 
 
Additional Investigators: 
Rebecca Hoban MD MPH 
Seattle Children’s Hospital, Division of Neonatology 
4800 Sand Point Way NE 
Seattle, WA 98105, USA 
Rebecca.hoban@seattlechildrens.org 
 
Sharon Unger MD 
Mount Sinai Hospital, Department of Paediatrics 
600 University Ave., Toronto, M5G 1X5 
Sharon.unger@sinaihealth.ca 
416-586-8593 
 
Sponsor:  
The Hospital for Sick Children 
 
Funded by: CIHR 
 
Version Date: 
18 Sept 2023 

  
 
ii 
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 2 
1.1 
Synopsis ................................................................................................................................................ 2 
1.2 
Schema .................................................................................................................................................. 3 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 3 
2 
INTRODUCTION ............................................................................................................................................ 4 
2.1 
Study Rationale .................................................................................................................................... 4 
2.2 
Background ........................................................................................................................................... 5 
2.3 
Risk/Benefit Assessment .................................................................................................................... 6 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 6 
4 
STUDY DESIGN ............................................................................................................................................. 7 
4.1 
Overall Design ...................................................................................................................................... 7 
4.2 
Scientific Rationale for Study Design ................................................................................................ 8 
4.3 
End of Study Definition ........................................................................................................................ 8 
5 
STUDY POPULATION ................................................................................................................................... 8 
5.1 
Inclusion Criteria................................................................................................................................... 8 
5.2 
Exclusion Criteria ................................................................................................................................. 8 
5.3 
Screen Failures .................................................................................................................................... 9 
5.4 
Strategies for Recruitment and Retention ........................................................................................ 9 
6 
STUDY INTERVENTION ............................................................................................................................. 10 
6.1 
Study Intervention(s) Administration ............................................................................................... 10 
6.1.1 
Study Intervention Description ..................................................................................... 10 
6.2 
Study Intervention Compliance ........................................................................................................ 11 
7 
DISCONTINUATION and WITHDRAWAL ................................................................................................ 11 
7.1 
Discontinuation of Study Intervention ............................................................................................. 11 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 11 
7.3 
Lost to Follow-Up ............................................................................................................................... 12 
8 
STUDY ASSESSMENTS AND PROCEDURES...................................................................................... 12 
8.1 
Assessments  ..................................................................................................................................... 12 
8.2 
Adverse Events and Serious Adverse Events ............................................................................... 13 
8.2.1 
Definition of Adverse Events (AE) ............................................................................... 13 
8.2.2 
Definition of Serious Adverse Events (SAE) .............................................................. 13 
8.2.3 
Classification of an Adverse Event .............................................................................. 13 
8.2.4 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 14 
8.2.5 
Adverse Event Reporting .............................................................................................. 14 
8.2.6 
Serious Adverse Event Reporting ............................................................................... 15 
8.2.7 
Reporting Events to Participants ................................................................................. 15 
9 
STATISTICAL CONSIDERATIONS ........................................................................................................... 15 
9.1 
Statistical Hypotheses ....................................................................................................................... 15 
9.2 
Sample Size Determination .............................................................................................................. 15 
9.3 
Populations for Analyses .................................................................................................................. 15 
9.4 
Statistical Analyses ............................................................................................................................ 16 
9.4.1 
General Approach .......................................................................................................... 16 
9.4.2 
Analysis of the Primary Endpoint(s) ............................................................................ 16 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 16 
9.4.4 
Baseline Descriptive Statistics ..................................................................................... 17 

  
 
iii 
9.4.5 
Sub Group Analyses ...................................................................................................... 17 
9.4.6 
Tabulation of Individual Participant Data .................................................................... 17 
9.4.7 
Exploratory Analyses ..................................................................................................... 17 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 17 
10.1 
Regulatory, Ethical, and Study Oversight Considerations........................................................... 17 
10.1.1 
Study Discontinuation and Closure ............................................................................. 18 
10.1.2 
Future Use of Stored Specimens and Data ............................................................... 18 
10.1.3 
Key Roles and Study Governance .............................................................................. 18 
10.1.4 
Safety Oversight ............................................................................................................. 18 
10.1.5 
Data Handling and Record Keeping ............................................................................ 19 
10.1.6 
Protocol Deviations ........................................................................................................ 20 
10.1.7 
Conflict of Interest Policy............................................................................................... 20 
10.2 
Abbreviations ...................................................................................................................................... 20 
11 
REFERENCES .............................................................................................................................................. 20 
 

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28 April 2023 
 
 
 
 
1 
STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with this protocol, International Council on 
Harmonization Good Clinical Practice (ICH GCP) and applicable regulatory requirements.  The 
Principal Investigator (PI) will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the Sponsor and documented approval from the Research 
Ethics Board (REB), except where necessary to eliminate (an) immediate hazard(s) to the trial 
participants.  
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the REB for review and approval.  Approval of both the protocol and the 
consent form(s) must be obtained before any participant is enrolled.  Any amendment to the 
protocol will require review and approval by the REB before the changes are implemented to 
the study.  All changes to the consent form will be REB approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who provided 
consent, using a previously approved consent form. 
 
Name of Principal Investigator (Print):  __Samantha Anthony PhD_____________  
 
 
Signature of Principal Investigator: ________________    Date:  _________ 2023 
 
 
 
 
 
 
 
     <DD Month YYYY> 
 
 
Site Addresses  
The Hospital for Sick Children, Division of Neonatology 
555 University Ave., Toronto, M5G 1X8 
Canada 
 
University of Washington Medical Center 
1959 NE Pacific St 
Seattle, WA 98195 
USA 
 
 

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1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Partnering with Parents for Pumping Success: Feasibility of Personalized 
Lactation Support Utilizing Point-of-Care Human Milk Biomarkers  
Short title: Sodium Awareness in Lactation Trial [SALT]) 
Study Description: 
Data-driven interventions to improve early lactation success are lacking, 
and parents who deliver preterm are at high risk of lactation challenges. 
SALT is a multi-centre, non-blinded, non-randomized prospective 
interventional pilot study.  We will be studying feasibility, acceptability, 
and time cost of teaching lactating parents of hospitalized preterm infants 
how to test their breastmilk sodium (Na) using point-of-care (POC) meters.   
As a secondary aim, we will assess the potential to use these POC sodium 
results to guide personalized lactation care in the form of altered pumping 
schedules in an attempt to reduce breastmilk Na.  A drop in Na is a sign of 
secretory activation in the breast that is associated with adequate short 
and long-term breast milk volumes in this vulnerable population.   
Objectives: 
 
Primary Objective: Establish feasibility and acceptance of parent-led 
longitudinal parent milk Na testing in the first 14 days postpartum 
 
Secondary Objective: Further investigate relationships between pumping 
behaviours, lactation risk factors, daily PM Na and lactation outcomes 
 
Exploratory Objective: Explore how POC Na data may be used to modify 
pumping behaviour and milk volumes; 
Endpoints: 
Primary Endpoints: Ease and time cost of teaching and performing milk Na 
testing for parents; Parent perceptions of performing and interpreting milk 
Na measurements: balancing empowerment and stress 
 
Secondary Endpoint: Confirmation of previously utilized Na cut-offs with 
“coming to volume” (pumping at least 500mL/day) in this population; 
relationships between pumping behaviours and longitudinal Na changes 
 
Exploratory Endpoints: Longitudinal changes in Na with changes in 
pumping and determinations if parents have followed pumping advice 
Study Population: 
Pump dependent, lactating parents of viable preterm infants born <35 
weeks gestation admitted to study NICU with an expected length of stay of 
at least 2 weeks.  
Description of Study 
Intervention: 
Parents will learn to use a commercially available sodium analyzer for the 
novel use of point-of-care sodium testing.  If sodium levels are abnormal, 
pumping recommendations will be given in an attempt to modify sodium.  
Study Duration: 
12 months 
Participant Duration: 
Active participation/intervention: first 14 days post delivery 
Passive data collection: until infant NICU discharge or transfer from study 
NICU 
 

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1.2 
SCHEMA 
Prior to  
Enrollment 
 
 
 
Enrollment 
 
 
 
 
 
 
 
Visit 1 
 
 
 
 
Visits 2-14* 
 
 
 
Last visit  
Around  
day 14 
 
 
 
 
 
 
 
 
 
 
 
 
 
*actual # will depend on day of enrollment; milk Na testing ends on day 14 post-partum 
 
 
 
 
 
1.3 
SCHEDULE OF ACTIVITIES (SOA) 
Total N=40:  Screen potential participants by inclusion and exclusion criteria 
Refer to Schedule of Activities 
Perform baseline assessments: parent medical/lactation history, parent/infant 
sociodemographic information 
Perform milk Na testing teaching  
Perform first milk Na testing 
Start to collect daily infant feeding information (all/some/no parent milk or NPO) 
.Start purposeful sampling for qualitative interviews (n=20). 
Survey re. milk Na testing 
Schedule subset (n=20) parents for qualitative interview in coming days 
Copy pumping logs 
Continued data collection from 
medical record on infant feeding data 
until NICU discharge/transfer 
 refer to Schedule of Activities> 
Refer to Schedule of Activities> 
Daily milk Na testing and milk weights through day 14 post partum (inclusive) 
Continue to collect daily infant feeding information 
Obtain informed consent 

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Procedures 
Screening 
 
Enrollment/Baseline 
Day 1 
Day 2-13 
Day 14 
Day 15 through NICU 
discharge 
Informed consent 
X 
 
 
 
 
Demographics (race/ethnicity, 
infant gestational age, etc) 
X 
 
 
 
 
Parent medical/lactation history 
X 
 
 
 
 
Parent milk sodium teaching 
 
X 
* 
* 
 
Lactation consultation (standard 
of care) 
X 
X 
* 
* 
* 
Milk collection (1 drop) for Na 
testing  
 
X 
X 
  X 
 
Record time required for milk 
testing/teaching 
 
X 
X* 
X* 
 
Weighing of all pumped milk 
 
X 
X 
X 
 
Milk pumping log/record 
(recommended standard of care) 
 
X 
X 
X 
 
Survey** 
 
 
 
X 
 
Interview** 
 
 
 
*** 
 
Infant milk/feeding data collected 
 
X 
X 
X 
X 
*as needed (for time records, depending on variation in initial sampling, may 
discontinue for remainder of subjects) ; ** around day 14- flexible; *** subset of 
parents 
 
 
2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
In Canada, 8% of births are preterm, with limits of viability continuing to decrease.  Thus, strategies to 
reduce risks of potentially preventable complications of prematurity are a Canadian priority.  Parent’s 
milk (PM) is the only “medicine” that reduces necrotizing enterocolitis, chronic lung disease, sepsis, 
retinopathy of prematurity, and neonatal intensive care unit (NICU) length of stay, while improving 
chronic disease rates that are costly to families and society, like obesity and asthma. It does so in a dose-
response manner, with even a 10% increase in NICU PM dose showing clinically significant effects and 
cost effectiveness; 50% of total feeds as PM during the first month of NICU admission has been shown 
to be a critical threshold to further reduce risks. Further, Dr Johnson, a grant collaborator, found that 
every mL/kg/day of PM in the first 14 days of life reduced NICU costs by US$534. For a very preterm 
infant, this translates to cost savings with an increased PM dose of even 1.5-2mL of milk a day! When 
PM is unavailable, the substitute for preterm infants is pasteurized donor milk, which lacks the 

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28 April 2023 
 
 
 
 
5 
personalized nutritional and bioactive components of PM and carries far fewer benefits.  Therefore, 
there is no substitute for high-dose PM, with an urgent need for lactation strategies to improve PM dose 
in this vulnerable population. Given that infant feeding requirements are uncoupled from lactation in 
pump-dependent parents of NICU infants, and the typical supply and demand mechanisms of 
breastfeeding/chestfeeding are absent, parents must rely on guidance from medical and lactation 
professionals to initiate lactation with an artificial pump.  Lactating parents have a time-limited 
opportunity to ‘program the breasts’ for the higher volume PM production that will eventually be 
required by the growing infant. We know that achieving a threshold PM supply in the first two weeks 
postpartum, specifically CTV (making 500mL/day PM by day 14), is critical to predicting continued 
lactation through to NICU discharge.  
 
Unfortunately, individualized protocols to optimize breast programming do not exist, with little 
evidence to assist pump-dependent parents who struggle with low volumes other than ‘pump more. 
Importantly, recognition of low volumes does not occur in real-time, but retrospectively when PM 
volumes fail to increase as expected by 1-2 weeks postpartum and parents do not CTV. In addition, for 
new NICU parents, who may be experiencing stress due to their infant’s illness and recovering from 
delivery themselves, ‘pump more’, especially when advised after this initial 2-week period, may not 
initially result in real-time visible PM volume changes, making parental motivation to continue pumping 
challenging.  Instead, parents should be encouraged to ‘pump smarter’ with personalized, data-driven, 
real-time lactation care that could predict or diagnose concerns in near real time before they are 
clinically apparent (ie., before the lactating parent fails to achieve CTV) and still be potentially 
physiologically modifiable, an actionable opportunity to increase parent motivation. The use of point-of-
care (POC) PM Na to help parents ‘pump smarter’ is an opportunity to optimize lactation care to 
attempt to increase PM dose. Increased PM dose directly improves short and long-term outcomes to 
reduce racial disparities in health for preterm infants and their families. 
 
2.2 
BACKGROUND   
Parents of preterm NICU infants initiate lactation at rates that approach those for healthy populations. 
However, these rates are not sustained through to NICU discharge and beyond.[1-3].  Insufficient PM 
volume is cited as the primary reason, preventing parents from following evidence-based 
recommendations for a minimum of 6 months of lactation [1,3-5] to optimize health outcomes for all 
infants.  Strategies to address insufficient PM must start at birth, but preterm delivery is associated with 
morbidities including pre-eclampsia, diabetes, obesity, and mammary gland underdevelopment, which 
are independently linked with lactation difficulties in term populations [1,6]. Pump dependency for 
lactation initiation further increases risk [1,3].  Due to a higher burden of medical morbidities, combined 
with socioeconomic challenges and effects of systemic racism like chronic stress and decreased access to 
quality care, parents of colour are more likely to deliver preterm and less likely to provide PM [2,7,8], 
further exacerbating disparities in health outcomes.  Although breast ‘programming’ that facilitates 
long-term lactation occurs in the first days postpartum, insufficient PM supply is often diagnosed weeks 
later when preterm infant requirements increase as they grow.  By this time, problems are no longer 
physiologically actionable, reducing PM dose [1,3] and placing preterm infants at risk.  
PM biomarkers, such as sodium (Na), change longitudinally in the first days postpartum as the 
breast ideally undergoes secretory activation (SA), a critical phase required for long-term lactation.[1,9-
12]. Some, but not all lactating parents, subjectively feel SA as ‘milk coming in’, but this is not universal 
and these subjective breast sensations have not been proven to accurately time SA [1,12]. Trends of 
pumped PM volumes, which require accurate data collection, have been used to estimate SA, but 
measured PM volume assesses both milk production and removal, and is therefore an indirect measure 
of SA subject to error [12]. PM biomarkers, in contrast, provide an objective, real-time assessment of SA. 

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6 
Research has demonstrated potential for point-of-care (POC) measures to identify impaired SA using ion 
selective electrodes with comparable accuracy to laboratory-based spectrometry[13]. Although POC PM 
Na has never been done by parents, parent-led testing in the NICU has been championed by the PI’s 
mentor, Dr. Meier, for milk fat (creamatocrit) and breastfeeding intake (test weights).  Testing was 
accurate, valued by parents, and saved staff time[14,15].  As milk Na should dramatically fall in the first 
days postpartum as SA approaches, we can utilize Na level as an early “upstream marker” of PM 
volumes.  Our previous work has shown that Na cutoffs could predict and dichotomize parents into ‘at 
risk’ vs ‘not at risk’ of not achieving CTV (making at least 500mL/day of PM by postpartum day 14) as 
early as day 3, well before clinicians would raise concern for low PM volumes[9-12].   We shown that 
CTV correlates with longer-term PM provision weeks to months later at NICU discharge [9,16]. In 
addition, these biomarkers change in near real-time with modifications in pumping behaviour, making 
them a target for personalized, data-driven lactation care that could increase PM supply, care which is 
lacking in this high-risk, often racialized preterm population[11]. 
 
2.3 
RISK/BENEFIT ASSESSMENT   
We don’t expect any risks or harms of the study.  As bedside PM Na testing has never been done by 
parents before, it is possible some parents might find testing their milk or finding out the results 
stressful.  If they find knowing the Na value stressful (aka if Na levels are not going down), they can 
chose for the research coordinator to assist in testing and for the parent to be blinded to the number 
itself and/or interpretation of these data.  If they find the testing itself stressful, we will offer less 
frequent testing (aka not daily) or there is always the option to drop out of the testing portion of the 
study.  Since it is a feasibility and acceptability trial, knowledge of challenges that parents face will be 
critical and we will take them very seriously.  Parent representatives are involved in pre-trial 
discussions/final design and will continue to follow during the trial; enrolled parents will be encouraged 
to share any concerns with the study team and/or take the survey about study acceptability. 
 
It is possible that the study could have benefits - changing pumping schedules based on PM Na 
might help milk supply if the parent is having challenges with supply but we are not sure.  Although all 
parents receive lactation support in the NICU, parents in this study will have daily check ins regarding 
lactation with the research coordinator, so this additional support may also be helpful.  Even if parents 
in the study don’t directly benefit, we hope that the information learned from this study can be used in 
the future to benefit other pumping parents who deliver preterm (and help their infants to get more 
milk).  Given that there are minimal risks and there are potential benefit to the individual as well as 
society, the value of the information gained outweighs any risks of participation. 
 
3 
OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
 
 
Establish feasibility and acceptance 
of parent-led longitudinal PM Na 
testing in the first 14 days 
postpartum in this pilot study 
Ease and time cost of 
teaching and performing 
milk Na testing for parents 
Parent perceptions of 
performing and interpreting 
milk Na measurements: 
balancing empowerment 
and stress (surveys and in a 
subset, qualitative 
interviews) 
Point of care Na testing has 
never been done by pumping 
parents.  We have previously 
successfully recruited for lab-
based PM testing in which 
samples were not analyzed in 
real time and not shared with 
participants, but for future 
powered intervention studies, 
we would need to show that 

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28 April 2023 
 
 
 
 
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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
 
 
parents are willing and able to 
participate in POC NA testing. 
Secondary 
 
 
Investigate relationships between 
pumping behaviours, lactation risk 
factors, daily PM Na and lactation 
outcomes 
 
 
Confirmation of previously 
utilized Na cut-offs with 
“coming to volume” 
(pumping at least 
500mL/day) in this unique 
Canadian population; 
relationships between 
pumping behaviours and 
longitudinal Na changes. 
This is first study of this kind 
in Canada; previous PM 
Na/biomarker studies have 
primarily focused on African 
American and Caucasian 
American populations. 
Worldwide, only a few hundred 
pumping parents of preterm 
infants have any PM Na or 
biomarker data in addition to 
detailed lactational risk factors 
and pumping records.  We are 
currently working with other 
research groups to collate these 
few cohorts, and with data 
transfer agreements would add 
this study to this database. To 
add to these very limited data 
will help design and power 
future studies.   
Exploratory  
 
 
Explore how POC Na data may be 
used to modify pumping behaviour 
and milk volumes. 
 
Explore in parents with high 
PM Na the Longitudinal 
changes in Na with changes 
in pumping and 
determinations if parents 
have followed pumping 
advice 
PM Na has never been used in 
real time to attempt to drive 
lactation care. We will explore 
this outcome to plan for future 
RCTs. 
 
 
4 
STUDY DESIGN  
4.1 
OVERALL DESIGN 
This prospective, non-randomized feasibility study will collect longitudinal PM data for the first 14 days 
postpartum from 40 parents of preterm infants born <35 weeks gestation from a diverse cohort. In this 
1-year study, using mixed methods we will utilize parent-driven approaches to develop tools to educate 
and support parents to collect, measure, and interpret daily POC PM Na – our primary outcome is to 
explore feasibility and acceptability of this approach.  This feasibility study will not have a control arm, 
and all parents will have access to standard of care lactation support.  Barriers and facilitators of parent 
POC testing will be detailed by surveys with a subset (n=20) undergoing structured qualitative 
interviews; time costs for parents and staff will be collected.  As secondary outcomes, daily Na levels will 
be compared to published levels.   
As an exploratory intervention, we will utilize these Na levels suggest modifications in pumping 
behaviours, and follow subsequent Na levels and PM volumes.  We will also measure pumped PM 
volumes, record pumping information (which is recommended as standard of care), and collect lactation 
risk factors to assess how PM Na is associated with these parameters, as well as add to existing data sets 
in pump-dependent parents of preterm infants to study larger populations.  Our hypothesis is that 
postpartum parents of preterm infants are capable of using POC Na devices and will find this use, 
interpretation of results, and use of these results to suggest pumping modifications acceptable.   

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8 
 To avoid bias, we will utilize a prospective trial design, with quantitative and qualitative 
components both occurring at the time of active study involvement.  We will attempt to control for 
known confounders of lactation (which we will collect) during statistical analysis, although we will have a 
small, unpowered “n” for this exploratory study, so our ability to do so will be limited. 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
This is a non-randomized pilot study without a control group.  Point of care Na testing has never been 
done before in real time nor by a patient, so we need to first gather feasibility and acceptability data 
prior to larger powered trials. 
 
4.3 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in Section 1.3, Schedule of Activities 
(SoA). The active duration of participation for each individual participant who completes all study visits 
will be 2 weeks.   Data collection on infant feeding will continue via utilization of the electronic medical 
clinical records (without any need for additional parent/subject involvement) until infant NICU discharge 
or transfer. 
The end of the study is defined as completion of the last visit or procedure shown in the SoA in the 
trial globally. It is estimated that it will take 9 months from when the study opens to enrollment until the 
end of the study. 
 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Consent provided 
2. Have delivered a preterm singleton or twin infant at <35 weeks gestation admitted to a study 
NICU at birth or transferred into a study NICU from another NICU within the first 72 hours 
postpartum 
3. Day 5 or less postpartum (Day 1 = day of delivery) upon enrollment (ideally day 3 or less) 
4. Plans to lactate at least 2 weeks and initiate lactation with a breast pump 
5. Expected infant NICU stay of 7+ (ideally 14+) days in enrollment NICU(s)  
 
5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Potential study participant’s infant is critically ill and not expected to survive or has lethal diagnosis 
with plans by medical team/family to redirect care 
2. Has delivered triplets or higher order multiples (potential confounder for lactation challenges; of 
note, triplets or higher are rare, on the order of a few parents annually at all sites) 
3. Lactation contraindication(s) (i.e., active chemotherapy) or declines lactation initiation 
4. History of breast surgery that may affect ability to lactate (i.e., breast reduction; breast 
augmentation that utilized nipple incisions)  
5. Using or planning to use hormonal birth control in the first 14 days post-partum as may affect 
secretory activation/lactation 

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9 
6. Unable/unwilling to be present in study NICU during any of first 5 days postpartum  
7. Presumption by the medical team that infant will be in study NICU for <5 days 
 
5.3 
SCREEN FAILURES 
Screen failures are defined as participants who would be eligible to participate in the clinical trial but are 
not subsequently approached for consent in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants. Minimal information includes 
demography, screen failure details and eligibility criteria. 
Individuals who do not initially meet the criteria for participation in this trial because of an 
unclear infant prognosis (ie considering redirection of care) or an unclear plan for lactation (ie still 
deciding on whether to initiate lactation) may be rescreened after 2 days to a maximum of 1 time. 
Rescreened participants should be assigned the same participant number as for the initial screening. 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Prior to study launch, all study materials and planned recruitment strategies will be discussed with 
parent advisors to ensure acceptability with a vulnerable post-partum populations.  Participants will be 
recruited from parents of inpatient infants of the main perinatal center in urban Seattle, Washington, 
USA, as the original PI of the study, Dr Rebecca Hoban, has transferred her appointment to this 
institution, and is key for performing the daily study activities involving milk Na testing.  NICU 
admissions will be screened daily for eligible infant-parent dyads.  If a site has multiple active 
prospective studies in the same target population, a plan will be set in place a priori regarding allotment 
of study patients to prevent parents from being approached for multiple studies, although unlike this 
study, the majority of NICU studies would primarily involve the infants, not the parents.  Potential 
participants will first be approached by someone in their circle of care to give them an informational 
letter and ask permission for the study team to approach them to learn more about the study. 
All participants will be biologic women as they will be postpartum and lactating; we will use 
gender inclusive language such as parent milk that would apply to all regardless of gender identity.  
Ideally, we would have a study population representative of Seattle’s diverse population and specifically 
include racialized populations as well as low socioeconomic status patients – to assist in this pursuit we 
will perform purposeful sampling for race/ethnicity, socioeconomic status (utilizing Medicaid status as a 
proxy for mean household income), and factors that we a priori determine are important for 
acceptability such as primiparity/multiparity.  Our goal is to have racialized and/or lower resourced 
families as at least 30% of our enrollees. 
We hope to recruit approximately 6 parents/month for a total of 40; additional participants may 
be recruited if we have subjects drop out prior to providing at least 2 PM Na sample and/or there are 
participants who do not have at least 2 days of usable data for other reasons (repeat maternal 
hospitalization, etc).   
If patients are set to be transferred to a community hospital prior to day 14, we will discuss 
potential for continued study participation using home PM Na testing, with the parent bringing the 
analyzer home and keeping records at home (ideally using REDCap links), with study coordinator phone 
follow-up.  We would utilize a courier to return the analyzer (and provide the end of study gift cards) 
after day 14. 
To encourage compliance with daily Na testing and daily NICU visitation through day 14 
postpartum, we will provide transport/travel reimbursement/incentives of US$12/day for 10 days (total 
$120/subject with $60 given after 7 days and the final $60 at study completion in the form of gift cards).  
It is presumed that most parents would visit nearly daily in the first days/weeks of infant’s life regardless 
of study participation and the parents will be inpatient typically for 2-3 days postpartum and would visit 
the NICU while still inpatient, hence the 10 days of travel support. 

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10 
 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
Once daily for the first 14 days postpartum, when visiting the NICU, parents will pump as usual with a 
double electric pump (preferably the hospital pump).  After pumping, using a sterile enteral syringe, a 
drop of PM will be removed from the pumping container prior to sending the milk for infant feeds.  After 
parent teaching by study staff, this drop of milk will be placed on a sodium sensor at the bedside and the 
output recorded.  The Na sensor, the Horiba Compact Sodium Ion Meter (Horiba, Japan), is a commercially 
available product that can be used for any fluid and has been validated with breastmilk.  Of note, this is a 
general sodium analyzer (can be used to analyze any fluid, from foods to liquids in the environment to 
biologic/human samples), not specifically a healthcare product, so does not have a Health Canada 
number.  This drop of milk will then be discarded.  The sensor will be calibrated and cleaned per the 
company’s product recommendations.  PM Na norms, taken from term literature, will be used to 
dichotomize parents by postpartum day 5 into low and high-risk categories for later not CTV by day 14.   
In this initial pilot study, parents whose PM Na level is ‘high risk’ on postpartum day 5 (>366ppm, 
converted from the >16mM used in the literature), typically prior to clinically relevant low POM volumes 
are noted, will have their pumping assessed by lactation consultants to ensure no concerns with suction, 
flange fit, or pump operation.  If parents are open to modifying pumping based on PM Na ‘risk’, this will 
be noted, and we will start an optimization protocol based on recommendations for pumping at least 
8x/daily, as well as utilizing a ‘power pumping’ strategy, in which parents pump for 1 hour with breaks 
(pump 20 minutes, rest 10, pump 10, rest 10, pump 10). 
We will follow and graph daily POC Na until postpartum day 14 to determine if Na starts to 
fall/normalize based on changes in pumping, and continue to modify pumping as above.  In addition, we 
will record if parents have followed pumping advice (monitoring pumping logs that are standard of care 
and correlating with PM volumes brought to NICU).  All milk brought to the NICU will also be weighed on 
scientific scales to determine exact volumes (with 1g =1mL PM).  Milk weights will be performed by the 
 
• If pumping >7 times/daily, add 1 pumping session 
• If pumping ≤ 7 times/daily, add 2 pumping sessions 
Day 5 Na>366 
Maintain current pumping, continue 
standard lactation support 
Day 5 Na≤366 
Day 7 Na>366 
Day 7 Na≤366 
Maintain current pumping, continue 
standard lactation support 
• If pumping >9 times/daily, do 1 hour of power pumping 
in lieu of 1 pump 
• If pumping 8-9 times/daily, add 1 pumping session 
• If pumping ≤ 7 times/daily, add 2 pumping sessions 
Day 10 Na≤366 
Day 10 Na>366 and hasn’t come to volume 
Maintain current pumping, continue 
standard lactation support 
• If pumping >9 times/daily including 1 hour of power pumping, 
consider 2 hours of power pumping in lieu of 1 pumps 
• If pumping 8-9 times/daily, add 1 pumping session 
• If pumping ≤ 7 times/daily, add 2 pumping sessions 

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parents, study coordinator, bedside nurses, or the milk room, depending on the site and preference.  
Paper bedside study records will be utilized, although parents will have the option of using a secure 
REDCap link via email if they prefer an electronic option for pumping or other self-completed records.  We 
will ask parents to note how long it takes to sample the milk.  If the first 10-15 parents have very similar 
results, which we anticipate given the presumed ease of use of the meter, we may not continue this 
portion of the data collection for the entire sample to limit participant record burden. 
Of note, it is possible that some parents might find receiving the PM Na results stressful (such as 
if the Na levels aren’t decreasing).  At study entrance, we can discuss parents’ preferences about receiving 
results.  Options include (a) parents perform the daily Na testing data and receive interpretation/trend 
information, (b) parents perform the daily testing but do not receive interpretation/trend information, (c) 
test in a “blinded” manner with the research coordinator doing the testing and not sharing interpretation. 
If parents find the testing or finding out results stressful, they can modify their decision re. receiving 
results and/or decide to stop testing at any time. 
 
6.2 
STUDY INTERVENTION COMPLIANCE 
Participant milk pumping logs (recommended as standard of care) will be assessed during and at the end 
of the study to determine if those parents who were recommended to modify their pumping behaviour 
have recorded increased pumping sessions.  As self report isn’t always reliable, and parents may forget 
to record, we will also assess the more objective measure of daily PM output, weighed on a scientific 
scale. 
 
7 
DISCONTINUATION AND WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
If parents find knowing the Na value stressful (aka if Na levels are not going down), they can chose for 
the research coordinator to assist in testing and for the parent to be blinded to the number itself and/or 
interpretation of these data.  If they find the Na testing itself stressful, we will offer less frequent testing 
(aka not daily) or there is always the option to drop out of the testing portion of the study.  Since it is a 
feasibility and acceptability trial, knowledge of challenges that parents face will be critical and we will 
take them very seriously.  Parent representatives are involved in pre-trial discussions/final design and 
will continue to follow during the trial; enrolled parents will be encouraged to share any concerns with 
the study team and/or take the survey about study acceptability. 
Discontinuation from PM Na testing does not mean discontinuation from the study, and 
remaining study procedures (survey, daily milk weighing though postpartum day 14, and infant feeding 
data through NICU discharge) should be completed if the participant is agreeable as indicated by the 
study protocol.   
We do not anticipate any related serious adverse events (AEs) to PM testing, but if parents report 
significant stress and request to stop testing, that would be recorded as an AE and appropriate follow-up 
provided.  With the exploratory aim of pumping interventions, it is recommended as standard of care to 
pump at a minimum of 8 times daily, with parents pumping up to 12 times a day to mimic a newborn’s 
natural feeding schedule.  Pumping and breastfeeding in the first days postpartum often results in nipple 
discomfort and potential breakdown/abrasions/bleeding that would be expected at baseline regardless 
of study participation, and would not be considered an AE. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
An Investigator may discontinue or withdraw a participant from the study for the following reasons: 

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• 
Withdrawal of informed consent (participant withdrawal for any reason) 
• 
If any clinical Adverse Event (AE) or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the participant 
• 
Significant study intervention non-compliance or lack of visitation to the NICU in the first 5 days 
postpartum 
• 
Initiation of prohibited concomitant medication(s) (aka hormonal birth control) that requires 
discontinuation of the study intervention 
• 
Participant chooses to discontinue lactation/pumping 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Participant unable to perform at least 2 PM Na tests (2 days of testing) 
 
The reason for participant discontinuation or withdrawal from the study will be recorded in the study 
file. Participants who sign the informed consent form but do not receive the study intervention may be 
replaced.  Participants who sign the informed consent form, and receive the study intervention, and 
subsequently withdraw, or are withdrawn or discontinued from the study, may be replaced if we have 
subjects withdraw prior to providing at least 2 PM Na sample and/or there are participants who do not 
have at least 2 days of usable data for other reasons (repeat hospitalization, etc). The data collected up 
to the time a participant is withdrawn or discontinued from the study will be used in the analysis unless 
the participant requests otherwise. 
 
7.3 
LOST TO FOLLOW-UP 
Loss to follow-up is anticipated to be minimal as the participants’ infants are anticipated to be inpatients 
in the NICU for the duration of the study, hence parents typically would visit their infants.  A participant 
will be considered lost to follow-up if (s)he fails to return for a second Na PM testing session after the 
initial training and is unable to be contacted by the study site staff by postpartum day 15. 
 
The following actions must be taken if a participant fails to return to the NICU for a study visit: 
• 
The site will attempt to contact the participant and counsel the participant on the importance of 
maintaining the assigned visit schedule and ascertain if the participant wishes to and/or should 
continue in the study. 
• 
Before a participant is deemed lost to follow-up, the Principal Investigator or designee will make 
every effort to regain contact with the participant (3 telephone calls and/or emails if participant 
email address is on file with the NICU and we have permission to use it as well as discussion with 
the inpatient NICU medical team re. visitation). These contact attempts should be documented 
in the participant’s medical record or study file.  
• 
Should the participant continue to be unreachable, they will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ASSESSMENTS  
As part of the study, at study entry, study staff will obtain initial medical and lactation history.  They will 
then teach participants how to perform POC NA testing; study staff will record how long POC Na 
teaching/learning takes.  On subsequent days, daily PM Na testing will be performed and recorded by 
the parents if they feel comfortable.  The study staff will be available to ensure data are recorded 
properly, record the time testing takes, weigh all pumped milk brought to the NICU, and check pumping 

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records. Of note, keeping/checking pumping records and monitoring milk volumes is routine for 
lactation support in the NICU regardless of study participation.  As previously noted, paper records will 
be the standard unless parents prefer a secure REDCap link emailed by the study coordinator.  No PM 
samples will be kept/collected.  If Na levels are not decreasing appropriately, parents will be counseled 
as to the exploratory aims of modifying pumping schedules, and adherence to this advice will be 
assessed when pumping records are looked at by the study team. 
At the end of the active portion of the study, all participants will be asked to fill out a survey 
about their experience testing PM Na.  A subset will also be asked (with compensation for their time) to 
participate in a qualitative interview done by the SickKids PI over a secure online platform.   
Infant feeding outcomes (feeding parent’s own milk none/any/all) will be collected during the 
active study (first 14 days) as well as at NICU discharge.  If the infant is transferred out of the study 
NICU, we will ask parent permission to contact them around the time of expected discharge to follow up 
on infant’s feeding status at time of discharge to home. 
 
8.2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
We do not anticipate any related serious adverse events (AEs) to PM testing, but if parents report 
significant stress and request to stop testing, that would be recorded as an AE.  With the exploratory 
aim of pumping interventions, it is recommended as standard of care to pump at a minimum of 8 times 
daily, with parents pumping up to 12 times a day to mimic a newborn’s natural feeding schedule.  
Pumping and breastfeeding in the first days postpartum often results in nipple discomfort and potential 
breakdown/abrasions/bleeding that would be expected at baseline regardless of study participation, 
and would not be considered an AE or causal AE. 
 
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
Given the trial content, we do not anticipate the possibility of any related serious adverse events.  As 
stated above, in theory the PM testing could potentially be stressful in a vulnerable population.  
Postpartum depression/stress requiring medical/psychological assessment would be considered a SAE, 
although given the postpartum population, would be difficult to determine causality. 
 
8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.3.1 SEVERITY OF EVENT 
The severity of an AE is assessed by a qualified physician who is part of the study team, who should use 
the following definitions when assessing the intensity of an AE:  
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.2.3.2 RELATIONSHIP TO STUDY INTERVENTION 

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All Adverse Events (AEs) must have their relationship to the study intervention assessed by a qualified 
physician who is part of the study team based on temporal relationship and their clinical judgment. The 
degree of certainty about causality will be graded using the categories below.  
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event occurs in a plausible time relationship to 
study intervention administration and cannot be explained by concurrent disease. The response 
to discontinuation of the study intervention should be clinically plausible. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event occurs within a reasonable time after the study 
intervention, is unlikely to be attributed to concurrent disease, and follows a clinically 
reasonable response on discontinuation.  
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after the study intervention). However, other factors may 
have contributed to the event (e.g., the participant’s clinical condition, other concomitant 
events).  
• 
Unlikely to be related – A clinical event whose temporal relationship to study intervention 
makes a causal relationship improbable (e.g., the event did not occur within a reasonable time 
after the study intervention) and in which underlying disease provides plausible explanations 
(e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Unrelated – The AE is completely independent of study intervention, and/or evidence exists that 
the event is definitely related to another etiology. 
 
8.2.3.3 EXPECTEDNESS  
A qualified physician who is part of the study team will be responsible for determining whether an 
Adverse Event (AE) is expected or unexpected.  An AE will be considered unexpected if the nature, 
severity, or frequency of the event is not consistent with the risk information previously described for 
the study intervention. 
8.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
All Adverse Events (AEs) or Serious Adverse Events (SAEs) with start dates occurring any time after the 
study intervention until 2 days (for non-serious AEs) or 7 days (for SAEs) after the last day of study 
intervention will be documented.  The occurrence of an AE or SAE may be detected during 
spontaneously reported by the participant to the research team or elicited by appropriate questioning 
during clinical evaluations and/or the end of the study survey. At each study visit, the participant will be 
asked about any change in their health since the last visit and for any changes to AE and SAEs that were 
ongoing at the last visit.   
All AEs and SAEs occurring while on study must be documented regardless of relationship. 
Information to be collected includes event description, date and time (if possible) of onset, date and 
time (if possible) of resolution/stabilization of the event, outcome, and the assessment of seriousness, 
expectedness, relationship to study intervention and severity by a delegated qualified physician.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed.  
Events will be followed for outcome information until resolution or in the opinion of the PI or 
qualified physician delegate, the participant is stable and does not require further follow-up, or the 
participant is deemed lost to follow-up. 
 
8.2.5 ADVERSE EVENT REPORTING  

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AE will be reported to the Clinical Trials Ontario Research Ethics Board according to The Hospital for Sick 
Children’s Adverse Event Reporting requirements and as per local institutional and regulatory 
requirements at each site. 
As stated above, breast/nipple discomfort with pumping/breastfeeding is common/expected in 
the study population and will not be reported per the standard process for reporting. 
 
8.2.6 SERIOUS ADVERSE EVENT REPORTING  
Adverse Events will be reported to The Hospital for Sick Children Research Ethics Board according to The 
Hospital for Sick Children’s Adverse Event Reporting Requirements, as well as any applicable local 
institutional or regulatory regulations. 
 
8.2.7 REPORTING EVENTS TO PARTICIPANTS  
Participants will be informed in a timely manner of any new information that is relevant to that 
participant’s willingness to continue participation. The communication of this information will be 
documented through a revised REB approved Informed Consent Form, where possible, based on the 
timeliness of the information. 
In the event that the study procedure detects a new clinically important secondary 
finding/incidental finding, which in this study could be asymptomatic mastitis (which in studies has been 
shown to be associated with an acute elevation in milk Na when it has previously been normal/low), the 
qualified physician will notify the participant’s/NICU’s lactation consultant to assess the participant.  If 
there are any clinical concerns of mastitis, the patient would then, as per routine with mastitis, a 
common problem in the postpartum population, be encouraged to follow up with their primary doctor. 
 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
This is an unpowered pilot project with no comparison group. 
• 
Primary Endpoint(s):  Parent-performed PM Na testing will be feasible and acceptable in this 
pilot project that will not have a comparison group.   Time costs will be collected and reported 
for planning for future studies but again will not have a comparison group.  We will collect data 
from the first 10-15 parents on time data.  If times are all very similar in this initial sampling, we 
may not continue for the entire sample to reduce participant burden. 
• 
Secondary Endpoint(s):  Parent milk Na cutoffs used in a Chicago/midwest populations will hold 
true in a Seattle/west coast population with a different racial/ethnic makeup and will be 
associated with CTV (coming to volume) in our population.  Pumping behaviours will be 
associated with longitudinal Na changes and CTV. 
• 
Exploratory Endpoint(s): Parents will not always follow pumping advice, but when they do we 
hypothesize that PM Na will drop/start to normalize. 
 
9.2 
SAMPLE SIZE DETERMINATION 
This is an unpowered pilot project that will for the first time explore POC Na testing in the hands of 
parents.  The sample size of 40 is a convenience sample determined by amount of funding, with the 
subset of 20 for qualitative interviews based on expert opinion by Dr Anthony, a co-I, of the number 
required to reach saturation. 
 
9.3 
POPULATIONS FOR ANALYSES 

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In this pilot study, the following study populations are defined and will be analyzed as specified below.   
 
• 
Feasibility/acceptability population: all enrolled patients who completed at least one PM Na test 
and had adequate assessment of competence of doing so.  A subpopulation will be studied with 
more detailed qualitative interviews.  All enrolled patients who completed at least one PM Na 
test will also be included for descriptive analyses and associations between PM Na, milk 
volumes, and parental risk factors. 
• 
Efficacy population: in this exploratory aim, all enrolled patients who received modified 
pumping instructions based on high PM Na will be included to study associations with declining 
Na 
 
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
• 
For descriptive statistics, we will describe categorical data (such as primiparity vs multiparity) as 
n (percentage).  For continuous data (such as gestational age), we will test for normality. Given 
the small n, data will likely be non-normal.  We will then report means/standard deviations if 
normal or medians/interquartile ranges if non-normal.   
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
• 
Time cost of teaching and performing milk Na testing for parents 
o Means or medians of time required will be reported for initial as well as subsequent 
teaching (by study staff) as well as performing (by parents).  Our health economist will 
then convert these time requirements to time costs using standard methods such as 
minimum wage equivalents. 
• 
Parent perceptions of performing and interpreting milk Na measurements: balancing 
empowerment and stress  
o Survey results will be reported as n (percent) who agreed with each question, and a 
qualitative summary written about acceptability and feasibility 
o Qualitative interviews will be coded by qualitative specialists and described 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
For each secondary endpoint: 
• 
Confirmation of previously utilized Na cut-offs with “coming to volume” (CTV; pumping at least 
500mL/day) in this new geographic population, given the paucity of data overall in the preterm 
population 
o We will dichotomize parents into “CTV” vs “didn’t CTV,” and compare between-group 
differences with Fisher exact test and t tests for normally distributed data or the Mann–
Whitney U test for non-normally distributed data, assessing previously utilized Na cut-
offs as well as comparing mean/median Na on various postpartum days.  We will also 
make receiver operator characteristic curves for PM Na levels on specific days (such as 
day 3 and 5) and CTV to determine if in our unique population, if the areas under the 
curve are different than previously published cut-offs (aka Na <366ppm or <16mM as 
normal). 
• 
Relationships between pumping behaviours, maternal risk factors, and longitudinal Na changes 
o We have studied both of these endpoints in different prospective cohorts in the past, 
and will use similar statistical analyses.  To assess prediction of CTV, we will use 

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multivariable logistic regression with CTV achievement as the outcome variable, and add 
in maternal risk factors such as high BMI as well as day 5 Na.   We will use pumping 
frequency as both a continuous variable as well as categorize it (such as, pumped on 
average at least 5x/daily in the first 5 days) based on previous literature, and assess how 
these pumping behaviours are associated with both rate of change of Na as well as 
achievement of Na cut-offs.   
o As missing data are common for parent reported pumping data, we will also measure all 
pumped PM, which has the date/time of pumping recorded.  Using these PM volume 
records with the associated pumping date/time, we can have an additional “source of 
truth” for pumping records and fill in missing pumping sessions. 
 
9.4.4 BASELINE DESCRIPTIVE STATISTICS 
Summary statistics will be used to describe baseline characteristics and other outcomes of interest such 
as CTV and provision of PM at NICU discharge. Categorical endpoints (such as survery results) will be 
summarized using proportions and frequencies. Continuous endpoints (such as time cost) will be 
summarized using the mean, median, range or standard deviations.  
 
9.4.5 SUB GROUP ANALYSES 
Given the small “n” in a group of soley biologic females who are immediately postpartum, this pilot 
project will not perform sub group analyses based on age or sex. Regression analyses will attempt in this 
small study to assess parental risk factors, but separate subgroup analyses will not be performed. We 
will attempt, however, in survey results and qualitative interviews, if we have enough parents of 
differing racial/ethnic groups and socioeconomic status, to break down responses by group, as we 
hypothesize that parent’s response to this POC testing may differ by group.  Given the small n, we do 
not anticipate this portion to be powered, but we will attempt to describe any differences that we could 
then delve into more in larger powered trials.    
 
9.4.6 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Individual participant data will not be published, only summary data.  The exception to this may be 
deidentified graphs showing individual parent’s PM Na trend over time versus their pumping behaviours 
and milk volumes. 
 
9.4.7 EXPLORATORY ANALYSES 
 
We plan to explore in parents with high PM Na the longitudinal changes in Na (if any) with changes in 
pumping as well as determine, by looking at pumping records, if parents have followed pumping advice.  
We will perform descriptive statistics regarding the number of parents with high Na who eventually 
normalized their Na, and report percent who did this with increased pumping based on our protocol.  
We will explore with chi square whether a various thresholds (such as 8x/day) of pumping were 
associated with normalization of Na and CTV in those parents who initially had high Na.  
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 

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10.1.1 STUDY DISCONTINUATION AND CLOSURE 
In this pilot study that doesn’t involve active interventions other than pumping recommendations (aka 
no drugs/biologics, devices, labs, etc) we do not anticipate any circumstances in which we would have to 
discontinue/close the study.  That being said, this study may be prematurely terminated if there is 
sufficient reasonable cause.  If the study is prematurely terminated or suspended, the PI will promptly 
inform study participants, the REB and the funding agency and will provide the reason(s) for the 
termination or suspension.  Study participants will be contacted and be informed of changes to study 
visit schedules.  The study may resume once concerns are addressed, and satisfy the REB. 
Participant confidentiality and privacy is strictly held in trust by the participating Investigators 
and their staff. This confidentiality is extended to cover testing of biological samples in addition to the 
clinical information relating to participants. Therefore, the study protocol, documentation, data, and all 
other information generated will be held in strict confidence.   All research activities will be conducted in 
as private a setting as possible. 
Any research information obtained about the patient in this study will be kept confidential. A 
patient will not be identified by name, only by unique study ID number and all outcome/study 
information will be in this deidentified database. The patient’s name or any identifying information will 
not appear in any reports published as a result of this study. All identifying information will be kept 
behind at least 2 security measures (password protected document on a password protected computer 
in a locked office) or as per equivalent institutional policy, under the supervision of the study/site PI.  
Data transfer agreements will be utilized for all sites.  The study data entry and study management 
systems used by clinical sites will be secured and password protected.  Deidentified study participant 
research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted to 
and stored at SickKids, and an existing data transfer agreement will be utilized for statistical analysis.   
Representatives of the Research Ethics Board (REB) or regulatory agencies may inspect all 
documents and records required to be maintained by the Investigator, including but not limited to, 
medical records for the participants in this study. The clinical study site will permit access to such 
records. 
 
10.1.2 FUTURE USE OF STORED SPECIMENS AND DATA  
De-identified data collected for this study will be analyzed and stored at SickKids. After the study is 
completed, the de-identified, archived data from this pilot project may be added to larger datasets with 
which the PI is involved with REB approval, given the rarity of PM Na data in the preterm population.  
Permission to use deidentified data for future related studies or datasets will be included in the 
informed consent.   No biologic samples will be collected/stored. 
 
10.1.3 KEY ROLES AND STUDY GOVERNANCE 
Samantha Anthony SW PhD 
PGCRL 
Room 6.9710, 666 Bay St., Toronto, M5G 0A4 
Samantha.anthony@sickkids.ca 
416-813-7654 x 303126 
 
 
10.1.4 SAFETY OVERSIGHT 
Given that this is a feasibility study, the short duration of this study, and the lack of clinical intervention, 
adverse events will be reviewed by the study team every 3 months. They will evaluate individual and 
cumulative participant data to decide whether the study should continue as is or whether any changes 

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need to be made to the protocol. Parents will also be provided the contact information of the study 
team and the REB should they wish to express any issues.  
 
 
10.1.5 DATA HANDLING AND RECORD KEEPING  
10.1.5.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported.  All source documents should be completed in a neat, legible manner to 
ensure accurate interpretation of data and uploaded to REDCap in a timely manner for each participant.  
As potential participants will be approached due to their infants’ admission to the NICU, we won’t 
necessarily have access to the parents’ primary medical chart, depending on the site (aka at SickKids, 
which is not a delivery hospital).  Therefore, as we would not necessarily be able to note study 
participation in the parent’s chart, it will be noted instead in the infants’ chart.  We do not plan to access 
parent charts unless the parent gives us permission to do so if they do not, for example, know their 
relevant medical history to answer the questions in the ‘Health and Lactation History” form (ie did they 
have pre-eclampsia, chorioanmionitis, etc).  This access with permission would only be done if the 
parent delivered at the hospital in which the infant is admitted, facilitating easy record access. 
Where the source data is not collected as part of the participant’s medical record, hardcopies of 
the worksheets (such as for recording POC PM Na at bedside, recording milk weights, recording parental 
medical/lactation history or participant surveys) will be provided for use as source document 
worksheets for recording data for each participant enrolled in the study.  Copies will be made of 
participant’s paper pumping logs that they will fill out at home when pumping.  If parents prefer, 
electronic records (particularly for pumping) can be utilized using REDCap as a primary source.  For 
qualitative interviews, interviews will be audio recorded but all identifiers will be removed for analysis – 
this will be reiterated to participants at the beginning of the interview. 
Study data from all sites will be entered into REDCap (Research Electronic Data Capture), a 
secure, web-based application designed exclusively to support data capture for research studies. 
REDCap is developed and maintained by a team at Vanderbilt University and licensed free of charge by 
the Research Institute at The Hospital for Sick Children. The application and data are housed on servers 
provided by The Hospital for Sick Children. These servers are located within SickKids secure data center. 
Local support for REDCap is provided by SickKids Research IT.  The data will be transferred (with 
appropriate data transfer agreements) to UHN, which was previously associated with SickKids and is 
contracted with the SickKids Division of Neonatology for statistical analysis.  SickKids and UHN have a 
hospital to hospital executed master agreement in place for the provision of statistical support by the 
Ted Rogers Computational Program to various Divisions within SickKids. This agreement includes 
provisions for the transfer of data to UHN, and funds to pay for any analyses.  All work is billed to the 
appropriate SickKids Division. This agreement is not study specific and includes Neonatology.  UHN is a 
service provider with respect to this study and will be involved only for statistical analysis of de-
identified data. Only de-identified data is transferred to UHN for analysis using a secure file transfer 
portal. 
 
10.1.5.2 STUDY RECORDS RETENTION  
To enable evaluations and/or audits, the Principal Investigator agrees to keep records, including the 
identity of all participating patients (sufficient information to link records, CRFs and hospital records), all 
original signed informed consent forms, copies of all CRFs, source documents, and detailed records of 
treatment disposition in a secure location for a minimum of 7 years in accordance with SickKids policy.  

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If the Principal Investigator relocates, retires, or for any reason withdraws from the study, then 
the study records must be transferred to an acceptable designee, such as another Investigator. 
 
10.1.6 PROTOCOL DEVIATIONS  
In this feasibility and acceptability pilot study, protocol deviations may be possible, as we are unsure if 
parents will find PM Na testing acceptable (primary aim), or altered pumping schedules acceptable for 
the exploratory aim, for example.  All protocol deviations will be documented for future trial planning. 
The Principal Investigator is responsible for knowing and adhering to the reviewing REB requirements. 
 
10.1.7 CONFLICT OF INTEREST POLICY 
The independence of studies from any actual or perceived influence is critical.  Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of 
interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the design and conduct of this trial.  The Hospital for Sick Children has established 
policies and procedures to disclose all conflicts of interest and will establish a mechanism for the 
management of all reported dualities of interest. 
 
10.2 ABBREVIATIONS 
AE 
Adverse Event 
MRP Most Responsible Physician 
Na 
Sodium 
PM 
Parent Milk 
PI 
Principal Investigator 
POC 
Point of Care 
REB 
Research Ethics Board 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SoA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
 
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