Please note the ANZCTR will be unattended from Friday 20 December 2019 for the holidays. The Registry will re-open on Tuesday 07 January 2020. Submissions and updates will not be processed during that time.

Please be advised that as the ANZCTR is funded by Australia and New Zealand, we must prioritise submissions from these countries first. International submissions should allow additional time for registration. Apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12615000986572
Ethics application status
Approved
Date submitted
27/07/2015
Date registered
22/09/2015
Date last updated
26/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Glucose in Well Babies Study (GLOW): An observational study to determine the glucose profile in healthy babies within the first five postnatal days.
Scientific title
In healthy newborns, what are the blood glucose, lactate, and, ketone concentrations in the first five postnatal days measured by blood samples and by continuous interstitial monitoring.
Secondary ID [1] 286197 0
Nil
Universal Trial Number (UTN)
Trial acronym
Glucose in Well Babies (GLOW)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
To describe the normal concentrations of blood glucose, lactate and ketones within the first five postnatal days. 294233 0
Condition category
Condition code
Metabolic and Endocrine 294971 294971 0 0
Normal metabolism and endocrine development and function
Reproductive Health and Childbirth 296542 296542 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The study period is from immediately after birth until the completion of the first five postnatal days.

Blood glucose, lactate and beta-hydroxybutyrate analysis

The first blood sample will be taken from the umbilical cord immediately after birth. All other sampling will be sampled from the babies’ heel just prior to a feed is being initiated, in order to reduce the pain of heel lance. The heel will be warmed, in order to reduce the pain and to aid blood flow. Less than 1 ml (small drop) of blood will be taken.
The blood will be analysed for glucose and lactate using glucose oxidase and lactate oxidase on the portable epoc 'Registered Trademark' analyser (Epocal Inc. Ottawa. Canada). Beta-hydroxybutyrate will be analysed using the hand held StatStrip 'Registered Trademark' meter (Nova Biomedical, Waltham, MA, USA), which uses a beta-hydroxybutyrate dehydrogenase reaction for analysis. The results will be blinded to the researcher processing the blood sample and not available to any of the research team until the completion of the study. Experienced neonatal nurses or nurse practitioners will perform the heel lances.

Timing of the heel-lance blood samples

Day One. (Mirroring routine screening)
Immediately after birth a cord blood sample will be taken.
Heel-lance blood samples will commence at approximately one hour after birth, in accordance with the blood glucose screening protocol at Waikato Hospital, followed by three more samples, at least three to four hours apart.

Days Two to Five. Heel-lance samples will be measured every 8 to 10 hours (a 16 maximum of heel-lances will be performed). It is standard practice for the Newborn Screening Card to be collected on Day 3 after birth. Every attempt will be made to link this heel lance with the study blood sampling.
Continuous glucose monitor

As soon after birth as possible an Ipro2 continuous glucose monitor (Medtronic, Minimed `Registered Trademark', Northridge, USA) will be inserted subcutaneously into the baby’s thigh using the insertion device and remain in place for five days. The sensor will be secured with a transparent dressing.

The Ipro 2 does not prevent any normal activities of daily living. The baby can be bathed with the sensor in place. The sensor and dressing will be removed after five completed days, at time which is convenient to the parents. A Remove ' Registered Trademark' (Smith & Nephew, Inc., St Petersburg, USA) wipe will be used to remove the dressing, in order to decrease the potential discomfort. Following removal of the continuous glucose sensor the skin underneath the sensor will be assessed and cleaned. In the event of the sensor becoming dislodged, we will ask the parents if the sensor can be replaced. If the sensor requires replacement, an addition heel lance blood test will be required 1 to 2 hours after the insertion of the new sensor.

Feeding data

Parents will be encouraged to enter all feeds (breast or bottle) into a commonly used breastfeeding software application (Feed Baby Pro, Penguin Apps, Version 21.0.5, Victoria. Australia) on a small hand held computer device. At the completion of the five-day study period, data will be exported as a CVS file and stored in a secure database, for later analysis. If the parents wish to have a copy of the feeding data, in order to continue using the application on a personal device, we will email the information.

Daily Review

At enrolment each family will receive an individualised plan, which will indicate the time frames in which the research staff will be visiting the baby to perform the blood tests and daily review. A member of the research team will be on call for the parents at all times. In the unlikely event of a baby becoming unwell for any reason, the baby will be assessed and referred for treatment. A clinician, who is not part of the study team, will provide treatment. The principal investigator will also be notified. Any required blood samples will be taken as clinical indicated, independent of the study protocol. All babies will remain in the study, unless the parents request otherwise.

Intervention code [1] 292853 0
Not applicable
Comparator / control treatment
Not applicable - observational study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294727 0
To determine the range and variation of blood glucose concentrations.
Timepoint [1] 294727 0
within the first five postnatal days.
Primary outcome [2] 296108 0
To determine the range and variation of interstitial glucose concentrations within the first five postnatal days.
Timepoint [2] 296108 0
Within the first five postnatal days
Secondary outcome [1] 313934 0
To determine the incidence of blood glucose concentrations < 2.6mM within the first 48 hours after birth
Timepoint [1] 313934 0
Within the first 48 hours after birth
Secondary outcome [2] 313936 0
To determine the range and variation of blood lactate concentrations.
Timepoint [2] 313936 0
Within the first five postnatal days
Secondary outcome [3] 317529 0
To determine the range and variation of blood ketone concentrations.
Timepoint [3] 317529 0
Within the first five postnatal days
Secondary outcome [4] 317530 0
To determine the differences, if any, between breast-fed and formula fed babies in blood glucose concentrations.
Timepoint [4] 317530 0
Within the first five postnatal days
Secondary outcome [5] 317531 0
To determine the differences, if any, between breast-fed and formula fed babies in blood lactate concentrations.
Timepoint [5] 317531 0
within the first five postnatal days
Secondary outcome [6] 317553 0
To determine the differences, if any, between breast-fed and formula fed babies in blood ketone concentrations.
Timepoint [6] 317553 0
Within the first five postnatal days

Eligibility
Key inclusion criteria
Babies who are
1. 37 to 42 weeks’ gestation and assessed as appropriate for gestational age at birth.
2. Appropriate weight for gestational age (birth weight > 10th centime and < 90th centile).
3. Singletons
4. Living within 20 kilometers of Waikato Hospital
5. English-speaking parents
Minimum age
0 Hours
Maximum age
6 Days
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Babies will be excluded who have any of the following
1. Birthweight < 2500g or > 4500 g
2. Apgar score < 7 at five minutes of age
3. Skin conditions preventing the attachment of the continuous glucose monitor
4. Unwell for any reason
5. Major congenital abnormalities or terminal conditions.
6. Born to mothers with an antenatal history of diabetes, hypertension, drug dependency, or using medications, which may affect the newborns blood glucose concentration, e.g. corticosteroids, sodium valproate.
7. Born to mothers with a Body Mass Index < 18.5 or > 30 kg/m2

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Power and Sample size

Approximately 5,800 babies are born within the Waikato region each year. Of these babies 30 % are likely to be at risk of hypoglycaemia and therefore excluded from our possible study population, leaving approximately 4060 babies.


To reliably describe the range and variation of blood glucose in healthy term babies within the first five postnatal days, we have also used data from the CHLYD study. Glucose profiles from the 258 term babies within the CHYLD study showed the mean glucose concentration at 12 hours of age were 3.3 mM (SD 0.7). In order to have a 95% level of confidence to detect a difference of 0.17mM in the mean blood glucose concentration, between the at-risk babies within the CHYLD study and the healthy term babies we would need to recruit 50 babies.

However, we expect some families not to complete the study. Allowing for a 25% withdrawal we will need to recruit 63 babies. Due to equipment and staff availability only two babies will be enrolled in GLOW at any time. We aim to start recruiting to GLOW in October 2015 and will complete the data collection phase of the study within a one-year period.

To determine the incidence of neonatal hypoglycaemia within the first 48 hours, using the current definition of 2.6mM. Of the 404 at-risk babies recruited to the CHYLD Study, 258 were term babies and of these babies 240 (56 %) became hypoglycaemic (< 2.6mM). Authors from previous reports have reported the incidence of hypoglycaemia in the healthy newborn population is 15%. Using a two-tailed design with alpha at 0.05 and beta at 0.2 we will therefore need 19 babies for the sample size.

Data Analysis

Categorical variables will be analysed using number and percent. Continuous variables will be analysed to determine the distribution, range, and variance.
Interstitial blood glucose concentration profiles will be examined for episodes of hypoglycaemia, and quantified for frequency, duration, and severity. Each baby will have electronic feeding data, which will be time matched with the interstitial glucose concentrations profiles and examined for feed-related variation using regression analysis, box plots and area under the curve analyses.


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 outside Australia
Country [1] 6789 0
New Zealand
State/province [1] 6789 0

Funding & Sponsors
Funding source category [1] 291045 0
Charities/Societies/Foundations
Name [1] 291045 0
Waikato Medical Research Foundation
Address [1] 291045 0
Peter Rothwell Academic Centre
Waikato Hospital
Pembroke Street
Private Bag 3200
Waikato Mail Centre
Hamilton 3240
Country [1] 291045 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato District Health Board
Address
Corner Selwyn and Pembroke Street
Hamilton
West Hamilton
New Zealand 3204
Country
New Zealand
Secondary sponsor category [1] 290396 0
None
Name [1] 290396 0
Address [1] 290396 0

Country [1] 290396 0
Other collaborator category [1] 278425 0
University
Name [1] 278425 0
Liggins Institute, Auckland University
Address [1] 278425 0
The University of Auckland
Private Bag 92019
Victoria Street West
Auckland 1142
Country [1] 278425 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292629 0
Health and Disability Ethics Committee of New Zealand
Ethics committee address [1] 292629 0
Ministry of Health
Freyberg Building
20 Aitken Street
P O Box 5013
Wellington 6011
Ethics committee country [1] 292629 0
New Zealand
Date submitted for ethics approval [1] 292629 0
30/07/2015
Approval date [1] 292629 0
19/08/2015
Ethics approval number [1] 292629 0
15/NTA/104

Summary
Brief summary
Neonatal hypoglycaemia is important because it is linked with poor neurological outcome. In recent years, there has been considerable interest in the detection and management of neonatal hypoglycaemia. Babies who are identified as being at risk are screened using heel-lance blood tests for the first days after birth. If hypoglycaemia is diagnosed, then treatment is usually provided. Glucose is the primary cerebral fuel and the aim of treatment is to increase the blood glucose concentration to ensure adequate cerebral energy supply.

The definition of neonatal hypoglycaemia has caused considerable controversy. The current accepted definition < 2.6mM has been determined using limited, but the only available data. However, the normal glucose profile of healthy appropriately grown term newborns has never been reliably described, and it is possible that many babies are being unnecessarily treated. Babies have been shown to use alternative cerebral fuels, primarily lactate and ketones. The profiles of blood lactate and ketone blood concentrations in healthy newborns within the first week are also unclear.

We propose a prospective observational cohort study in healthy appropriately grown term newborns to describe the normal glucose, lactate and ketone concentration profiles over the first five postnatal days. Babies enrolled in the study will be cared for as normal newborns, largely by the parents as they progress from hospital, or birthing centre and home. Parents to capture data about every feed electronically.

Analysis of the blood will begin as soon as possible after birth, umbilical cord blood will be sampled for the measurement of glucose, lactate and ketones. During the first 24 hours, each baby will have three heel-lance blood tests for the measurement of glucose, lactate and ketones. The timing of these initial blood tests will mirror the current screening protocol for at-risk babies. Following which, babies will have heel-lances blood tests at 8 to 10 hourly intervals (maximum of 16 blood tests over the 5 day period). The results of the blood tests will not be available until the study is completed. In addition a continuous interstitial glucose monitor will be placed subcutaneously, into the baby’s thigh and remain in place for the five days.

If “neonatal hypoglycaemia” as currently defined is shown to be part of normal metabolic transition, it is likely that current clinical management will significantly change.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55030 0
Dr Deborah Harris
Address 55030 0
Newborn Intensive Care Unit
Waikato Hospital
Private Bag 3200
Hamilton
New Zealand 3204
Country 55030 0
New Zealand
Phone 55030 0
+64 21 471 790
Fax 55030 0
Email 55030 0
Deborah.Harris@waikatodhb.health.nz
Contact person for public queries
Name 55031 0
Dr Deborah Harris
Address 55031 0
Newborn Intensive Care Unit
Waikato Hospital
Private Bag 3200
Hamilton
New Zealand 3204
Country 55031 0
New Zealand
Phone 55031 0
+64 21 471 790
Fax 55031 0
Email 55031 0
Deborah.Harris@waikatodhb.health.nz
Contact person for scientific queries
Name 55032 0
Dr Deborah Harris
Address 55032 0
Newborn Intensive Care Unit
Waikato Hospital
Private Bag 3200
Hamilton
New Zealand 3204
Country 55032 0
New Zealand
Phone 55032 0
+64 07 8398899 ex 96750
Fax 55032 0
+64 07 8398742
Email 55032 0
Deborah.Harris@waikatodhb.health.nz

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