Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001241729
Ethics application status
Approved
Date submitted
7/07/2022
Date registered
14/09/2022
Date last updated
16/03/2023
Date data sharing statement initially provided
14/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Benefits of Analysing Brain
Biomarkers in perinatal care: a prospective observational cohort study
Scientific title
Benefits of Analysing Brain
Biomarkers in perinatal care: a prospective observational cohort study
Secondary ID [1] 307509 0
nil known
Universal Trial Number (UTN)
Trial acronym
BABBies
Linked study record

Health condition
Health condition(s) or problem(s) studied:
perinatal care
 326935 0
antenatal care 326936 0
neurological inflammation 326937 0
Condition category
Condition code
Reproductive Health and Childbirth 324119 324119 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 324120 324120 0 0
Antenatal care
Reproductive Health and Childbirth 324121 324121 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 324122 324122 0 0
Normal pregnancy
Neurological 324123 324123 0 0
Other neurological disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
We will prospectively collect umbilical 3ml of cord blood from 110 placentae. Umbilical cord blood samples will be collected by midwives in theatre or the birthing suite. All patients giving birth will be eligible for inclusion in the study. The exclusion of specific patients (e.g., category 1 emergency caesarean cases) may be at the discretion of the midwife, if collection of umbilical cord blood samples is not feasible. Cord blood required for standard of care testing of rhesus and blood gas analysis will be taken as a priority. Only once the required sample volume for this purpose has been obtained will the additional blood for this study be collected. Cases where the patient was consent but an adequate sample of blood was not able to be taken, for whatever reason, will be recorded. Blood will be stored by the midwives in the fridge in a labelled box, for later collection by a member of the Department of Anaesthetics. Biospecimens will be sent to an external lab for analysis.
Intervention code [1] 323971 0
Early Detection / Screening
Comparator / control treatment
Nil Control
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331930 0
Feasibility on testing umbilical cord blood for brain biomarkers by audit of recruitment log to assess number of consenting participants versus viable samples.
Timepoint [1] 331930 0
1 year after commencement of analysing biospecimens
Primary outcome [2] 331945 0
Feasibility of recruiting participants arriving to the hospital to give birth by assessing the screening and recruitment log to determine ratio of patients presenting to labour ward versus number consented
Timepoint [2] 331945 0
1 year following commencement of recruitment
Secondary outcome [1] 411613 0
Plasma NfL measured in umbilical cord blood associated from healthy deliveries (as determined by audit of medical records).
Timepoint [1] 411613 0
1 year following sample analysis.
Secondary outcome [2] 411614 0
Plasma tau measured from umbilical cord blood from healthy deliveries (as determined by audit of medical records).
Timepoint [2] 411614 0
1 year following sample analysis.
Secondary outcome [3] 411615 0
Plasma NfL measured from umbilical cord blood from deliveries with adverse events in pre-natal, in labour and post-natal stages (as gathered from data-linkage of antenatal records, labour records and eMR notes).
Examples of adverse events are listed below:
Pre-natal: abnormal ultrasounds, maternal iron deficiency, maternal infections, maternal infections (aids, HIV, hepatitis, sexually transmitted infections (STIs))
Antenatal: Pre-eclampsia, sepsis, placental abruption, haemorrhage, maternal embolism, restrictive growth, abnormal fetal lactate, prolonged labour stages, requirement for induction of labour.
Postnatal: low birth weight, resuscitation, infection, birth defects, genetic disorders, systemic abnormalities or disorders, re-admisison to hospital/admission to Neonatal care.
Timepoint [3] 411615 0
1 year following sample analysis.
Secondary outcome [4] 411616 0
Plasma tau measured from umbilical cord blood from deliveries with adverse events in pre-natal, in labour and post-natal stages (as gathered from data-linkage of antenatal records, labour records and eMR notes).
Examples of adverse events are listed below:
Pre-natal: abnormal ultrasounds, maternal iron deficiency, maternal infections, maternal infections (aids, HIV, hepatitis, sexually transmitted infections (STIs))
Antenatal: Pre-eclampsia, sepsis, placental abruption, haemorrhage, maternal embolism, restrictive growth, abnormal fetal lactate, prolonged labour stages, requirement for induction of labour.
Postnatal: low birth weight, resuscitation, infection, birth defects, genetic disorders, systemic abnormalities or disorders, re-admisison to hospital/admission to Neonatal care.
Timepoint [4] 411616 0
1 year following sample analysis.
Secondary outcome [5] 411617 0
Plasma NfL measured from umbilical cord blood from cesearean deliveries (as gathered from data-linkage labour records).
Timepoint [5] 411617 0
1 year following sample analysis.
Secondary outcome [6] 411618 0
Plasma tau measured from umbilical cord blood from cesearean deliveries (as gathered from data-linkage labour records).
Timepoint [6] 411618 0
1 year following sample analysis.
Secondary outcome [7] 411619 0
Plasma NfL measured from umbilical cord blood from babies with foetal abnormailites (as gathered from data-linkage labour records and post-natal documentation).
Timepoint [7] 411619 0
1 year following sample analysis.
Secondary outcome [8] 411620 0
Tau measured from umbilical cord blood from babies with foetal abnormailites (as gathered from data-linkage labour records and post-natal documentation).
Timepoint [8] 411620 0
1 year following sample analysis.
Secondary outcome [9] 411621 0
Plasma NfL measured from umbilical cord blood from babies with abnormalities on intrapartum monitoring (Cardiocartography (CTG), scalp lactate) (as gathered from data-linkage labour records and post-natal documentation).
Timepoint [9] 411621 0
1 year following sample analysis.
Secondary outcome [10] 411622 0
Tau measured from umbilical cord blood from babies with abnormalities on intrapartum monitoring (CTG, scalp lactate) (as gathered from data-linkage labour records and post-natal documentation).
Timepoint [10] 411622 0
1 year following sample analysis.
Secondary outcome [11] 411623 0
Plasma NfL measured in babies analysed against gestational age (as gathered from data linkage labour records).
Timepoint [11] 411623 0
1 year following sample analysis
Secondary outcome [12] 411624 0
Tau measured in babies analysed against gestational age (as gathered from data linkage labour records).
Timepoint [12] 411624 0
1 year following sample analysis
Secondary outcome [13] 411625 0
Plasma NfL measured in babies in second stage labour (as gathered from data linkage labour records).
Timepoint [13] 411625 0
1 year following sample analysis
Secondary outcome [14] 411626 0
Number of participants where samples were unable to be collected (as reported by midwifes in recruitment log).
Timepoint [14] 411626 0
1 year follow sample collection
Secondary outcome [15] 413748 0
Plasma NfL measured in babies analysed against birth weight (as gathered from data linkage labour records).
Timepoint [15] 413748 0
1 year following sample analysis
Secondary outcome [16] 413749 0
Tau measured in babies analysed against gestational age (as gathered from data linkage labour records).
Timepoint [16] 413749 0
1 year following sample analysis
Secondary outcome [17] 413750 0
Plasma tau measured in babies in second stage labour (as gathered from data linkage labour records).
Timepoint [17] 413750 0
1 year following sample analysis

Eligibility
Key inclusion criteria
Planned delivery at RPAH
Any route of delivery (vaginal delivery or elective/emergency caesarean sections)
Willingness to provide informed consent
English speaking to permit informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Expected infeasibility of sample collection (at midwife’s discretion)
Non-English speaking
Participants with a history of a psychological illness or other conditions which may interfere with their ability to understand the study requirements or provide consent

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
On the basis of preliminary data showing that umbilical cord blood NfL is significantly lower in placentae of women undergoing elective caesarean than women who underwent laboured delivery, we decided to analyse these two populations separately. Based on one study of NfL in cord blood, we anticipate the interquartile range (IQR) of umbilical vein NfL in non-elective caesarean deliveries to be 17pg/mL. We converted this is to a standard deviation (SD) using the rule of thumb SD = IQR/1.35. To ensure that the 95% confidence interval (CI) of the estimate of the true mean has does not exceed 3pg/mL, we calculated a required sample size of 68 patients. An additional 12 patients were added to account for issues with biospecimen collection and unforeseen emergencies that make collection unfeasible, for a total of 80 patients. For deliveries that were elective caesarean sections, based on another study that delineated caesarean sections from vaginal deliveries, we estimated the IQR to be 10pg/mL. This results in a sample of 24 participants required to establish a 95%CI of 3pg/mL for the true population mean. We increased this to 30 patients to account for issues with blood collection and storage. The total sample size including all modes of delivery is therefore 110. We will include consented patients in whom an adequate sample of cord blood is unable to be obtained in the 110 participants, in order to inform the feasibility and sample size calculation of a future study. However, given the NfL/tau concentrations will not be obtained, these patients will be omitted from the analysis.

Differences in plasma NfL and tau between healthy neonates and those with adverse outcomes will be assessed by independent samples t tests or Mann–Whitney U tests, depending on distribution.
The area under the curve (AUC) of the receiver operating characteristic (ROC) curve will be calculated to assess the test characteristics of elevated cord blood NfL and tau in the prediction of adverse perinatal outcomes. Outcomes will be selected for ROC analysis if there is a statistically significant difference observed between healthy/diseased neonates. The threshold elevation will be determined specifically for each outcome of interest, based on the observed difference in biomarker concentrations between groups. We will compare this to the AUC for CTG abnormalities (binary: present/absent) and scalp lactate elevation for the prediction of the same outcomes.
The normal range of plasma NfL and tau for healthy neonates will be established using the value range in which 95% of confirmed healthy neonates fall.
Scalp blood lactate concentrations with be compared to umbilical cord NfL and tau concentrations using linear regression. The correlation between the presence CTG abnormalities and NfL and tau concentrations will be assessed by independent samples t-test or Mann–Whitney U test, depending on distribution
Our initial analyses will be done independently for elective caesarean section deliveries vs. all other deliveries. However, further adjustments to baseline data may be required. Levels of tau and NfL for the above four analyses may be adjusted based on the multivariable regression analysis described below, if some factors (e.g., gestational age) are revealed to likely confound the outcome.
Linear regression models will be used to assess the correlation between gestational age, birth weight, and duration of 2nd stage of labour and plasma NfL/tau. The relationship between mode of delivery and plasma Nfl/tau will be compared using independent samples t test or Mann–Whitney U test, depending on distribution. All the aforementioned variables will be combined into a multivariable regression model for the prediction of plasma Nfl/tau to increase precision and adjust for confounders.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2022
Actual
24/10/2022
Date of last participant enrolment
Anticipated
Actual
12/12/2022
Date of last data collection
Anticipated
Actual
13/03/2023
Sample size
Target
110
Accrual to date
Final
110
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 22762 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 38041 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 311786 0
Hospital
Name [1] 311786 0
Royal Prince Alfred Hospital
Country [1] 311786 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Faculty of Health and Medicine
The University of Sydney
Science Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 313257 0
None
Name [1] 313257 0
Address [1] 313257 0
Country [1] 313257 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311230 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 311230 0
Ethics committee country [1] 311230 0
Australia
Date submitted for ethics approval [1] 311230 0
11/07/2022
Approval date [1] 311230 0
10/08/2022
Ethics approval number [1] 311230 0
2022/ETH01100

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120398 0
Dr David Zalcberg
Address 120398 0
Royal Prince Alfred Hospital
Department of Anaesthetics
50 Missenden Road
Camperdown NSW 2050
Country 120398 0
Australia
Phone 120398 0
+61 02 9515 7150
Fax 120398 0
Email 120398 0
[email protected]
Contact person for public queries
Name 120399 0
Kaitin Kramer
Address 120399 0
Royal Prince Alfred Hospital
Department of Anaesthetics
50 Missenden Road
Camperdown NSW 2050
Country 120399 0
Australia
Phone 120399 0
+61 02 9515 8789
Fax 120399 0
Email 120399 0
[email protected]
Contact person for scientific queries
Name 120400 0
Kaitin Kramer
Address 120400 0
Royal Prince Alfred Hospital
Department of Anaesthetics
50 Missenden Road
Camperdown NSW 2050
Country 120400 0
Australia
Phone 120400 0
+61 02 9515 8789
Fax 120400 0
Email 120400 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16548Study protocol    384335-(Uploaded-07-07-2022-10-35-25)-Study-related document.pdf
16549Informed consent form    384335-(Uploaded-07-07-2022-10-35-25)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.