Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000242729
Ethics application status
Approved
Date submitted
3/02/2022
Date registered
10/02/2022
Date last updated
10/02/2022
Date data sharing statement initially provided
10/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The Development of the Human Visual System In Utero: An Experimental Approach
Scientific title
The Development of the Human Visual System In Utero: Fetal Responding to Visual and Auditory Stimuli.
Secondary ID [1] 306303 0
Waikato District Health Board: RD021137
Secondary ID [2] 306304 0
Te Aparangi The Royal Society Marsden standard grant: 20-UOW-022
Universal Trial Number (UTN)
U1111-1273-7070
Trial acronym
FVP (Fetal Visual Perception)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pregnancy 325061 0
Condition category
Condition code
Reproductive Health and Childbirth 322498 322498 0 0
Normal pregnancy
Eye 322609 322609 0 0
Normal eye development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The overarching aim of this research is to investigate fetal visual perception. Recently it has been determined that the human fetus lives in an environment that is not dark. This project seeks to understand how human fetuses respond to aspects of visual and auditory stimuli presented in utero. The current research will use 2D ultrasound to visualize the fetal lens and record eye movements in response to light and auditory stimuli presented in utero.

Aims
Aim 1: Do fetuses preferentially orientate to light stimuli in their peripheral visual field?
Aim 2: To examine whether fetuses can perform anticipatory gaze. Specifically, can fetuses use an auditory cue to anticipate the appearance of a light stimulus?
Aim 3: To examine fetal sensitivity to spatio-temporal cues that correlate with adult interpretations of agentive motion.
Aim 4: To examine fetal eye movements in response to a moving visual stimulus.

Participants
Participants will be healthy volunteers with singleton pregnancies between 33 -36 weeks gestation.

Materials

Image Acquisition

Ultrasound scans will be performed at Waikato Hospital using a Philips Epiq7 Elite Ultrasound System using a 5C1, or 9C2 transducer, keeping TIb<0.3. Individual scans will be recorded in entirety and saved to an external hard drive for offline analysis.

Experienced and qualified sonographers will undertake the scanning. Images will be captured in the transverse and parasagittal plane of the fetal face.

Stimuli

Light Stimulus

The light source will consist of one red 4mm LED emitting at 650nm (for part one, two and three) and will consist of two red 2mm LEDs emitting at 650 nm (part four). The light source will be calibrated to specific optical powers dependant on the maternal tissue thickness. This will ensure that consistent levels of light are delivered to the fetus irrespective of variation in maternal tissue thickness. It is estimated that when accounting for dispersion, the light stimuli will broaden to a diameter of 22mm (Del Giudice, 2011). The light stimulus will be presented within the predicted range of the fetal visual system. Presenting this light stimulus to the fetus is completely safe. The level of luminance is lower than what a fetus could be exposed to on a sunny day and poses no risk of damage to the fetal visual system (Del Giudice, 2011).

Auditory Stimulus

The auditory cue stimulus will be a 500 Hz tone. The intensity of the tone recorded at the maternal abdomen will be 70 dB. The auditory stimulus will be delivered to the fetus by a speaker positioned within 1 meter of the maternal abdomen. Auditory stimulus will be produced using MATLAB. (2018). Tone intensity and frequency are safe and within the range of the fetal auditory system (Graven, 2000) proposed tone frequency and intensity is consistent with experimental studies examining auditory processing in utero (Dunn et al., 2015)

Method

Study participation consists of attending one 2D ultrasound scan.

Time: 60 minutes (approximately). The total time of the sonography scan is approximately 25-30 minutes. The session time of 60 minutes allows the participants to locate the study room, ask questions and familiarise themselves with the researchers and study equipment and debriefing.

Study Location: Women’s Health Clinic. Level 1 Elizabeth Rothwell Building, Waikato Hospital.
Mothers will lie in a comfortable position as in any normal 2D ultrasound scan. If the fetus is not in a position that will allow an adequate image of the face region or delivery of the visual stimuli, the mother will be asked to take a short walk and/or take a drink of water in order to stimulate movement within the fetus.

The following measurements will be taken at the beginning of the scan: fetal biometric measurements including fetal heart rate (FHR), biometric measurements including bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) and single deepest pocket (SDP) of amniotic fluid. The measurements will be considered normal for the purposes of this study if:

- FHR = 120-180bpm
- AC >= 10th percentile
- EFW >= 10th percentile
- SDP >= 2cm
- The fetal eyes are morphologically normal

Once these measurements are completed the researchers will move on to presenting the stimuli to the fetus for the separate experiments.

• Part One: Anticipatory Gaze
1.) Familiarisation Trails: Present auditory and light stimuli pairing (6x) 12 seconds per trial, 72 seconds total.
2.) Test trails: sound and light present (3x) and sound and no light stimuli (x3) 12 seconds per trial, 72 seconds total.
Total time = 144 second (2.4 minutes)


• Part 2: Peripheral vs Nasal Responding
1.) Present light stimuli (dot) to the fetal peripheral visual field for 60 secs
2.) Rest period (no stimulus present) for 180 second (3 minutes)
3.) Present light stimuli (dot) to the fetal nasal visual field for 60 secs
4.) Order Counterbalanced
Total Time = 300 seconds (5 minutes)

• Part 3: Detecting and inducing eye movements
1.) Present light stimuli (dot) to the fetal peripheral visual field for 60 seconds
2.) Light absent (no light stimulus present) for 60 seconds (1 minute)
3.) Order Counterbalanced
Total time =120 seconds (2 minutes)

• Part 4: Motion Cues
1.) Present agentive motion light stimuli to the fetus 120 seconds (2 minutes)
2.) Present independent motion light stimuli to the fetus 120 seconds (2 minutes)
3.) Order counterbalanced
Total time = 300 seconds (5 minutes)

Following birth, patient and baby notes will be accessed to gain health information regarding mother and baby. This information will be entered into analysis to account for any potential causes of movement in the fetus during the study.

References

del Giudice, M. (2011). Alone in the dark? Modeling the conditions for visual experience in human fetuses. Developmental Psychobiology, 53(2), 214–219. https://doi.org/10.1002/dev.20506

Dunn, K., Reissland, N., & Reid, V. M. (2015). The functional foetal brain: A systematic preview of methodological factors in reporting foetal visual and auditory capacity. Developmental Cognitive Neuroscience, 13, 43–52. https://doi.org/10.1016/j.dcn.2015.04.002

Graven, S. N. (2000). Sound and the Developing Infant in the NICU: Conclusions and Recommendations for Care. Journal of Perinatology, 20(S1). https://doi.org/10.1038/sj.jp.7200444
Intervention code [1] 322734 0
Behaviour
Comparator / control treatment
Within subjects experimental design. Participants act as their own control.

Control Condition: three minute baseline period before light and sound stimuli are presented. Eye movements (duration and direction) will be recorded over this period. There is a 2 minute period of no stimulus presentation (washout) between separate experiment presentations.

Control group
Active

Outcomes
Primary outcome [1] 330287 0
Number, duration and direction of fetal eye movements
Instrument: 2D ultrasound scan
Timepoint [1] 330287 0
At the time of the recorded 2D ultrasound scan and stimulus presentation
Secondary outcome [1] 405582 0
Number, direction and duration of fetal head movements recording with a 2D ultrasound
Instrument: 2D ultrasound
Timepoint [1] 405582 0
At the time of the recorded 2D ultrasound scan and stimulus presentation

Eligibility
Key inclusion criteria
Inclusion Criteria

1 Healthy pregnancy
2 BMI < 30
4 Singleton Pregnancy
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
None

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample Size

The sample size was determined on the basis of the attrition rate of these studies in infant research. A generous number was added to allow for additional attrition in fetal studies caused by excessive movement or the inability to present stimuli/gain an adequate image of the fetus.

Statistical Analysis

Group comparison will be conducted using dependent sample paired t-tests and Wilcoxan ranked sign tests as per prior studies in this field.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2022
Actual
Date of last participant enrolment
Anticipated
1/03/2023
Actual
Date of last data collection
Anticipated
1/03/2023
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment outside Australia
Country [1] 24529 0
New Zealand
State/province [1] 24529 0
Waikato

Funding & Sponsors
Funding source category [1] 310649 0
Charities/Societies/Foundations
Name [1] 310649 0
Royal Society Te Aparangi
Country [1] 310649 0
New Zealand
Primary sponsor type
University
Name
University of Waikato
Address
Professor Vincent Reid
University of Waikato
Te Whare Wananga o Waikato
Gate 1, Knighton Road
Hamilton 3240
Country
New Zealand
Secondary sponsor category [1] 311960 0
None
Name [1] 311960 0
Address [1] 311960 0
Country [1] 311960 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310245 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 310245 0
Ethics committee country [1] 310245 0
New Zealand
Date submitted for ethics approval [1] 310245 0
10/11/2021
Approval date [1] 310245 0
25/01/2022
Ethics approval number [1] 310245 0
2021EXP11521

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

Contacts
Principal investigator
Name 116986 0
Prof Vincent Reid
Address 116986 0
Professor Vincent Reid
The University of Waikato
Private Bag 3105
Hamilton 3240
New Zealand
Country 116986 0
New Zealand
Phone 116986 0
+64 07 8384466 9593
Fax 116986 0
Email 116986 0
[email protected]
Contact person for public queries
Name 116987 0
Vincent Reid
Address 116987 0
Professor Vincent Reid
The University of Waikato
Private Bag 3105
Hamilton 3240
New Zealand
Country 116987 0
New Zealand
Phone 116987 0
+64 07 8384466
Fax 116987 0
Email 116987 0
[email protected]
Contact person for scientific queries
Name 116988 0
Vincent Reid
Address 116988 0
Professor Vincent Reid
The University of Waikato
Private Bag 3105
Hamilton 3240
New Zealand
Country 116988 0
New Zealand
Phone 116988 0
+64 07 8384466
Fax 116988 0
Email 116988 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified individual participant data underlying published results.
When will data be available (start and end dates)?
Beginning three months and ending seven years following the publication of the main results.
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
To achieve the aims stated in the approved proposal
How or where can data be obtained?
Access subject to approval by the Principal Investigator ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



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.