ANZCTR - Registration

Registration number

ACTRN12615000380594

Ethics application status

Approved

Date submitted

3/03/2015

Date registered

27/04/2015

Date last updated

30/07/2018

Type of registration

Retrospectively registered

Titles & IDs

Public title

Description of Lung Ultrasound From Initial Neonatal Transition, The DOLFIN Study

Scientific title

Capturing and evaluating lung ultrasound images, heart rate, and saturation of peripheral oxygen in term and late preterm (>32/40 weeks) infants not expected to require respiratory support at birth to determine whether ultrasound images of lungs have predictable changes in the first few hours of life.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Neonatal resuscitation

Lung aeration at birth

Condition category

Condition code

Reproductive Health and Childbirth

Childbirth and postnatal care

Reproductive Health and Childbirth

Complications of newborn

Respiratory

Normal development and function of the respiratory system

Intervention/exposure

Study type

Observational

Description of intervention(s) / exposure

This is a prospective, observational study of spontaneously breathing term and late preterm infants in the delivery room. The primary outcome will be to determine if ultrasound images of the lungs have predictable changes during the first few hours of life.

Antenatal consent will be obtained from the parents prior to enrolment after admission to birth suites and initial assessment of the obstetric team or during the final prenatal visit. Consent will only obtained if not in established labour.

Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA). An investigator will perform serial lung ultrasound exams, recordings 3-5 second clips of the right and left lung fields using 2D imaging and M-mode. The lung ultrasound exams will be brief. We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained. Prior to application to the baby’s skin, the ultrasound gel will warmed by placing it on a clean gauze under the radiant warmer in the patient’s room. After the exam, the ultrasound gel will be removed from the baby’s skin.

At the one hour exam, ultrasound images of the will be obtained from the anterior, axillary, and posterior chest of the baby. The purpose of obtaining additional images at the one hour exam will be to test if there is a difference in lung aeration and fluid clearance with the probe positioned at different areas of the chest. In a study of 154 term and late preterm babies, Raimondi and colleagues performed lung ultrasound exams at 1-2 hours of life. Nine percent, 30%, and 61% had type 1, 2, and 3 lung ultrasound findings respectively. Therefore, the one hour exam may be ideal to compare images in different sections of the chest because of the variety of lung aeration grades and less potential to interfere with maternal bonding. The information obtained from the additional images will help standardize the lung ultrasound exam. The one hour exam will be limited to 5 minutes.

Lung ultrasound clips will be independently collected by an investigator (DB). Two 2-D clips and 2 images captured with M-mode for each exam will be de-identified, coded, and blindly graded by 3 consultants with expertise in ultrasonography (LF, OK, SR). The degree of lung aeration will be assigned based on the grade of these images at type 1, 2, or 3 using a previously published grading system. In the event of a disagreement among the blinded consultants, if 2/3 consultants agree, that grade will be assigned. If all three consultants assign a different grade, we will review the images openly in a group discussion. We will test inter-rater reliability of characterizing lung ultrasound images as type 1, 2, or 3 by having the three blinded ultra-sonographers independently evaluate each ultrasound clip using a Spearman’s rank-order test.

Before the ultrasound exams, we will place a pulse oximetry sensor on the baby’s right hand or wrist to measure the baby’s heart rate and oxygen levels. These measurements can be obtained while the baby is on the mother’s chest or being held by the family. Heart rate and SpO2 will be obtained using either an NM3 Respiratory Profile Monitor (Philips Respironics, The Netherlands) or Radical 7 pulse oximeter (Masimo, California, USA). The heart rate, and SpO2 will be converted from analog to digital signal for statistical analysis. Measurements recorded will be analyzed using Stata Software (StataCorp, College Station, Texas, USA) for statistical analysis. The pulse oximeter will be applied to the baby’s right hand or wrist at each prior to each of the ultrasound examinations and be removed after the ultrasound exam is finished. If available, we will also record the umbilical arterial cord blood gas for analysis.

If the investigators observe any concerning findings on lung ultrasound (evidence of pneumothorax or effusion) or pulse oximetry, they will immediately notify the clinical team caring for the baby.

Our goal is obtain the desired data without altering the experience of the parents as they introduce a new member to their family and to avoid any interference with the clinicians caring for the baby. The lung ultrasound exams may be performed on the warming bed with the agreement of the clinician caring for the baby. If the clinical team decides that the baby is well enough to be moved from the warming bed to be with the mother, lung ultrasound exams can also with the infant on the mother’s chest or while being held by a family member. If the baby cannot be held by the mother (or other family member) but the baby can be positioned close to the mother, there will be a dedicated research trolley with a warming mattress available to place the baby as close as possible to the mother for lung ultrasound exams. The natural transition of the healthy newborn includes bonding with the mother after birth. The study should not preclude skin to skin contact of babies or breastfeeding with their mothers in the first ten minutes of life.

We will review the data collected after enrolling 10 and 50 babies. The purpose will be to review for adverse outcomes, quality of ultrasound images, efficacy of data collection and grading. Specifically, we will monitor the baby’s first temperature collected by the clinical team, the potential of interfering with patient care, review the quality of ultrasound images using different exam techniques and settings (like location of ultrasound probe, gain, and depth), and the inter-relater reliability.

The research team has over 10 years of experience studying neonatal transition in the delivery room The measurements obtained from this cohort of babies constitutes an observational study. This data will provide valuable information on the appearance of the lungs on ultrasound from birth through the first day of life and may serve as crucial baseline data for future interventional studies intended to improve respiratory care of newborns.

The measurements and images obtained from this cohort of babies constitutes an observational study. The data will provide valuable information on lung ultrasound in the first minutes to hours after birth.

Intervention code [1]

Not applicable

Comparator / control treatment

Nil

Control group

Uncontrolled

Outcomes

Primary outcome [1]

The primary outcome will be to determine if ultrasound images of the lungs have predictable changes during the first few hours of life. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).

Timepoint [1]

We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.

Secondary outcome [1]

To determine the proportion of babies with aerated lungs at designated time points listed in the research plan. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).

Timepoint [1]

We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.

Secondary outcome [2]

To determine the average time to a fully aerated lung based on ultrasound imaging. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).

Timepoint [2]

We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.

Secondary outcome [3]

To correlate the degree of lung aeration with the heart rate (HR) and saturation of peripheral oxygen (SpO2). Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA). HR and SpO2 will be obtained using an NM3 Respiratory Function Monitor (Philips, California USA) or a Radical-7 Pulse Oximeter (California, USA).

Timepoint [3]

We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained. Prior to each lung ultrasound exam, we will place a pulse oximetry sensor on the baby's right wrist, then remove the sensor once the exam is completed.

Secondary outcome [4]

To determine the time needed to perform a lung ultrasound exam that yields clean images easily reviewed by blinded expert sonographers. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).

Timepoint [4]

We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.

Secondary outcome [5]

To document abnormalities of lung pathology using ultrasound. Ultrasound images will be obtained using the Vividi (GE Healthcare, Wauwatosa, USA).

Timepoint [5]

We will use a timer to limit exams to 2 minutes or less from the time of placing the ultrasound gel on the baby’s skin. Lung ultrasound exams will be performed at 6 time points: less than 10 minutes of life, 10-20 minutes of life, 1 hour of life, 2 hours of life, 4-6 hours of life, and 24-72 hours of life (the final exam targeting the time frame closest to discharge). If the lungs appear to have reached full aeration on two consecutive exams by the ultrasonographer (bilateral presence of A-lines with normal lung sliding), the study will be considered complete and no further images will be obtained.

Eligibility

Key inclusion criteria

All inborn infants greater or equal to 33/40 weeks gestation, who are not expected to require respiratory support at birth, are eligible for this study. Antenatal consent from the parents will be required for enrolment.

Minimum age

No limit

Maximum age

0 Hours

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Infants will be excluded from analysis if they have a congenital abnormality. Infants will be excluded if their parents decline to give consent to this study. If there are signs of respiratory compromise or distress after birth, data collection will be delayed and ventilatory support given according to the Australian Neonatal Resuscitation guidelines. Infants who receive respiratory support for a brief period of time may still be eligible with the agreement of the clinician in charge of the infant’s care.

Study design

Statistical methods / analysis

We plan to recruit a convenience sample of 100+ infants, born at >34 weeks gestational age. We will enrol 50 born via elective c-section and 50 born vaginally. A third group of infants to be included will be infants born via unplanned c-section after a trial of labour. We have no target size for this 3rd group. We believe that serial lung ultrasound on 100+ term and late preterm babies will be an adequate sample size to perform basic statistical evaluations, like repeated measured ANOVAs, with a chance of a type 1 error <0.05 and a power of 80%. The sample size is also adequate to test intra-relater reliability and inter-relater reliability.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

4/03/2015

Actual

4/03/2015

Date of last participant enrolment

Anticipated

3/03/2016

Actual

10/02/2016

Date of last data collection

Anticipated

Actual

28/02/2016

Sample size

Target

114

Accrual to date

Final

114

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Royal Women's Hospital - Parkville

Recruitment postcode(s) [1]

3052 - Parkville

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council Program Grant

Country [1]

Australia

Funding source category [2]

Hospital

Name [2]

The Royal Women's Hospital

Country [2]

Australia

Primary sponsor type

Individual

Name

Prof Peter Davis

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Prof Stuart Hooper

Country [1]

Australia

Other collaborator category [1]

Individual

Name [1]

Dr Omar Kamlin

Country [1]

Australia

Other collaborator category [2]

Individual

Name [2]

Dr Lisa Fox

Country [2]

Australia

Other collaborator category [3]

Individual

Name [3]

Dr Sheryle Rogerson

Country [3]

Australia

Other collaborator category [4]

Individual

Name [4]

Dr Graeme Polglase

Country [4]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Royal Women's Hospital Research and Human Research Ethics Committees

Ethics committee address [1]

The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

07/01/2015

Approval date [1]

27/02/2015

Ethics approval number [1]

15/01

Summary

Brief summary

Before birth, while a baby is in the mother’s womb, the baby’s lungs are filled with fluid and the baby gets oxygen from the placenta. Once the baby is born, the baby needs to transition to using the lungs to get oxygen. In the hours after birth, the baby’s body will reabsorb the lung fluid and the lungs will fill with air. The purpose of this study is to describe the normal filling of a newborn baby’s lungs with air over the first few hours of life using an ultrasound machine. We believe that with the knowledge gained in this study, we can improve our care for babies that need help breathing at birth.  

The lung ultrasound exams will be brief, limited to 2 minutes or less from the time of placing the ultrasound probe gently to your baby’s chest. The first two exams will be during the first 20 minutes after your baby is born and will be repeated when your baby is 1 hour old, 2 hours old, 4 to 6 hours old and 24 to 72 hours old. At 1 hour of life, the lung ultrasound exam will be slightly longer as we take images of the front, back and side of your baby’s chest to test if a specific location to place the probe is better than another.

Trial website

Public notes

Attachments [1]

/AnzctrAttachments/368087-DOLFIN Study Protocol V4 26.02.2015.doc

Attachments [2]

/AnzctrAttachments/368087-DOLFIN Study Consent V4 26.02.2015.doc

Attachments [3]

/AnzctrAttachments/368087-DOLFIN Study Patient Data Form V4 26.02.2015.doc.docx

Contacts

Principal investigator

Name

Dr Douglas Blank

Address

The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052

Country

Australia

Phone

+61422305487

Email

[email protected]

Contact person for public queries

Name

Douglas Blank

Address

The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052

Country

Australia

Phone

+61422305487

Email

[email protected]

Contact person for scientific queries

Name

Douglas Blank

Address

The Royal Women's Hospital
Locked Bag 300
Cnr of Grattan Street and Flemington Road
Parkville, VIC 3052

Country

Australia

Phone

+61422305487

Email

[email protected]

Source	Title	Year of Publication	DOI
Embase	Lung ultrasound during the initiation of breathing in healthy term and late preterm infants immediately after birth, a prospective, observational study.	2017	https://dx.doi.org/10.1016/j.resuscitation.2017.02.017
Embase	Lung ultrasound immediately after birth to describe normal neonatal transition: An observational study.	2018	https://dx.doi.org/10.1136/archdischild-2017-312818
Embase	Respiratory changes in term infants immediately after birth.	2018	https://dx.doi.org/10.1016/j.resuscitation.2018.07.008

Trial Review

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