Substantial Amendment 1 i) Addition of a Secondary Outcome: The health economic outcomes have been amended to include survival at one year of age, corrected for prematurity; ii) Local Translation Services: Following feedback from sites, regarding the importance of not excluding those that do not have a good understanding of-English, detail has been included in the Protocol to allow the use of routinely used translation services in obtaining consent; iii) Surfactant being Animal Derived: In the REC’s initial application review, it was requested that the PIL include detail that surfactant is an animal derived product. This has now been included in both the PIL and Protocol; iv) Personal Identifiers to be Shared with National Databases: As requested by NHS Digital, details have been included in the Consent Form and PIL, regarding the personal identifiers that will be shared with National Databases, when collecting follow-up data; v) Additional Detail on Safety Reporting: Further detail is provided on serious adverse events that are foreseeable in the patient population and do not require reporting as SAEs. Amends have also been made to the review and reporting of SAEs. Replaces the first Protocol, PIL and Consent Form V2.0 5th Feb 2020 on the study.

Substantial Amendment 2 i) Addition of 8x Recruiting Sites; ii) Change of Principal Investigator (PI) at Royal Devon and Exeter NHS Foundation Trust; iii) Addition of 150x Continuing Care Sites. During their postnatal stay, infants on SurfON study could be transferred from their Recruiting Site to another hospital. By gaining approval pre-emptively for as many Continuing Care Sites as possible, we hope to allow transferred infants to continue to participate in SurfON without disruption and to allow Recruiting Sites to complete data collection using Case Report Forms by liaising with the Continuing Care Sites.

Substantial Amendment 3 i) Addition of 1x Recruiting Site; ii) Change of PI at Northern Lincolnshire & Goole NHS Foundation Trust.

Substantial Amendment 4 i) Protocol updated to include: change of Trial Manager; addition of use of Laryngeal Mask for method of administration of IMP; clarification of SAE reporting in relation to category level of infant transfers; removal of reference to SAE reporting method via Fax; removal of ‘Once reported online, forms will be printed by the local PI to perform a causality review’; ii) Change of Trust Name to previously approved sites: Luton & Dunstable University Hospital NHS Foundation Trust changed to Bedfordshire Hospitals NHS Foundation Trust; Poole Hospital NHS Foundation Trust changed to University Hospitals Dorset NHS Foundation Trust: iii) Addition of new recruiting site: Birmingham Women’s & Children’s NHS Foundation Trust.

Substantial Amendment 5 i) Addition of OID for Continuing Care Sites; ii) Addition of new recruiting site - North Bristol NHS Trust; iii) Change of PI - at Countess of Chester Hospital NHS Foundation Trust and University Hospitals Coventry and Warwickshire NHS Trust.

Substantial Amendment 6 i) Protocol updated to include: Clarification regarding counter-signature by mother on consent form; change of place of data entry for Mothers Trial Entry and Trial Discharge questionnaires; ii) Addition of 11x Continuing Care Sites.

Substantial Amendment 7 i) Protocol Changes: Rationale & inclusion of ANNPs to confirm eligibility; Minor formatting errors corrected and contact details updated; Recently published systematic review included; Inclusion of Special Care Units as participating centres; Clarification on optional participation for mother when they have provided consent to complete questionnaire; Clarification on hospital transfers only related to early respiratory management will need to be reported to the trial team as a SAE and further explanation; ii) Consent Form Changes: Minor formatting and guidance provided to indicate that the mother’s countersignature must be obtained as soon as possible if other parent has provided original consent; Guidance provided to indicate that the mother can complete questionnaires only if consent has been provided in the mother’s section which will also require signature from health professional obtaining consent; iii) Trial Questionnaire Changes: Donor breast milk added as an option in the question pertaining to how the baby has fed since delivery in both questionnaires; iv) Changes to Trial Timeline: Extension approved by funder for a further period of 7 months taking the overall trial end date to June 2023. No change in research activities or recruitment numbers.

Substantial Amendment 8 Protocol changes: 1) Addition of a reference to the 'Background and rationale' section 2) Clarification for inclusion criteria #3: Definition of 'respiratory distress' has been refined 3) Sentence about providing women having a planned caesarean section at 37-38 weeks with study information antenatally reworded for clarity 4) The timeframe for completing the Discharge Questionnaire has been updated to reflect that it occurs around the time of discharge. 5) Sentance about withdrawal of participants reworded for clarity. 6) Section defining events that need to be reported as SAEs reworded for clarity. 7) Development Safety Update Reports' section updated to reflect that the trial is now approved under the notification scheme rather than expected to be. 8) Edit to reflect that the HTA Programme Manager will not be invited to attend all TSC meetings. Minor changes to study documents 1) New document - SurfON Parent Card - QR card to scan to access SurfON Introduction Podcast 2) Amendments to SurfON General Data Protection Regulation (GDPR) for Patients - to reflect changes to the HRA Patient Data and Research leaflet. Study Design Extension approved by funder for a further period of 26 months taking the overall trial end date to 31st August 2025. No change in research activities or recruitment numbers.