The following changes have been made to create Protocol Version 3.0 3rd December 2015: 8.3. Exclusion Criteria (page 16) In the point ‘Note that receiving antenatal or postnatal antibiotics e.g. for maternal Group B Streptococcal carriage or prolonged rupture of membranes, is not a reason for exclusion if there is no indication for ongoing antibiotic prescription post-delivery.’ the words ‘or postnatal’ have been removed because this wording was incorrect and contradicts the previous sentence. Reporting Serious Adverse Events (SAEs) and Procedure for immediate reporting of Serious Adverse Events (pages 25-26): Wording amended improve consistency and to make it clear that events which commence prior to the administration of the trial Intervention do not require reporting as an SAE. 9.5. Randomisation, blinding and code-breaking (pages 20) Text edited regarding balance and unpredictability from 'within centre' to 'overall' by Trial Statistician. Text edited to show that an emergency code-breaking procedure will not be required; as only a single dose of co-amoxiclav will be administered there is no need to code-break if further antibiotics are required. If a woman was to have an anaphylactic reaction she would be treated as if she has been given the active drug. Other edits to the Protocol in Version 3.0 are listed below: 1. The list of Investigators has been removed from the cover page to make the Protocol clearer and to ensure that the ANODE Trial team at the Clinical Trials Unit are approached with any Protocol queries in the first instance rather than a Co-investigator. The Investigators will be listed on the ANODE website. 2. The confidentiality statement has been removed from page 2 as the Protocol is no longer confidential and is available publicly.

The following changes have been made to create Protocol Version 4.0 22nd April 2016: Section 7.0 Trial Design (page 15) Edits to this section have been made to specify exactly who will not be blinded to allocation to clarify that this also includes the person responsible for checking the intervention. The people not blinded to intervention will be the person who prepared the trial intervention and the person who checks the intervention prior to administration. Training will be provided to all unblinded staff on the importance of maintaining blinding and unblinded staff will not be involved in the collection of outcomes information. Other edits to the ANODE Protocol - Page 1 - ISRCTN added and signature blocks for the Chief Investigator and the Statistician have been removed; they will be documented separately and filed with the Protocol in the Trial Master File. - Global edit - where Hospital Episode Statistics (HES) is referenced 'or NHS Wales Informatics Service' has been added. HES will be accessed for participants recruited in England; NHS Wales Informatics Service will be accessed for those participants recruited in Wales. - Pages 15-16 and Appendix A - duration of study edited to reflect the change in start date agreed with the HTA. - Page 19 - edited to clarify that the original signed consent forms will be sent the coordinating centre and a copy retained at site. - Page 20 - section 9.5 edited to clarify the roles of the Senior Trials Statistician and the Senior Trial Programmer with regard to their responsibilities regarding the randomisation schedule generation.

The following changes have been made to create Protocol Version 5.0 30th November 2017: Amendment to the definition of the primary outcome (pages 7, 9 (in flowchart), 14 and 20) Primary outcome refined to the amended text below: • A new prescription of antibiotics for presumed perineal wound-related infection, endometritis or uterine infection, urinary tract infection with systemic features or other systemic infection • Confirmed systemic infection on culture • Endometritis as defined by the US Centers for Disease Control and Prevention (Centers for Disease Control and Prevention 2013) Trial timeline updated to reflected changes following an extension to the duration of the trial (page 16 and page 39) 12.2 Description of Statistical Methods (page 27) The statistics section of the protocol has been updated to make it consistent with the current strategy detailed in the statistical analysis plan as requested by the ANODE Data Monitoring Committee in a meeting held on the the 27th November 2017.