PLatform for Adaptive Trials In Perinatal UnitS - [Core Protocol]

The PLATIPUS-Ordinal Outcome Scale ranks the most severe core short-term infant health outcome in the specified time frame.

Levels 1-15: 1= Well, liveborn infant; 2= Neonatal unit admission for <48 hours; 3= Neonatal unit admission for >/= 48 hours; 4= Non-invasive respiratory support for ≥ 4 hours & < 5 days; 5= Non-invasive respiratory support >/= 5 days; 6= Mechanical ventilation via endotracheal tube for ≥ 4 hours & <7 days; 7= Mechanical ventilation via endotracheal tube for >/=7 days; 8= Moderate respiratory morbidity; 9=Necrotising enterocolitis AND/OR Sepsis; 10= Severe Respiratory Morbidity; 11= Major Surgery; 12= Brain Injury; 13= TWO of severe respiratory morbidity OR major surgery OR brain injury; 14= Severe respiratory morbidity & major surgery & brain injury; 15 = Death.

Well, liveborn infants who have not met the diagnostic criteria for worse scale outcomes.

The ordinal outcome scale ranks short-term neonatal outcomes associated with longer-term health in ascending severity. An infant is assigned the outcome that is the highest (worst) for which they have met diagnostic criteria at any time prior to 42 weeks PMA or first hospital discharge (whichever is earlier).

Infants admitted to the neonatal unit during primary hospital admission for 48 hours or more.

Infants admitted to any level of neonatal unit during the birth admission, for less than 48 hours.

Infants who received non-invasive positive pressure respiratory support for ≥ 4 hours (excluding delivery room) and less than 5 days.

Infants who received non-invasive positive pressure respiratory support for 5 days or more.

Infants who received mechanical ventilation via endotracheal tube for ≥ 4 hours (excluding delivery room) and <7 days.

Infants who received mechanical ventilation via endotracheal tube for 7 days or more.

Infants with a gestational age <37 weeks who received oxygen therapy at 40 weeks' postmenstrual age.

A. Infants with necrotising enterocolitis (NEC), defined as one or more of the following:

• Radiological diagnosis: Clinical history plus imaging consistent with NEC (pneumatosis intestinalis AND/OR portal venous gas AND/OR persistently dilated loop of bowel on serial imaging)
• Clinical diagnosis: Clinical history plus abdominal wall cellulitis and a palpable abdominal mass

AND an intention to treat with broad-spectrum antibiotics for 7 days or more

OR

B. Infants with Sepsis Organism (bacterial, fungal or viral) isolated in the blood or CSF by culture or PCR AND an intention to treat with antimicrobials/antivirals for 5 days or more.

NOTE: Exclude if culture is mixed coagulase negative staphylococcus and/or other skin flora contaminant.

Infants with severe respiratory morbidity defined as one or more of the following:

• Tracheostomy, assessed at 42+0 weeks' PMA
• Discharge home on oxygen AND/OR respiratory support, if discharged prior to or on the day of 40+0 weeks' PMA
• Born at <37 weeks' GA AND received respiratory support for 12 hours or more on the day of 40+0 weeks PMA.

Infants who underwent major surgery, defined as one of the following:

• Laparotomy /Laparoscopy
• Thoracotomy/Thoracoscopy (e.g. ligation of a ductus arteriosus, surgery for NEC etc)
• Craniotomy / Cranioscopy

Excludes inguinal hernia repair. Note: Tracheostomy and neurosurgical intervention for post-haemorrhagic hydrocephalus are included in other categories.

Infants with brain injury may be diagnosed on ultrasound or magnetic resonance imaging where there is clinical suspicion or request, and includes one or more of the following:

a. Major intraventricular haemorrhage, unilateral or bilateral, defined as i. Papile Grade 3 or 4 AND/OR ii. Moderate-severe periventricular haemorrhagic infarction b. Cystic periventricular leukomalacia, unilateral or bilateral c. Moderate or severe white matter injury on MRI.Other major ischaemic injury such as arterial stroke or hypoxic ischaemic injury d. Post haemorrhagic hydrocephalus requiring drainage. e. Any cerebellar haemorrhage, excluding punctate lesions (<4mm) that occur in the absence of other brain injury as defined above (12 a, b, c, d and e).

Infants that meet the definition of TWO of Brain Injury OR Major Surgery OR Severe Respiratory Morbidity (as defined in Scale Categories 10, 11 and 12)

Infants that meet the definition of Brain Injury AND Major Surgery AND Severe Respiratory Morbidity (as defined in Scale Categories 10, 11 and 12)

Death includes fetal death in utero, intrapartum stillbirth, neonatal death, and death before hospital discharge of a liveborn infant.

Total duration of infant's first hospitalisation, in days. An average of three months.

Any breastmilk feeding at 42 weeks' postmenstrual age or on day of first hospital discharge home (whichever occurs earliest). Data will be collected as yes/no.

Number of infants diagnosed with PDA.

Number of infants diagnosed with retinopathy of prematurity (ROP). Worst stage and treatment will also be collected.

Any postnatal corticosteroid and any mode of administration.

Infants birth weight z-score.

This is a secondary outcome for Pregnancy Domains only.

Infant's gestational age at birth.

This is a secondary outcome for Pregnancy Domains only.

Death of the mother or pregnant person.

This is a secondary outcome for Pregnancy Domains only.

Includes Intensive Care Unit (ICU) admission to an intensive care unit, sepsis, eclampsia, amniotic fluid embolism, pregnancy-related hysterectomy, severe primary postpartum haemorrhage, uterine rupture, cardiac arrest, endometritis, mechanical ventilation (not for birth), stroke).

This is a secondary outcome for Pregnancy Domains only.

Number of days from trial entry to hospital discharge, in days. An average of three weeks.

This is a secondary outcome for Pregnancy Domains only.

Readmission to hospital (any reason) after first hospital discharge and before 42 days postpartum.

This is a secondary outcome for Pregnancy Domains only.

Includes: vaginal birth, assisted vaginal birth, caesarean.

This is a secondary outcome for Pregnancy Domains only.