Table 1 Primary and secondary outcome measures
Domain | Specific measurement | Specific metrics | Method of aggregation | Time point |
|---|---|---|---|---|
Primary outcome | ||||
Length of hospital stay | Date of hospital discharge | Difference between the date the infant is discharged and date of randomisation | Mean and standard deviation (SD), per group | Hospital discharge |
Secondary outcomes | ||||
Survival | Date of death as recorded on eCRF. Date of death as recorded on eCRF | Death between date of randomisation and date of hospital discharge. Death between date of randomisation and 6 weeks corrected gestational age | Proportion of infants alive, per group. Proportion of infants alive, per group | Hospital discharge 6 weeks corrected gestational age |
Microbiologically confirmed (positive blood/cerebrospinal fluid culture) or clinically suspected late-onset sepsis | Presence of confirmed or suspected late-onset sepsis on microbiology report and recorded in eCRF1 | Microbiologically confirmed late-onset sepsis between date of randomisation and hospital discharge | Proportion of infants with microbiologically confirmed late-onset sepsis, per group | Hospital discharge |
Necrotising enterocolitis (NEC) (Bell’s stage 2 or 3) [19] | Presence of NEC (stage 2 or 3) recorded on eCRF1 | Diagnosis of NEC (stage 2 or 3) between date of randomisation and hospital discharge | Proportion of infants with NEC (stage 2 or 3), per group | Hospital discharge |
Time taken to maintain full milk feeding | Full milk feeds reached, defined as at least 140 ml/kg/day for three consecutive days2, as recorded on eCRF | Derived from the date the infant achieves full feeds, recorded on CRF, and date of randomisation | Mean (and SD) and/or median (and IQR), per group | During hospital admission, in accordance with criteria for reaching full milk feeds |
Time to regain birth weight | Birth weight regained, as recorded on eCRF | Derived from the date the infant regains birth weight and date of randomisation | Mean (and SD) and/or median (and IQR), per group | During hospital admission |
Growth of infant | Growth Z scores (length, weight and head circumference), corrected for gestational age as per UK-NICM growth charts [20] | Derived from growth Z scores, expected date of delivery and infant sex | Mean (and SD) and/or median (and IQR), per group | Hospital discharge |
Breast-feeding | Infant being breast-fed, as recorded on CRF. Infant being breast-fed, as recorded on 6-week parent-completed questionnaire | Infant being breast-fed at time of hospital discharge. Infant being breast-fed at 6 weeks (corrected gestational age) | Proportion of infants breast-feeding, per group. Proportion of infants breast-feeding, per group | Hospital discharge. 6 weeks corrected gestational age |
Breast milk feeds | Infant being fed mother’s breast milk, as recorded on eCRF. Infant being fed mother’s breast milk, as recorded on 6-week parent-completed questionnaire | Infant being fed mother’s breast milk at time of hospital discharge. Infant being breast fed mother’s breast milk at 6 weeks (corrected gestational age) | Proportion of infants being fed mother’s breast milk, per group. Proportion of infants being fed mother’s breast milk, per group | Hospital discharge. 6 weeks, corrected gestational age |
Number of days of cannulae | Number of days of peripheral cannula and IV cannulae inserted, as recorded on eCRF | Number of days of peripheral cannula and IV cannulae inserted, until infant reaches full milk feeds | Mean (and SD) and/or median (and IQR), per group | Date infant reaches full milk feeds, whilst in hospital |
Number of days of infant receiving parenteral nutrition | Number of days of infant receiving parenteral nutrition, as recorded on eCRF | Number of days of infant receiving parenteral nutrition until hospital discharge | Mean (and SD) and/or median (and IQR), per group | Hospital discharge |
Number of central venous lines inserted | Number of central venous lines, including umbilical and percutaneous or surgically inserted venous lines), as recorded on eCRF | Number of central venous lines between date of randomisation and date of hospital discharge | Mean (and SD) and/or median (and IQR), per group | Hospital discharge |
Number of central line days | Number of days infant has a central line, as recorded on eCRF | Number of central line days between date of randomisation and date of hospital discharge | Mean (and SD) and/or Median (and IQR), per group | Hospital discharge |
Time until objective discharge criteria are met | Objective discharge criteria, as recorded on eCRF | Derived from the date the objective discharge criteria is met and date of randomisation | Mean (and SD) and/or median (and IQR), per group | During hospital admission |
Length of neonatal unit stay | Length of stay in (i) neonatal intensive care, (ii) high dependency care, (iii) special care, (iv) translational care, as recorded on eCRF | Derived from days spent in each type of neonatal unit between date of randomisation and date of discharge | Mean (and SD) and/or median (and IQR), per group | Hospital discharge |
Retinopathy of prematurity (ROP) | Diagnosis of ROP, as recorded on eCRF | Diagnosis of ROP between date of randomisation and date of hospital discharge | Proportion of infants with ROP, per group | Hospital discharge |
Chronic lung disease (CLD) | Diagnosis of CLD, as recorded on eCRF | Diagnosis of CLD between date of randomisation and date of hospital discharge | Proportion of infants who are mechanically ventilated or on nasal CPAP or in supplemental oxygen at 36 weeks corrected gestational age, per group | Hospital discharge |
Brain injury | Diagnosis of intraventricular haemorrhage (grade 3 or 4), periventricular leukomalacia or hydrocephalus (requiring a shunt) on cranial ultrasound, recorded on eCRF | Diagnosis of brain injury (as per definitions) between date of randomisation and date of hospital discharge | Proportion of infants with recorded evidence of brain injury (grade 3 or 4 intraventricular haemorrhage, periventricular leukomalacia or hydrocephalous requiring shunt, per group | Hospital discharge |
Blood glucose/hypoglycaemia | Number of blood glucose tests, as recorded on eCRF. Number of blood glucose tests indicating hypoglycaemia (< 2.2 mmol/L). Number of blood tests indicating severe hypoglycaemia (< 1.0 mmol/L) | Number of blood glucose tests, between date of randomisation and date of hospital discharge. Number of blood glucose tests < 2.2 mmol/L, between date of randomisation and date of hospital discharge. Number of blood glucose tests < 1.0 mmol/L between date of randomisation and date of hospital discharge | Mean (and SD) and/or median (and IQR), per group. Mean (and SD) and/or median (and IQR), per group. Mean (and SD) and/or median (and IQR), per group | Hospital discharge. Hospital discharge. Hospital discharge |
Hospital visits | Number of hospital visits, including day care and overnight admissions, as recorded on 6-week parent-completed questionnaire | Number of hospital visits between date of hospital discharge and 6 weeks corrected gestational age | Mean (and SD) and/or median (and IQR), per group | 6 weeks corrected gestational age |
Parental satisfaction and wellbeing | Preterm birth experience and satisfaction scale (P-BESS) [21], completed by parents | P-BESS total score (and subscales for interpersonal care, information and explanations, lack of confidence in staff) at 6 weeks corrected gestational age | Mean (and SD) and/or median (and IQR), per group | 6 weeks corrected gestational age |