Caffeine for Infants Born at 28 to 34 Weeks Receiving Respiratory Support

Time to Discharge Alive from the NICU

Hours from the time of randomization to the time of discharge alive from the NICU

Time frame: From the date of randomization until the date of discharge alive from NICU, assessed up to 24 months

Parent/Guardian Acceptability

Frequency distribution of Likert-scale responses on the parent satisfaction survey

Time frame: Within 7 days prior to infant's NICU discharge

Healthcare Provider Acceptability

Thematic analysis of healthcare provider focus group transcripts regarding protocol viability

Time frame: Through recruitment completion, an average of 24 months

Data Completeness

Proportion of missing data points across all secondary clinical outcomes.

Time frame: At the end of the recruitment period, approximately 24 months

Significant Apnea Frequency

Mean number of apneas per day requiring intervention (stimulation, or ventilation)

Time frame: From randomization until 24 hours after weaning from respiratory support

Total Duration of Respiratory Support

Total hours spent on invasive and non-invasive mechanical ventilation

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months

Duration of Invasive Support

Total hours spent specifically on invasive mechanical ventilation (intubation)

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months

Time to Full Enteral Feeding

Hours from the first feed until the infant reaches the protocol-defined "full" enteral volume

Time frame: From the date of first enteral feeding until the date when the targeted feeding volume is achieved, average of 14 days

Time to Full Oral Feeding

Hours from birth until the infant is successfully taking all feeds by mouth (no tube)

Time frame: From the date of birth until the date of full oral feeding is achieved, an average of 6 weeks

Duration of Total Parenteral Nutrition (TPN)

Total number of days during which the infant received any volume of parenteral nutrition

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

PMA at Weaning

Mean post-menstrual age of the infant when respiratory support is successfully discontinued

Time frame: At the time of weaning from respiratory support, an average of 4 to 6 weeks after birth

PMA at Discharge

Mean post-menstrual age of the infant at the time of discharge alive from the NICU.

Time frame: At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age

Rate of New Invasive Ventilation

Proportion of infants not intubated at enrollment who require intubation during the study.

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months

In-hospital Mortality

Proportion of enrolled infants who die during their initial NICU stay.

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months

Test of Infant Motor Performance (TIMP) Score

Mean score on the Test of Infant Motor Performance (TIMP). Scores range from 0 to 142, with higher scores indicating better motor maturity and performance

Time frame: At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age

Bronchopulmonary dysplasia (BPD)

Proportion of enrolled infants with BPD defined as: For infants born prior to 32 weeks of gestation, this will be defined as oxygen treatment for at least 28 days with oxygen need at 36 weeks' postmenstrual age or at discharge from the NICU, whichever occurs earlier. For infants born at 32 weeks or later, this will be defined as oxygen treatment at 56 days of life or at discharge from the NICU, whichever occurs earlier.

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Pulmonary Hemorrhage

Proportion of enrolled infants with pulmonary hemorrhage defined as the presence of sanguineous fluid in the trachea associated with clinical respiratory deterioration and new radiographic opacities.

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Pneumothorax

Proportion of enrolled infants with pneumothorax defined as accumulation of air in the pleural space, confirmed by chest radiograph, requires intervention such as needle aspiration or chest tube insertion

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Necrotizing Enterocolitis (NEC) Bell's Stage 2 or more

Proportion of enrolled infants with a diagnosis of NEC meeting at least Bell's Stage II criteria

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Gastrointestinal Surgery

Proportion of enrolled infants with any invasive surgical procedure related to the gastrointestinal tract, including laparotomy for NEC, intestinal resection, or the insertion of a peritoneal drain

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Intraventricular hemorrhage (IVH)

Proportion of enrolled infants with any grade of bleeding into the cerebral ventricular system of the brain. This will be graded according to the Papile classification (Grades I-IV) diagnosed by head imaging.

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Periventricular Leukomalacia (PVL)

Proportion of enrolled infants with localized areas of cystic necrosis in the periventricular white matter, diagnosed by serial cranial ultrasound or Magnetic Resonance Imaging (MRI)

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Seizure

Proportion of enrolled infants with clinical seizure identified by clinical observation

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Patent ductus arteriosus (PDA) Treatment

Proportion of enrolled infants who received a pharmacological therapy or surgical ligation intended to close a hemodynamically significant PDA.

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Retinopathy of Prematurity (ROP) Stage

Mean of the highest stage of RoP (Stages 1-5) recorded in either eye during the infant's hospital stay based on formal ophthalmological retinal examinations

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age

Late Onset Sepsis

Proportion of enrolled infants with a positive blood or cerebrospinal fluid culture obtained after day 3 (72 hours) of life in an infant with clinical signs of infection

Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age