Table 4.

Adverse Event Table Clinical Entities

	Adverse Event	Serious Adverse Event
Gastrointestinal
Necrotizing enterocolitis [40,41]		Bell Stage II or III
Intestinal perforation [42]		Intra-abdominal free air without preceding  pneumatosis
Musculoskeletal
Fracture	Fracture treated with immobilization	Fracture with any surgical intervention needed or  known lasting sequelae
Respiratory
Respiratory failure		Initiation of mechanical ventilation or some defined  change
Pneumothorax	Present but no intervention required	Intervention required (e.g., chest tubes, sclerosis  therapy and/or operative)
Apnea		Requiring initiation of mechanical ventilation
Pulmonary hypertension		Present and initiation of medical therapy to treat  pulmonary hypertension (e.g., nitric oxide,  milrinone, sildenafil)
Neurological
Seizure [43]		Present and treated with anticonvulsant
Intraventricular hemorrhage [44,45]		Grade 3-4
Periventricular leukomalacia [46]		Present on imaging
Cardiology
Hypotension [47]		Requiring pressors
ECG QTc prolongation [48]	460 – 485 ms	> 485 ms
Supraventricular tachycardia [49]	Episode resolves spontaneously or with vagal  maneuvers	Requiring medical drug therapy or electroconversion  to revert to sinus rhythm
Infectious disease
Wound infection	Requiring only local intervention (e.g., topical  antimicrobial)	Requiring systemic antimicrobial therapy or surgery
Urinary tract infection		Positive urine culture treated with systemic  antibiotics or antifungals
Cellulitis	Requiring only local intervention (e.g., antimicrobial)	Requiring systemic antimicrobial therapy or surgery
Bloodstream infection		Positive blood culture requiring systemic  antimicrobial
Meningitis		Positive cerebral spinal fluid culture requiring  systemic antimicrobial
Ophthalmologic
Conjunctivitis [50]	Requiring only local intervention (e.g., topical  antimicrobial)	Requiring systemic antimicrobial therapy or surgery
Retinopathy of prematurity [45]	Any stage	Any stage requiring surgical or medical intervention
Otolaryngology
Hearing impairment [51]		Confirmed hearing loss, either unilateral or bilateral
Drug mediated
Infusion related reaction	Mild transient reaction or reaction that responds  promptly to symptomatic treatment (e.g.,  antihistamines, NSAIDS, narcotics, IV fluids)	Prolonged reaction that does not respond promptly to  symptomatic treatment (e.g., antihistamines,  NSAIDS, narcotics, IV fluids) or life-threatening  reaction that requires urgent intervention
Infusion site extravasation	Erythema with or without associated symptoms (e.g.,  edema, pain, induration, phlebitis)	Significant tissue injury leading to ulceration,  necrosis, operative intervention indicated, or urgent  intervention indicated
Injection site reaction	Tenderness with or without associated symptoms  (e.g., warmth, erythema, itching, lipodystrophia,  edema)	Significant tissue injury leading to ulceration,  necrosis, operative intervention indicated, or urgent  intervention indicated
Allergic reaction	Transient flushing, rash, drug fever that responds  promptly to symptomatic treatment (e.g.,  antihistamines, NSAIDS, narcotics)	Prolonged reaction that does not respond promptly to  symptomatic treatment (e.g., antihistamines,  NSAIDS, narcotics, IV fluids) or life-threatening  reaction that requires urgent intervention
Anaphylaxis [52]	Acute onset of illness with skin and/or mucosal tissue  manifestations and either respiratory compromise or  hypotension that requires parental medication  intervention	Acute onset of illness with skin and/or mucosal tissue  manifestations and either respiratory compromise  or hypotension that is life-threatening and requires  urgent intervention