The purpose of this study is to investigate how acetaminophen (APAP) is released into the urine and blood; to determine how the blood levels of acetaminophen and its breakdown products affect the preterm infant's health; to decrease adverse drug reactions; and to collect data on how the genetic make-up or characteristics affect how APAP is handled within the preterm infant. By taking several blood and urine samples during the study, we will be able to check the blood levels (called pharmacokinetics) of APAP in preterm babies.

Study procedures: The decision to replace standard intravenous morphine therapy with APAP will be made by the attending neonatologist.

Length of participation: 60 hours. No patient will be prescribed the medication specifically for the study purposes in the study protocol.

Inclusion Criteria:

• Preterm and term neonates of both genders and all races
• a postnatal age of less than 28 days
• GA's of from 22 to less than 37 weeks
• an indwelling (peripheral or umbilical) arterial line
• a clinical indication for intravenous administration of pain relief medication

Exclusion Criteria:

• Neonates with severe asphyxia
• grade III or IV intraventricular hemorrhage, major congenital malformations/facial malformations (e.g., cleft lip and palate),
• neurological disorders
• those receiving continuous or intermittent neuromuscular blockers
• clinical or biochemical evidence of hepatic renal failure (including systemic hypoperfusion)

There is no plan to share individual participant data. Preliminary data published Published manuscripts in 2015 & 2016