Association Between the Number of US Food and Drug Administration–Warned Anesthetic Exposures and Full-Scale Intelligence Quotient at Age 3 Years in Very Preterm Infants

Objective: In 2016, the US Food and Drug Administration (FDA) warned that general anesthetics and sedative agents in children younger than 3 years may impair neurodevelopment. Very preterm infants could be especially vulnerable because of brain immaturity. We examined the association between the number of US FDA-warned anesthetic and sedative agents and full-scale intelligence quotient (FSIQ) at age 3 years in infants born < 29 weeks' gestational age (GA). Study Design: In this retrospective study, all infants born (< 29 weeks' gestation) between January 2006 and December 2012 were evaluated for exposure to FDA-warned anesthetic and sedative agents from birth through 45 weeks' postconceptual age. The agents included volatile anesthetics, propofol, benzodiazepines, ketamine, chloral hydrate, and barbiturates. Exposure count was defined by the number of different agents administered: 1 exposure (1 agent); 2 exposures (2 agents); and ≥ 3 exposures (≥ 3 agents), irrespective of the number of procedures. We analyzed the association between FSIQ and exposure count using imputed and complete case univariable and multivariable linear regressions adjusted for neonatal and maternal factors. Results: = 0.079) points, respectively. Conclusion: Exposure to 1, 2, or ≥ 3 different FDA-warned anesthetic and sedative agents (volatile anesthetics, propofol, benzodiazepines, barbiturates, and ketamine) in very preterm infants born < 29 weeks' GA was not associated with a clinically meaningful decrease in FSIQ points at 36 months' corrected age.