Morphine use in the neonatal period and later neuropsychological development: a systematic review

To identify and evaluate the evidence documenting the association between neonatal morphine and later childhood neuropsychological development.

We conducted a systematic literature search of eight electronic databases from inception until June 2019. We included all randomized controlled trials (RCTs) and cohort studies recruiting neonates who received morphine treatment, and measuring neuropsychological development outcomes with a minimum follow-up of 6 months.

Twelve separate reports from three RCTs and five cohort studies met our inclusion criteria. Owing to the small number of the included trials and the variable study designs, a meta-analysis was not performed. The findings from this review indicated that neonatal morphine use had no adverse effects on behaviour, cognition, motor, and executive function development at 8 to 9 years and earlier; except for the inconsistent conclusions on internalizing behavioural problems at 5 to 7 years and cognitive and motor developments at 18 months.

Why a child needs morphine may have a more profound impact on later neuropsychological development than morphine itself. The small number, high heterogeneity, and limitations of the included studies limit confidence in the result of this systematic review.