Impact of procedural pain during NICU hospitalization on sleep, physical growth, brain maturation and neurobehavioral development in preterm infants: A prospective longitudinal study

Abstract

Study objectives

To assess procedural pain's effects on sleep patterns from discharge through 3 months corrected age (CA), physical growth trajectories from admission through 3 months CA, brain maturation at discharge and neurobehavior at term-equivalent age, while investigating sleep's moderating role in these pain-development relationships.

Methods

In 99 preterm infants (gestational age <37 weeks), procedural pain frequency was recorded. Sleep was assessed using amplitude-integrated electroencephalography (aEEG) combined with behavioral observation at discharge and the Brief Infant Sleep Questionnaire at 1 and 3 months CA. Growth parameters were measured and converted to Z-scores. Brain maturation and neurobehavior were quantified using Burdjalov aEEG score and Neonatal Behavioral Neurological Assessment (NBNA), respectively. Linear mixed-effects models, multivariate regression, and PROCESS moderation analyses were employed.

Results

Higher procedural pain exposure was associated with: (1) Reduced active sleep at discharge (B = −1.42, p = 0.006), persisting as less nighttime sleep at 1 month CA (B = −1.14, p = 0.013) and more awakenings at 3 months CA (B = 1.57, p < 0.001); (2) lower weight Z-scores up to 3 months CA (B = −0.44, p = 0.016), with no significant associations in length or head circumference Z-scores after correction; and (3) poorer brain maturation at discharge (B = −1.50, p = 0.002), but not with NBNA score at 40 weeks. Sleep moderated the pain–weight relationship (p < 0.05), but not pain-brain maturation.

Conclusions

Procedural pain persistently disrupts sleep, weight growth, brain maturation, but not early neurobehavior in preterm infants. Sleep moderates its impact on weight growth, suggesting dual interventions-pain reduction and sleep optimization-are critical for mitigating developmental impairment.