Long-term impact of systematic pain and sedation management on cognitive, motor, and behavioral outcomes of extremely preterm infants at preschool age

Neonatal opioids and preschool outcomes

“…After implementing a standardized analgesia/sedation protocol in two NICUs, Diendl and colleagues found 6–7-fold increases in opioid exposures but no effects on their in-hospital morbidity or mortality( 19 ), slightly lower behavior rating scores at 1 year( 20 ) and 3 years( 21 ), but no differences in their long-term mental, psychomotor, or behavioral development compared to historical controls( 19 – 21 ). Steinbauer et al now report their preschool outcomes from cognitive, neuromotor, and behavioral assessments performed at age 5–6 years in the protocol-treated cohort and historical controls( 22 ). Other than slightly increased autism spectrum features and withdrawn behavior in the protocol-treated group, or oppositional defiant behaviors and sleep problems in the control group, they again found no differences in the cognitive, neuromotor, or behavioral outcomes between the two groups( 22 ).…”

“…Steinbauer et al now report their preschool outcomes from cognitive, neuromotor, and behavioral assessments performed at age 5–6 years in the protocol-treated cohort and historical controls( 22 ). Other than slightly increased autism spectrum features and withdrawn behavior in the protocol-treated group, or oppositional defiant behaviors and sleep problems in the control group, they again found no differences in the cognitive, neuromotor, or behavioral outcomes between the two groups( 22 ). Though reassuring, these results must be interpreted with caution because of substantial weaknesses in their study design.…”

“…Thus, only 27% of the 367 VLBW survivors contributed to these results( 23 ). Also missing from prior or current descriptions of this cohort are the clinical indications for using opioids( 19 – 22 ). This is critically important because opioids given in the presence of pain are much less likely to alter brain development as compared to opioids given in the absence of pain( 24 ).…”

“…Clinical use or avoidance of opioid analgesia has achieved a cult-like status in some NICUs, with every new finding interpreted to support strongly held views on opposite sides of this divide. Those who prescribe opioids will suggest that protocol-driven neonatal analgesia/sedation, with routine assessments of pain/distress using validated scales, will not lead to adverse outcomes even at preschool age, whereas those who avoid opioids may be concerned about their reported association with autism spectrum features and withdrawn behaviors( 22 ). CBCL scores of children in this study were included in 12 logistic regression analyses using a penalized likelihood approach designed for maximum likelihood estimation of rare events, reporting 96 p-values with no correction for multiple testing.…”

“…For clinicians faced with the decision of treating moderate/severe and/or prolonged neonatal pain, the potential risks for long-term neurodevelopmental sequelae from opioids should not be considered in the risk-benefit equation( 28 ). Just like changes in the gut microbiome or associations with future inflammatory bowel disease do not enter into the decisions for neonatal antibiotic use( 29 ), similarly, concerns about anesthetic-related neurotoxicity in animals( 24 , 30 ) or humans( 15 , 31 ), or subtle findings from population-based studies of neurodevelopmental outcomes( 6 , 21 , 22 , 28 , 31 ) should not interfere with evaluating the clinical need for opioid analgesia in that moment for any individual patient.…”