. 2020 Nov 29;41(3):383–395. doi: 10.1038/s41372-020-00878-7

Table 4.

Early sedative/analgesic exposure and long-term outcome.

Agent	Preclinical data	Clinical data
Opioids	– Neuroapoptosis – Reduced neuronal density and dendritic length – Reduced brain growth – Persistently decreased motor activity – Persistently impaired learning ability	– Reduced cerebellar growth^a – Increased muscle tone at 36 weeks postmenstrual age^a – Impaired cognitive and motor outcome at 18 months of age^a – Lower scores on the visual analysis domain of intelligence quotient at 5 years of age^b – Superior executive function by parent report at 8–9 years of age^b
Benzodiazepines	– Neuroapoptosis – Suppressed neurogenesis – Delayed motor development	– None
Alpha-2 agonists	– Neuroprotection and decreased lesion size in models of periventricular leukomalacia – Neuroprotection and improved developmental outcome in models of hypoxia-ischemia and isoflurane exposure	– None

Agent

Preclinical data

Clinical data

Opioids

– Neuroapoptosis

– Reduced neuronal density and dendritic length

– Reduced brain growth

– Persistently decreased motor activity

– Persistently impaired learning ability

– Reduced cerebellar growth^a

– Increased muscle tone at 36 weeks postmenstrual age^a

– Impaired cognitive and motor outcome at 18 months of age^a

– Lower scores on the visual analysis domain of intelligence quotient at 5 years of age^b

– Superior executive function by parent report at 8–9 years of age^b

Benzodiazepines

– Neuroapoptosis

– Suppressed neurogenesis

– Delayed motor development

– None

Alpha-2 agonists

– Neuroprotection and decreased lesion size in models of periventricular leukomalacia

– Neuroprotection and improved developmental outcome in models of hypoxia-ischemia and isoflurane exposure

– None

^aRetrospective and prospective studies of relatively high-level opioid exposure.

^bProspective study of relatively low-level opioid exposure.