The Paediatrics Research Review has published some interesting study outcomes in 2019 which will be of interest to those Nurses who work with neonates.

“Early caffeine administration and neurodevelopmental outcomes in preterm infants Authors: Lodha A et al.


This study examined the impact of early caffeine therapy for apnoea of prematurity on long-term neurodevelopmental outcomes in preterm infants. 2108 infants born at <29 weeks’ gestation who were admitted to a Canadian Neonatal Network (CNN) unit were included.

Neonates who received caffeine were divided into early (received within 2 days after birth; n=1545) and late (received >2 days after birth; n=563) caffeine groups. Rates of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), and severe neurologic injury at 18–24 months’ corrected age were lower in the early caffeine group than in the late caffeine group.

Multivariate analysis showed that the risk of significant neurodevelopmental impairment was lower in the early caffeine group (adjusted OR, 0.68) due to a decreased risk of cerebral palsy and hearing impairment.


Data supportive of prophylactic use was provided by a large retrospective study from the CNN of preterm infants (gestational age <29 weeks) that compared early administration of caffeine within the first 2 days of life with late administration on or after the third day of life.

In this cohort, 75% were given early caffeine, and the remaining patients received late administration of caffeine. In a multivariate analysis, neonates in the early caffeine group had a small but statistically significant lower risk of a composite outcome of death or BPD (31.5% vs 31.1%; OR 0.81, 95% CI 0.67–0.98). However, most of this effect was due to a reduction in the incidence of BPD, as there was no difference in mortality (5.7% vs 5.8%; OR, 0.98, 95% CI 0.7–1.37).

In addition, the early caffeine group was less likely to develop a PDA or undergo surgical intervention for PDA. There were no differences in other secondary outcomes including NEC, severe neurological injury, or severe retinopathy of prematurity. In this study, a follow-up report of the cohort at 18–24 months corrected age reported better neurodevelopmental outcome with early versus late administration, providing additional support for the early use of caffeine.”

Reference: Pediatrics 2019;143(1):e20181348 Abstract 

Influence of surgical procedures and general anesthesia on child development before primary school entry among matched sibling pairs Authors: O’Leary J et al.

”This retrospective cohort study examined the association between surgical procedures requiring general anaesthesia before age 5 years and child development. 2346 sibling pairs (only 1 child in each pair was exposed to surgery) who completed Early Development Instrument (EDI) testing at age 5–6 years were included.

The EDI assessed the children’s readiness to learn in 5 major domains (physical health and well-being, social knowledge and competence, emotional health and maturity, language and cognitive development, and communication skills and general knowledge). After adjustment for confounding factors, no significant differences were seen between exposed and unexposed children in early developmental vulnerability, or in any of the 5 major EDI domains.


This study highlights a risk that is increasingly being recognised in the medical community. Studies in animals have shown that anaesthetic and sedative drugs can cause neuronal damage to the developing brain, and can cause lasting behavioural and cognitive deficits. Some human studies suggest an association between exposure of young children to anaesthesia and subsequent neurodevelopmental deficits. Any degree of neurotoxicity of anaesthetic and sedative drugs in humans may have widespread implications. In the US, over 1.3 million children under the age of 5 years undergo surgical procedures each year.

Most of these children need and receive general anaesthesia, and most of these procedures cannot be delayed without adding substantial risk. In addition, an increasing number of young children receive sedatives or general anaesthesia for neuroimaging studies, and many more require procedural sedation in the emergency department. In 2016, the US Food and Drug
Administration (FDA) issued a warning about potential risks of negative effects on the developing brain from administration of anaesthetics for children under age 3, especially for repeated exposures or procedures lasting more than 3 hours.

Most children who undergo general anaesthesia are exposed for less than the FDA defined high-risk 3 hours. In a retrospective
cohort analysis of approximately 1.5 million paediatric (<18 years of age) anaesthetic billing records from the National Anaesthesia Clinical Outcomes Registry, the median anaesthetic duration was 57 minutes, with 6% of anaesthetics lasting longer than 3 hours. But in children under 1 year old, 13.7% of anaesthetics lasted longer than 3 hours. In another retrospective
study of approximately 21,000 children born between 1994 and 2007 in Minnesota, 14.9% of children were exposed to anaesthesia before 3 years of age. Of the children exposed to anaesthesia, 26.3% had either 1 exposure longer than 3 hours or multiple anaesthetic exposures.”
Reference: JAMA Pediatr 2019;173(1):29-36 Abstract