The choice of population and outcomes in neonatal trials on hyperbilirubinaemia: are they relevant? an analysis of Cochrane Neonatal reviews




Poster session 3


Tuesday 18 September 2018 - 12:30 to 14:00

All authors in correct order:

Lai NM1, Lee SWH2, Wai SX1, Teh ZW1, Chang SMW1, Lim YS1, Roger S3, Colleen O3
1 School of Medicine, Faculty of Health and Medical Sciences Taylor's University, Malaysia
2 Monash University Malaysia, Malaysia
3 Cochrane Neonatal, USA
Presenting author and contact person

Presenting author:

Nai Ming Lai

Contact person:

Abstract text
Neonatal jaundice (hyperbilirubinaemia) is the most common condition managed by neonatal practitioners, with bilirubin encephalopathy and kernicterus as the most serious complications. Neonates with jaundice are usually managed according to their serum bilirubin, despite an overall unclear association between bilirubin levels and clinical complications.

We examined Cochrane neonatal review data to assess whether major clinical complications associated with neonatal jaundice were included as key outcomes, and how commonly they occurred overall.

Among Cochrane Neonatal reviews published till November 2017, we identified reviews that evaluated interventions for neonatal hyperbiliubinaemia, and extracted the following data at the review and individual study levels: population included, outcomes assessed, in particular, whether patient-important outcomes such as bilirubin encephalopathy and kernicterus were listed as the primary outcomes and their cumulative incidences.

Among 311 reviews, 11 assessed interventions for neonatal hyperbiliubinaemia with 79 RCTs included (total participants: 8262). Overall, 148 outcomes (33 primary, 115 secondary) were listed in the reviews, and 27 were major clinical outcomes. Ten of these 27 outcomes were listed as primary outcomes. Among the included studies, 35 enrolled predominantly high-risk and 44 enrolled predominantly low-risk population. A total of 276 outcomes were represented, among which only 11 (4%) were major clinical outcomes, with only one listed as the primary outcome. Two reviews presented data for bilirubin encephalopathy/abnormal neurological signs and/or kernicterus, but cumulatively, no infant in these reviews developed any of these complications.

Major clinical outcomes related to hyperbilirubinaemia were not listed as primary outcomes in over half of the relevant Cochrane Reviews, and were very rarely reported in neonatal trials. Cumulatively, no infant developed these complications in the trials that reported those outcomes. Future trials should focus on evaluating the incidence of bilirubin encephalopathy and kernicterus as key outcomes in high-risk population to justify resources used in such studies.

Patient or healthcare consumer involvement:
Two authors consulted their lay relatives when making judgment on patient-important outcomes.

Relevance to patients and consumers: 

Clinical studies that are conducted on patients should assess outcomes that matter to them. We examined whether the major outcome that matter to a newborn with jaundice, namely, bilirubin-associated brain damage, were given appropriate emphasis by the authors of a series of studies on newborn infants. We also examined the population enrolled by the study authors to see if they were actually the population at risk of serious problems resulting from jaundice. Our findings will guide future researchers in selecting appropriate population and setting serious patient-important outcomes in studies on neonatal jaundice to justify their resources.