Neonatal hyperbilirubinemia and childhood allergic diseases: a systematic review

Studies have found a link between neonatal hyperbilirubinemia (NNH) and/or neonatal phototherapy (NPT) and childhood allergic diseases. The present systematic review was conducted to provide updated evidence and to provide direction regarding future research. A systematic search of the published literature was carried out. Observational studies including children up to 12 yr of age were included. Data extraction was carried out using a standardized data extraction form that was designed and pilot tested a priori. The analysis was carried out with the statistical software RevMan (version 5.2) [Protocol is registered at

Prospero: CRD42014009943]. Of 79 citations retrieved, a total of 7 good quality studies (n = 101,499) were included in the final analysis. There was a significant increase in the odds of asthma and allergic rhinitis (AR) after NNH [asthma, OR 4.26 (95% CI 4.04-4.5); AR, OR 5.37 (95% CI 4.16-6.92)] and after NPT [asthma, OR 3.81 (95% CI 3.53-4.11); AR, OR 3.04(95% CI 2.13-4.32)]. A similar increase in the trend was noted for late onset of asthma after NNH [OR 4.1 (95% CI 2.82-5.94)], and hospitalization due to asthma after NPT [OR 3.56 (95% CI 2.93-4.33)]. The GRADE evidence generated was of 'low quality'. The current evidence finds a significant increase in the odds of childhood allergic diseases after NNH and/or NPT. As observational studies were included, the evidence generated was of 'low quality'. Future studies should try to elucidate the pathophysiologic link between NNH and/or NPT and childhood allergic diseases.