Neonatal hyperbilirubinaemia is associated with a subsequent increased risk of childhood-onset type 1 diabetes

ABSTRACT

Background: Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood. Whether neonatal hyperbilirubinaemia increases the risk of T1D remains unclear.

Aim: To estimate the association between neonatal hyperbilirubinaemia and phototherapy and the risk of T1D using a large nationwide population-based cohort.

Methods: This retrospective study was conducted using data from the National Health Insurance Research Database in Taiwan from 2001 until 2005. Altogether, 23,784 neonates aged <30 days diagnosed with hyperbilirubinaemia and 47,568 neonates without hyperbilirubinaemia were enrolled and frequency-matched to the hyperbilirubinaemia group by gender, age, parental occupation and urbanisation. Cox regression analysis was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI).

Results: Of the 71,352 neonates included, those with hyperbilirubinaemia had a higher incidence of T1D (4.76 vs 2.68 per 10,000 person-years, p < 0.001) and an earlier mean age at onset of T1D [4.13 (2.80) vs 5.80 (2.67) years, p < 0.001] than those without hyperbilirubinaemia. After adjusting for confounding factors in multivariable analysis, the neonates with hyperbilirubinaemia had a 66% increased risk of developing T1D (HR 1.66, 95% CI 1.26–2.18). Girls had a 1.41-fold (HR 1.41, 95% CI 1.10–1.82) greater risk of T1D than boys. Additionally, neonates with a history of perinatal complications (HR 1.66, 95% CI 0.99–2.80) and neonatal infections (HR 2.13, 95% CI 1.45–3.15) had an increased subsequent risk of T1D.

Conclusions: The results suggest that neonatal hyperbilirubinaemia is associated with a subsequently increased risk of childhood-onset T1D.

Abbreviations: T1D, type 1 diabetes; CI, confidence interval; NHI, national health insurance; NHIA, National Health Insurance Administration; NHIRD, National Health Insurance Research Database; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; G6PD, glucose-6-phosphate dehydrogenase; LBW, low birthweight; HRs, hazard ratios.

KEYWORDS:

• Neonatal hyperbilirubinaemia
• comorbidities
• risk factor
• type 1 diabetes

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was supported by Chung Shan Medical University Hospital, Taichung, Taiwan (CSH-2013-C-011), the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021) and MOST Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005).

Notes on contributors

Pei-Fen Liao

Pei-Fen Liao is a Lecturer of Paediatrics and consultant paediatrician in Chung Shan Medical University Hospital, Taichung, Taiwan. His research interests include epidemiology and treatment of childhood allergic diseases.

Jeng-Dau Tsai

Jeng-Dau Tsai an Assistant Professor of Paediatrics and consultant paediatric neurologist in Chung Shan Medical University Hospital, Taichung, Taiwan. His research interests include treatment of tuberous sclerosis complex and epilepsy in childhood and in particular in early intervention medical service for developmental delay children.

Hsuan-Ju Chen

Hsuan-Ju Chen is a statistician in Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan. Her research interests include statistical modelling, especially in managing the big data of national health insurance.

Hui-Hsien Pan

Hui-Hsien Pan is a Lecturer of Paediatrics and consultant paediatrician in Chung Shan Medical University Hospital, Taichung, Taiwan. She is also a PhD candidate of School of Medicine, Chung Shan Medical University, Taichung, Taiwan. Her research interests include Paediatric infectious diseases and childhood allergic diseases.

Tung-Wei Hung

Tung-Wei Hung is an Assistant Professor of Internal Medicine and consultant internist in Chung Shan Medical University Hospital, Taichung, Taiwan. His research interests include epidemiology of chronic kidney disease and critical care medicine.

Hsing-Yi Chang

Hsing-Yi Chang is a researcher of Biostatics in Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan. His research interests include statistical modelling and research in population health science.

Ji-Nan Sheu

Ji-Nan Sheu is a Professor of Paediatrics, a senior consultant paediatrician and director of Department of Medical Education in Chung Shan Medical University Hospital, Taichung, Taiwan. His research interests include treatment of childhood urinary tract infections and kidney diseases, critical care medicine and medical education.