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Mildly Elevated Bilirubin Levels are Associated with Increased Magnetic Resonance Imaging Signal Intensity in the Basal Ganglia of Preterm Neonates
Objective This study aimed to test whether mildly elevated bilirubin levels in preterm infants are associated with increased signal intensity (SI) on magnetic resonance imaging (MRI) of the basal ganglia (BG).
Study Design MRI was performed at term equivalent age in 55 postpreterm infants using a neonatal MRI 1-T scanner. SI of the BG was correlated with mild hyperbilirubinemia.
Results BG MRI SI was significantly increased in infants with mild hyperbilirubinemia on T1-weighted image (T1; p = 0.0393) and T2-weighted image (T2; p = 0.0309). We found no effect of gestational age or sepsis on BG MRI intensity; however, there was a significant effect of acidosis on T1 (p = 0.0223) but not on T2 (p = 0.2316). Infants with combined hyperbilirubinemia and acidosis had the most significant increase in SI on both T1 and T2 respectively (p = 0.0072 and 0.0195, respectively).
Conclusion We found a positive association between increased BG MRI SI and mildly elevated bilirubin levels. The effect was greatly strengthened when hyperbilirubinemia was associated with acidosis.
Excessive bilirubin is neurotoxic to the neonatal brain. It is deposited in the BG.
BG MRI SI is increased with bilirubin deposition.
The premature brain is more vulnerable to bilirubin associated MRI changes.
The images used in this study were acquired from MRI scans that were funded by Aspect Imaging LTD for another study. The sponsor had no further involvement in the current study. Data collection, analysis and interpretation, writing, and submitting the manuscript for publication were made by the authors. No honorarium, grant, or other forms of payment were given to anyone to produce the manuscript. The authors have no financial relationships relevant to this article to disclose.
This trial was registered with the Israel Ministry of Health, no.: MOH_2017–08–31_000339.
A.B.N. conceptualized and designed the study and supervised data acquisition and reviewed the manuscript for intellectual content.
C.F. conceptualized the study, coordinated and supervised data acquisition, drafted the initial manuscript, and reviewed and revised the manuscript.
A.H.-R. performed the initial data analysis and provided statistical consultation and reviewed the manuscript for intellectual content.
O.B.Y., N.M., and E.B.D. conceptualized and designed the MRI aspects of the study, MRI data acquisition and implemented the MRI analyses, and reviewed the manuscript for intellectual content.
Y.K. and I.S. assisted in clinical data acquisition and interpretation.
All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
* These authors contributed equally to this work as first authors.
Received: 06 July 2021
Accepted: 13 September 2021
20 September 2021 (online)
© 2021. Thieme. All rights reserved.
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- 1 Wisnowski JL, Panigrahy A, Painter MJ, Watchko JF. Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise. Semin Perinatol 2014; 38 (07) 422-428
- 2 Wisnowski JL, Panigrahy A, Painter MJ, Watchko JF. Magnetic resonance imaging abnormalities in advanced acute bilirubin encephalopathy highlight dentato-thalamo-cortical pathways. J Pediatr 2016; 174: 260-263
- 3 Coskun A, Yikilmaz A, Kumandas S, Karahan OI, Akcakus M, Manav A. Hyperintense globus pallidus on T1-weighted MR imaging in acute kernicterus: is it common or rare?. Eur Radiol 2005; 15 (06) 1263-1267
- 4 Penn AA, Enzmann DR, Hahn JS, Stevenson DK. Kernicterus in a full term infant. Pediatrics 1994; 93 (6, pt. 1): 1003-1006
- 5 Wang X, Wu W, Hou BL. et al. Studying neonatal bilirubin encephalopathy with conventional MRI, MRS, and DWI. Neuroradiology 2008; 50 (10) 885-893
- 6 Yilmaz Y, Ekinci G. Thalamic involvement in a patient with kernicterus. Eur Radiol 2002; 12 (07) 1837-1839
- 7 Gkoltsiou K, Tzoufi M, Counsell S, Rutherford M, Cowan F. Serial brain MRI and ultrasound findings: relation to gestational age, bilirubin level, neonatal neurologic status and neurodevelopmental outcome in infants at risk of kernicterus. Early Hum Dev 2008; 84 (12) 829-838
- 8 Govaert P, Lequin M, Swarte R. et al. Changes in globus pallidus with (pre)term kernicterus. Pediatrics 2003; 112 (6, pt. 1): 1256-1263
- 9 Erdei C, El-Dib M. Pediatric newborn medicine clinical practice guidelines. Accessed July 24, 2019 at: https://www.brighamandwomens.org/assets/BWH/pediatric-newborn-medicine/pdfs/te-mris-for-very-preterm-infants-final.pdf
- 10 Jaundice in newborn babies under 28 days: NICE guideline. Accessed September 30, 2021 at: https://www.nice.org.uk/guidance/cg98
- 11 Coskun A, Lequin M, Segal M, Vigneron DB, Ferriero DM, Barkovich AJ. Quantitative analysis of MR images in asphyxiated neonates: correlation with neurodevelopmental outcome. AJNR Am J Neuroradiol 2001; 22 (02) 400-405
- 12 Watchko JF. Bilirubin-induced neurotoxicity in the preterm neonate. Clin Perinatol 2016; 43 (02) 297-311
- 13 Watchko JF, Maisels MJ. The enigma of low bilirubin kernicterus in premature infants: why does it still occur, and is it preventable?. Semin Perinatol 2014; 38 (07) 397-406
- 14 Okumura A, Kidokoro H, Shoji H. et al. Kernicterus in preterm infants. Pediatrics 2009; 123 (06) e1052-e1058
- 15 Assefa Neknek G, Woldemichael K, Moges A, Zewdneh Solomon D. MRI of bilirubin encephalopathy (kernicterus): a case series of 4 patients from Sub-Saharan Africa, May 2017. Radiol Case Rep 2018; 13 (03) 676-679
- 16 Yilmaz Y, Alper G, Kiliçoglu G, Celik L, Karadeniz L, Yilmaz-Değirmenci S. Magnetic resonance imaging findings in patients with severe neonatal indirect hyperbilirubinemia. J Child Neurol 2001; 16 (06) 452-455