Jaundice (unconjugated hyperbilirubinemia), which is extremely common in neonates, has been shown to cause chronic post-kernicteric encephalopathy (CPKE), a life-long disorder, characterized by dental enamel hypoplasia, athetoid cerebral palsy, and hearing loss. Premature infants are at increased risk of CPKE compared to term infants. Current literature suggests that premature infants have a higher prevalence of dental enamel hypoplasia compared to term infants, however, the reasons for higher prevalence and its associations with hyperbilirubinemia have not been well studied. Dental enamel hypoplasia is known to increase the risk of dental caries and related morbidity, therefore, prevention of enamel hypoplasia is of paramount importance. The primary focus of this research is to establish the association between neonatal jaundice and dental enamel hypoplasia and related dental caries in premature infants. Currently, total serum bilirubin (TSB) is used to evaluate and manage jaundice in premature infants, although studies have shown that TSB is a poor indicator of CPKE. Recently, unbound bilirubin has been shown by the Principal Investigator to be a better predictor than TSB of bilirubin-induced auditory toxicity in premature infants. Therefore, our secondary objective is to expand this research to establish the usefulness of unbound bilirubin as a more sensitive and specific predictor than TSB of bilirubin-induced dental toxicity (dental enamel hypoplasia and severe early childhood caries) in premature infants. The project is being proposed as an R-21 since very little data exist regarding bilirubin- induced dental toxicity in premature infants. We are in a unique opportunity to conduct these studies as we have a cohort of 250 premature infants with unbound bilirubin levels and relevant clinical information prospectively collected as part of NIH-funded bilirubin study. Experienced investigators with common interest and complimentary roles will collaborate to evaluate bilirubin-induced dental toxicity in 150 infants d 33 weeks gestational age over two year period who participated in bilirubin study. Calibrated dental examinations will be performed by an experienced pediatric dentist without knowledge of risk factors, including unbound bilirubin levels at 3 years corrected age. The unbound bilirubin was measured by the peroxidase method using FDA approved UB analyzer. Regression analyses will be performed to evaluate the strength of association between neonatal jaundice and dental toxicity. Receiver operating characteristic curves will be performed to compare sensitivity and specificity of unbound bilirubin, bilirubin:albumin ratio, and TSB for bilirubin-induced dental toxicity. The findings of this study may provide additional insight regarding bilirubin-induced toxicity during a developmental period and extend the evidence for usefulness of unbound bilirubin for predicting other manifestation of CPKE such as dental enamel hypoplasia in premature infants. The ultimate goal will be to reduce: 1) jaundice related dental toxicity, 2) identify at-risk premature infants for dental enamel hypoplasia and caries for future interventions, and 3) establish usefulness of unbound bilirubin for predicting CPKE.

Public Health Relevance

Public Health Significance Early childhood caries is the most common childhood disease and is often associated with detrimental effects on health and quality of life affecting children, their families, and the community. This clinical project to be performed by experienced US investigators will prospectively evaluate the association of unconjugated hyperbilirubinemia (jaundice) with dental enamel hypoplasia and related caries (bilirubin toxicity) and also examine the usefulness of unbound bilirubin as a predictor of bilirubin-induced dental toxicity in a diverse racial population of premature infants with jaundice. If jaundice is associated with dental enamel hypoplasia and related caries in premature infants and unbound bilirubin is a better predictor than total serum bilirubin of bilirubin-induced toxicity, it will greatly improve identification of infants who are at risk for bilirubin-induced dental toxicity and in need of therapeutic intervention. The overall findings of this study have ramifications for public health globally as it will help decrease jaundice associated dental enamel hypoplasia and early childhood caries, and will also help reduce costs associated with the treatment of early childhood caries and its associated co-morbidities.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Fischer, Dena
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Rochester
Schools of Dentistry
United States
Zip Code
Amin, Sanjiv B (2016) Bilirubin Binding Capacity in the Preterm Neonate. Clin Perinatol 43:241-57
Amin, Sanjiv B; Lamola, Angelo A (2011) Newborn jaundice technologies: unbound bilirubin and bilirubin binding capacity in neonates. Semin Perinatol 35:134-40