Enamel Hypoplasia and Early Childhood Caries in Preterms with Jaundice

黄疸早产儿牙釉质发育不全和儿童早期龋齿

• 批准号: 7976060
• 负责人: SANJIV B AMIN
• 金额: $ 15.22万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7976060
• 关键词: Acute; Affect; Age; Albumins; Athetoid cerebral palsy; Auditory; Bilirubin; Binding; Biochemical Markers; Birth; Blinded; Child; Childhood; Chronic; Chronic Brain Damage; Clinical; Communities; Comorbidity; Coupled; Data; Defect; Dental; Dental Enamel; Dental Enamel Hypoplasia; Dental caries; Dentists; Detection; Development; Disease; Encephalopathies; Enteral Feeding; FDA approved; Family; Follow-Up Studies; Funding; Future; Gestational Age; Goals; Health; High Prevalence; Hyperbilirubinemia; Hypocalcemia result; Icterus; Incidence; Infant; Infection of amniotic sac and membranes; International; Intervention; Intubation; Kernicterus; Knowledge; Laboratories; Life; Literature; Measures; Mechanical Ventilators; Medical center; Methods; Morbidity - disease rate; Neonatal; Neonatal Jaundice; Neuropathy; Paralysed; Peroxidases; Population; Premature Infant; Prevalence; Prevention; Principal Investigator; Prospective Studies; Public Health; Quality of life; Receiver Operating Characteristics; Regression Analysis; Research; Research Personnel; Retrospective Studies; Risk; Risk Factors; Role; Sensitivity and Specificity; Serum; System; Therapeutic Intervention; Toxic effect; Universities; Work; base; cohort; cost; early childhood; experience; gaze palsy; hearing impairment; improved; indexing; insight; interest; neonatal sepsis; neonate; premature; prospective; public health relevance; total measurement Bilirubin

DESCRIPTION (provided by investigator): 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.

描述（由研究者提供）：新生儿中极为常见的Jaurine（非结合型高胆红素血症）已被证明可引起慢性核小体后脑病（CPKE），这是一种终身疾病，特征为牙釉质发育不全、手足徐动样脑瘫和听力丧失。与足月儿相比，早产儿发生CPKE的风险增加。目前的文献表明，早产儿牙釉质发育不全的患病率高于足月儿，然而，患病率较高的原因及其与高胆红素血症的关系尚未得到很好的研究。牙釉质发育不全会增加患龋齿及相关疾病的风险，因此，预防牙釉质发育不全至关重要。本研究的主要焦点是建立新生儿黄疸和牙釉质发育不全以及早产儿相关龋齿之间的联系。目前，总血清胆红素（TSB）用于评估和管理早产儿黄疸，尽管研究表明TSB是CPKE的不良指标。最近，主要研究者已经证明，未结合胆红素是比TSB更好的早产儿胆红素诱导的听觉毒性的预测因子。因此，我们的次要目的是扩展本研究，以确定未结合胆红素作为早产儿中胆红素诱导的牙齿毒性（牙釉质发育不全和严重的幼儿龋齿）的比TSB更敏感和更特异的预测因子的有用性。该项目被提议作为R-21，因为关于胆红素诱导的早产儿牙齿毒性的数据很少。我们有一个独特的机会来进行这些研究，因为我们有一个队列的250名早产儿与未结合胆红素水平和相关的临床信息前瞻性收集作为NIH资助的胆红素研究的一部分。具有共同兴趣和互补作用的经验丰富的研究者将合作评估150名参与胆红素研究的胎龄33周的婴儿在两年期间内的胆红素诱导的牙齿毒性。将由经验丰富的儿科牙医进行校准牙科检查，不了解风险因素，包括3岁矫正年龄时的未结合胆红素水平。使用FDA批准的UB分析仪通过过氧化物酶法测量未结合胆红素。将进行回归分析，以评估新生儿黄疸和牙齿毒性之间的关联强度。将绘制受试者工作特征曲线，以比较未结合胆红素、胆红素：白蛋白比值和TSB对胆红素诱导的牙齿毒性的敏感性和特异性。这项研究的结果可能会提供额外的见解胆红素诱导的毒性在发育期间，并扩展的证据未结合胆红素预测CPKE的其他表现，如牙釉质发育不全的早产儿有用。最终目标将是减少：1）黄疸相关的牙齿毒性，2）识别有牙釉质发育不全和龋齿风险的早产儿，以便将来进行干预，3）确定未结合胆红素对预测CPKE的有用性。 公共卫生相关性：幼儿龋齿是最常见的儿童疾病，通常与影响儿童、其家庭和社区的健康和生活质量的有害影响有关。本临床项目将由经验丰富的美国研究者进行，将前瞻性评价未结合高胆红素血症（黄疸）与牙釉质发育不全和相关龋齿（胆红素毒性）的相关性，并在不同种族的黄疸早产儿人群中检查未结合胆红素作为胆红素诱导的牙齿毒性预测因子的有效性。如果黄疸与早产儿牙釉质发育不全和相关龋齿相关，并且未结合胆红素是比血清总胆红素更好的预测胆红素诱导的毒性的指标，则将大大提高对有胆红素诱导的牙齿毒性风险和需要治疗干预的婴儿的识别。这项研究的总体结果对全球公共卫生产生了影响，因为它将有助于减少与牙釉质发育不全和幼儿龋齿相关的黄疸，也将有助于降低与幼儿龋齿及其相关共病治疗相关的成本。