Management of Neonatal Hyperbilirubinemia: Shedding Light on the American Academy of Pediatrics 2022 Clinical Practice Guideline Revision.

Neonatal hyperbilirubinemia is one of the most common conditions managed by pediatricians. Although many infants are affected, most will experience complete resolution without complication. Acute bilirubin encephalopathy and kernicterus are rare yet debilitating sequelae of severe hyperbilirubinemia that can be avoided through careful monitoring and treatment with phototherapy. Appropriate management of neonatal hyperbilirubinemia must balance the risks of these severe conditions with the effects of overtreatment. Released in 2022, the American Academy of Pediatrics revised the clinical practice guideline for the management of hyperbilirubinemia, which aims to provide that balance through updates to the previous guideline. This article will provide the reader with (1) an evidence-based harm and benefit analysis of the guideline, (2) an overview of key changes and clarifications made in the new guideline, and (3) a practical summary of guideline updates. [Pediatr Ann. 2024;53(6):e208-e216.].

Transcutaneous bilirubinometry for detecting jaundice in term or late preterm neonates.

BACKGROUND: The American Academy of Pediatrics and the Canadian Paediatric Society both advise that all newborns should undergo bilirubin screening before leaving the hospital, and this has become the standard practice in both countries. However, the US Preventive Task Force has found no strong evidence to suggest that this practice of universal screening for bilirubin reduces the occurrence of significant outcomes such as bilirubin-induced neurologic dysfunction or kernicterus. OBJECTIVES: To evaluate the effectiveness of transcutaneous screening compared to visual inspection for hyperbilirubinemia to prevent the readmission of newborns (infants greater than 35 weeks' gestation) for phototherapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, ICTRP, and ISRCTN in June 2023. We also searched conference proceedings, and the reference lists of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, or prospective cohort studies with control arm that evaluated the use of transcutaneous bilirubin (TcB) screening for hyperbilirubinemia in newborns before hospital discharge. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) and 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to evaluate the certainty of evidence. MAIN RESULTS: We identified one RCT (1858 participants) that met our inclusion criteria. The study included 1858 African newborns at 35 weeks' gestation or greater who were receiving routine care at a well-baby nursery, and were randomly recruited prior to discharge to undergo TcB screening. The study had good methodologic quality. TcB screening versus visual assessment of hyperbilirubinemia in newborns: - may reduce readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - probably has little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - may increase the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - probably has little or no effect on the rate of acute bilirubin encephalopathy (RR 0.33, 95% CI 0.01 to 8.18; low-certainty evidence). The study did not evaluate or report cost of care. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that TcB screening may reduce readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening probably has little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening may increase the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening probably has little or no effect on the rate of acute bilirubin encephalopathy compared to visual inspection. Given that we have only identified one RCT, further studies are necessary to determine whether TcB screening can help to reduce readmission and complications related to neonatal hyperbilirubinemia. In settings with limited newborn follow-up after hospital discharge, identifying newborns at risk of severe hyperbilirubinemia before hospital discharge will be important to plan targeted follow-up of these infants.

Comparative analysis of the quantitative point-of-care CareSTART™ total bilirubin with central laboratory total bilirubin assays in neonatal blood samples.

This study aimed to assess and compare the accuracy of point-of-care CareSTART™ S1 Total Bilirubin test with a central laboratory total bilirubin assay using neonatal samples. This study was conducted using 152 paired measurements obtained from 122 neonates admitted to the neonatal intensive care unit. Total serum bilirubin (TSB) levels assayed with the central laboratory assay, laboratory bilirubinomter, trancutaneous bliribubin (TcB) instrument and CareSTART were compared using Bland-Altman analysis. The mean difference between the CareSTART and TSB values was -1.43 mg/dL and the 95% limit of agreement (LoA) was -4.25 to 1.39 mg/dL. CareSTART tended to underestimate total bilirubin concentrations compared with TcB, however, the LoA was narrower due to the smaller SD of mean difference for CareSTART. The CareSTART Total Bilirubin test provides an accurate alternative to TcB for total serum bilirubin measurement. Given its low-cost, ease-of-use, and portability, the use of CareSTART is expected to provide point-of-care measurements, especially in low-resource settings.

Evaluating the relationship between aEEG findings and two-year prognosis in neonates with severe hyperbilirubinemia.

OBJECTIVE: Identifying factors that can better predict the prognosis of neonates with hyperbilirubinemia is important. In this study, we aimed to evaluate the relationship between electroencephalography (EEG) findings and two-year prognosis in neonates with severe hyperbilirubinemia. METHODS & MATERIALS: In a cohort prospective study, we studied neonates with a total serum bilirubin level of higher than 18 mg/dL, who were admitted to the neonatal intensive care unit (NICU) of Ghaem hospital, Mashhad, Iran. EEG was recorded upon admission, for all neonates. Patients' data, including demographic characteristics, admission information, and pregnancy and birth data were gathered by obtaining history from parents and studying case files. Also, the relationship between initial EEG findings and final developmental status was assessed. RESULTS: Mean and standard deviation age of patients were 5.46 ± 3.13 days and average serum total bilirubin level was 23.97 ± 4.34 mg/dL at admission. Our findings revealed a significant correlation between the presence of trace alternant on EEG and developmental delay (P = .001). Presence of trace alternant waves on initial EEG at admission was significantly associated with developmental delay in the two year (P = .005). CONCLUSION: These results indicate a relationship between developmental prognosis and the severity of hyper bilirubinemia in neonates. Also, our findings show that the presence of trace alternate waves on the initial EEG is significantly associated with developmental delay of the neonate in the future.

[Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia].

Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) µmol/L, with a range of 23.7-717.0 µmol/L. The JCard level was (221.4±77.0) µmol/L and the TcB level was (252.5±76.0) µmol/L. Both the JCard and TcB values showed good correlation (r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 µmol/L. The TcB value of 205.2 µmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 µmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 µmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 µmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 µmol/L (both P<0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 µmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 µmol/L).

End-tidal carbon monoxide concentrations measured within 48 hours of birth predict hemolytic hyperbilirubinemia.

OBJECTIVES: To determine, among neonates at-risk for hyperbilirubinemia, whether measuring end-tidal carbon monoxide concentration (ETCOc) twice before 48 hours could identify those who would develop hyperbilirubinemia and differentiate hemolytic vs. non-hemolytic causes. METHODS: Prospective study on neonates meeting criteria "at-risk for hyperbilirubinemia." Routine bilirubin measurements and 10-day follow-up were used to categorize neonates as; (1) normal (no hyperbilirubinemia, all bilirubins <95th percentile of Bhutani nomogram), (2) having hemolytic hyperbilirubinemia (bilirubin ≥95th percentile, DAT+, elevated retic, or G6PD+), or (3) having non-hemolytic hyperbilirubinemia. RESULTS: 386 neonates were enrolled. 321 (83%) did not develop hyperbilirubinemia and 65 (17%) did, of which 29 were judged hemolytic and 36 non-hemolytic. High ETCOc differentiated the hemolytic group (p < 0.001). First-day ETCOc correlated with bilirubin and with reticulocyte count (r = 0.896 and 0.878) and sensitivity and specificity for predicting hyperbilirubinemia were excellent (83% and 95%). CONCLUSIONS: ETCO measurement in the first 48 hours after birth predicts hemolytic hyperbilirubinemia.

Innovative approaches to neonatal jaundice diagnosis and management in low-resourced settings.

Persistent challenges in addressing severe neonatal hyperbilirubinaemia in resource-constrained settings have led to ongoing and often unacceptable rates of morbidity, disability and mortality. These challenges stem from limitations such as inadequate, inefficient or financially inaccessible diagnostic and therapeutic options. However, over the past decade, noteworthy innovations have emerged to address some of these hurdles, and these innovations are increasingly poised for broader implementation. This review provides a concise summary of these novel, economically viable diagnostic solutions, encompassing point-of-care assays and smartphone applications, as well as treatment modalities, notably more effective phototherapy and filtered sunlight. These advancements hold promise and have the potential to meaningfully reduce the burden of neonatal hyperbilirubinaemia, signifying a promising shift in the landscape of neonatal healthcare.

Is it time for a precision health approach to the management of newborn hyperbilirubinemia?

Newborn hyperbilirubinemia during the first two weeks of life is one of most common problems requiring management decisions by a pediatrician. However, high bilirubin levels in the circulation have been associated with neurologic injury under a variety of conditions encountered in the newborn infant, such as hemolysis. The risk for developing dangerous hyperbilirubinemia is multifactorial and is determined by a complex set of factors related to a newborn infant's genetic capacities as well as intra- and extrauterine exposures. To this end, a precision health approach based on the integration of prenatal genetic and postnatal diagnostic measures might improve the management of neonatal hyperbilirubinemia.

Application of machine learning algorithms for accurate determination of bilirubin level on in vitro engineered tissue phantom images.

Neonatal Jaundice is a common occurrence in neonates. High excess bilirubin would lead to hyperbilirubinemia, leading to irreversible adverse damage such as kernicterus. Therefore, it is necessary and important to monitor neonates' bilirubin levels in real-time for immediate intervention. However, current screening protocols have their inherent limitations, necessitating more convenient measurements. In this proof-of-concept study, we evaluated the feasibility of using machine learning for the screening of hyperbilirubinemia in neonates from smartphone-acquired photographs. Different machine learning models were compared and evaluated to gain a better understanding of feature selection and model performance in bilirubin determination. An in vitro study was conducted with a bilirubin-containing tissue phantom to identify potential biological and environmental confounding factors. The findings of this study present a systematic characterization of the confounding effect of various factors through separate parametric tests. These tests uncover potential techniques in image pre-processing, highlighting important biological features (light scattering property and skin thickness) and external features (ISO, lighting conditions and white balance), which together contribute to robust model approaches for accurately determining bilirubin concentrations. By obtaining an accuracy of 0.848 in classification and 0.812 in regression, these findings indicate strong potential in aiding in the design of clinical studies using patient-derived images.

Hyperbilirubinemia screening and treatment in neonates born prior to 35 weeks of gestation.

BACKGROUND: Guidelines on when to screen for neonatal hyperbilirubinemia apply to infants born at 35 weeks or later of gestation. It is unknown whether infants born earlier would benefit from similar guidelines. Our objective was to examine hyperbilirubinemia screening and phototherapy prescription among early preterm infants during the first 6 days of life. METHODS: We reviewed the charts of 193 infants born prior to 35 weeks of gestation who were admitted to a tertiary care NICU in Southeastern Ontario in 2018-2019. Information on total serum bilirubin (TSB) measurements over each 12-hour interval during the first six days of life and the treatment decision (no treatment, initiate, continue, or stop phototherapy) was extracted. We also examined what proportion of infants were prescribed phototherapy during each 12-hour interval. RESULTS: Of 1006 TSB measurements performed over the first 6 days of life, 605 were done to determine whether phototherapy should be initiated. Treatment was prescribed in 275 instances (45%). A higher proportion of infants born prior to 28 weeks of gestation required phototherapy in the first 12 hours of life (37%) compared to those born at 28-32 weeks (20%) and 33-34 weeks (5.7%). CONCLUSIONS: Our results suggest that TSB measurements are often poorly timed to detect treatment need in infants born prior to 35 weeks of gestation. This unnecessarily increases the risk of complications from phlebotomy and is an ineffective use of health care resources. There is a need to develop guidelines to optimize hyperbilirubinemia screening among early preterm infants.

A Significant Increase in the Incidence of Neonatal Hyperbilirubinemia and Phototherapy Treatment Due to a Routine Change in Laboratory Equipment.

CONTEXT.­: Total serum bilirubin (TSB) analysis is pivotal for diagnosing neonatal hyperbilirubinemia. Because of a routine change in laboratory equipment, our TSB assay changed from a diazo to a vanadate oxidase method. Upon implementation, TSB results were substantially higher in newborns than expected based on the validation. OBJECTIVE.­: To investigate the application of TSB and intermethod differences in neonates and their impact on phototherapy treatment. DESIGN.­: The diazo and vanadate methods were compared directly using neonatal and adult samples. Anonymized external quality control data were analyzed to explore interlaboratory differences among 8 commercial TSB assays. Clinical patient data were extracted from the medical records to investigate the number of newborns receiving phototherapy. RESULTS.­: The mean bias of the vanadate versus the diazo TSB method was +17.4% and +3.7% in neonatal and adult samples, respectively. External quality control data showed that the bias of commercial TSB methods compared with the reference method varied from -3.6% to +20.2%. Within-method variation ranged from 5.2% to 16.0%. After implementation of the vanadate TSB method, the number of neonates treated with phototherapy increased approximately threefold. CONCLUSIONS.­: Currently available TSB assays lack harmonization for the diagnosis of neonatal hyperbilirubinemia. Between-methods differences are substantially higher in neonatal compared with adult samples, highlighting the importance of including neonatal samples during assay validation. Close collaboration between laboratory specialists and clinicians is essential to prevent overtreatment or undertreatment upon the implementation of novel analyzers or assays. Also, harmonization of TSB assays, with an emphasis on neonatal application, is warranted.

Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study.

BACKGROUND: Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD. METHODS: The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit. MRI signal alteration of the globus pallidus was scored using the Hyperbilirubinemia Imaging Rating Tool (HIRT). RESULTS: Of 25 neonates enrolled, 13/25 completed 12-month follow-up and six developed KSD. Neonatal BIND-M ≥ 3 was 100% sensitive and 83% specific for KSD. Neonatal ABR was 83% specific and sensitive for KSD. Neonatal HIRT score of 2 was 67% sensitive and 75% specific for KSD; this increased to 100% specificity and sensitivity at 12 months. BAD ≥ 2 was 100% specific for KSD at 3-12 months, with 50-100% sensitivity. CONCLUSIONS: Neonatal MRIs do not reliably predict KSD. BIND-M is an excellent screening tool for KSD, while the BAD or HIRT score at 3 or 12 months can confirm KSD, allowing for early diagnosis and intervention. IMPACT: The first prospective study of children with acute bilirubin encephalopathy evaluating brain MRI findings over the first year of life. Neonatal MRI is not a reliable predictor of kernicterus spectrum disorders (KSD). Brain MRI at 3 or 12 months can confirm KSD. The modified BIND scale obtained at admission for neonatal hyperbilirubinemia is a valuable screening tool to assess risk for developing KSD. The Barry Albright Dystonia scale and brain MRI can be used to establish a diagnosis of KSD in at-risk infants as early as 3 months.

Magnetic resonance spectroscopy and auditory brain-stem response audiometry as predictors of bilirubin-induced neurologic dysfunction in full-term jaundiced neonates.

The purpose of this research was to define the functions of MRS and ABR as predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy and/or exchange transfusion). This prospective cohort study was done at the NICU of Tanta University Hospitals over a 2-year duration. Fifty-six full-term neonates with pathological unconjugated hyperbilirubinemia were divided according to MRS and ABR findings into 2 groups: group (1) included 26 cases with mild acute bilirubin encephalopathy (BIND-M score 1-4). Group (2) included 30 cases with neonatal hyperbilirubinemia only. In addition, 20 healthy neonates with similar ages were employed as the controls. When compared to group 2 and the control group, group 1's peak-area ratios of NAA/Cr and NAA/Cho were found to be significantly reduced (P < 0.05). As compared to group 2 and the control group, group 1's Lac/Cr ratio was significantly greater (P < 0.05), but the differences were not significant for group 2 when compared to the control group. Waves III and V peak latencies, I-III, and I-V interpeak intervals were significantly prolonged in group 1 in comparison to group 2 and controls (P < 0.05) with no significant difference between group 2 and control group.   Conclusion: When the symptoms of ABE are mild and MRI does not show any evident abnormalities, MRS and ABR are helpful in differentiating individuals with ABE from patients with neonatal hyperbilirubinemia.    Trial registration:  ClinicalTrials.gov , Identifier: NCT06018012. What is Known: • MRS can be used as a diagnostic and prognostic tool for the differential diagnosis of patients with acute bilirubin encephalopathy, from patients with neonatal hyperbilirubinemia What is New: • ABR is a useful diagnostic and prognostic tool in the care and management of neonates with significantly raised bilirubin. It can be used as early predictor of acute bilirubin encephalopathy in the earliest stage of auditory damage caused by bilirubin.

Automated ABR screening for hearing loss and its clinical determinants among newborns with hyperbilirubinemia in National Hospital, Abuja, Nigeria.

Background: Severe neonatal hyperbilirubinemia is a known risk factor for sensorineural hearing loss which is usually undiagnosed in our environment until school age due to a lack of routine screening programs. Materials and Methods: This cross-sectional study conducted between August 2020 and February 2021 employed a universal sampling of consecutive eligible participants after their mothers' consent. Hearing screening was conducted using an automated auditory brainstem response (AABR) device (Otoport OAE + ABR®). The proportion of AABR screening failure was assessed while associated clinical risk factors were determined using logistic regression. Statistical significance was set at 5% for all comparative analyses. Results: One hundred and sixty newborns below 28 days of age, delivered at 34 weeks gestation and above, who had jaundice were recruited. The prevalence of screening AABR failure in at least one ear was 26.2%. Significant risk factors for AABR screening failure in addition to extreme and hazardous hyperbilirubinemia were acute bilirubin encephalopathy (ABE) (Odds Ratio (OR) =4.44, 95% CI = 3.19-6.17), birth weight below 2500 g (OR = 3.16, 95% CI = 1.48-6.77), dull tympanic membrane (TM) (OR = 5.94, 95% CI = 2.36-14.92) and exchange blood transfusion (OR = 4.84, 95% CI = 1.87-12.58). Conclusion and Recommendations: The prevalence of AABR screening failure was high, and a dull TM was its strongest predictor among late preterm and term neonates with hyperbilirubinemia. Otoscopy should be included in the care of newborn with hyperbilirubinemia and screening programs established to mitigate hearing loss among high-risk neonates in Abuja.

Prospective cohort study of neurodevelopmental outcomes following extreme neonatal hyperbilirubinaemia in Australia.

AIM: This study aimed to establish the incidence and nature of neurodevelopmental outcomes following extreme neonatal hyperbilirubinaemia in an Australian cohort. METHODS: A prospective cohort study of neurodevelopmental outcomes up to 3 years of age of infants born between 2010 and 2013 at ≥34 weeks gestation, with total serum bilirubin ≥450 µmol/L and/or clinical signs of acute bilirubin encephalopathy. Outcome measures comprised neurological examination, Bayley Scales of Infant and Toddler Development, 3rd edition and Ages and Stages Questionnaire, 3rd edition. RESULTS: The Australian estimated incidence of kernicterus is 0.35 per 100 000 live births. Within the follow-up cohort of 26, three children have clinical neurodevelopmental impairment: one has gross motor function classification system level 4 cerebral palsy, audiological deficiency and visual impairment; the second has gross motor function classification system level 1 cerebral palsy and the third has global developmental delay with autism spectrum disorder. Mean Bayley Scales of Infant and Toddler Development, 3rd edition scores were: cognition 10.3 (SD 1.5), receptive communication 9.4 (SD 1.8), expressive communication 9.2 (SD 2.4), fine motor 10.4 (SD 2.6) and gross motor 9.2 (SD 2.3). CONCLUSION: The Australian national rate of kernicterus compares favourably with global estimates. Future preventative strategies in this context include universal neonatal hyperbilirubinaemia assessment and mandated adverse outcome reporting and investigation.

The use of transcutaneous bilirubin nomograms for the prevention of bilirubin neurotoxicity in the neonates.

Purpose: Although neonatal jaundice is a ubiquitous and predominantly benign phenomenon, the risk of neurotoxicity exists in a number of infants with unconjugated hyperbilirubinemia. Plotting bilirubin values on nomograms enables clinicians to employ an anticipatory and individualized approach with the goal of avoiding excessive hyperbilirubinemia and preventing acute bilirubin encephalopathy and its progression to kernicterus. We aimed to construct nomograms for White term infants based on transcutaneous bilirubin (TcB) measurements using a JM-105 device. Methods: TcB measurements were taken in infants at ages ranging from 0 to 96 postnatal hours. We then constructed hour-specific TcB nomograms from forehead and sternum measurements in infants who did not require subsequent phototherapy. Results: We included 2,981 TcB measurements taken on the forehead and 2,977 measurements taken on the sternum in 301 White term newborn infants. We assessed the predictive abilities of the nomograms at six postnatal time intervals using receiver operating characteristic curves. The areas under the curves indicated reasonable prediction of hyperbilirubinemia requiring phototherapy, except for the forehead measurement taken within the first 12 h of life. Sensitivity tended to rise as postnatal age increased. Conclusion: The nomograms illustrate dermal bilirubin dynamics in White term neonates during the first 4 days of life. They may be useful tools to predict individualized risk of hyperbilirubinemia requiring treatment, and to plan optimal follow-up of infants at risk of bilirubin neurotoxicity.

Kernicterus on the Spectrum.

Kernicterus is the potential toxic sequela of extreme neonatal hyperbilirubinemia resulting from the passage of excess free, unconjugated bilirubin across the blood-brain barrier, irreversibly and selectively damaging vulnerable target brain cells including the basal ganglia, the cerebellum, and the auditory system. Kernicterus continues to plague the modern world. Not only does it continue to be uncontrolled in developing countries with underdeveloped medical systems, and health organizations rendered ineffective by the ravages of war, but it also remains prevalent in industrialized countries. In this review, we attempt to clarify the different and overlapping nomenclature used in the past to describe this entity and aim to offer a uniform approach to defining kernicterus spectrum disorder. We also discuss the different spectrum subtypes including motor-predominant kernicterus, auditory neural sensory dysfunction, subtle kernicterus, and kernicterus plus. In addition to reviewing several genetic factors that increase the risk of developing kernicterus, we also present some exciting potential therapeutic approaches.