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.

Parental detection of neonatal jaundice using a low-cost colour card: a multicentre prospective study.

BACKGROUND: Since most infants are usually discharged before age 48-72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates. METHODS: We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB. RESULTS: JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents' and paediatricians' JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents' and paediatricians' JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians. CONCLUSION: The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.

Better assessment of neonatal jaundice at home (BEAT Jaundice @home): protocol for a prospective, multicentre diagnostic study.

INTRODUCTION: Severe neonatal hyperbilirubinaemia can place a neonate at risk for acute bilirubin encephalopathy and kernicterus spectrum disorder. Early diagnosis is essential to prevent these deleterious sequelae. Currently, screening by visual inspection followed by laboratory-based bilirubin (LBB) quantification is used to identify hyperbilirubinaemia in neonates cared for at home in the Netherlands. However, the reliability of visual inspection is limited. We aim to evaluate the effectiveness of universal transcutaneous bilirubin (TcB) screening as compared with visual inspection to: (1) increase the detection of hyperbilirubinaemia necessitating treatment, and (2) reduce the need for heel pricks to quantify bilirubin levels. In parallel, we will evaluate a smartphone app (Picterus), and a point-of-care device for quantifying total bilirubin (Bilistick) as compared with LBB. METHODS AND ANALYSIS: We will undertake a multicentre prospective cohort study in nine midwifery practices across the Netherlands. Neonates born at a gestational age of 35 weeks or more are eligible if they: (1) are at home at any time between days 2 and 8 of life; (2) have their first midwife visit prior to postnatal day 6 and (3) did not previously receive phototherapy. TcB and the Picterus app will be used after visual inspection. When LBB is deemed necessary based on visual inspection and/or TcB reading, Bilistick will be used in parallel. The coprimary endpoints of the study are: (1) hyperbilirubinaemia necessitating treatment; (2) the number of heel pricks performed to quantify LBB. We aim to include 2310 neonates in a 2-year period. Using a decision tree model, a cost-effectiveness analysis will be performed. ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethical Committee of the Erasmus MC Rotterdam, Netherlands (MEC-2020-0618). Parents will provide written informed consent. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NL9545).

Assessment, management, and incidence of neonatal jaundice in healthy neonates cared for in primary care: a prospective cohort study.

Jaundice caused by hyperbilirubinaemia is a common phenomenon during the neonatal period. Population-based studies evaluating assessment, management, and incidence of jaundice and need for phototherapy among otherwise healthy neonates are scarce. We prospectively explored these aspects in a primary care setting via assessing care as usual during the control phase of a stepped wedge cluster randomised controlled trial.We conducted a prospective cohort study embedded in the Screening and TreAtment to Reduce Severe Hyperbilirubinaemia in Infants in Primary care (STARSHIP) Trial. Healthy neonates were included in seven primary care birth centres (PCBCs) in the Netherlands between July 2018 and March 2020. Neonates were eligible for inclusion if their gestational age was ≥ 35 weeks, they were admitted in a PCBC for at least  2 days during the first week of life, and if they did not previously receive phototherapy. Outcomes were the findings of visual assessment to detect jaundice, jaundice incidence and management, and the need for phototherapy treatment in the primary care setting.860 neonates were included of whom 608 (71.9%) were visibly jaundiced at some point during admission in the PCBC, with 20 being 'very yellow'. Of the latter, four (20%) did not receive total serum bilirubin (TSB) quantification. TSB levels were not associated with the degree of visible jaundice (p = 0.416). Thirty-one neonates (3.6%) received phototherapy and none received an exchange transfusion. Five neonates did not receive phototherapy despite having a TSB level above phototherapy threshold.Jaundice is common in otherwise healthy neonates cared for in primary care. TSB quantification was not always performed in very jaundiced neonates, and not all neonates received phototherapy when indicated. Quality improvement initiatives are required, including alternative approaches to identifying potentially severe hyperbilirubinaemia.Trial registration: NL6997 (Dutch Trial Register; Old NTR ID 7187), registered 3 May 2018.

Clinical outcomes and cost-effectiveness of large-scale midwifery-led, paediatrician-overseen home phototherapy and neonatal jaundice surveillance: A retrospective cohort study.

AIM: To evaluate a large midwifery-led, paediatrician-overseen home jaundice surveillance and home phototherapy (HPT) programme. METHODS: We conducted a retrospective cohort study over 2019. Included were all infants with birth gestation ≥35 weeks, discharged at 4-96 h and receiving care from midwifery-at-home (a 12-h daily, 365-days hospital-based outreach service, supported by hospital paediatricians). Phototherapy was delivered via BiliSoft blanket with treatment thresholds determined by standard nomograms. The main outcomes of interest were unplanned readmissions, and cost-effectiveness based on hospital finance department actual costs. Also examined were parental compliance, device issues and safety. RESULTS: During 2019, 4308 infants received home jaundice surveillance with 86% hospital-discharged before 72 h, 82% exclusively breastfed and 69% having overseas-born mothers. Four hundred infants received HPT, comprising 101 continuing from inpatient phototherapy (IPT), 56 rebounding after IPT, and 243 home-diagnosed as needing phototherapy and triaged to HPT. Only 1 of 400 (0.25%) HPT infants required readmission. Additionally, there were 80 home-diagnosed jaundiced infants triaged to immediate readmission for IPT. Maximal serum bilirubin was 454 µmol/L. No exchange transfusion, encephalopathy or HPT-device problems occurred. An early 2019 bilirubin analyser upgrade resulted in higher bilirubin readings and some unintended subthreshold phototherapy. Supported by midwives, most parents managed HPT with ease. HPT cost $640/day compared to $2100/day for infant IPT readmission and $1000/day for a longer birth-admission stay. Up to 2 weeks' midwifery-at-home care for the whole cohort cost $2 m less than a 2-day longer birth-admission stay. CONCLUSION: Large-scale, midwifery-led, paediatrician-overseen jaundice surveillance and HPT can achieve very low unplanned readmission rates and be cost-effective.

Reliability of visual assessment of neonatal jaundice among neonates of black descent: a cross-sectional study from Tanzania.

BACKGROUND: Jaundice is common among neonates and if untreated can lead to kernicterus. Diagnosing neonatal jaundice (NJ) using Kramer's method (visual assessment) is considered user-friendly in resource-limited areas. However, there are conflicting findings on reliability of the Kramer's method in the diagnosis of NJ, particularly of black descent. Therefore, study aimed to determine the accuracy of Kramer's method in comparison to the total serum bilirubin (TSB) test in the diagnosis of NJ among neonates of black descent in Tanzania. METHODS: A cross-sectional study was conducted between June and July 2020 at Muhimbili National Hospital (MNH) in Dar es Salaam Tanzania. A total of 315 neonates were recruited consecutively. In each neonate, jaundice was assessed using Kramer's method and TSB test. NJ A total of 315 neonates were recruited i. A 2 X 2 table was created for the determination of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (+LR/-LR), and diagnostic accuracy (effectiveness) of Kramer's method. Cohen kappa (κ) was used to analyze the agreement between Kramer's method and TSB. Association between independent variables and presence of jaundice were assessed using the chi-square test and the p < 0.05 was considered to be statistically significant. RESULTS: The prevalence of NJ was 49.8% by Kramer's method and 63.5% by TSB. The Sensitivity, Specificity, PPV, and NPV of Kramer's method were 70.5, 86.1, 89.8, and 62.6%, respectively. The +LR and -LR were 5.07 and 0.34, respectively. The diagnostic accuracy of Kramer's method was 76.1%. There was a moderate agreement between Kramer's method and TSB results (κ = 0.524, P<0.001). No significant relationship was observed between the independent variables and the presence of NJ. CONCLUSION: Kramer has a good positive predictive value. However, due to low sensitivity and NPV one cannot say that overall predictive ability is good. Also, clinical assessment by Kramer's method should not be used for screening of NJ. Further studies are needed to investigate the utility of other non-invasive techniques in detecting NJ among neonates of black descent.

Validity of maternal visual assessment of neonatal jaundice: a hospital-based study in Thailand.

BACKGROUND: Hyperbilirubinaemia is a common cause of hospital admission of newborn infants; however, maternal visual assessment of jaundice may reduce unnecessary hospital visits. AIMS: To investigate the validity of maternal visual assessment of neonatal jaundice to identify infants with hyperbilirubinaemia requiring phototherapy or who have significant hyperbilirubinaemia ≥239.4 µmol/L (14 mg/dL). METHODS: A prospective study of the diagnostic accuracy of maternal visual assessment of jaundice was conducted at a university hospital in Bangkok. Mothers were trained to assess for neonatal jaundice using their infant's palms as a skin colour reference. Trained mothers who were blinded to transcutaneous bilirubin or serum bilirubin values assessed their infants and reported 'jaundice' or 'no jaundice', and determined jaundice severity using dermal icterus zones. Sensitivity and negative predictive values were used to assess the validity of visual assessment for neonatal jaundice. RESULTS: In 180 mothers, the median (min/max) transcutaneous or serum bilirubin value in their infants was 177.8 µmol/L (119.7-309.5). The sensitivity and negative predictive values (95% CI) of maternal assessment for detecting hyperbilirubinaemia requiring phototherapy were 91.7% (73.0-99.0) and 96.6% (87.9-99.1), respectively, and for identifying significant hyperbilirubinaemia were 92.9% (76.5-99.1) and 96.6% (87.9-99.1), respectively. The accuracy of maternal report of dermal zones for serum bilirubin levels was only 44.5%. In 56 infants who received a second jaundice assessment, the sensitivity of maternal assessment for detecting increased transcutaneous or serum bilirubin was 93.9% (83.1-98.7). CONCLUSION: Teaching mothers to visually assess their infants for neonatal jaundice was demonstrated to be feasible. ABBREVIATIONS: CI, confidence interval; MB, microbilirubin; min/max, minimum/maximum; NPV, negative predictive value; OPD, outpatient department; PPV, positive predictive value; SD, standard deviation; TcB, transcutaneous bilirubin.

Accuracy of Bilistick (a Point-of-Care Device) to Detect Neonatal Hyperbilirubinemia.

INTRODUCTION: Early diagnosis and appropriate management of neonatal jaundice is crucial in avoiding severe hyperbilirubinemia and brain injury. A low-cost, minimally invasive, point-of-care (PoC) tool for total bilirubin (TB) estimation which can be useful across all ranges of bilirubin values and all settings is the need of the hour. OBJECTIVE: To assess the accuracy of Bilistick system, a PoC device, for measurement of TB in comparison with estimation by spectrophotometry. DESIGN/METHODS: In this cross-sectional clinical study, in infants who required TB estimation, blood samples in 25-µl sample transfer pipettes were collected at the same time from venous blood obtained for laboratory bilirubin estimation. The accuracy of Bilistick in estimating TB within ±2 mg/dl of bilirubin estimation by spectrophotometry was the primary outcome. RESULTS: Among the enrolled infants, 198 infants were eligible for study analysis with the mean gestation of 36 ± 2.3 weeks and the mean birth weight of 2368 ± 623 g. The median age at enrollment was 68.5 h (interquartile range: 48-92). Bilistick was accurate only in 54.5% infants in measuring TB within ±2 mg/dl difference of TB measured by spectrophotometry. There was a moderate degree of correlation between the two methods (r = 0.457; 95% CI: 0.339-0.561, p value < 0.001). Bland-Altman analysis showed a mean difference of 0.5 mg/dl (SD ± 4.4) with limits of agreement between -8.2 and +9.1 mg/dl. CONCLUSION: Bilistick as a PoC device is not accurate to estimate TB within the clinically acceptable difference (±2 mg/dl) of TB estimation by spectrophotometry and needs further improvement to make it more accurate.

Impact of a standardized protocol for the Management of Prolonged Neonatal Jaundice in a regional setting: an interventional quasi-experimental study.

BACKGROUND: Prolonged neonatal jaundice (PNNJ) is often caused by breast milk jaundice, but it could also point to other serious conditions (biliary atresia, congenital hypothyroidism). When babies with PNNJ receive a routine set of laboratory investigations to detect serious but uncommon conditions, there is always a tendency to over-investigate a large number of well, breastfed babies. A local unpublished survey in Perak state of Malaysia revealed that the diagnostic criteria and initial management of PNNJ were not standardized. This study aims to evaluate and improve the current management of PNNJ in the administrative region of Perak. METHODS: A 3-phase quasi-experimental community study was conducted from April 2012 to June 2013. Phase l was a cross-sectional study to review the current practice of PNNJ management. Phase ll was an interventional phase involving the implementation of a new protocol. Phase lll was a 6 months post-interventional audit. A registry of PNNJ was implemented to record the incidence rate. A self-reporting surveillance system was put in place to receive any reports of biliary atresia, urinary tract infection, or congenital hypothyroidism cases. RESULTS: In Phase I, 12 hospitals responded, and 199 case notes were reviewed. In Phase II, a new protocol was developed and implemented in all government health facilities in Perak. In Phase III, the 6-month post-intervention audit showed that there were significant improvements when comparing mean scores of pre- and post-intervention: history taking scores (p < 0.001), family history details (p < 0.05), physical examination documentation (p < 0.001), and total investigations done per patient (from 9.01 to 5.81, p < 0.001). The total number of patient visits reduced from 2.46 to 2.2 per patient. The incidence of PNNJ was found to be high (incidence rate of 158 per 1000 live births). CONCLUSIONS: The new protocol standardized and improved the quality of care with better clinical assessment and a reduction in unnecessary laboratory investigations. TRIAL REGISTRATION: Research registration number: NMRR-12-105-11288 .

A Novel Icterometer for Hyperbilirubinemia Screening in Low-Resource Settings.

BACKGROUND: Severe neonatal hyperbilirubinemia (>20 mg/dL) affects ∼1 million infants annually. Improved jaundice screening in low-income countries is needed to prevent bilirubin encephalopathy and mortality. METHODS: The Bili-ruler is an icterometer for the assessment of neonatal jaundice that was designed by using advanced digital color processing. A total of 790 newborns were enrolled in a validation study at Brigham and Women's Hospital (Boston) and Sylhet Osmani Medical College Hospital (Sylhet, Bangladesh). Independent Bili-ruler measurements were made and compared with reference standard transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) concentrations. RESULTS: Bili-ruler scores on the nose were correlated with TcB and TSB levels (r = 0.76 and 0.78, respectively). The Bili-ruler distinguished different clinical thresholds of hyperbilirubinemia, defined by TcB, with high sensitivity and specificity (score ≥3.5: 90.1% [95% confidence interval (CI): 84.8%-95.4%] and 85.9% [95% CI: 83.2%-88.6%], respectively, for TcB ≥13 mg/dL). The Bili-ruler also performed reasonably well compared to TSB (score ≥3.5: sensitivity 84.5% [95% CI: 79.1%-90.3%] and specificity 83.2% [95% CI: 76.1%-90.3%] for TSB ≥11 mg/dL). Areas under the receiver operating characteristic curve for identifying TcB ≥11, ≥13, and ≥15 were 0.92, 0.93, and 0.94, respectively, and 0.90, 0.87, and 0.86 for identifying TSB ≥11, ≥13, and ≥15. Interrater reliability was high; 97% of scores by independent readers fell within 1 score of one another (N = 88). CONCLUSIONS: The Bili-ruler is a low-cost, noninvasive tool with high diagnostic accuracy for neonatal jaundice screening. This device may be used to improve referrals from community or peripheral health centers to higher-level facilities with capacity for bilirubin testing and/or phototherapy.

Filtered sunlight, solar powered phototherapy and other strategies for managing neonatal jaundice in low-resource settings.

Challenges in treating severe neonatal jaundice in low and middle-income country settings still exist at many levels. These include: a lack of awareness of causes and prevention by families, communities and even sometimes health care professionals; insufficient, ineffective, high quality affordable diagnostic and therapeutic options; limited availability of rehabilitation provision for kernicterus. Collectively these challenges lead to an unacceptably high global morbidity and mortality from severe neonatal jaundice. In the past decade, there has been an explosion of innovations addressing some of these issues and these are increasingly available for scale up. Scientists, healthcare providers, and communities are joining hands to explore educational tools, low cost screening and diagnostic options including at point-of-care and treatment modalities including filtered sunlight and solar powered phototherapy. For the first time, the possibility of eliminating the tragedy of preventable morbidity and mortality from severe NNJ is on the horizon, for all.

Diagnosing Jaundice by Eye-Outpatient Assessment of Conjunctival Icterus in the Newborn.

In pediatric office practices, we compared transcutaneous bilirubin levels in 689 newborns, age 3-10 days, with and without conjunctival icterus. In this age range, and in the absence of other clinical or laboratory indications, the presence of conjunctival icterus does not imply the need to measure the transcutaneous bilirubin or serum bilirubin level, but the absence of conjunctival icterus helps to rule out significant hyperbilirubinemia.

Influence of assessment site in measuring transcutaneous bilirubin.

OBJECTIVE: To investigate the influence of the site of measurement of transcutaneous bilirubin (forehead or sternum) in reproducibility of results as compared to plasma bilirubin. METHODS: A cohort study including 58 term newborns with no hemolytic disease. Transcutaneous measurements were performed on the forehead (halfway between the headline and the glabella, from the left toward the right side, making consecutive determinations, one-centimeter apart) and the sternum (five measurements, from the suprasternal notch to the xiphoid process with consecutive determinations, one-centimeter apart) using Bilicheck® (SpectRx Inc, Norcross, Georgia, USA). The correlation and agreement between both methods and plasma bilirubin were calculated. RESULTS: There was a strong linear correlation between both determinations of serum bilirubin at the forehead and sternum (r=0.704; p<0.01 and r=0.653; p<0.01, respectively). There was correspondence of the mean values of transcutaneous bilirubin measured on the sternum (9.9 ± 2.2mg/dL) compared to plasma levels (10.2 ± 1.7 mg/dL), but both differ from the values measured on the forehead (8.6 ± 2 .0mg/dL), p<0.05. CONCLUSION: In newborn term infants with no hemolytic disease, measuring of transcutaneous bilirubin on the sternum had higher accuracy as compared to serum bilirubin measurement on the forehead.

Influence of assessment site in measuring transcutaneous bilirubin / Influência do local de avaliação na mensuração da bilirrubina transcutânea / Influência do local de avaliação na mensuração da bilirrubina transcutânea

Objective : To investigate the influence of the site of measurement of transcutaneous bilirubin (forehead or sternum) in reproducibility of results as compared to plasma bilirubin. Methods : A cohort study including 58 term newborns with no hemolytic disease. Transcutaneous measurements were performed on the forehead (halfway between the headline and the glabella, from the left toward the right side, making consecutive determinations, one-centimeter apart) and the sternum (five measurements, from the suprasternal notch to the xiphoid process with consecutive determinations, one-centimeter apart) using Bilicheck® (SpectRx Inc, Norcross, Georgia, USA). The correlation and agreement between both methods and plasma bilirubin were calculated. Results : There was a strong linear correlation between both determinations of serum bilirubin at the forehead and sternum (r=0.704; p<0.01 and r=0.653; p<0.01, respectively). There was correspondence of the mean values of transcutaneous bilirubin measured on the sternum (9.9±2.2mg/dL) compared to plasma levels (10.2±1.7mg/dL), but both differ from the values measured on the forehead (8.6±2.0mg/dL), p<0.05. Conclusion : In newborn term infants with no hemolytic disease, measuring of transcutaneous bilirubin on the sternum had higher accuracy as compared to serum bilirubin measurement on the forehead. .

Objetivo : Verificar a influência do local da mensuração da bilirrubina transcutânea (fronte ou esterno) na reprodutibilidade dos resultados, quando comparada à bilirrubina plasmática. Métodos : Estudo tipo coorte incluindo 58 recém-nascidos a termo sem doença hemolítica. Foram realizadas determinações transcutâneas na fronte (a meia distância entre a raiz do couro cabeludo e a glabela, iniciando do lado esquerdo em direção ao direito, realizando determinações consecutivas, separadas por 1cm) e no esterno (cinco mensurações iniciando da fúrcula até o apêndice xifoide, com determinações consecutivas, separadas por 1cm), utilizando o equipamento Bilicheck® (SpectRx Inc, Norcross, Geórgia, Estados Unidos). Foram calculadas as correlações e a concordância entre ambos os métodos, e a bilirrubina plasmática. Resultados : Foi encontrada forte correlação linear tanto entre a determinação na fronte quanto no esterno, com nível sérico de bilirrubina (r=0,704; p<0,01 e r=0,653; p<0,01, respectivamente). Houve correspondência dos valores médios de bilirrubina transcutânea aferidos no esterno (9,9±2,2mg/dL) com os valores plasmáticos (10,2±1,7mg/dL), porém ambos diferiram dos valores medidos na fronte (8,6±2,0mg/dL), com p<0,05. Conclusão : Em recém-nascidos a termo sem doença hemolítica, a mensuração da bilirrubina transcutânea realizada no esterno apresenta maior acurácia em relação à mensuração na fronte, quando comparada à bilirrubina sérica. .

Initial assessment of jaundice in otherwise healthy infants--a comparison of methods in two postnatal units.

Transcutaneous bilirubin (TcB) has the potential to reduce total serum bilirubin (TS) sampling. The principal aim of this study was to determine and compare the number of initial TSB samples (TSBs) in two postnatal units (hospitals A & B) whereby hospital A used TcB and hospital B did not. A secondary aim was to determine the clinical factors that led to initial TSBs exceeding exchange transfusion level in both hospitals. Results demonstrated both hospitals had similar populations and patient numbers following selection criteria. 1645 neonates (10.4%) had one or more TSBs performed in hospital A, versus 2373 neonates (15.1%) in hospital B (p < 0.01). Fourteen neonates in hospital A and 3 neonates in hospital B had initial TSBs above exchange transfusion level. For neonates with TSBs above exchange, preventable factors related to earlier testing and follow up. In routine clinical practice, TcB is associated with a significantly reduced number of TSB measurements. TSB levels above exchange transfusion are linked to preventable factors, in otherwise healthy neonates.

Visual assessment of jaundice in term and late preterm infants.

OBJECTIVE: To determine the accuracy of predischarge visual assessment of jaundice for estimating bilirubin concentration and predicting risk of significant neonatal hyperbilirubinaemia. DESIGN: Prospective cohort study. SETTING: Well Baby Nursery at the Hospital of the University of Pennsylvania. PATIENTS: 522 term and late preterm newborns. INTERVENTIONS: Nurses used a 5-point scale to grade the maximum cephalocaudal extent of jaundice prior to discharge. MAIN OUTCOME MEASURES: (1) Correlation between jaundice grade and bilirubin concentration. (2) Predictive accuracy of jaundice grade for identifying infants who developed significant hyperbilirubinaemia, defined as a bilirubin level that at any time after birth exceeded or was within 1 mg/dl (17 micromol/l) of the American Academy of Pediatrics-recommended hour-specific phototherapy treatment threshold. RESULTS: Nurses' assessment of jaundice extent was only moderately correlated with bilirubin concentration and was similar in black and non-black infants (Spearman's rho = 0.45 and 0.55, respectively (p = 0.13)). The correlation was particularly weak among infants <38 weeks' gestational age (rho = 0.29) compared with infants > or = 38 weeks' gestation (rho = 0.53, p = 0.05). Jaundice extent had poor overall accuracy for predicting risk of significant hyperbilirubinaemia (c-statistic = 0.65) but complete absence of jaundice had high sensitivity (95%) and excellent negative predictive value (99%) for ruling out the development of significant hyperbilirubinaemia. CONCLUSIONS: Clinicians should not use extent of cephalocaudal jaundice progression to estimate bilirubin levels during the birth hospitalisation, especially in late preterm infants. However, the complete absence of jaundice can be used to predict with very high accuracy which infants will not develop significant hyperbilirubinaemia.