Bilirubin measurements in neonates: uniform neonatal treatment can only be achieved by improved standardization.

Measurement of total bilirubin (TBil) concentration in serum is the gold standard approach for diagnosing neonatal unconjugated hyperbilirubinemia. It is of utmost importance that the measured TBil concentration is sufficiently accurate to prevent under treatment, unnecessary escalation of care, or overtreatment. However, it is widely recognized that TBil measurements urgently require improvement in neonatal clinical chemistry. External quality assessment (EQA) programs for TBil assess for differences between laboratories and provide supporting evidence of significant differences between various methods, manufacturers and measurement platforms. At the same time, many countries have adopted or only slightly adapted the neonatal hyperbilirubinemia management guidelines from the USA or UK, often without addressing differences in the methodology of TBil measurements. In this report, we provide an overview of the components of bilirubin that are measured by laboratory platforms, the availability of current reference measurement procedures and reference materials, and the role of EQA surveys in this context. Furthermore, the current status of agreement in neonatal bilirubin against clinical decision thresholds is reviewed. We advocate for enhancements in accuracy and comparability of neonatal TBil measurements, propose a path forward to accomplish this, and reflect on the position of the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Working Group Neonatal Bilirubin (WG-NB) in this matter.

Hyperbilirubinemia and retinopathy of prematurity: a retrospective cohort study.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g.    Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP.    Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP.

Neonatal phototherapy and risk of epilepsy-A Danish population based study.

To evaluate the risk of epilepsy in children who received neonatal phototherapy. A cohort of live singletons born at a Danish hospital (2002-2016) with a gestational age ≥ 35 weeks. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of epilepsy in children treated with neonatal phototherapy compared to children not treated with neonatal phototherapy in the general population, and in a subpopulation of children who had serum bilirubin measurement. Adjusted HRs (aHR) were computed using multivariable and propensity score matching models to take maternal and neonatal factors into consideration. Children were followed from day 29 after birth to diagnosis of epilepsy, death, emigration, or December 31, 2016. Among 65,365 children, 958 (1.5%) received neonatal phototherapy. Seven children (incidence rates (IRs): 10.8 /10,000 person-years) who received neonatal phototherapy and 354 children (IR: 7.7) who did not receive neonatal phototherapy were diagnosed with epilepsy. Neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 0.95, 95% CI: 0.43-2.09) and propensity score matched (aHR 0.94, 95% CI: 0.39-2.28) models. In the subpopulation of 9,378 children with bilirubin measurement, 928 (9.9%) received neonatal phototherapy. In the analysis of the subpopulation in which bilirubin level and age at the time of bilirubin measurement were further taking into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 1.26, 95% CI: 0.54-2.97) and propensity score matched (aHR 1.24, 95% CI: 0.47-3.25) models,Conclusions: Neonatal phototherapy was not associated with an increased risk of epilepsy after taking maternal and neonatal factors into consideration. What is known: • A few studies have suggested that neonatal phototherapy for hyperbilirubinemia may increase the risk of childhood epilepsy. • Whether the observed associations contribute to hyperbilirubinemia, phototherapy, or underlying factors requires further investigation. What is new: • This study revealed no increased risk of epilepsy in children treated with neonatal phototherapy compared to children not treated with phototherapy after taking maternal and neonatal factors into consideration. • After further taking bilirubin level and age at the time of bilirubin measurement into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy.

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 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: - probably reduces readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - may have little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - probably increases the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - may have 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 probably reduces hospital readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening may have little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening probably increases the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening may have 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.

Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses.

Phototherapy is the standard treatment for neonatal jaundice. We aimed to review the efficacy and safety of fenofibrate as an adjunct therapy. Twelve databases were searched and a systematic review and meta-analysis were conducted. Mean change (MC), mean difference (MD), and risk ratios (RR) with a 95% confidence interval (CI) were calculated using a random effects model. The GRADE approach was used to evaluate the evidence's certainty. Nine randomized trials were included. The MC of total serum bilirubin (mg/dL) was significant at 12, 24, 36, 48, and 72 h with respective MC (95% CI) values of -0.46 (-0.61, -0.310), -1.10 (-1.68, -0.52), -2.06 (-2.20, -1.91), -2.15 (-2.74, -1.56), and -1.13 (-1.71, -0.55). The FEN + PT group had a shorter duration of phototherapy (MD: -14.36 h; 95% CI: -23.67, -5.06) and a shorter hospital stay (MD: -1.40 days; 95% CI: -2.14, -0.66). There was no significant difference in the risk of complications (RR: 0.89; 95% CI: 0.54, 1.46) or the need for exchange transfusion (RR: 0.58; 95% CI: 0.12, 2.81). The certainty of the evidence was very low for all outcomes. In conclusion, fenofibrate might be a safe adjunct to neonatal phototherapy. Larger randomized controlled trials are needed for the confirmation of these results.

Acceptability and operational feasibility of community health worker-led home phototherapy treatment for neonatal hyperbilirubinemia in rural Bangladesh.

There is an unmet need for phototherapy treatment in low- and middle-income countries (LMICs) to prevent disability and death of newborns with neonatal hyperbilirubinemia. Home phototherapy deployed by community health workers (CHWs) in LMICs may help increase access to essential newborn postnatal care in a more acceptable way for families and lead to an increase in indicated treatment rates for newborns with hyperbilirubinemia. We aimed to investigate the operational feasibility and acceptability of a CHW-led home phototherapy intervention in a rural sub-district of Bangladesh for families and CHWs where home delivery was common and a treatment facility for neonatal hyperbilirubinemia was often more than two hours from households. We enrolled 23 newborns who were ≥ 2 kg in weight and ≥ 35 weeks gestational age, without clinical danger signs, and met the American Academy of Pediatric treatment criteria for phototherapy for hyperbilirubinemia. We employed a mixed-method investigation to evaluate the feasibility and acceptability of home phototherapy through surveys, in-depth interviews and focus group discussions with CHWs, mothers, and grandparents. Mothers and family members found home phototherapy worked well, saved them money, and was convenient and easy to operate. CHWs found it feasible to deploy home phototherapy and identified hands-on training, mHealth job aids, a manageable workload, and prenatal education as facilitating factors for implementation. Feasibility and acceptability concerns were limited amongst parents and included: a lack of confidence in CHWs' skills, fear of putting newborn infants in a phototherapy device, and unreliable home power supply. CHW-led home phototherapy was acceptable to families and CHWs in rural Bangladesh. Further investigation should be done to determine the impact of home phototherapy on treatment rates and on preventing morbidity associated with neonatal hyperbilirubinemia. Clinical Trial (CT) registration ID: NCT03933423, full protocol can be accessed at https://doi.org/10.1186/s13102-024-00824-6 . Name of the trial registry: clinicaltrials.gov. Clinical Trial (CT) registration Date: 01/05/2019.

The Effect of Abdominal Massage on Bilirubin Levels in Term Infants Receiving Phototherapy: A Randomized Controlled Trial.

BACKGROUND: The incidence of neonatal hyperbilirubinemia in Europe and the United States is estimated to be 3.2 and 4.4 per 10,000 live births, respectively. Abdominal massage for hyperbilirubinemia is considered a safe complementary treatment for infants that may increase number of defecations and decrease bilirubin levels. PURPOSE: This study was designed as a randomized controlled trial to determine the effect of abdominal massage on bilirubin levels in term infants receiving phototherapy. METHODS: The sample consisted of 43 term newborns (intervention group: 23; control group: 20) who received phototherapy in a university hospital between June 2019 and February 2021. Information and observation forms were used for data collection. The intervention group received 6 abdominal massages over 2 days, performed 3 times a day, 6 hours apart, and lasting 5 minutes each. RESULTS: Transcutaneous bilirubin levels and heart rate were significantly lower in the intervention group than in the control group at 48 hours (P = .015 and P = .033, respectively). Number of defecations was higher in the intervention group at 24 hours (P = .007) but there was no significant difference at 48 hours. The decrease in serum bilirubin between 24 and 48 hours was significantly greater in the intervention group (P = .005). IMPLICATION FOR PRACTICE AND RESEARCH: Abdominal massage was effective in reducing bilirubin levels and may increase the number of defecations. Providing massage training to the parents of infants who are discharged early could be a protective approach to prevent the rise in bilirubin levels.

Neonatal hyperbilirubinemia and repercussions on neurodevelopment: A systematic review.

BACKGROUND: Accumulation of bilirubin above normal levels is considered a neurological risk factor for both premature and full-term newborns. This systematic review aimed to determine the effect of neonatal hyperbilirubinemia on neurodevelopment in preterm and full-term newborns. METHODS: PubMed, EMBASE, Cochrane Library, CINAHL, PsycINFO, Scopus and Lilacs databases were searched for articles published until 1 June 2022. The quality of cohort and case-control studies was assessed with the Newcastle-Ottawa Scale, and the MINCir scale was used to evaluate the methodological quality of therapy studies or the therapeutic procedures. Premature neonates without neurological conditions and those born at term with hyperbilirubinemia as the sole risk factor were included. Studies reporting one or more neurodevelopmental outcomes were included with an inter-group comparison of a hyperbilirubinemia group versus a non-hyperbilirubinemia or non-pathological hyperbilirubinemia group. The main outcomes were auditory function, visual function, cognitive function, motor function, behavior, global development and neurological risk. RESULTS: The search identified 951 studies, 19 of which (n = 2210 newborns) were finally included. Fifteen of the cohort and case-control studies presented low risk of bias, and six studies showed high methodological quality. Within the preterm population, hyperbilirubinemia as the sole risk factor was not shown to affect neurodevelopment. Auditory, neurological and motor development alterations were found in the population of full-term newborns with hyperbilirubinemia, which were more evident during the first year of life. CONCLUSIONS: Elevated bilirubin levels may be a trigger for the onset of neurodevelopmental disorders in full-term infants during the first year of life. More studies are warranted in the preterm population with hyperbilirubinemia to draw conclusions about its impact on their neurodevelopment.

Incidence, aetiology and short term outcomes of extreme hyperbilirubinaemia, in term infants born in the Western health subdistrict of Cape Town, South Africa between 2019 and 2020.

Extreme levels of bilirubin in newborn is a major cause of lifelong neurodevelopmental impairment, which places a financial burden on healthcare resources and caregivers. To determine the incidence, aetiology and short-term outcomes of extreme hyperbilirubinaemia in term infants born in a resource-limited setting. This is a retrospective observational study looking at term neonates with a birth weight ≥2500 g, born in the Western health subdistrict of Cape Town, South Africa, between 1 January 2019 and 31 December 2020, who were exposed to a serum bilirubin level of ≥430 µmol/L in the first week of life and received care in the public health system. Extreme hyperbilirubinaemia occurred in 59 term infants. The incidence was 74 cases per 100 000 (<0.01%) live births equating to 1 case in every 1345 live births. The cause of hyperbilirubinaemia was identified in 51 of the cases (86%), the most common being ABO incompatibility (31/51, 61%), followed by glucose-6-phosphate dehydrogenase deficiency (11/51, 22%). Twelve infants (20 %) underwent an exchange transfusion. Six infants were encephalopathic. Forty-seven infants (80%) were readmitted after initial post-natal discharge, with a mean age of readmission of 113 h old (SD 31 h). The incidence of extreme hyperbilirubinaemia in the Western health subdistrict of Cape Town is higher than in high-income settings. Further work should focus on training of healthcare workers and education of caregivers, for the early detection of significant hyperbilirubinaemia to prevent neurological complications caused by bilirubin toxicity.

The Effect of Tub Bathing on the Skin and Bilirubin Levels of Babies Receiving Tunnel and Light-Emitting Diode Phototherapies: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of tub bathing on the skin and bilirubin levels of newborns receiving tunnel and light-emitting diode phototherapy. METHODS: In this randomized controlled trial, hospitalized newborns diagnosed with hyperbilirubinemia treated with a tunnel or light-emitting diode device were randomly assigned to either the experimental (bath) or control (no bath) groups using a computer program. The skin integrity moisture balance of all groups was recorded using the Newborn Skin Condition Score at 6, 12, and 24 hours after phototherapy, and their total serum bilirubin measurements were evaluated. RESULTS: A statistically significant difference was observed in the babies' total serum bilirubin levels; this decrease was the highest in the experimental groups. Further, the skin integrity-moisture balance was higher in the experimental groups than in the control groups; it was highest in the tunnel-experimental group and lowest in the tunnel control group. CONCLUSIONS: These results show that bathing is effective in reducing total bilirubin levels. This study adds to the evidence on skin integrity and moisture balance in newborns who were bathed during phototherapy.

Managing neonatal hyperbilirubinemia: An updated guideline.

ABSTRACT: More than 80% of newborn infants experience jaundice as a result of elevated bilirubin during the first few weeks after birth. In most cases, hyperbilirubinemia is physiologic, but persistent and extreme elevations can lead to serious long-term complications, such as kernicterus. To avoid these complications and help clinicians in the successful assessment, evaluation, and treatment of hyperbilirubinemia, the American Academy of Pediatrics updated its clinical practice guideline for neonatal hyperbilirubinemia. This article reviews the guideline and highlights significant updates, such as an elevation in the threshold for phototherapy and exchange transfusion, inclusion of gestational age, and removal of racially based norms.

Pre-phototherapy total serum bilirubin levels in extremely preterm infants.

BACKGROUND: Extremely preterm infants are prone to hyperbilirubinemia and its sequelae. Currently recommended thresholds for initiating phototherapy in these newborns are consensus-based (CB). METHODS: A multi-site retrospective cohort study of 642 infants born at 240/7 to 286/7 weeks' gestation, between January 2013 and June 2017, was conducted at three NICUs in Canada. Pre-phototherapy TSB percentile levels at 24 h of age were generated and contrasted with published CB thresholds. RESULTS: Among infants born 240/7 to 256/7 weeks' gestation, the differences between our TSB percentiles vs. the CB threshold of 85.0 µmol/L were 10.0 µmol/L (95% CI, 6.0-16.0) at the 75th percentile and 35.3 µmol/L (95% CI, 26.1-42.8) at the 95th percentile. Respectively, among infants born at 260/7 to 276/7 weeks, differences were 19.4 µmol/L (95% CI, 16.8-23.4) and 43.3 µmol/L (95% CI, 34.7-46.9). Born at 280/7 to 286/7 weeks' gestation, differences between our 75th and 95th TSB percentiles and the CB threshold of 103 µmol/L were 6.9 µmol/L (95% CI, 3.2-12.0) and 36.0 µmol/L (95% CI, 31.0-44.3), respectively. CONCLUSIONS: We provide statistically derived pre-phototherapy TSB levels that may clarify patterns of pre-phototherapy TSB levels in extremely preterm infants. IMPACT: We present statistically derived pre-phototherapy total serum bilirubin levels in a cohort of extremely preterm infants. Most of these preterm infants received phototherapy-some at below currently published thresholds. There are notable differences between our statistically derived pre-phototherapy TSB levels and currently published lower limit TSB thresholds for phototherapy. Our study results assist in the understanding of pre-phototherapy TSB levels in extremely preterm infants.

Association between neonatal phototherapy and future cancer: an updated systematic review and meta-analysis.

Phototherapy is the main treatment of neonatal hyperbilirubinemia to prevent encephalopathy. It is generally believed to be safe; however, some studies have shown it might be associated with cancer development. In this systematic review and meta-analysis, we aimed to assess the effect of neonatal phototherapy on future cancer risk. A systematic search in 13 databases was conducted in December 2018 and updated in August 2022 to identify studies that report cancer development after exposure to phototherapy. Throughout the study period, regular manual searches were also conducted to include new studies. A meta-analysis using R programming language was done in which the odds ratios (ORs) with 95% confidence intervals (CIs) were estimated and pooled using the reported adjusted and unadjusted data. Fifteen studies were included. A statistically significant association was detected between neonatal phototherapy and any type of cancer (OR 1.24; 95% CI 1.1, 1.4), any hematopoietic cancer (OR 1.49; 95% CI 1.17, 1.91), any leukemia (OR 1.35; 95% CI 1.08, 1.67), and myeloid leukemia (OR 2.86; 95% CI 1.4, 5.84). The other investigated cancers (lymphoid leukemia, Hodgkin's lymphoma, kidney cancer, nervous system cancer, and skin cancer) were not associated with phototherapy.  Conclusions: Phototherapy may carry a possible risk of future cancers. Future research is needed to quantify the magnitude of the cancer risk. These future studies should consider predictors of preterm birth or exclude premature babies from their analysis. What is Known • There were various reports about the possible association between phototherapy in neonates and the increased risk of cancer in the future. What is New • A statistically significant association between phototherapy and various hematopoietic cancers (especially myeloid leukemia) was recorded. • The effect of the duration of phototherapy on the increased risk of hematopoietic cancers is yet unclear.

Neonatal Hyperbilirubinemia: Evaluation and Treatment.

Neonatal jaundice due to hyperbilirubinemia is common, and most cases are benign. The irreversible outcome of brain damage from kernicterus is rare (1 out of 100,000 infants) in high-income countries such as the United States, and there is increasing evidence that kernicterus occurs at much higher bilirubin levels than previously thought. However, newborns who are premature or have hemolytic diseases are at higher risk of kernicterus. It is important to evaluate all newborns for risk factors for bilirubin-related neurotoxicity, and it is reasonable to obtain screening bilirubin levels in newborns with risk factors. All newborns should be examined regularly, and bilirubin levels should be measured in those who appear jaundiced. The American Academy of Pediatrics (AAP) revised its clinical practice guideline in 2022 and reconfirmed its recommendation for universal neonatal hyperbilirubinemia screening in newborns 35 weeks' gestational age or greater. Although universal screening is commonly performed, it increases unnecessary phototherapy use without sufficient evidence that it decreases the incidence of kernicterus. The AAP also released new nomograms for initiating phototherapy based on gestational age at birth and the presence of neurotoxicity risk factors, with higher thresholds than in previous guidelines. Phototherapy decreases the need for an exchange transfusion but has the potential for short- and long-term adverse effects, including diarrhea and increased risk of seizures. Mothers of infants who develop jaundice are also more likely to stop breastfeeding, even though discontinuation is not necessary. Phototherapy should be used only for newborns who exceed thresholds recommended by the current AAP hour-specific phototherapy nomograms.

Light-Emitting Diode (LED) Phototherapy versus Non-LED Phototherapy Devices for Hyperbilirubinemia in Neonates: A Systematic Review and Meta-analysis.

This review was conducted to evaluate the efficacy of light-emitting diode (LED) phototherapy as compared with the conventional phototherapy in neonates with unconjugated hyperbilirubinemia and their adverse effects. We searched the following databases right from their inception till April, 2021: MEDLINE, EMBASE, Cochrane Library, and LILACS. Randomized clinical trials (RCTs) comparing the LED phototherapy with other light sources, which enrolled newborns (term and preterm) with unconjugated hyperbilirubinemia were included. We included 21 articles in this review. The treatment with the LED light therapy had a lower failure rate as compared with the non-LED one (RR = 0.60, 95% CI: 0.39-0.94). The mean duration of phototherapy was significantly shorter in the group with the LED light source as compared with the one with the non-LED light source (mean difference [hours]: -8.07, 95% CI: -8.45 to -7.68), regardless of the type of non-LED units. However, the rate of bilirubin showed a comparable decline (mean difference [mg/dL/h]: 0.01, 95% CI: -0.00, 0.03) in both the light sources, irrespective of irradiance or distance. No studies reported primary outcomes related to the neurotoxicity effects of hyperbilirubinemia in neonates. The LED light devices caused a significantly higher risk of hypothermia. Neonates were at a lower risk of developing hyperthermia and skin rash with the LED light therapy. Our findings provide support for the use of LED light source phototherapy due to its better clinical efficacy, which is evidenced by its shorter duration and lower rate of treatment failure, as compared with the non-LED light sources. KEY POINTS: · The efficacy of phototherapy is dependent on specific characteristics of light sources of phototherapy devices.. · LED phototherapy demonstrated better efficacy with shorter duration and lower rate of treatment failure.. · Adverse effects of phototherapy devices such as hypothermia, hyperthermia, and skin rash should be monitored..

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The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.

Maternal Exposure to Air Pollution Is Associated with Neonatal Jaundice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the association between maternal ambient pollutant exposure and neonatal jaundice in multiple pollutant species and examine sex differences. STUDY DESIGN: Epidemiologic study: Records of 13 297 newborns (6153 male, 7144 female) born in Taichung, Taiwan were obtained from a national database. Average concentrations of prenatal air pollutants 3 months prior to birth were divided into low, middle, and high levels. Neonatal jaundice phototherapy rates between mothers who suffered varying air pollutant levels were compared. Clinical study: Three hundred seventy-six newborns (189 male, 187 female) born and received jaundice treatment with phototherapy in a hospital in Taichung, Taiwan were recruited. The correlation between prenatal exposure to air pollutants 3 months prior to birth, newborn's serum bilirubin, and serum hemoglobin were calculated. RESULTS: Epidemiologic study: Male newborns born to mothers exposed to high carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), and methane (CH4) levels had higher phototherapy rates. In female newborns, the same was noted for CO and CH4. Clinical study: Male newborns had a positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO, NO2, nonmethane hydrocarbon, and CH4 exposure 3 months prior to birth and serum bilirubin levels. Female newborns had a positive correlation for CH4. A positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO2, nonmethane hydrocarbon, CH4 exposure, and serum hemoglobin levels was noted in male newborns. CONCLUSION: Maternal exposure to air pollutants may increase neonatal jaundice treatment rates for phototherapy and higher neonatal serum total bilirubin level. Higher hemoglobin levels because of higher pollutant exposures may explain our findings. The association was more obvious in male newborns.

Association Between Neonatal Phototherapy Exposure and Childhood Neoplasm.

OBJECTIVE: To study the association between phototherapy for the treatment of neonatal jaundice and the risk of childhood neoplasms. STUDY DESIGN: This population-based retrospective cohort study included all infants born at ≥32 weeks of gestation at a single medical center between 1988 and 2018. The incidence of neoplastic diseases was compared between infants exposed to phototherapy and those unexposed. Kaplan-Meier curves and log-rank tests were used for cumulative incidence comparison, and multivariable Cox and Weibull survival analysis were used to adjust for confounding or clinically significant variables. RESULTS: The study population included 342 172 infants, of whom 18 797 (5.5%) were exposed to phototherapy. The median duration of follow-up was 9.5 years (range, birth to 18 years). Phototherapy was associated with a significantly increased risk for childhood malignancies and benign tumors (preterm birth and maternal age-adjusted hazard ratio, 1.89 [95% CI, 1.35-2.67] for malignancies and 1.27 [95% CI, 1.02-1.57] for benign tumors) Specifically, phototherapy was associated with hematopoietic cancers and leukemia (hazard ratio, 2.29 [95% CI, 1.48-3.54; P < .01] for hematopoietic cancers and 2.51 [95% CI, 1.52-4.14; P < .001] for leukemia), but not with solid tumors and lymphoma. CONCLUSIONS: Phototherapy may be associated with a slightly increased childhood risk of neoplasm. It is important to strictly follow phototherapy treatment guidelines to minimize unnecessary exposure.

Irradiance footprint of phototherapy devices: a comparative study.

BACKGROUND: Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. The irradiance footprint, i.e., the illuminated area by the PT device with sufficient spectral irradiance, is essential for PT to be effective. Irradiance footprint measurements are not performed in current clinical practice. We describe a user-friendly method to systematically evaluate the high spectral irradiance (HSI) footprint (illuminated area with spectral irradiance of ≥30 µW cm-2 nm-1) of PT devices in clinical practice. MATERIALS AND METHODS: Six commercially available LED-based overhead PT devices were evaluated in overhead configuration with an incubator. Spectral irradiance (µW cm-2 nm-1) and HSI footprint were measured with a radiospectrometer (BiliBlanket Meter II). RESULTS: The average measured spectral irradiance ranged between 27 and 52 µW cm-2 nm-1 and HSI footprint ranged between 67 and 1465 cm2, respectively. Three, two, and one PT devices out of six covered the average BSA of an infant born at 22, 26-32, and 40 weeks of gestation, respectively. CONCLUSION: Spectral irradiance of LED-based overhead PT devices is often lower than manufacturer's specifications, and HSI footprints not always cover the average BSA of a newborn infant. The proposed measurement method will contribute to awareness of the importance of irradiance level as well as footprint measurements in the management of neonatal jaundice. IMPACT: While a sufficient spectral irradiance footprint is essential for PT to be effective, some PT devices have spectral irradiance footprints that are too small to cover the entire body surface area (BSA) of a newborn infant. This study introduces a user-friendly, accessible method to systematically evaluate the spectral irradiance level and footprint of PT devices. This study supports awareness on the role of the spectral irradiance footprint in the efficacy of PT devices. Irradiance footprint can be easily measured during phototherapy with the proposed method.

Action spectrum of phototherapy in hyperbilirubinemic neonates.

BACKGROUND: Phototherapy with blue light matching plasma absorption spectrum of the bilirubin-albumin complex with peak at 460 nm is standard treatment of neonatal hyperbilirubinemia. AIM: To demonstrate clinically the action (efficacy) spectrum of phototherapy in hyperbilirubinemic neonates, through determination of the fraction of total serum bilirubin (TSB) decreased by phototherapy with peak emission wavelengths ≥478 nm (blue-green) compared with that of light of 459/452 nm (blue). METHODS: TSB values were compiled from three earlier trials, in which hyperbilirubinemic neonates were randomized to receive 24 h of either blue-green light (478/490/497 nm) (intervention groups) or blue light (459/452/459 nm) (control groups) with equal irradiance and exposed body surface areas. Ratios (efficacy) between the decrease in TSB between intervention and control groups were calculated and graphed versus peak wavelengths, demonstrating the course of the action spectrum. RESULTS: Calculated efficacy ratios were 1.31, 1.18, and 1.04 for light with peak wavelengths of 478, 490, and 497 nm, respectively. The action spectrum increases from 452/459 to maximum at 478 nm, from where it decreases to 1.18 and finally to 1.04. CONCLUSION: For optimal phototherapeutic treatment, neonates need to be exposed to light with peak wavelength some 20 nm longer than is presently used. IMPACT: The action (efficacy) spectrum of phototherapy for hyperbilirubinemic neonates has its peak wavelength at 478 nm. The peak wavelength of this action spectrum is 20 nm longer than the wavelength presently believed to be most efficient. The peak is also different from the peak found in vitro. For optimal phototherapeutic effect, neonates need to be treated with light of wavelengths some 20 nm longer than are presently used.