Treatment Of Neonatal Hyperbilirubinemia Research Articles

Effect of Phototherapy on Liver and Kidney Functions during Treatment of Neonatal Hyperbilirubinemia.

Effect of Phototherapy on Liver and Kidney Functions during Treatment of Neonatal Hyperbilirubinemia.

Rationale, completeness and quality of evidence for the use of ursodeoxycholic acid in neonatal hyperbilirubinemia

Background. Systematic reviews are considered the highest evidence of the effectiveness and safety of treatment methods used in clinical practice. The veracity of a results and conclusions of systematic reviews is directly related to their quality. The aim of the study is an assessment of the currency, completeness and methodological quality of published systematic reviews on the evaluation of the effectiveness of ursodeoxycholic acid (UDCA) for the treatment of neonatal hyperbilirubinemia. Materials and methods. A meta-epidemiological methodological study was conducted. The search for evidence sources was performed in November 2023 in the specialized databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), LILACS, CNKI, LENS.ORG, еLibrary.Ru, in registers ClinicalTrials.gov, ICTRP, ISRCTN, PROSPERO, as well as in the Google Academy and Google search engines. Additionally, the lists of references and citations of selected publications have been reviewed. Only systematic reviews and randomized clinical trials are included in the study. The search was carried out to assess the currency and completeness of systematic reviews. A systematic review is considered currency if the most recent studies are included in its analysis. A systematic review is considered complete if its analysis includes all identified studies that meet the inclusion criteria set by the review authors and are published no later than the date of the last search conducted by the review authors. The methodological quality of the systematic reviews was assessed using the AMSTAR-2 tool. Results. As a result of the search, 4 systematic reviews and 23 randomized trials were identified. All reviews evaluated the effect of UDCA in combination with phototherapy on the level of total serum bilirubin, the duration of phototherapy and the frequency of adverse events (for example, loose stools, vomiting, rash) compared with phototherapy alone and/or placebo. All systematic reviews have been published over the past two years, but have already lost their currency. There are missing studies and/or outcomes in each review. The methodological quality of the reviews was found to be extremely low. Conclusion. Given the listed shortcomings of systematic reviews, their results and conclusions should be treated with caution. In order to obtain the most accurate and reliable evidence, a new systematic review is needed.

Beneficial changes in gut microbiota after phototherapy for neonatal hyperbilirubinemia.

Phototherapy is the most commonly used treatment for neonatal hyperbilirubinemia (NH). Gut microbiota is involved in bilirubin metabolism; however, it is uncertain whether this is affected by phototherapy. The present study included 43 newborns with hyperbilirubinemia and collected fecal samples for high-throughput sequencing before and after phototherapy. Selection α diversity analysis was used to determine the differences in diversity and abundance between the two groups, whereas similarity was determined using β diversity analysis. Linear discriminant analysis effect size analysis was used to screen for markedly different bacteria. The structure of the gut microbiota in newborns with hyperbilirubinemia changed after phototherapy, with a significant decrease in abundance and diversity. The changes in the key bacterial species were characterized by an increase in the abundance of Streptococcus salivarius and a decrease in the abundance of Escherichia, Klebsiella pneumoniae, Rothia mucilaginosa and Streptococcus oralis. These changes mainly manifested as an increase in beneficial bacteria and a decrease in opportunistic bacteria, which may not be related to the side effects of phototherapy. These results can provide theoretical assistance for microbiological research on the later stages of NH.

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.

Community health worker-led household screening and management of neonatal hyperbilirubinemia in rural Bangladesh: a cluster randomized control trial protocol

Background Extreme hyperbilirubinemia leading to neurologic disability and death is disproportionately higher in low- and middle-income countries (LMIC) such as Bangladesh, and is largely preventable through timely treatment. In LMICs, an estimated half of all newborns are born at home and few receive screening or treatment for hyperbilirubinemia, leading to 6 million newborns per year who need phototherapy treatment for hyperbilirubinemia but are untreated. Household screening and treatment for neonatal hyperbilirubinemia with phototherapy administered by a trained community health worker (CHW) may increase indicated treatment for neonatal hyperbilirubinemia in comparison to the existing care system in Bangladesh. Methods 530 Bangladeshi women in their second or third trimester of pregnancy from the rural community of Sakhipur, Bangladesh will be recruited for a cluster randomized trial and randomized to the intervention arm — home screening and treatment for neonatal hyperbilirubinemia — or the comparison arm to receive usual care. In the intervention arm, CHWs will provide mothers with two prenatal visits, visit newborns by 2 days of age and then daily for 3 days to measure transcutaneous bilirubin (TcB) and monitor for clinical danger signs. Newborns without danger signs but with a TcB above the treatment threshold, but >15 mg/dL will be treated with light-emitting diode (LED) phototherapy at home. Newborns with danger signs or TcB ≥15 mg/dL will be referred to a hospital for treatment. Treatment rates for neonatal hyperbilirubinemia in each arm will be compared. Conclusion This study will evaluate the effectiveness of CHW-led home phototherapy to increase neonatal hyperbilirubinemia treatment rates in rural Bangladesh. LMICs are expanding access to postnatal care by using CHWs, and our work will give CHWs a curative treatment option for neonatal hyperbilirubinemia. Similar projects in other LMICs can be pursued to dramatically extend healthcare access to vulnerable newborns with hyperbilirubinemia.

The association of oxidative stress of neonatal hyperbilirubinemia and vitamin E supplementation.

Jaundice in newborns is a sign of skin and sclera pigmentation. Hyperbilirubinemia and these phenomena do, however, have a relationship. According to many clinical studies, elevated blood bilirubin and low vitamin E (VE) levels in newborns are associated. The aim of the study was to investigate the association of oxidative stress of neonatal hyperbilirubinemia in patients who underwent phototherapy with additional vitamin E supplementation (25 mg/kg/day over the course of three days) and patients without additional vitamin E. A set of 100 neonatal indirect hyperbilirubinemia patients was enrolled at neonatal intensive care units (NICUs) of the pediatric departments at Al Azhar University Hospitals during the period from February 2021 to October 2022 after obtaining signed written informed consent of all neonates' parents with an explanation of the aim of study. Significant differences were found between the studied groups regarding serum bilirubin on the third day of admission (p = 0.039). Patients who were treated with vitamin E had lower serum bilirubin on the third day of admission (8.25 ±3.41) than the control group (11.66 ±3.22). Also, among the VE group, serum bilirubin was significantly decreased on the third day of admission (8.25 ±3.41) compared to zero days of admission (14.10 ±4.39) (p = 0.041). Vitamin E supplementation has an important role in treatment of indirect hyperbilirubinemia in neonates. Early administration of vitamin E in preterm neonates resulted in a significant decrease of serum bilirubin and increased total antioxidant capacity. Vitamin E supplementation in full term decreased the duration of phototherapy.

Comparison of the Effectiveness of Single and Double Surface Light Emitting Diodes Phototherapy and Intensive Compact Fluorescent Phototherapy in the Treatment of Neonatal Hyperbilirubinemia

Comparison of the Effectiveness of Single and Double Surface Light Emitting Diodes Phototherapy and Intensive Compact Fluorescent Phototherapy in the Treatment of Neonatal Hyperbilirubinemia

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.

Neonatal Hyperbilirubinemia Admissions Following Clinical Practice Guideline Implementation.

Treatment of neonatal hyperbilirubinemia remains one of the most common reasons for readmission following delivery. Revised clinical practice guidelines (CPGs) for the treatment of neonatal hyperbilirubinemia were published on August 5, 2022. This report describes the preliminary outcomes following implementation of the new CPGs at Tripler Army Medical Center. A retrospective chart review was performed for the 12 months prior to implementation and the 5 months post implementation. Bilirubin admissions decreased from 15.6% of total admissions during the 12 months prior to the new guidelines (69/441) to 4.1% of admissions (8/194) during the 5 months after implementation of the new guidelines (P < 0.001). This corresponds to a 74% reduction (risk ratio = 0.26, 95% confidence interval [CI] 0.13 to 0.54). The decrease in admissions was found to correlate to greater than $140,000 in annual savings. Adhering to the revised CPGs has the potential to increase resource availability at a time when nursing shortages and financial instability are impacting health care systems nationwide. No short-term adverse events were noted; however, long-term follow up will be needed.

Implementing Higher Phototherapy Thresholds for Jaundice in Healthy Infants 35 Plus Weeks.

To determine the impact of higher bilirubin thresholds on testing and treatment of healthy infants during the neonatal period. This quality improvement study included infants born at ≥35 weeks gestation and admitted to the well-baby nursery between July 2018 and December 2020. We assessed the transition from infants treated according to the 2004 AAP guidelines (pregroup) with those following the Northern California Neonatal Consortium guidelines (postgroup). We examined the proportion of infants receiving phototherapy and total serum bilirubin (TSB) assessments as outcome measures. We examined critical hyperbilirubinemia (TSB above 25 mg/dL or TSB within 2 mg/dL of threshold for exchange transfusion), exchange transfusion, and readmission for jaundice as balancing measures. We compared the differences in outcomes over time using Statistical Process Control p charts. Balancing measures between the pre and postgroups were compared using χ square tests and t-tests. In our population of 6173 babies, there was a significant shift in the proportion receiving phototherapy from 6.4% to 4%. There were no significant changes in incidences of bilirubin >25 mg/dL (0 of 1472 vs 7 of 4709, P = .37), bilirubin within 2 mg/dL of exchange transfusion thresholds (4 of 1472 vs 5 of 4709, P = .15), exchange transfusion (0 of 1472 vs 1 of 4709, P = .70) or readmission for phototherapy (2.9% versus 2.4%, P = .30), between the 2 groups. Higher thresholds for phototherapy treatment of neonatal hyperbilirubinemia can decrease the need for phototherapy without increasing critical hyperbilirubinemia or readmission rate.

The Effect of Tunnel versus Conventional Phototherapy on the T Lymphocytes in Full Term Neonates with Hyperbilirubinemia

Background Neonatal jaundice is one of the most common conditions. Phototherapy has been accepted as the standard treatment for neonatal jaundice and the decline in the number of exchange transfusions in recent years is, at least in part, likely a direct reflection of the effectiveness of phototherapy at treating hyperbilirubinemia. However, this treatment modality also has some complications. One possible harmful consequence is potential immunotoxic effects by affection of lymphocytes subtypes which can affect the immune system functions in infants. Aim of the Work current study was performed to compare the effect of both conventional and tunnel phototherapy on lymphocytes subsets in term neonates (≥37weeks) with unconjugated hyperbilirubinemia. Patients and Methods The present study was conducted on 60 term neonates (≥37weeks) 40 of them with unconjugated hyperbilirubinemia admitted to NICUs in Ain-Shams University hospital during the period from January 2019 to July 2019. They were randomly assigned to 3 groups: 20 patients were exposed to conventional phototherapy and 20 patients were exposed to tunnel phototherapy and the other 20 healthy full term were assigned as control group. Total serum bilirubin (TSB), direct serum bilirubin (DSB), CBC, CD4 and CD8 percentages and absolute count were measured before and 48 h after phototherapy in the phototherapy groups. Baseline lab was done in the control group at once. Results significant decrease in total and direct bilirubin post-phototherapy in both phototherapy groups proved that tunnel phototherapy is as effective as conventional phototherapy as both provided rapid decrease in bilirubin levels. As regards the effect of phototherapy on lymphocytic count, we found that lymphocytic count significantly decreased post-phototherapy in both phototherapy groups. As regards the effect of phototherapy on CD4+ and CD8+ percentages, we found that CD4+ % significantly decreased postphototherapy in conventional phototherapy group. Moreover, when we measured CD4+ and CD8+ absolute counts, we found that CD4+ and CD8+ absolute counts significantly decreased post-phototherapy in both phototherapy groups. In the view of the effect of phototherapy on CD4/CD8 ratio, we found that the ratio significantly increased in tunnel phototherapy group. Conclusion Conventional and tunnel phototherapy which are used in the treatment of neonatal hyperbilirubinemia, affects the function of the immune system in newborns via alterations in CD4+ and CD8+ absolute counts.

Bilirubin- and Blue-Green Light-Induced Damage of Human Erythrocytes

Phototherapy is widely used for neonatal hyperbilirubinemia treatment; however, the most important but not completely recognized issue is the determination of the optimal spectral range of light that provides an effective reduction of bilirubin level in the blood of a newborn with minimal adverse side effects. This study demonstrates that the exposure of radiation from LED sources of blue (emission wavelength λ max = 463 nm, FWHM 20 nm) and green (λ max = 517 nm, FWHM 38 nm) spectral regions to the erythrocyte suspension with the same energy dose (D = 14.4 J/cm 2 ) leads to approximately equally effective hemolysis of erythrocytes. It is concluded that the damage of erythrocyte membranes is caused by the excitation of endogenous porphyrin and flavin photosensitizers contained in the cells in low concentrations, but characterized by high efficiency of singlet oxygen generation. When bilirubin is added to the erythrocyte suspension, a spontaneous (dark) erythrocyte hemolysis intensifies, but the light-induced hemolysis slows down (compared to cells containing no bilirubin). Under the same conditions, the leakage of potassium ions from light-exposed erythrocytes is accelerating, with the light of green spectral region has a more pronounced effect, despite more intense absorption of blue light by bilirubin localized in cells.

Community health worker-led household screening and management of neonatal hyperbilirubinemia in rural Bangladesh: a cluster randomized control trial protocol

Background: Extreme hyperbilirubinemia leading to neurologic disability and death is disproportionately high in low to middle income countries (LMIC) such as Bangladesh, and is largely preventable through timely treatment. Of the estimated 50% of newborns born in LMICs born at home, few receive screening or treatment for hyperbilirubinemia, leading to 6 million newborns per year who need phototherapy treatment for hyperbilirubinemia but are untreated. Household screening and treatment for neonatal hyperbilirubinemia with phototherapy administered by a trained community health worker (CHW) may increase indicated treatment for neonatal hyperbilirubinemia in comparison to the existing care system in Bangladesh. Methods: 530 Bangladeshi women in their 2nd or 3rd trimester of pregnancy from the rural community of Sakhipur, Bangladesh will be recruited for a cluster randomized trial and randomized to the intervention arm — home screening and treatment for neonatal hyperbilirubinemia — or the comparison arm to receive usual care. In the intervention arm, CHWs will provide mothers with two prenatal visits, visit newborns by 2 days of age and then daily for 3 days to measure transcutaneous bilirubin (TcB) and monitor clinical danger signs. Newborns without danger signs but with a TcB above the treatment threshold &lt;15 mg/dL will be treated with light-emitting diode (LED) phototherapy at home. Newborns with danger signs or TcB &gt;15 mg/dL will be referred to a hospital for treatment. Treatment rates for neonatal hyperbilirubinemia in each arm will be compared. Conclusion: This study will evaluate the effectiveness of CHW-led home phototherapy to increase neonatal hyperbilirubinemia treatment rates in rural Bangladesh. LMICs are expanding access to postnatal care by using CHWs, and our work will give CHWs a curative treatment option for neonatal hyperbilirubinemia. Similar projects in other LMICs can be pursued to dramatically extend healthcare access to vulnerable newborns with hyperbilirubinemia.

Diagnostic Accuracy of Portable, Handheld Point-of-Care Tests vs Laboratory-Based Bilirubin Quantification in Neonates

Quantification of bilirubin in blood is essential for early diagnosis and timely treatment of neonatal hyperbilirubinemia. Handheld point-of-care (POC) devices may overcome the current issues with conventional laboratory-based bilirubin (LBB) quantification. To systematically evaluate the reported diagnostic accuracy of POC devices compared with LBB quantification. A systematic literature search was conducted in 6 electronic databases (Ovid MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar) up to December 5, 2022. Studies were included in this systematic review and meta-analysis if they had a prospective cohort, retrospective cohort, or cross-sectional design and reported on the comparison between POC device(s) and LBB quantification in neonates aged 0 to 28 days. Point-of-care devices needed the following characteristics: portable, handheld, and able to provide a result within 30 minutes. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Data extraction was performed by 2 independent reviewers into a prespecified, customized form. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was performed of multiple Bland-Altman studies using the Tipton and Shuster method for the main outcome. The main outcome was mean difference and limits of agreement in bilirubin levels between POC device and LBB quantification. Secondary outcomes were (1) turnaround time (TAT), (2) blood volumes, and (3) percentage of failed quantifications. Ten studies met the inclusion criteria (9 cross-sectional studies and 1 prospective cohort study), representing 3122 neonates. Three studies were considered to have a high risk of bias. The Bilistick was evaluated as the index test in 8 studies and the BiliSpec in 2. A total of 3122 paired measurements showed a pooled mean difference in total bilirubin levels of -14 μmol/L, with pooled 95% CBs of -106 to 78 μmol/L. For the Bilistick, the pooled mean difference was -17 μmol/L (95% CBs, -114 to 80 μmol/L). Point-of-care devices were faster in returning results compared with LBB quantification, whereas blood volume needed was less. The Bilistick was more likely to have a failed quantification compared with LBB. Despite the advantages that handheld POC devices offer, these findings suggest that the imprecision for measurement of neonatal bilirubin needs improvement to tailor neonatal jaundice management.

Ursodeoxycholic acid and phototherapy versus phototherapy and placebo on neonatal indirect hyperbilirubinemia

Introduction: Recently ursodeoxycholic acid was recommended for the treatment of neonatal hyperbilirubinemia in a few studies. Objectives: This study aimed to compare ursodeoxycholic acid and phototherapy versus phototherapy in lowering the level of bilirubin in neonates who was admitted due to hyperbilirubinemia. Patients and Methods: This randomized double-blind study was carried out in the department of neonatology at the children’s medical center of Ahvaz Jundishapur of the University of Medical Sciences. Inclusion criteria were weight 2500-4200 g and exclusive breastfeeding. Gestational age between 38-41 weeks and age between 3-7 days were included. Total bilirubin between 14-20 according to Bhutani nomogram and direct bilirubin was less than 2 mg/dl was included. Exclusion criteria were ABO incompatibility, Rh incompatibility, G6PD (glucose6-phosphate dehydrogenase) deficiency, sepsis, hypothyroidism, liver problem, prematurity and newborn of diabetic mothers. A dose of 5 mg/kg per dose of ursodeoxycholic acid (UDCA) was prescribed for neonates every 12 hours. Placebo is also prescribed for other neonates. Unconjugated bilirubin was measured after 4 hours and every 12 hours till total bilirubin=12 mg/dL. The primary outcome measures were total bilirubin level four hours and every 12 hours after admission till reached 12 mg/dL. The secondary outcome measure was total bilirubin=12 mg/dL at 12-24 hours after admission and diarrhea, vomiting, skin rash or any adverse effect in the neonates who received UDCA. Neonates who underwent phototherapy and UDCA were the case group. Neonates who received phototherapy and placebo were allocated in the control group. Data were analyzed using SPSS version 16.0. Kolmogorov-Smirnov test was conducted to evaluate data distribution. Intention-to-treat analysis was used. Mann-Whitney U test was conducted for data analysis. Results: In the current study, 30 cases and 30 control were included. Discharged neonates were 96% among the UDCA group and 87% among the control group in the 1st 24 hours after admission. Among the UDCA group, 100% were discharged at the 2nd 24 hours of admission and 96% among the control. The duration of phototherapy was shorter in the case group than in the control group, however this difference had no statistical difference. Conclusion: No significant difference between neonates who underwent phototherapy and phototherapy+ UDCA in terms of duration of phototherapy and bilirubin reduction was found. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20181003041225N1; https://en.irct.ir/trial/34272, ethical code; IR.AJUMS.REC.1397.899).

Neonatal Phototherapy and Clinical Characteristics: The Danish National Patient Registry 2000-2016.

Phototherapy is the standard treatment for neonatal hyperbilirubinemia. It is important to collect data on phototherapy to support research related to the efficacy and safety of phototherapy. We explored the registration of phototherapy in the Danish National Patient Registry (DNPR) and the clinical characteristics of neonates treated with phototherapy. We identified children born alive in Denmark from 1 January 2000 through 30 November 2016 from the DNPR (N=1,044,502). We calculated the proportion of children registered that received phototherapy during the neonatal period and examined temporal trends, both nationwide and at the level of individual hospitals. In a sub-cohort of children born at Aarhus University Hospital (AUH) in 2002-2016 (N=71,781), we analyzed the proportions of children registered that received phototherapy, according to sex, gestational age, birth weight, and neonatal characteristics, like Apgar score, birth asphyxia, and infections. We identified 11,295 (1.1%) registered that received phototherapy. The proportions of children registered that received phototherapy differed among hospitals (range: 0 to 4.1%). Nationwide registration was low during the study period, but it increased to 1.8% in 2016. For the AUH sub-cohort the proportion of children registered with phototherapy averaged 4.4% (N=3182, range:3.9-5.1%). The proportion of children registered with phototherapy was inversely correlated with gestational age and birth weight, and positively correlated with neonatal characteristics, including low Apgar score, birth asphyxia, and infections. Phototherapy was under-reported in the DNPR and the proportions of children registered that received phototherapy differed among hospitals. The non-compulsory policy for reporting treatment and care in hospitals to the DNPR might explain the variation. The most consistent reporting was observed among children born in an university hospital, where 4.4% of children registered that received phototherapy, and phototherapy was inversely associated with gestational age, birth weight, and positively associated with clinical characteristics like birth asphyxia, and infections.

Cardiovascular changes during phototherapy in newborns.

Phototherapy is the most effective non-invasive method of neonatal hyperbilirubinemia treatment. Application of this method can be associated with side effects including changes in the cardiovascular system. During phototherapy, the primary effects in the cardiovascular system include cutaneous vasodilation leading to skin hyperperfusion and subsequent redistribution of blood. The increased blood flow through the skin is associated with increased transepidermal water loss. Further effects include an increase in cerebral blood flow. Redistribution of blood to the cutaneous bed is compensated by hypoperfusion in the splanchnic area (mostly postprandial) and a significant reduction of the renal blood flow. Regarding closure/reopening of the ductus arteriosus, the results suggest that that phototherapy does not affect ductal patency. During phototherapy the cardiac output can be slightly reduced due to a decreased stroke volume, especially in preterm newborns. Systemic blood pressure is decreased and heart rate is elevated in both preterm and term newborns during phototherapy. The heart rate variability is slightly reduced. Symbolic dynamics analysis of the short-term HRV showed that during phototherapy the activity of the ANS regulating the heart rate is shifted towards the dominancy of the sympathetic activity. The responses in the cardiovascular system of premature/mature newborns without other pathology confirm a well physiologically functioning control of this system, even under specific conditions of phototherapy.

A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia.

Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1-1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55-1), as revealed by receiver operating characteristic analysis. Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.

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.

Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Yinzhihuang Oral Liquid in Treating Neonatal Hyperbilirubinemia.

Objective Neonatal hyperbilirubinemia is caused by the excessive production of bilirubin and decreased excretion ability in the neonatal period. It leads to a concentration of blood bilirubin that exceeds a certain threshold. Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine mixture used in the treatment of neonatal hyperbilirubinemia in China. This article systematically explores the pharmacological mechanisms by which YZH acts in the treatment of neonatal hyperbilirubinemia through network pharmacology at the molecular level. Methods We adopted the method of network pharmacology, which includes active component prescreening, target gene prediction, gene enrichment analysis, and network analysis. Results According to the network pharmacological analysis, 8 genes (STAT3, AKT1, MAPK14, JUN, TP53, MAPK3, ESR1, and RELA) may be targets of YZH in the treatment of neonatal hyperbilirubinemia. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that YZH may regulate antioxidation, modulate lipid metabolism, and have anti-infective properties. Conclusion In this study, the pharmacological action and molecular mechanisms of YZH were predicted as a whole. It was found that YZH is a promising drug for treating oxidative stress due to bilirubin, as it reduces immunosuppression and helps to eliminate virus infection.