Forgoing Exchange Transfusion in Neonatal Hyperbilirubinemia: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Unconjugated hyperbilirubinemia is part of the everyday life of the neonatal period as it reflects the adaptation of the metabolism of bilirubin. The neonatal hyperbilirubinemia usually resolves spontaneously, but it can also be the cause of an acute or chronic encephalopathy known as kernicterus. Regardless of the cause, the goal of therapy is to prevent this neurotoxicity while not causing undue harm. Phototherapy and, if it is unsuccessful, exchange transfusion (ECT) remain the primary treatment modalities used to keep the maximal total serum bilirubin (TSB) below pathologic levels. MATERIALS AND METHODS: This is a descriptive retrospective cohort study of 69 live neonates hospitalized in the Department of Neonatology and Neonatal Resuscitation of Mohammed VI University Hospital with unconjugated hyperbilirubinemia requiring ECT and treated with intensive phototherapy instead, spanning five years from March 2016 to March 2021. We aim to demonstrate the effectiveness of phototherapy in achieving prolonged reduction of bilirubin levels and the prevention of neurological complications and to compare our results with those in the literature. RESULTS: The use of intensive phototherapy in the treatment of neonatal unconjugated hyperbilirubinemia is very effective in lowering total serum bilirubin when its level is in the range of exchange transfusion, and it has succeeded in preventing the neurological complications of severe hyperbilirubinemia. CONCLUSION: Through this study, it can be seen that phototherapy is an efficacious, simpler, and less hazardous alternative to exchange transfusion in achieving a sustained reduction of bilirubin levels and preventing neurological complications.

Implementation of neonatal phototherapy with the BiliCocoon Bag® device in the maternity ward and impact on mother-infant separation.

BACKGROUND: Free bilirubin jaundice is a frequent pathology in the neonatal period. The major complication is neurological toxicity, the most severe form of which is kernicterus. Overall, 5%-10% of jaundiced neonates require treatment. The first-line treatment is phototherapy, with intensive phototherapy being the gold standard. Other equipment is also available, including the BiliCocoon Bag®. It is a safe and controlled therapy that can be performed in the mother's room in the maternity ward, thereby avoiding separation and allowing for breast- or bottle-feeding during treatment. It is easy to install and does not require protective glasses, thus no scope or hospitalization. In our maternity ward, all neonates requiring intensive phototherapy are hospitalized in the neonatology ward. OBJECTIVE: The objective of our study was to evaluate the number of avoided hospitalizations in neonatology for free bilirubin jaundice since the introduction, according to a strict protocol, of the BiliCocoon Bag® device. MATERIAL AND METHOD: This was a single-center retrospective cohort study using data of newborns usually collected as part of standard care. Children born in our maternity ward during an 18-month period (August 1, 2020 to January 31, 2022) were included. Causes of jaundice, age at the beginning and mode of treatment, number of sessions for each device, and length of stay were compared. Results are presented as number and percentage with median (25th-75th) or mean (extremes) values for categorical and continuous variables, respectively. A t-test was used to compare the means of the independent groups. RESULTS: A total of 316 newborns were included. Physiological jaundice was the main cause of jaundice. The median age for the first phototherapy treatment was 54.5 h (30-68). The 316 neonates needed 438 phototherapy sessions: 235 (74%) neonates required only one phototherapy session, 85 (36%) of them were treated with the BiliCocoon Bag®. For the 81 children who needed two or more phototherapy sessions, 19 children (23.5%) were treated by tunnel phototherapy and then the BiliCocoon Bag®, and eight children (10%) by BiliCocoon Bag® alone. The BiliCocoon Bag® enabled a relative reduction in the hospitalization rate of 38% and avoided hospitalization for approximately one third of the newborns treated. The BiliCocoon Bag® failure rate was 3.6% and the average length of stay was comparable between the two types of treatment. CONCLUSION: Following a strict protocol of use, the BiliCocoon Bag® is a reliable method and a good alternative to intensive phototherapy for newborns in the maternity ward, as it avoids hospitalization and mother-infant separation.

Single-surface Intensive Phototherapy or Double-Surface Intensive Phototherapy in Neonatal Non-Hemolytic Hyperbilirubinemia: A Comparison of Effectiveness and Complications.

Background: Severe indirect hyperbilirubinemia causes neurotoxicity, leading to potential permanent injuries to the neonatal nervous system. The present study intended to compare the effectiveness and complications of Single-Surface Intensive Phototherapy (SSIP) and Double-Surface Intensive Phototherapy (DSIP) in treating non-hemolytic hyperbilirubinemia in the neonatal ward of the Besat Hospital, Hamadan, Iran. Methods: In this prospective randomized clinical trial, 150 healthy full-term neonates born between 37-42 weeks gestation with ages <14 days old and birth weights ≥2500 gr who were affected by non-hemolytic hyperbilirubinemia with total serum bilirubin of 15-20 mg/dL were randomly allocated to two groups. Each group (n=75) underwent either SSIP or DSIP. Demographics, bilirubin level alterations, weight, platelet count, number of defecation per day, and body temperature of the patients were monitored and recorded in a specific questionnaire. Data analysis was performed using SPSS version 26.0 software, with the Chi-square and independent t-test. Results: The pre-intervention levels of indirect bilirubin were 17.07±1.46 mg/dL in the SSIP group and 17.10±1.54 mg/dL in the DSIP group (P-value = 0.853). After 24 and 48 hours of treatment, the mean indirect bilirubin level of the SSIP group reduced to 13.12±1.71 mg/dL and 9.69±1.68 mg/dL, respectively. In the DSIP group, the levels were 11.85±2.17 mg/dL and 8.43±1.56 mg/dL after 24 and 48 hours of treatment, respectively. The absolute reductions of indirect bilirubin were 7.76±3.28 mg/dL for the SSIP group and 8.96±4.49 mg/dL for the DSIP group (P-value = 0.458). Therefore, the indirect bilirubin levels were significantly different between the groups after 24 and 48 hours of treatment and at the time of discharge (P<0.05). There were no significant inter-group differences in weight, platelet count, and incidence of skin rash, while the number of defecation and body temperature were higher in the DSIP group (P <0.05). However, body temperature alterations had no clinical relevance. Conclusion: Compared to the SSIP, the DSIP showed faster effectiveness and led to a shorter hospital stay, while it did not entail higher levels of complications.

Efficacy of newer modalities in the management of indirect hyperbilirubinaemia at a secondary care hospital: A prospective study from 2015-2018.

OBJECTIVE: To evaluate the efficacy of current practices and new modalities for the management of neonatal indirect hyperbilirubinaemia. METHODS: The prospective study was conducted at King Khalid Hospital, Al Majmaah, Saudi Arabia, from September 2015 to September 2018, and copmprised neonates with hyperbilirubinaemia who were managed using the National Institute for Health and Clinical Excellence 2010 guidelines. The outcomes were measured in terms of decrease in total serum bilirubin and clinical improvement. Data was analysed using SPSS 25. RESULTS: Of the 233 subjects, there were 119(51%) girls and 114(49%) boys. Phototherapy was used in 162(69.5%) cases, intensive phototherapy in 36(15.5%) and intravenous immunoglobulin in 35(15%). Exchange transfusion was done in 2(0.85%) patients. All the 233(100%) patients improved with the management and total serum bilirubin significantly reduced (p<0.05). CONCLUSIONS: Newer techniques were found to have a vital role in the management of neonatal hyperbilirubinaemia.

Conventional intensive versus LED intensive phototherapy oxidative stress burden in neonatal hyperbilirubinaemia of haemolytic origin.

Background: Phototherapy causes oxidative stress which is of particular importance in neonates because of the increased susceptibility of neonatal red blood cell membranes to oxidative damage.Aim: To evaluate the oxidant/antioxidant status in neonates with haemolytic hyperbilirubinaemia before and after exposure to two different intensive phototherapy light sources.Patients and Methods: A randomised controlled study was undertaken in 54 full-term neonates with indirect haemolytic hyperbilirubinaemia admitted to a neonatal intensive care unit in the first week of life. They were randomly divided into two equal groups. Group 1 infants were exposed to intensive conventional phototherapy (Bilisphere 360) and Group 2 were exposed to an intensive light-emitting diode (LED) phototherapy device (Bilitron bed 3600). Total serum bilirubin (TSB), total oxidative stress (TOS), total antioxidant capacity (TAC) and the oxidative stress index (OSI) were measured before and 48 hours after initiation of phototherapy.Results: There was a significant decrease in TSB after phototherapy in both groups (p < 0.001). The TOS and OSI were significantly increased after phototherapy in both groups (p < 0.001) but more so in Group 1 with conventional phototherapy (p = 0.05 and 0.01, respectively). TAC was significantly decreased after phototherapy in both groups (p < 0.00) but more so in Group 1 (p = 0.03).There were significant increases in the incidence of dehydration, hyperthermia and skin rash in the conventional compared with the LED phototherapy group (p = 0.02, 0.01 and 0.02, respectively). However, there was a significant increase in the incidence of hypothermia in the LED compared with the conventional phototherapy group (p = 0.001).Conclusion: Both intensive conventional and LED phototherapy are equally effective in decreasing TSB, but intensive LED phototherapy is safer than intensive conventional phototherapy with regard to oxidative stress and oxidant/antioxidant imbalance.Abbreviations: DSB: direct serum bilirubin; G6PD: glucose-6-phosphate dehydrogenase enzyme; LED: light-emitting diode; OSI: oxidative stress index; TAC: total antioxidant capacity; TOS: total oxidative stresses; TSB: total serum bilirubin.

A clinical study on the effects of exchange transfusion and intensive phototherapy on neurodevelopment in neonates with severe hyperbilirubinemia / 中国新生儿科杂志

Objective To study the effects of exchange transfusion(ET) and intensive phototherapy (IPT) on neurodevelopment in neonates with severe hyperbilirubinemia reaching ET criteria.Method From January 2015 to March 2016,neonates with severe hyperbilirubinemia reaching ET criteria with gestational age ≥35 weeks,and hospitalized in the Department of Neonatology of our hospital were enrolled in the study.The parents were informed of the risks of acute bilirubin encephalopathy (ABE) and both the advantages and disadvantages of IPT and ET.Based on the different choices of their parents,the neonates were assigned into the ET group and the IPT group.General conditions,treatment effects,the incidences of ABE and the prognosis were recorded and analyzed.Result A total of 335 patients were included in this study,147 in the ET group and 188 in the IPT group.Before intervention,the peak of total serum bilirubin (TSB) in ET group (475.8± 100.6 μmol/L) was higher than IPT group (398.3±39.8 μmol/L) (the difference of TSB between two groups was 77.4 μmol/L,P＜0.001),and the incidences of high risk factors such as blood incompatibilities,sepsis,cranial hematoma and intracranial hemorrhage in ET group were higher than IPT group (P＜0.05).Compared with at admission,the incidence of ABE in the ET group increased from 32.0％ to 34.0％ at discharge,mainly due to moderate and severe ABE (the ratio of moderate ABE increased from 2.7％ to 10.2％,and severe ABE increase from 2.7％ to 4.8％).Statistically significant differences existed in the proportion of ABE with different severity at admission and discharge in ET group (P＜0.05),while that in IPT group wasn't statistically significant.241 patients were followed up (follow-up rate 71.9％),with the age ranging from 20 to 36 months.6 cases (5.7％,6/106) in the ET group showed hearing disorder while none (0％,0/135) in the IPT group (P＜0.05).The incidences of neuromotor dyskinesia,language development disorder and spasm in ET group were higher than IPT group(7.5％ vs.3.7％,3.8％ vs.1.5％,4.7％ vs.4.4％,respectively),but the differences weren't statistically significant(P＞ 0.05).No deaths were observed in both groups.Conclusion In neonates with severe hyperbilirubinemia whose TSB exceeding the upper limit of current ET criteria (and within upper limit+5 mg/dl),if the neonates have no risk factors nor clinical symptoms of moderate or severe ABE,only IPT and without ET does not increase the incidence of unfavourable prognosis of central nervous system.

Incidence and risk factors of post-phototherapy neonatal rebound hyperbilirubinemia.

BACKGROUND: To determine the incidence and risk factors of post-phototherapy rebound hyperbilirubinemia because data about bilirubin rebound in neonates are lacking and few studies have concerned this condition. METHODS: A prospective observational study was conducted on 500 neonates with indirect hyperbilirubinemia who were treated according to standard guidelines. Total serum bilirubin (TSB) was measured at 24-36 h after phototherapy; significant bilirubin rebound (SBR) is considered as increasing TSB that needs reinstitution of phototherapy. RESULTS: A total of 124 (24.9%) neonates developed SBR with TSB increased by 3.4 (2.4-11.2) mg/dL after stopping phototherapy. Multiple logistic regression model revealed the following significant risk factors for rebound: low birth weight (B = 1.3, P <  0.001, OR 3.5), suspected sepsis (B = 2.5, P <  0.001, OR 12.6), exposure to intensive phototherapy (B =  0.83, P =  0.03, OR 2.3), hemolysis (B =  1.2, P <  0.001, OR 3.1), high discharge bilirubin level (B =  0.3, P =  0.001, OR 1.3), and short duration of conventional phototherapy (B =  - 1.2, P <  0.001, OR 0.3). CONCLUSIONS: SBR should be considered in neonates with hemolysis, low birth weight, suspected sepsis, short duration of conventional phototherapy, exposure to intensive phototherapy, and relatively high discharge TSB. These risk factors should be taken into account when planning post-phototherapy follow-up.

Facility-based constraints to exchange transfusions for neonatal hyperbilirubinemia in resource-limited settings.

Several clinical guidelines for the management of infants with severe neonatal hyperbilirubinemia recommend immediate exchange transfusion (ET) when the risk or presence of acute bilirubin encephalopathy is established in order to prevent chronic bilirubin encephalopathy or kernicterus. However, the literature is sparse concerning the interval between the time the decision for ET is made and the actual initiation of ET, especially in low- and middle-income countries (LMICs) with significant resource constraints but high rates of ET. This paper explores the various stages and potential delays during this interval in complying with the requirement for immediate ET for the affected infants, based on the available evidence from LMICs. The vital role of intensive phototherapy, efficient laboratory and logistical support, and clinical expertise for ET are highlighted. The challenges in securing informed parental consent, especially on religious grounds, and meeting the financial burden of this emergency procedure to facilitate timely ET are examined. Secondary delays arising from post-treatment bilirubin rebound with intensive phototherapy or ET are also discussed. These potential delays can compromise the effectiveness of ET and should provide additional impetus to curtail avoidable ET in LMICs.

High-intensity light-emitting diode vs fluorescent tubes for intensive phototherapy in neonates.

BACKGROUND: Special blue fluorescent tubes are recommended by the American Academy of Pediatrics (AAP) as the most effective light source for lowering serum bilirubin. A high-intensity light-emitting diode ('super LED') could render intensive phototherapy more effective than the above conventional methods. This study compared the efficacy and safety of a high-intensity light-emitting diode bed vs conventional intensive phototherapy with triple fluorescent tube units as a rescue treatment for severe unconjugated neonatal hyperbilirubinaemia. METHOD: This was a randomised, prospective trial. Two hundred jaundiced neonates ≥ 35 weeks gestation who met the criteria for intensive phototherapy as per AAP guidelines were randomly assigned to be treated either with triple fluorescent tube units (group 1, n = 100) or a super LED bed (group 2, n = 100). The outcome was the avoidance of exchange transfusion by successful control of hyperbilirubinaemia. RESULTS: Statistically significant higher success rates of intensive phototherapy were achieved among neonates treated with super LED (group 2) than in those treated conventionally (group 1) (87% vs 64%, P = 0.003). Significantly higher 'bilirubin decline' rates were reported in both haemolytic and non-haemolytic subgroups treated with the super LED bed compared with a similar sub-population in the conventionally treated group. Comparable numbers of neonates in both groups developed rebound jaundice (8% vs 10% of groups 1 and 2, respectively). Side-effects were mild in both groups, but higher rates of hyperthermia (12% vs 0%, P = 0.03), dehydration (8% vs 2%, P = 0.26) and skin rash (39% vs 1%, P = 0.002) were reported in the fluorescent tubes-treated group compared with the LED group. CONCLUSIONS: Super LED is a safe rescue treatment for severe neonatal hyperbilirubinaemia, and its implementation may reduce the need for exchange transfusion.

Investigation on malondialdehyde, S100B, and advanced oxidation protein product levels in significant hyperbilirubinemia and the effect of intensive phototherapy on these parameters.

BACKGROUND: The parameters of oxidative stress [advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and S100B] and the effect of intensive phototherapy (PT) on these parameters have not been studied extensively in newborns with significant hyperbilirubinemia (SH). We aimed to measure the levels of MDA, S100B, and AOPPs in newborns with SH, and to compare newborns with healthy control newborns without hyperbilirubinemia on the basis of these parameters of oxidative stress. In addition, we investigated the effect of intensive PT on these parameters during the treatment of SH and report our findings for the first time in the literature. METHODS: The study was performed in newborns (n = 62) who underwent intensive PT because of SH. Newborns without jaundice constituted the control group (n = 30). Both groups were compared with respect to demographic characteristics and biochemical (laboratory) parameters including MDA, AOPPs, and S100B. MDA, AOPPs, and S100B were also compared before and after intensive PT in the PT group. In the study group, a correlation analysis of demographic characteristics; MDA, AOPP, and S100B values; and changes occurring in MDA, AOPPs, and S100B values due to the effect of intensive PT was performed. RESULTS: Serum total bilirubin, S100B, and MDA levels in the PT group before performing PT were significantly higher than those in the control group. In newborns receiving PT serum total bilirubin, MDA and AOPP levels decreased significantly after intensive PT. In correlation analysis, a statistically significant negative correlation was found only between the amount of bilirubin decrease with PT and AOPP levels after PT in the study group. CONCLUSION: Whether the significant decrease in MDA levels, which was higher prior to PT, is due to the decrease in serum bilirubin levels or due to the effect of intensive PT itself remains to be determined in further studies. The decrease in AOPP levels after PT implies that intensive PT has protective effects on oxidative stress.