Hyperbilirubinemia In Preterm Infants Research Articles

Impaired excitability of nucleus tractus solitarius neurons in a neonatal rat model of hyperbilirubinemia

Hyperbilirubinemia is associated with multiple morbidities including apnea of prematurity in preterm infants. Bilirubin, a byproduct of hemoglobin breakdown, is not excreted normally and results in high circulating levels giving rise to a state of hyperbilirubinemia. Free bilirubin (not bound to albumin) can cross the blood-brain barrier and be neurotoxic. Prior studies have shown that a systemic injection of bilirubin accumulates in the brainstem and is associated with an impaired ventilatory response to hypercapnia and an augmented hypoxic ventilatory depression. Here, using the Gunn rat model of endogenous hyperbilirubinemia, we investigated its effects on the excitability of neurons of the nucleus tractus solitarius (NTS). The homozygous Gunn rat (jj) model of hyperbilirubinemia lacks uridine diphosphate-glucuronosyltransferase-1A1, an enzyme which is needed to catabolize bilirubin. Heterozygous Nj Gunn rat pups were used for control. On postnatal (P) day 5, Nj and jj rat pups received either a 200mg/kg intraperitoneal injection of sulfadimethoxine (SDMX), which dissociates bilirubin from albumin resulting in increased levels of circulating free bilirubin, or an equivalent amount of saline as a vehicle control. Whole cell patch clamp was performed on NTS neurons two days later (P7) to assess characteristics of evoked excitatory postsynaptic currents (eEPSC).The amplitude of the evoked stimulus response to a 20Hz stimulus train was significantly increased in NTS neurons from jj+saline pups when compared to cells from Nj+saline and Nj+SDMX animals (p<0.05). This increased amplitude was no longer present after SDMX treatment of jj pups. Additionally, jj+saline NTS neurons did not exhibit any failure to solitary tract stimulation, whereas SDMX treatment significantly increased the failure rate during a 20Hz stimulus train (jj+saline =0.0%±0.0, jj+SDMX= 18.63%±8.82, p<0.05). Comparison of failure rate of jj+saline to Nj+saline (6.63%±3.12, p<0.05) was also statistically significant. The hyper-responsive NTS neurons of jj+saline rats may be an adaptive response to the deleterious effects of circulating (bound and unbound) bilirubin. However, the impaired response of neurons in jj+SDMX rats may reflect neurotoxic effects of increased free bilirubin leading to impaired neurotransmission. The latter is consistent with the high failure rate of NTS neurons in jj+SDMX rats. These data may have implications for impaired respiratory control mechanisms involved in mediating essential vagally mediated ventilatory defense responses to hypoxemia and may contribute to the apnea of prematurity associated with hyperbilirubinemia in preterm infants. William and Lois Briggs Endowment. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prematuritas Berdampak Terjadinya Hiperbilirubinemia Pada Neonatus Di Perinatologi RS Dr. Hafiz Cianjur

Prematurity is the birth or delivery of a baby that occurs between 20 weeks gestation to less than 37 weeks. About 25-50% of newborns suffer from jaundice in the first week. Hyperbilirubinemia in infants less months has a higher incidence rate. These developmental and clinical phenomena contribute to a greater degree and duration of neonatal hyperbilirubinemia in premature infants. Objective: to analyze the relationship of prematurity with hyperbilirubinemia in neonates at Perinatology Dr. Hafiz Cianjur Hospital. Method: The design used is quantitative observational with a cross-sectional approach. Samples were taken as many as 60 neonates using total sampling techniques. The research data was taken using medical record sheets in October – December 2023. Results: After analyzing the data was tabulated using a chi square test with a meaning level of 0.05. The results showed Prematurity (51.7%) as many as 31 neonates gestation period 31-36 weeks and Hyperbilirubinemia (86.7%) as many as 52 neonates in the severe category. The results of statistical testing obtained a significancy value of 0.003. Based on the results of p value < 0.05. Conclusion: it can be concluded that there is a relationship between prematurity and hyperbilirubinemia in neonates in Hospital Perinatology.

Value of cord blood albumin and bilirubin in the prediction of pathological hyperbilirubinemia in preterm neonates

Background: Preterm infants have a higher incidence of indirect hyperbilirubinemia than term infants in about 80% of cases. Approach to initial screening for hyperbilirubinemia in preterm infants by cord blood is practical, cheap and noninvasive. Objectives: To determine the value of cord blood albumin, bilirubin and bilirubin/albumin ratio to predict pathological hyperbilirubinemia in preterm infants. Materials and method: A prospective cohort study was carried out all preterm infants < 37 weeks, were born at Hospital of University of Medicine and Pharmacy, Hue, Viet Nam from 4/2018 to 8/2020. Cord blood albumin and bilirubin was collected after birth. Neonates were followed up daily for hyperbilirubinemia. Check serum bilirubin levels on the second day after birth and whenever an infant has significant hyperbilirubinemia. Results: We studied 176 preterm infants with jaundice, 88/176 (50%) infants had pathological hyperbilirubinemia. At the cut-off point for total cord bilirubin > 1.818 mg/dl and bilirubin/albumin ratio > 0.518 had a good predictive in detecting pathological hyperbilirubin in preterm infants with an AUC 0.854 and 0.842 respectively. However, cord blood albumin had no predictive value with an AUC of 0.524. Conclusion: Cord blood bilirubin and bilirubin/albumin ratio have a good discrimination in predicting pathological hyperbilirubinemia in preterm infants Key words: neonate, preterm, hyperbilirubinemia, cord blood albumin, cord blood bilirubin, bilirubin/albumin ratio.

Implementation and Assessment of a SmartZone Alert to Notify Clinicians of Critical Hyperbilirubinemia in Preterm Infants Less Than 35 Weeks Gestation

Abstract Background Neonatal jaundice, also known as hyperbilirubinemia in term and preterm infants, is treated with phototherapy when bilirubin results exceed gestational age- and age-specific medical decision levels (MDL) to prevent kernicterus and bilirubin-induced neurological damage. During phototherapy, unconjugated bilirubin is converted to water-soluble isomers that are excreted in the urine. Presently, the electronic medical record (EMR) at our hospital cannot use gestational age to stratify reference ranges thereby the associated flags and alerts would not be triggered, leading to delays in reviewing bilirubin results and placing phototherapy orders. The aim of this project is to replace the current manual assessment process for phototherapy with a newly designed alert to notify clinicians of elevated bilirubin results for preterm infants (<35 weeks gestation) and to minimize prolonged delays in placing phototherapy orders. We hypothesized that the SmartZone alert will encourage consistent and timely consideration of phototherapy. Method A SmartZone alert, built with Cerner command language and Discern Expert rules, evaluates total or neonatal bilirubin results for patients in the Newborn and Infant Critical Care Unit (NICCU), calculates the patient’s age using the recorded gestational age and birth time, and utilizes the following rules: 1) bilirubin result must exceed the pre-defined gestational age-specific MDLs, and 2) calculated gestational age is <35 weeks. Additionally, the SmartZone alert will not be triggered if there is an active phototherapy order. Once triggered, the alert will be visible for four hours to all caregivers who view the patient’s EMR. We compared the duration of time between verified bilirubin results and phototherapy orders before and after the implementation of the SmartZone alert. Result The SmartZone alert was implemented on 01/11/2022. Between 1/1/2021 - 1/11/2022, 95 preterm infants in the NICCU had neonatal and total bilirubin results, in which 19 met the criteria for the alert to be triggered, and 17 had phototherapy orders. Further analysis revealed that 12 orders were placed <24 hours, four orders were placed 24 - 72 hours, and one order was placed >72 hours after bilirubin results were verified. Between 1/12/2022 – 2/13/2022, 13 newly admitted preterm infants in the NICCU had neonatal and total bilirubin results, in which one triggered the alert, and phototherapy was ordered within 15 hours. Conclusion A SmartZone alert was implemented to encourage consistent and timely consideration of phototherapy for preterm infants <35 weeks with critical hyperbilirubinemia. The alert is functioning as intended. This alert will be continuously monitored to further optimize its functionality and utilization.

Clofibrate in the Treatment of the Non-hemolytic Hyperbilirubinemia in Preterm Neonates in Western Iran

Background: No studies, to the best of our knowledge, have been conducted on the effect of Clofibrate in reducing hyperbilirubinemia in preterm infants. Therefore, this study aimed at investigating the therapeutic effect of Clofibrate in treating hyperbilirubinemia of preterm neonates. Methods: This clinical trial was performed from April 4 to December 20, 2019, on neonates in Hamadan in western Iran. The allocation remained concealed to the researcher, neonates’ parents, and analyzer during the study. A dose of Clofibrate of 25 kg/mg was given on the first day of hospitalization. The neonates in the placebo group received the oral placebo 25 kg/mg in the same way as the oral Clofibrate. The data were analyzed using SPSS 16 with P-value < 0.05. Results: No statistically significant difference was observed in the baseline characteristics of the two groups based on the neonate’s age and gender, delivery method, and gestational age. The prescription of Clofibrate significantly reduced the duration of hospitalization (p= 0.002) and phototherapy (p= 0.001). Prescribing a single oral dose of Clofibrate (25 mg/Kg) along with phototherapy in preterm neonates significantly reduced total serum bilirubin levels at 24 and 48 hours after treatment compared with phototherapy alone (p= 0.001). However, this association was not significant in admission (p= 0.095). Conclusion: The findings of this study showed the effect of Clofibrate in treating hyperbilirubinemia of preterm neonates. In addition, prescribing Clofibrate significantly reduced the duration of hospitalization and phototherapy.

Bilirubin/albumin (B/A) ratios correlate with unbound bilirubin levels in preterm infants.

A strong correlation between the bilirubin/albumin (B/A) ratio and unbound bilirubin (UB) levels in newborns ≥35 weeks of gestation has been reported. However, in preterm infants, the usefulness of B/A ratios remains unclear. We obtained serum from 381 newborns <35 weeks of gestation. UB levels were measured using the glucose oxidase-peroxidase method. Total serum bilirubin (TB) and albumin (Alb) concentrations were measured spectrophotometrically. Samples were then stratified into two groups based on the infant's phototherapy use. B/A ratios were calculated and correlated with UB levels. Samples taken from infants prior to or never receiving phototherapy (No PTx) were then stratified by gestational age (GA) epochs: 22-27, 28-29, 30-31, and 32-34 weeks and B/A ratios correlated with UB levels. B/A ratios significantly correlated with UB levels in samples from the No PTx cohort (n = 1250; y = 1.83x - 0.15, r2 = 0.93) when compared with samples from infants post-phototherapy (Post-PTx, n = 2039; y = 1.05x + 0.09, r2 = 0.69). Even when stratified by GA, the correlation remained. In preterm infants <35 weeks of gestation, B/A ratios correlated with UB levels better in infants prior to or never receiving phototherapy than in those infants receiving phototherapy. The bilirubin/albumin (B/A) ratio significantly correlates with unbound bilirubin (UB) levels in preterm infants <35 weeks of gestation. The B/A ratio can be used as an index of UB levels in preterm infants <35 weeks of gestation. The B/A ratio is useful, especially when UB measurements are not available, for managing hyperbilirubinemia in preterm infants.

Efficacy of zinc sulfate on indirect hyperbilirubinemia in premature infants admitted to neonatal intensive care unit: a double-blind, randomized clinical trial

BackgroundHyperbilirubinemia is a common neonatal problem. Studies conducted on the effectiveness of zinc salts on serum indirect bilirubin levels in newborns have yielded different results, all calling for further research. This study aimed to determine the effect of oral zinc sulfate on indirect hyperbilirubinemia in preterm infants admitted to the neonatal intensive care unit.MethodsA randomized double-blind clinical trial was performed in the neonatal intensive care unit of Vali-e-Asr Hospital in Birjand, Iran. The study population comprised neonates aged between 31 and 36 gestational weeks, who required phototherapy in the neonatal intensive care unit. A total of 60 neonates were selected by census and allocated into an experimental group and a control group. In addition to phototherapy, the experimental group received 1 cc/Kg zinc sulfate syrup (containing 5 mg/5 cc zinc sulfate; Merck Company, Germany), and the control group received a placebo syrup (containing 1 cc/kg sucrose). Data were analyzed in SPSS-21 software using the independent t-test, repeated-measures ANOVA, Bonferroni post-hoc test, and Mann-Whitney test. P-values smaller than 0.05 were considered significant.ResultsBilirubin level changes in the experimental and control groups six hours after intervention were − 1.45 ± 3.23 and − 0.49 ± 0.37 (p = 0.024), respectively. The changes 24 and 48 h after intervention were-3.26 ± 2.78 and − 1.89 ± 1.20 (p = 0.017) in the experimental group and − 4.89 ± 2.76 and − 3.98 ± 2.32 (p = 0.23) in the control group, respectively. There was no significant difference in the phototherapy duration between the two groups (p = 0.24).ConclusionsThe results of this study showed that the use of zinc sulfate syrup in preterm infants with indirect hyperbilirubinemia significantly reduced bilirubin levels within 48 h of treatment.Trial registrationTrial registration: IRCT, IRCT2015120825439N1. Registered 21 February 2016, http://irct.ir/trial/21277

Hyperbilirubinemia in Preterm Infants Admitted to Neonatal Intensive Care Units in Ethiopia.

Background. Hyperbilirubinemia is prevalent and protracted in preterm infants. This study assessed the pattern of hyperbilirubinemia in preterm infants in Ethiopia. Methods. This study was part of multi-centered prospective, cross-sectional, observational study that determined causes of death among preterm infants. Jaundice was first identified based on clinical visual assessment. Venous blood was then sent for total and direct serum bilirubin level measurements. For this study, a total serum bilirubin level ≥5 mg/dL was taken as the cutoff point to diagnose hyperbilirubinemia. Based on the bilirubin level and clinical findings, the final diagnoses of hyperbilirubinemia and associated complications were made by the physician. Result. A total of 4919 preterm infants were enrolled into the overall study, and 3852 were admitted to one of the study’s newborn intensive care units. Of these, 1779 (46.2%) infants were diagnosed with hyperbilirubinemia. Ten of these (0.6%) developed acute bilirubin encephalopathy. The prevalence of hyperbilirubinemia was 66.7% among the infants who were less than 28 weeks of gestation who survived. Rh incompatibility (P = .002), ABO incompatibility (P = .0001), and sepsis (P = .0001) were significantly associated with hyperbilirubinemia. Perinatal asphyxia (P-value = 0.0001) was negatively associated with hyperbilirubinemia. Conclusion. The prevalence of hyperbilirubinemia in preterm babies admitted to neonatal care units in Ethiopia was high. The major risk factors associated with hyperbilirubinemia in preterm babies in this study were found to be ABO incompatibility, sepsis, and Rh isoimmunization.

A Gunn rat model of preterm hyperbilirubinemia.

BackgroundThe impact of bilirubin in preterm infants is poorly understood. An animal model would assist in improving understanding. The Gunn rat lacks uridine diphosphate-glucuronylsyl transferase 1 and can be made acutely hyperbilirubinemic by injection of sulfodimethoxine (sulfa), a drug that displaces bilirubin from albumin and thus increases free bilirubin.MethodsOn postnatal day (P) 5, Gunn rats either heterozygous (Nj) or homozygous (jj) for glucuronosyltransferase activity were injected with either saline or sulfa. Behavior and cerebellar weight were measured.ResultsPups did not show any signs of acute bilirubin encephalopathy. Pup weight dropped significantly on P8 only in the jj-sulfa group. Behavior was affected only in the jj-sulfa group. Cerebellar weight was significantly less in the jj-sulfa group.DiscussionThe Gunn rat pup model may be a good model to study hyperbilirubinemia in preterm infants.

Does the Use of Antenatal Corticosteroids Decrease Levels of Neonatal Hyperbilirubinemia in Preterm Infants? [15K

INTRODUCTION: The use of prenatal corticosteroids for pregnant women between 34-36 6/7 weeks of pregnancy is recommended to reducing the morbidity of late preterm infants. METHODS: This is a secondary analysis of a randomized clinical trial conducted to determine the effectiveness of corticosteroids in reducing respiratory disorders in infants born at 34-36 weeks' gestation Trial registration Clinical Trials NCT00675246. This study was approved by IRB and all participants signed an informed consent term. RESULTS: Of 245 preterm infants, the number of newborns with gestational age 34, 35 and 36 was 30 (12.2%), 110 (45.1%), and 105 (42.7%), respectively. Jaundice occurred in 150 (62.5%) newborns and 70 among them required phototherapy during hospitalization. Late preterm infants exposed to corticosteroids started treatment with lifetime of 61.2± 33.6 h vs. 48.3± 25.3 h (p = 0.03) with similar levels of bilirubin (12.1± 3.2 mg/dL vs. 12.8± 3.7 mg/dL, p = 0.38) when compared to the control group. They required less treatment compared to the placebo group (n = 27 vs. n = 42, p = 0.025), and spent less days on phototherapy (1.7± 1.7 vs. 2.6± 2.2, p = 0.05). CONCLUSION: Late preterm infants exposed to prenatal corticosteroids had less need for phototherapy and shorter treatment. Also, they developed elevated level of bilirubin later. This result suggests that prenatal corticosteroids decrease the levels of hyperbilirubinemia in late preterm infants.

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria.

In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2-weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7days of age, and on the reference values for corrected gestational age at ≥7days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.

INVESTIGATING THE PHOTOTHERAPY THRESHOLDS IN PRETERM INFANTS

Abstract BACKGROUND Currently there are limited guidelines for the management of hyperbilirubinemia in preterm infants. Current guidelines are limited to individual sites and are consensus-based opinions. The current decrease in chronic bilirubin encephalopathy in preterm infants is a result of liberal use of phototherapy that are not based on evidence from a large dataset of preterm infants. The pattern of bilirubin levels in preterm is unclear and currently based on clinical judgement. Nomograms in term infants has been proven to be beneficial and effective in reducing unnecessary treatment of hyperbilirubinemia. A nomogram designed for preterm infants would allow health professionals to quantify risk based on evidence based methods and reduce the number of test done on preterm infants. OBJECTIVES The objectives of this study are 1) To determine photherapy thresholds in preterm infants and 2) To determine the normative pattern of bilirubin values in preterm infants. DESIGN/METHODS A multi-site retrospective chart review of preterm infants ≤ 35 weeks gestation born between January 2012- November 2017 was conducted. The following data was collected; all TSB, postnatal hours of age, duration of phototherapy, infant characteristics (gestational age, birth weight, outcomes) and maternal history (inter and anter partum medication). TSB samples prior to the initiation of phototherapy were analyzed per hour and stratified by gestational age groups. RESULTS A total of 330 preterm infants were included in the retrospective review (50 24-28 weeks gestation, 100 29-32 weeks gestation, and 180 33–35 weeks gestation). The mean peak bilirubin in infants 33-35 week gestation was 198 umol/L at 4 days. These infants were started on phototherapy at a mean age of 89 hours. At 24 hours of age these infants’ bilirubin was 104 umol/L (72-189umol/L). The mean peak bilirubin in infants 29–32 weeks gestation was 181umol/L at 5 days. At 24 hours of age the mean bilirubin was 109 umol/L. Finally in infants 24–28 weeks gestation the mean peak bilirubin was 127 umol/L at 4 days. These infants were started on phototherapy at 44 hours of age. CONCLUSION Bilirubin values in preterm infants is hetergenous across gestional ages. Phototherapy treatment thresholds are lower in preterm infants between 24–28 weeks gestation. A nomogram for preterm infants maybe possible in infants between 29–35 weeks. Further research is required to determine hour specific bilirubin levels in preterm infants.

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants

To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day. For the 166 infants studied, peak UB significantly correlated with concomitant Ka (r = -0.44, P = .001) but not with concomitant TSB or BAMR after adjusting for GA. On multiple regression analyses, there was a significant association of concomitant Ka (-0.06, 95% CI -0.08 to -0.04, P = .0001), but not concomitant TSB or BAMR with peak UB after controlling for GA, birth weight, race, and sex. GA group was a significant effect modifier for the association between Ka and peak UB (0.03, 95% CI 0.02-0.04, P < .001). Interaction analyses showed the association between concomitant Ka and peak UB was significant for the 24-30 weeks GA group infants, but not for the 301/7-33 weeks GA group infants. Peak UB was primarily associated with a decrease in binding affinity in infants ≤30 weeks GA. Interventions aimed at improving binding affinity may be important in decreasing the risk of bilirubin-induced neurotoxicity.

Bilirubin Uridine Diphosphate-glucuronosyltransferase Polymorphism as a Risk Factor for Prolonged Hyperbilirubinemia in Japanese Preterm Infants

To determine whether a variant of the bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1*6) is a risk factor for prolonged hyperbilirubinemia in preterm infants. UGT1A1 genotypes in 46 Japanese preterm infants (<37 weeks of gestation) were compared with UGT1A1 genotypes in 38 control infants, using polymerase chain reaction-direct sequencing. Prolonged unconjugated hyperbilirubinemia was defined as serum total bilirubin concentration of >150 µmol/L (8.77 mg/dL) beyond 14 days of life. In the case group, 41 of 46 infants (89.1%) had a polymorphic variant, c.211G>A, p.G71R (UGT1A1*6). In the control group, 7 of 38 (18.4%) had UGT1A1*6. The allele frequency of UGT1A1*6 was 0.641 in the prolonged hyperbilirubinemia group, which was significantly higher than in the control group (0.092; P < .001). In total, 39 of 46 infants in the case group were breast fed, and only 10 infants in the control group were breast fed. These data suggest that UGT1A1*6 is a risk factor for prolonged unconjugated hyperbilirubinemia in preterm infants in Japan. Given the different rate of breast feeding in this study, additional data are necessary for drawing a definitive conclusion.

Hyperbilirubinemia management in neonates &lt;2000 g screened for glucose-6-phosphate dehydrogenase deficiency in a tertiary neonatal unit

Background: Prematurity and glucose-6-phosphate dehydrogenase (G6PD) deficiency are considered important risk factors in neonatal hyperbilirubinemia. G6PD screening is performed by many neonatal units to identify this risk factor. Few studies evaluated the role of this screening on the management of hyperbilirubinemia in preterm infants during their neonatal hospitalization. This study aims to evaluate effects of G6PD screening on treatment of hyperbilirubinemia in infants <2000 g admitted to Neonatal Intensive Care Unit. Methods: All neonates <2000 g who were admitted to neonatal unit for 3 years (2013–2015) were retrospectively included in the study. Data related to risk factors and management of hyperbilirubinemia were collected and analyzed on these infants. A number of phototherapy units used for treatment, duration phototherapy, and level of bilirubin were compared between G6PD deficient and nondeficient infants and presented. Results: Included in this retrospective study were 621 infants. About half on included infants were < 1500 g. Gestational age groups as follow: ≤28 weeks, 23.3%; 29–32 weeks, 37.5%; 33–36 weeks, 33.6%; and ≥37 weeks, 5.6%. Prevalence of G6PD deficiency was 10.3%. The highest recorded serum bilirubin was significantly higher in G6PD deficient group compared with nondeficient one (161.6 μmol/l ± 57.5 vs. 145.4 μmol/l ± 46.4, P = 0.01). G6PD deficient infants were treated with more phototherapy than nondeficient group (85.9% vs. 64.5%, P < 0.001). G6PD deficient low birth weight neonates were more likely to receive intensive phototherapy. None of the G6PD deficient patients was treated with exchange transfusion. Conclusion: Prevalence of G6PD deficiency among low birth weight infant in the United Arab Emirates is similar to data reported in full-term infants. Screening for G6PD in preterm infant is associated with more treatment using phototherapy and may contribute in preventing severe hyperbilirubinemia.

Neonatologists' opinions about the 'foreseeable risks' in comparative effectiveness research: Results from an online survey.

To examine how neonatologists determine which risks require inclusion for informed consent per the 'Common Rule' and 'Draft Guidance' regulations in comparative effectiveness research (CER). Neonatologists active in research were invited to complete an online survey. Questions focused on clinical practices for treating hyperbilirubinemia in premature infants and about risk disclosure related to a hypothetical randomized trial. Response rate was 57%. 43% were primarily researchers; 31% primarily clinicians. 69% had conducted CER. 81% thought hypothetical study enrollment was not riskier than receiving routine care. 76% labeled the study 'minimal risk' by comparing study risks to clinical care risks. Respondents would not currently disclose many of the treatment risks but would disclose more if the Draft Guidance were enacted into law. Findings suggest the Draft Guidance requires disclosure of more risks than does the Common Rule; applying either rule results in disclosure of more risks than in standard clinical care.

Management of hyperbilirubinemia in preterm infants in Turkey.

Prematurity is a significant risk factor for developing unconjugated hyperbilirubinemia. This study investigated the current approach to managing hyperbilirubinemia in preterm newborns in Turkey. A study-specific questionnaire on the management of jaundice in preterm infants was sent to 100 level III neonatal intensive care units in Turkey. Responses were obtained from 84 centers from all regions of Turkey. Of the centers, 75.3% used the Turkish Neonatology Society guidelines for deciding to start phototherapy, and 24.7% used different guidelines. The monitoring of bilirubin varied among the participants. Of the participants, 53.6% believed that prophylactic phototherapy was necessary if the infant's birth weight was below 1000 g. The participants reported 6 cases of kernicterus in preterm infants in recent years. There is no single standard approach for managing neonatal hyperbilirubinemia in preterm infants in Turkey. Prophylactic phototherapy for extremely low birth-weight infants might be added to the guidelines for Turkey.

Клінічна ефективність вітчизняного препарату урсодеоксихолієвої кислоти в комплексному лікуванні гіпербілірубінемій у недоношених немовлят

Результати кількох невеликих пілотних клінічних досліджень свідчать, що використання урсодеоксихолієвої кислоти (УДХК) може полегшувати перебіг неонатальних жовтяниць. Метою роботи була оцінка клінічної ефективності препарату Укрлів® суспензія в комплексному лікуванні гіпербілірубінемій у недоношених немовлят. У відкрите рандомізоване дослідження були залучені 35 передчасно народжених дітей (19 — в основній, 16 — у контрольній групі). Критеріями включення були передчасне народження й гіпербілірубінемія (загальний білірубін сироватки крові &gt; 225 мкмоль/л) у ранній неонатальний період. Новонародженим в основній групі на додаток до фототерапії призначали Укрлів® суспензію в добовій дозі 20 мг/кг упродовж 14 днів. Сформовані групи не відрізнялися за основними клінічними показниками й вихідними концентраціями білірубіну в сироватці крові. У дітей з обох груп відбувалося вірогідне зниження початкових концентрацій загального білірубіну сироватки крові. За перші 3 дні лікування відповідна динаміка становила 44% в основній проти 32% в контрольній групі, забезпечуючи досягнення вірогідної відмінності між групами за рівнем загального і прямого білірубіну на момент закінчення курсу УДХК. У немовлят з основної групи жовтяниця була менш тривалою. Препарат добре переносився немовлятами, не зауважено будь-яких побічних ефектів його призначення. Таким чином, отримані результати дозволяють зробити висновки про доцільність застосування Укрлів® суспензії в комплексному лікуванні гіпербілірубінемій у передчасно народжених немовлят.

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

Background and ObjectiveHigh bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.MethodsIn a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.ResultsComposite motor (100±13 vs. 101±12) and cognitive (101±12 vs. 101±11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.ConclusionsThe additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.Trial RegistrationControlled-Trials.com ISRCTN74465643

Transcutaneous bilirubinometry is not influenced by term or skin color in neonates

BackgroundThe utility of transcutaneous bilirubin measurements (TcB) in screening for hyperbilirubinemia in preterm infants (<34weeks) and in non-white infants remains a matter of debate. AimTo evaluate accuracy of TcB in preterm and term infants of different ethnic backgrounds, using a second generation bilirubinometer. Study designThe Draeger JM-103® device was used to measure TcB. Eighty five measurements of TcB and total serum bilirubin (TSB) were retrospectively compared. Neonates were stratified into groups according to gestational age: <34weeks (group 1, n=44) and >34weeks (group 2, n=41), and according to ethnic origin: Caucasians (group A, n=49) and non-Caucasians (group B, n=36).Statistical analysis, using Pearson's correlation coefficient (r) and Bland–Altman analysis were performed to evaluate correlation and agreement between TSB and TcB values. Multiple linear regression was used to control for confounders for TSB values. ResultsCorrelation between TSB and TcB was high. Pearson's correlation coefficients were over 0.9 in all groups (0.910, 0.908, 0.916 and 0.934, p<0.0001 in groups 1, 2, A, and B respectively). Bland–Altman plots showed acceptable and close limits of agreements (56.8/−57.7, 54.2/−67.2, 57.7/−55.8, and 51.3/−69.9μmol/L in groups 1, 2, A and B respectively) with a trend for TcB to overestimate TSB in groups 2 and B. Birth term and skin color were not identified as confounding factors for predicting TSB in multiple linear regression. ConclusionsTcB measurements using the Draeger JM-103® device correlate significantly with TSB, regardless of term and skin color. Transcutaneous bilirubinometry seems to be a safe and cost-effective screening method for severe hyperbilirubinemia in newborns of different terms and ethnic origins.