|
1
|
Diala UM, Usman F, Appiah D, Hassan L, Ogundele T, Abdullahi F, Satrom KM, Bakker CJ, Lee BW, Slusher TM. Global Prevalence of Severe Neonatal Jaundice among Hospital Admissions: A Systematic Review and Meta-Analysis. J Clin Med 2023; 12:3738. [PMID: 37297932 PMCID: PMC10253859 DOI: 10.3390/jcm12113738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/03/2023] [Accepted: 05/05/2023] [Indexed: 06/12/2023] Open
Abstract
Evidence regarding the adverse burden of severe neonatal jaundice (SNJ) in hospitalized neonates in resource-constrained settings is sparse. We attempted to determine the prevalence of SNJ, described using clinical outcome markers, in all World Health Organization (WHO) regions in the world. Data were sourced from Ovid Medline, Ovid Embase, Cochrane Library, African Journals Online, and Global Index Medicus. Hospital-based studies, including the total number of neonatal admissions with at least one clinical outcome marker of SNJ, defined as acute bilirubin encephalopathy (ABE), exchange blood transfusions (EBT), jaundice-related death, or abnormal brainstem audio-evoked response (aBAER), were independently reviewed for inclusion in this meta-analysis. Of 84 articles, 64 (76.19%) were from low- and lower-middle-income countries (LMICs), and 14.26% of the represented neonates with jaundice in these studies had SNJ. The prevelance of SNJ among all admitted neonates varied across WHO regions, ranging from 0.73 to 3.34%. Among all neonatal admissions, SNJ clinical outcome markers for EBT ranged from 0.74 to 3.81%, with the highest percentage observed in the African and South-East Asian regions; ABE ranged from 0.16 to 2.75%, with the highest percentages observed in the African and Eastern Mediterranean regions; and jaundice-related deaths ranged from 0 to 1.49%, with the highest percentage observed in the African and Eastern Mediterranean regions. Among the cohort of neonates with jaundice, the prevalence of SNJ ranged from 8.31 to 31.49%, with the highest percentage observed in the African region; EBT ranged from 9.76 to 28.97%, with the highest percentages reported for the African region; ABE was highest in the Eastern Mediterranean (22.73%) and African regions (14.51%). Jaundice-related deaths were 13.02%, 7.52%, 2.01% and 0.07%, respectively, in the Eastern Mediterranean, African, South-East Asian and European regions, with none reported in the Americas. aBAER numbers were too small, and the Western Pacific region was represented by only one study, limiting the ability to make regional comparisons. The global burden of SNJ in hospitalized neonates remains high, causing substantial, preventable morbidity and mortality especially in LMICs.
Collapse
Affiliation(s)
- Udochukwu M. Diala
- Department of Paediatrics, Faculty of Clinical Sciences, College of Health Sciences, University of Jos, University of Jos Lamingo Campus, Jos 930232, Nigeria
| | - Fatima Usman
- Department of Paediatrics, Faculty of Clinical Services, College of Health Sciences, Bayero University, Aminu Kano Teaching Hospital Campus, Kano 700006, Nigeria
| | - Duke Appiah
- Department of Public Health, School of Population and Public Health, Faculty of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Laila Hassan
- Department of Paediatrics, Faculty of Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Main Campus, Zaria 810211, Nigeria
| | - Tolulope Ogundele
- Department of Paediatrics, Obafemi Awolowo University Teaching Hospital, Ile-Ife 220005, Nigeria
| | - Fatima Abdullahi
- Department of Paediatrics, Faculty of Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Main Campus, Zaria 810211, Nigeria
| | - Katherine M. Satrom
- Department of Pediatrics, Faculty of Medical School, School of Medicine, University of Minnesota, University of Minnesota Twin Cities Campus, Minneapolis, MN 55455, USA
| | - Caitlin J. Bakker
- Dr. John Archer Library and Archives, University of Regina, Regina, SK S4S 0A2, Canada
| | - Burton W. Lee
- National Institute of Health, Bethesda, MD 20892, USA
| | - Tina M. Slusher
- Department of Pediatrics, Faculty of Medical School, School of Medicine, University of Minnesota, University of Minnesota Twin Cities Campus, Minneapolis, MN 55455, USA
- Hennepin Healthcare, Minneapolis, MN 55415, USA
| |
Collapse
|
|
2
|
Akinyosoye G, Akinola IJ, Lamina AB, Akinsola CM. Peripheral arterial disease among children with type 1 diabetes mellitus in a Nigerian teaching hospital. J Pediatr Endocrinol Metab 2023; 36:378-383. [PMID: 36935567 DOI: 10.1515/jpem-2022-0504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/18/2023] [Indexed: 03/21/2023]
Abstract
OBJECTIVES The study aimed to determine the prevalence of PAD in children with T1DM and to correlate PAD with clinical characteristics in children with T1DM. METHODS A comparative cross-sectional study was conducted involving 90 subjects (forty-five with T1DM and 45 apparently healthy comparative subjects that were matched for age and gender). Systolic blood pressure was measured in all limbs using the pocket Doppler machine (Norton Doppler scan machine). Ankle brachial index (ABI) was calculated as a ratio of ankle to arm systolic blood pressure. Peripheral arterial disease was defined as ABI less than 0.9. RESULTS The prevalence of PAD was significantly higher in children with T1DM than in the matched comparison group (37.8% vs. 6.7%, p<0.001). Average values of waist circumference, hip circumference, weight, height and body mass index were comparable in subjects with TIDM and the comparison group (p>0.05). Subjects with PAD had a poorer glucose control evident by higher average values of glycated haemoglobin than those without PAD (13.47 ± 3.2% vs. 8.16 ± 2.3%, p<0.001). There is a strong negative correlation between ABI scores and glycated haemoglobin among subjects with T1DM (r=-0.626, p<0.001). CONCLUSIONS With these findings, it is recommended that screening for PAD in children who have T1DM and poor glycaemic control should be done early to prevent cardiovascular complications before they arise.
Collapse
Affiliation(s)
- Gbenga Akinyosoye
- Department of Paediatrics, Lagos State University Teaching Hospital, Lagos, Nigeria
| | - Ibironke Jadesola Akinola
- Department of Paediatrics, Lagos State University Teaching Hospital, Lagos, Nigeria
- Department of Paediatrics and Child Health, Lagos State University College of Medicine, Lagos, Nigeria
| | | | | |
Collapse
|
|
3
|
Exchange blood transfusion for hyperbilirubinaemia: Neonatal characteristics and short-term outcomes. SOUTH AFRICAN JOURNAL OF CHILD HEALTH 2022. [DOI: 10.7196/sajch.2022.v16i4.1794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background. Factors that have been associated with severe hyperbilirubinaemia requiring exchange blood transfusion (EBT) are early discharge, late preterm birth and haemolytic disease. Early discharge is a common practice in neonatal care, so it is important to identify and audit neonates who received EBT, in order to identify modifiable factors.
Objectives. To describe the characteristics and outcomes of infants requiring EBT.
Methods. We reviewed records of infants admitted with severe jaundice requiring EBT from January 2009 to December 2013. Descriptive analysis of characteristics, clinical presentation, laboratory findings and outcome at discharge was performed.
Results. A total of 150 neonates received EBT (30 per year), and 101 were reviewed. Of these, 34 (33.7%) were inpatients and 67 (66.3%) were new admissions (2.34/1 000 new admissions). The majority of neonates requiring EBT were born vaginally (86.1%), were late preterm births (20.8%) and were exclusively breastfed (82.2%). The median postnatal age at presentation was 5 days. Clinical signs suggestive of acute bilirubin encephalopathy were present in 24.8% of cases. Among mother-infant pairs with known blood groups, 9.3% and 70.4% had rhesus (Rh) and ABO incompatibility, respectively. A Coombs test was positive in 62.5% of those with Rh incompatibility compared with 31.7% of those with ABO incompatibility. A total of 6 patients (5.9%) died, all within 7 days of EBT, but none during EBT.
Conclusion. The majority of neonates requiring EBT presented post discharge after birth and had been born vaginally at term, suggesting early discharge after delivery. More than two-thirds of cases were related to ABO incompatibility. Screening for jaundice before discharge must be prioritised, especially for infants born to mothers who are Rh negative or ABO blood group O.
Collapse
|
|
4
|
Zhang R, Kang W, Zhang X, Shi L, Li R, Zhao Y, Zhang J, Yuan X, Liu S, Li W, Xu F, Cheng X, Zhu C. Outcome Analysis of Severe Hyperbilirubinemia in Neonates Undergoing Exchange Transfusion. Neuropediatrics 2022; 53:257-264. [PMID: 35038754 DOI: 10.1055/s-0041-1742156] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVE Severe neonatal hyperbilirubinemia can cause neurological disability or mortality if not effectively managed. Exchange transfusion (ET) is an efficient treatment to prevent bilirubin neurotoxicity. The purpose of this study was to evaluate outcomes in severe neonatal hyperbilirubinemia with ET and to identify the potential risk factors for poor outcomes. METHODS Newborns of ≥28 weeks of gestational age with severe hyperbilirubinemia who underwent ET from January 2015 to August 2019 were included. Demographic data were recorded and analyzed according to follow-up outcomes at 12 months of corrected age. Poor outcomes were defined as death due to bilirubin encephalopathy or survival with at least one of the following complications: cerebral palsy, psychomotor retardation (psychomotor developmental index < 70), mental retardation (mental developmental index < 70), or hearing impairment. RESULTS A total of 524 infants were eligible for recruitment to the study, and 62 infants were lost to follow-up. The outcome data from 462 infants were used for grouping analysis, of which 398 cases (86.1%) had normal outcomes and 64 cases (13.9%) suffered poor outcomes. Bivariate logistic regression analysis showed that peak total serum bilirubin (TSB) (odds ratio [OR] = 1.011, 95% confidence interval [CI] = 1.008-1.015, p = 0.000) and sepsis (OR = 4.352, 95% CI = 2.013-9.409, p < 0.001) were associated with poor outcomes of hyperbilirubinemia. Receiver operator characteristic curve analysis showed that peak TSB ≥452.9 µmol/L could predict poor outcomes of severe hyperbilirubinemia. CONCLUSION Peak TSB and sepsis were associated with poor outcomes in infants with severe hyperbilirubinemia, and peak TSB ≥452.9 µmol/L could predict poor outcomes.
Collapse
Affiliation(s)
- Ruili Zhang
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Wenqing Kang
- Department of Neonatology, Children's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Xiaoli Zhang
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Lina Shi
- Department of Neonatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Rui Li
- Department of Neonatology, Children's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Yanmei Zhao
- Department of Neonatology, Children's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Jing Zhang
- Department of Neonatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Xiao Yuan
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Shasha Liu
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Wenhua Li
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Falin Xu
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Xiuyong Cheng
- Department of Neonatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Changlian Zhu
- Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.,Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.,Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
5
|
Abolurin OO, Adekoya AO, Ogunlesi TA, Ajibola ED, Adekanye TE, Adeniran EM. Pattern of serum bilirubin changes following double volume exchange blood transfusion in neonates at a tertiary health facility in Nigeria. Pan Afr Med J 2021; 39:60. [PMID: 34422183 PMCID: PMC8363959 DOI: 10.11604/pamj.2021.39.60.26408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 05/12/2021] [Indexed: 11/11/2022] Open
Abstract
Introduction exchange blood transfusion (EBT) is a form of massive transfusion useful in rapidly reducing serum bilirubin levels, but serum bilirubin levels frequently rebound within hours of completing the procedure, due to equilibration of extravascular bilirubin as well as on-going hemolysis. The study was carried out to determine the pattern of reduction in serum bilirubin levels following EBT among neonates with severe hyperbilirubinemia, as well as the factors contributing to this pattern, so as to establish evidence-based expectations following EBT. Methods a retrospective descriptive study covering a two-year period in a Nigerian tertiary hospital. Details of the EBT procedures, including serial serum bilirubin levels, were obtained from the hospital records of all newborn babies who had double volume EBT done for severe hyperbilirubinaemia during the study period. Data was analyzed using the statistical software SPSS version 21.0. Results the mean total serum bilirubin (TSB) before EBT in the 36 babies was 17.9 ± 6.3 mg/dl. The mean percentage decrease in TSB immediately following EBT was 44.3 ± 10.2%. Six hours after EBT, TSB levels had increased from the immediate post-EBT values by an average of 57.5 ± 32.2%. Twenty-four hours after the procedure, TSB values in most (87.1%) cases were still higher than the immediate post-EBT values, but lower than the pre-EBT values. Post-EBT anemia was recorded among 33.3% of the babies. Conclusion EBT is effective in rapidly reducing serum bilirubin levels and preventing acute bilirubin encephalopathy in neonates with severe hyperbilirubinemia, despite the rebound increase that occurs in TSB values after the procedure.
Collapse
Affiliation(s)
| | | | - Tinuade Adetutu Ogunlesi
- Department of Paediatrics, Babcock University Teaching Hospital, Ilishan, Ogun State, Nigeria.,Department of Paediatrics, Olabisi Onabanjo University, Sagamu, Ogun State, Nigeria
| | | | | | - Eniola Mary Adeniran
- Nursing Services Unit, Department of Paediatrics, Babcock University Teaching Hospital, Ilishan, Ogun State, Nigeria
| |
Collapse
|
|
6
|
Olatunde OE, Christianah OA, Olarinre BA, Bidemi AA, Temidayo AA, Adebukola FO, Tolulope AO, Bamidele TA, Oludare OI, Simeon OO. Neonatal Jaundice: Perception of Pregnant Women Attending Antenatal Clinic at a Tertiary Hospital in Southwest, Nigeria. Glob Pediatr Health 2021; 7:2333794X20982434. [PMID: 33426182 PMCID: PMC7756043 DOI: 10.1177/2333794x20982434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 11/02/2020] [Accepted: 12/01/2020] [Indexed: 11/22/2022] Open
Abstract
Background: Severe neonatal jaundice (NNJ) remains a leading cause of preventable brain damage, mental handicap, physical disabilities, and early death among infants. Methods: Using a descriptive cross-sectional study design, information was gathered using a structured, pretested questionnaire from 518 pregnant women who attended the antenatal clinic at a tertiary Hospital in Southwest Nigeria. Results: Most (77%) of the respondents have heard about NNJ prior the survey. Most respondents (69.5%) demonstrated poor knowledge of the causes of NNJ. The majority, 98.4% had good attitude toward treatment of NNJ. Most respondents (72.1%) demonstrated poor knowledge of the correct treatment of NNJ. A quarter of the respondents knew no danger sign of NNJ. Conclusion: There is serious knowledge gap among the respondents about the causes, treatment, dangers signs and complications of NNJ. There is need for increased awareness campaign using every available means of reaching women of reproductive age group to reduce the consequences of this common neonatal problem.
Collapse
|
|
7
|
Rajan M, Singh J, Singh Dalal J. Exchange blood transfusion in neonates with severe hyperbilirubinemia in a lower-middle-income country: can we minimise the incidence? Trop Doct 2020; 51:146-150. [PMID: 32981475 DOI: 10.1177/0049475520959731] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Our descriptive study examines the clinical profile of referred neonates who underwent exchange blood transfusion (EBT) and identifies possible interventions at peripheral hospitals to decrease their severe hyperbilirubinemia. Among the 38 neonates enrolled, the following were identified as potential clinical gaps in management: early discharge within 24 h of birth (57%); non-availability of ABORh blood grouping (43%); lack of anti-D immunoprophylaxis (75%); pathological weight loss because of inadequate breastfeeding (42%); and low usage of phototherapy. Because of late recognition, the mean age at admission was 5.4 ± 3.3 days, levels of total serum bilirubin (TSB) were 516.4 ± 123.1 µmol/L, and acute bilirubin encephalopathy (ABE) was seen in 45% of neonates. Rh iso-immunisation (39.5%), ABO iso-immunisation (21%) and sepsis (8%) were major risk factors for severe hyperbilirubinaemia. Quality prenatal screening identifying at-risk newborns, preventing early discharge after birth, a bilirubin nomogram risk assignment before discharge and assuring early recognition of hyperbiliubinaemia by parents may well minimise the incidence of EBT.
Collapse
Affiliation(s)
- Mahima Rajan
- Senior Resident, Department of Pediatrics, PGIMS, Rohtak, Haryana, India
| | - Jasbir Singh
- Senior Resident, Department of Pediatrics, PGIMS, Rohtak, Haryana, India
| | - Jagjit Singh Dalal
- Associate Professor and Head, Department of Neonatology, PGIMS, Rohtak, Haryana, India
| |
Collapse
|
|
8
|
Abstract
PURPOSE OF REVIEW Infants of women with diabetes are at risk for specific morbidities including congenital anomalies, abnormalities of fetal growth, neonatal hypoglycemia, electrolyte abnormalities, polycythemia, hyperbilirubinemia, and respiratory distress syndrome. Recent studies have shed light on long-term outcomes of these infants and presented advances in treatment. The purpose of this review is to outline the most common neonatal morbidities affecting infants of women with diabetes, the pathophysiology and prevalence of these conditions, and contemporary approaches to treatment. RECENT FINDINGS Recent investigative findings have led to advances in treatment approaches for these infants, particularly regarding risks of neonatal hypoglycemia. Optimizing maternal glycemic control during pregnancy is imperative to improving infant outcomes. However, on a population level, maternal diabetes still poses significant risks to the infant. Timely and appropriate treatment of infants of women with diabetes is imperative to decrease short- and long-term morbidity.
Collapse
Affiliation(s)
- Sydney Peters
- Tufts University, 419 Boston Avenue, Medford, MA, USA
| | - Chloe Andrews
- Department of Newborn Medicine, Brigham & Women's Hospital, 75 Francis St, Boston, MA, USA
| | - Sarbattama Sen
- Department of Newborn Medicine, Brigham & Women's Hospital, 75 Francis St, Boston, MA, USA.
- Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
| |
Collapse
|
|
9
|
Amadi HO, Abdullahi RA, Mokuolu OA, Ezeanosike OB, Adesina CT, Mohammed IL, Olateju EK, Abubakar AL, Bello MA, Eneh AU, Onwe Ogah E, Eziechila BC, Chapp-Jumbo AU, Jimoh A, Udo JJ. Comparative outcome of overhead and total body phototherapy for treatment of severe neonatal jaundice in Nigeria. Paediatr Int Child Health 2020; 40:16-24. [PMID: 31142230 DOI: 10.1080/20469047.2019.1610607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Background: In Nigeria, neonatal jaundice is commonly treated by overhead phototherapy with neonates lying supine, often with effective exposure of less than one half of the body surface. Total body exposure in phototherapy has been in use for less than 2 years in Nigeria, but is available in only five neonatal centres.Aim: To compare the effectiveness of total body exposure (TBPE) with the conventional partial exposure (COPT) for treatment of hyperbilirubinaemia.Methods: Eleven datasets from 10 neonatal units across Nigeria were retrieved. They included neonates with severe hyperbilirubinaemia treated with TBPE using the Firefly® device (MTTS Asia) as a test group. The remainder of the patients, the controls, were treated with COPT. Any requirement for exchange blood transfusion (EBT) in either group was documented. Total serum bilirubin (TSB) >213.8 μmol/L (12.5 mg/dL) was treated as severe hyperbilirubinaemia. The efficiency of the intervention was determined according to the time taken for a severe case to be downgraded to mild at ≤213.8 μmol/L.Results: A total of 486 patients were studied, 343 controls and 143 cases. Mean (SD) postnatal age was 6 days (0.7) for cases and 5 (0.9) for controls, for gestational age (GA) in completed weeks was 36 (0.5) for cases and 37 (0.7) for controls and for birthweight was 2.7 kg (0.25) for cases and 2.7 (0.22) for controls. Mean (SD) pre-intervention TSB was 299.3 (35.7) μmol/L for cases and 327.3 (13.9) for controls. Severity downgrade day was Day 2 (0.4) for cases and Day 5 (1.1) for controls. Overall relative EBT rate was 6% for cases and 55% for controls (p= 0.0001), and early preterm relative EBT rate was 0% for cases and 68% for controls (p < 0.01).Conclusion: TBPE was quicker and safer for reduction of hyperbilirubinaemia and patients rarely required EBT. TBPE is recommended for rapid reduction of serum bilirubin levels and the reduction of treatment costs, morbidity and mortality in low- and middle-income countries.Abbreviations: EBT, exchange blood transfusion; TBPE, total body exposure technique; COPT, conventional partial exposure; TSB, total serum bilirubin; SB, serum bilirubin; NNJ, neonatal jaundice; SCNU, special care neonatal unit; LMIC, low- and middle-income countries; HIC, high-income countries; LED, light-emitting diode.
Collapse
Affiliation(s)
- Hippolite O Amadi
- Department of Bioengineering, Imperial College London, London, UK.,Neonatal Unit, Jummai Babangida Maternal and Neonatal Hospital, Minna, Nigeria
| | - Ruqayya A Abdullahi
- Neonatal Unit, Jummai Babangida Maternal and Neonatal Hospital, Minna, Nigeria
| | - Olugbenga A Mokuolu
- Department of Paediatrics, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | | | - Christiana T Adesina
- Department of Paediatrics, University of Abuja Teaching Hospital, Abuja, Nigeria
| | | | - Eyinade K Olateju
- Department of Paediatrics, University of Abuja Teaching Hospital, Abuja, Nigeria
| | - Amina L Abubakar
- Neonatal Unit, Jummai Babangida Maternal and Neonatal Hospital, Minna, Nigeria
| | - Mustapha A Bello
- Department of Paediatrics, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
| | - Augusta U Eneh
- Department of Paediatrics, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria
| | - Emeka Onwe Ogah
- Department of Paediatrics, Federal Teaching Hospital, Abakaliki, Nigeria
| | | | | | - Abdulrasheed Jimoh
- Department of Paediatrics, University of Calabar Teaching Hospital, Calabar, Nigeria
| | - Jacob J Udo
- Department of Paediatrics, University of Calabar Teaching Hospital, Calabar, Nigeria
| |
Collapse
|
|
10
|
Experimental models assessing bilirubin neurotoxicity. Pediatr Res 2020; 87:17-25. [PMID: 31493769 DOI: 10.1038/s41390-019-0570-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/29/2019] [Accepted: 08/16/2019] [Indexed: 02/08/2023]
Abstract
The molecular and cellular events leading to bilirubin-induced neurotoxicity, the mechanisms regulating liver and intestine expression in neonates, and alternative pathways of bilirubin catabolism remain incompletely defined. To answer these questions, researchers have developed a number of model systems to closely recapitulate the main characteristics of the disease, ranging from tissue cultures to engineered mouse models. In the present review we describe in vitro, ex vivo, and in vivo models developed to study bilirubin metabolism and neurotoxicity, with a special focus on the use of engineered animal models. In addition, we discussed the most recent studies related to potential therapeutic approaches to treat neonatal hyperbilirubinemia, ranging from anti-inflammatory drugs, activation of nuclear receptor pathways, blockade of bilirubin catabolism, and stimulation of alternative bilirubin-disposal pathways.
Collapse
|
|
11
|
Vodret S, Bortolussi G, Iaconcig A, Martinelli E, Tiribelli C, Muro AF. Attenuation of neuro-inflammation improves survival and neurodegeneration in a mouse model of severe neonatal hyperbilirubinemia. Brain Behav Immun 2018; 70:166-178. [PMID: 29458193 DOI: 10.1016/j.bbi.2018.02.011] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 02/06/2018] [Accepted: 02/15/2018] [Indexed: 01/21/2023] Open
Abstract
All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities. Current therapies rely on the use of phototherapy and, in unresponsive cases, exchange transfusion, which is performed only in specialized centers. During bilirubin-induced neurotoxicity different molecular pathways are activated, ranging from oxidative stress to endoplasmic reticulum (ER) stress response and inflammation, but the contribution of each pathway in the development of the disease still requires further investigation. Thus, to increase our understanding of the pathophysiology of bilirubin neurotoxicity, encephalopathy and kernicterus, we pharmacologically modulated neurodegeneration and neuroinflammation in a lethal mouse model of neonatal hyperbilirubinemia. Treatment of mutant mice with minocycline, a second-generation tetracycline with anti-inflammatory and neuroprotective properties, resulted in a dose-dependent rescue of lethality, due to reduction of neurodegeneration and neuroinflammation, without affecting plasma bilirubin levels. In particular, rescued mice showed normal motor-coordination capabilities and behavior, as determined by the accelerating rotarod and open field tests, respectively. From the molecular point of view, rescued mice showed a dose-dependent reduction in apoptosis of cerebellar neurons and improvement of dendritic arborization of Purkinje cells. Moreover, we observed a decrease of bilirubin-induced M1 microglia activation at the sites of damage with a reduction in oxidative and ER stress markers in these cells. Collectively, these data indicate that neurodegeneration and neuro-inflammation are key factors of bilirubin-induced neonatal lethality and neuro-behavioral abnormalities. We propose that the application of pharmacological treatments having anti-inflammatory and neuroprotective effects, to be used in combination with the current treatments, may significantly improve the management of acute neonatal hyperbilirubinemia, protecting from bilirubin-induced neurological damage and death.
Collapse
Affiliation(s)
- Simone Vodret
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy
| | - Giulia Bortolussi
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy.
| | - Alessandra Iaconcig
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy
| | - Elena Martinelli
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy
| | - Claudio Tiribelli
- Centro Studi Fegato, Fondazione Italiana Fegato, AREA Science Park, Campus Basovizza, Trieste, Italy
| | - Andrés F Muro
- International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149 Trieste, Italy.
| |
Collapse
|
|
12
|
Mabogunje CA, Olaifa SM, Olusanya BO. Facility-based constraints to exchange transfusions for neonatal hyperbilirubinemia in resource-limited settings. World J Clin Pediatr 2016; 5:182-90. [PMID: 27170928 PMCID: PMC4857231 DOI: 10.5409/wjcp.v5.i2.182] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 12/15/2015] [Accepted: 01/05/2016] [Indexed: 02/06/2023] Open
Abstract
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.
Collapse
|
|
13
|
Abstract
OBJECTIVES To identify the predictors of repeat exchange transfusion among infants with severe hyperbilirubinemia. DESIGN Retrospective cross-sectional study. SETTING A referral children's hospital in inner-city Lagos, Nigeria. PATIENTS Infants who received exchange transfusion for severe hyperbilirubinemia from January 2012 to December 2014. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS The predictors of repeat exchange transfusion were identified among all infants who had at least one exchange transfusion using multivariable logistic regression. A total of 352 infants with mean peak total serum bilirubin of 26.32 ± 7.96 mg/dL received exchange transfusion; of these, 49 (13.9%) with mean peak total serum bilirubin of 32.85 ± 10.54 mg/dL had repeat exchange transfusion. More than two thirds of infants who received exchange transfusion and repeat exchange transfusion were male, and at least one third had ABO incompatibility. No infant had more than two exchange transfusions. The mean age of admission was approximately 5 days (range, 1-14 d). Peak total serum bilirubin greater than or equal to 30 mg/dL (odds ratio, 2.88; 95% CI, 1.46-5.70) and acute bilirubin encephalopathy (odds ratio, 2.37; 95% CI, 1.18-4.77) were predictive of repeat exchange transfusion. CONCLUSIONS Acute bilirubin encephalopathy and excessive total serum bilirubin levels at least 30 mg/dL are predictive of repeat exchange transfusion. A risk assessment framework that combines total serum bilirubin levels, acute bilirubin encephalopathy status, and risk factors of neurotoxicity should be considered for the timely detection and monitoring of infants at risk of repeat exchange transfusion.
Collapse
|
|
14
|
|
|
15
|
Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia. Sci Rep 2015; 5:16203. [PMID: 26541892 PMCID: PMC4635426 DOI: 10.1038/srep16203] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 10/12/2015] [Indexed: 11/12/2022] Open
Abstract
Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required.
Collapse
|
|
16
|
Olusanya BO, Ogunlesi TA, Kumar P, Boo NY, Iskander IF, de Almeida MFB, Vaucher YE, Slusher TM. Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings. BMC Pediatr 2015; 15:39. [PMID: 25884679 PMCID: PMC4409776 DOI: 10.1186/s12887-015-0358-z] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Accepted: 03/30/2015] [Indexed: 11/16/2022] Open
Abstract
Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels.
Collapse
MESH Headings
- Critical Pathways
- Developing Countries
- Exchange Transfusion, Whole Blood
- Humans
- Hyperbilirubinemia, Neonatal/complications
- Hyperbilirubinemia, Neonatal/diagnosis
- Hyperbilirubinemia, Neonatal/therapy
- Infant, Newborn
- Infant, Premature
- Infant, Premature, Diseases/diagnosis
- Infant, Premature, Diseases/therapy
- Phototherapy
- Poverty
- Practice Guidelines as Topic
- Primary Prevention
Collapse
Affiliation(s)
- Bolajoko O Olusanya
- Centre for Healthy Start Initiative, 286A, Corporation Drive, Dolphin Estate, Ikoyi, Lagos, Nigeria.
| | - Tinuade A Ogunlesi
- Department of Paediatrics, Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria.
| | - Praveen Kumar
- Department of Paediatrics, Neonatal Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
| | - Nem-Yun Boo
- Department of Population Medicine, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Bandar Sungai Long, Selangor, Malaysia.
| | | | | | - Yvonne E Vaucher
- Division of Neonatal/Perinatal Medicine, School of Medicine, University of California at San Diego, San Diego, USA.
| | - Tina M Slusher
- Division of Global Paediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
- Hennepin County Medical Centre, Minneapolis, Minnesota, USA.
| |
Collapse
|
|
17
|
Han GY, Li CY, Shi HB, Wang JP, Su KM, Yin XL, Yin SK. Riluzole is a promising pharmacological inhibitor of bilirubin-induced excitotoxicity in the ventral cochlear nucleus. CNS Neurosci Ther 2014; 21:262-70. [PMID: 25495717 DOI: 10.1111/cns.12355] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 10/15/2014] [Accepted: 10/20/2014] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND AND PURPOSE Bilirubin encephalopathy as a result of hyperbilirubinemia is a devastating neurological disorder that occurs mostly in the neonatal period. To date, no effective drug treatment is available. Glutamate-mediated excitotoxicity is likely an important factor causing bilirubin encephalopathy. Thus, drugs suppressing the overrelease of glutamate may protect the brain against bilirubin excitotoxicity. Riluzole is a prescription drug known for its antiglutamatergic function. This study was conducted in the rat's ventral cochlear nucleus, a structure highly sensitive to bilirubin toxicity, to find whether riluzole can be used to inhibit bilirubin toxicity. EXPERIMENTAL APPROACH Electrophysiology changes were detected by perforated patch clamp technique. Calcium imaging using Rhod-2-AM as an indicator was used to study the intracellular calcium. Cell apoptosis and necrosis were measured by PI/Hoechst staining. KEY RESULTS In the absence of bilirubin, riluzole effectively decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and suppressed neuronal firing but did not change the amplitude of sEPSC and glutamate-activated currents (I(Glu)). Moreover, riluzole inhibited bilirubin-induced increases in the frequency of sEPSC and neuronal firing. Riluzole could prevent the bilirubin-induced increase in intracellular calcium, mediated by AMPA and NMDA receptors. Furthermore, riluzole significantly reduced bilirubin-induced cell death. CONCLUSIONS AND IMPLICATIONS These data suggest that riluzole can protect neurons in the ventral cochlear nucleus from bilirubin-induced hyperexcitation and excitotoxicity through reducing presynaptic glutamate release.
Collapse
Affiliation(s)
- Guo-Ying Han
- Department of Otorhinolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | | | | | | | | | | | | |
Collapse
|