Scientific Letter
Neonatal haemochromatosis: 10 years into a paradigm shift
Hemocromatosis neonatal. Diez años en un cambio de paradigma
Elena García Victori
, Raquel Mañas, Yolanda Castilla Fernández, Cèsar W. Ruiz Campillo, Félix Castillo Salinas
Corresponding author
Servicio de Neonatología, Hospital Vall d’Hebron, Barcelona, Spain
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Ruiz Campillo, Félix Castillo Salinas" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Elena" "apellidos" => "García Victori" "email" => array:1 [ 0 => "e.gvictori@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Raquel" "apellidos" => "Mañas" ] 2 => array:2 [ "nombre" => "Yolanda" "apellidos" => "Castilla Fernández" ] 3 => array:2 [ "nombre" => "Cèsar W." "apellidos" => "Ruiz Campillo" ] 4 => array:2 [ "nombre" => "Félix" "apellidos" => "Castillo Salinas" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neonatología, Hospital Vall d’Hebron, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hemocromatosis neonatal. Diez años en un cambio de paradigma" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 660 "Ancho" => 1583 "Tamanyo" => 369330 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Haematoxylin–eosin stain. Giant cell hepatitis with extensive fibrosis and cholestasis. (B) Perls’ Prussian blue. Iron deposition in the liver.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Neonatal haemochromatosis (NH) is the leading cause of acute liver failure in the neonatal period.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Recent discoveries on its aetiology and pathogenesis have led to a radical shift in its management and prognosis.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,2</span></a> In 95% of cases, the aetiology involves an alloimmune disease occurring in the gestational period.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3</span></a> The clinical presentation of NH varies widely and is nonspecific. The classic presentation includes hypoglycaemia, jaundice and coagulopathy. The definitive diagnosis is based on the detection of iron accumulation in extrahepatic tissues<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> through examination of biopsy samples or magnetic resonance imaging (MRI). Immunochemical evidence of complement-mediated liver injury is characteristic of gestational alloimmune liver disease (GALD).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> Traditional treatment (iron chelators and antioxidants) was associated with a survival of less than 20%, and patients typically required a liver transplant.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> New treatments (exchange transfusion and intravenous immunoglobulin therapy [IVIG]) have increased survival without transplantation to 75%.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> The most important change is that prenatal prevention has now become possible with administration of IVIG during pregnancy, with an efficacy nearing 100%,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> once the diagnosis of GALD is confirmed.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The aim of the review presented here was to analyse the cases of NH managed in our department in a period of 10 years and to assess the impact of recent advances in terms of patient outcomes and survival. We conducted a retrospective study by reviewing the cases of NH diagnosed between January 2005 and December 2014 in our hospital. We collected data on gestational age and birth weight, family history, obstetric history (including findings of prenatal ultrasound examinations), clinical manifestations and timing of onset, manifestations during the course of the disease, laboratory abnormalities, findings of imaging tests, comorbidities, histopathological features, time elapsed to diagnosis, treatment received and patient outcomes.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We identified 6 cases of NH in the past 10 years (4 in girls and 2 in boys). There was no relevant family history in any case. All mothers were healthy, all but one had had previous pregnancies, and 3 had a history of miscarriage. In 4 cases, there was a history of oligohydramnios and in 3 cases a history of intrauterine growth restriction. Three of the patients were born preterm and another 3 were small for gestational age.</p><p id="par0020" class="elsevierStylePara elsevierViewall">There was considerable variation in the clinical presentation. Three patients had onset within 24<span class="elsevierStyleHsp" style=""></span>h from birth with jaundice and exhibited progressive liver injury. Another patient required admission to the neonatal intensive care unit due to extreme prematurity and developed hepatomegaly and cholestasis at 12 days post birth, with subsequent progression of liver injury. Another patient was admitted due to a prenatal diagnosis of congenital heart disease and dysmorphic features, and developed refractory shock of unknown origin, oliguria and liver failure in the first hours of life. The last patient presented with refractory shock and multiple organ failure from birth and had a fulminant progression that led to death 5 days post birth. All patients had kidney failure. Two patients had hypothyroidism, one of them associated with pancreatic insufficiency. All had anaemia, 4 had thrombocytopenia and 1 pancytopenia. There was a moderate transaminase elevation. All patients had coagulopathy, cholestasis, hypoalbuminemia, elevation of serum ferritin and iron and saturation of transferrin and α-fetoprotein. The initial abdominal ultrasound scan was normal in 4 patients, with abnormal findings in subsequent scans. Four patients underwent an MRI examination, which evinced iron overload in the liver and pancreas.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The diagnosis was made by examination of open liver (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and oral mucosa biopsy samples in 5 patients, and during the post-mortem examination in the remaining patient. In one of the patients, the diagnosis was also made based on the positive results of immunohistochemical analysis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">As regards treatment, 3 patients received exchange transfusions and 2 received IVIG. Three were treated with antioxidants and iron chelators. All patients showed a limited response to treatment. Two of the patients treated most recently received a liver transplant, and they are the patients that have survived to present. All other patients died (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The mother of one of the patients received prenatal preventive treatment in the following pregnancy and gave birth to a healthy child.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The findings of our review are mostly consistent with other reports in the literature with a few exceptions. There is no previous description of the comorbidities we found in 2 of the patients (hypothyroidism and pancreatic insufficiency), and we believe they may be of interest, as they could be related to the alloimmune aetiology. Also, survival without transplantation in our patients was not as good as reported by other authors, while the age at diagnosis and the time of treatment initiation were similar to those described in other case series.</p><p id="par0040" class="elsevierStylePara elsevierViewall">To conclude, in the past few years neonatal haemochromatosis has gone from being an untreatable orphan disease to a preventable and curable disease. A high level of suspicion for this diagnosis is key to initiate treatment that has proven effective as early as possible. Diagnosis of this disease is essential for its prevention in future generations.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: García Victori E, Mañas R, Castilla Fernández Y, Ruiz Campillo CW, Castillo Salinas F. Hemocromatosis neonatal. Diez años en un cambio de paradigma. An Pediatr (Barc). 2019;91:124–126.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 660 "Ancho" => 1583 "Tamanyo" => 369330 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Haematoxylin–eosin stain. Giant cell hepatitis with extensive fibrosis and cholestasis. (B) Perls’ Prussian blue. Iron deposition in the liver.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine aminotransferase; AST, aspartate aminotransferase; dpb, days post birth; GA, gestational age; IVIG, intravenous immunoglobulin therapy.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GA (weeks) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Weight (g) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age at onset \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical features at onset \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comorbidities \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Peak total/direct bilirubin (mg/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PeakAST/ALT(IU/L) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age at diagnosis (dpb) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Transplant \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Death (dpb) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">610 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12<span class="elsevierStyleHsp" style=""></span>dpb \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abdominal distension, hepatomegaly and cholestasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11/10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29/21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Supportive care \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes (67) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2290 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First 24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shock, anasarca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dysmorphic features and heart disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30/20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">199/63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ChelatorsAntioxidants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes (>134) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2650 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First 24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Jaundice \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52/36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1445/260 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ChelatorsAntioxidants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes (85) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2360 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First 24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Episodes of hypoglycaemia, hepatomegaly, jaundice, ascites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HypothyroidismPancreatic insufficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25/20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">229/110 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>Exchange transfusionIVIG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First 24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shock, anasarca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">115/38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Post mortem</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>Exchange transfusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes (5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2370 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First 24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oedema, jaundice \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37/23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100/37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>Exchange transfusionIVIGChelatorsAntioxidants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2096136.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Early: prior to 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 2 | 4 |
| 2024 October | 56 | 33 | 89 |
| 2024 September | 59 | 33 | 92 |
| 2024 August | 90 | 56 | 146 |
| 2024 July | 102 | 21 | 123 |
| 2024 June | 91 | 24 | 115 |
| 2024 May | 70 | 34 | 104 |
| 2024 April | 87 | 27 | 114 |
| 2024 March | 92 | 20 | 112 |
| 2024 February | 75 | 27 | 102 |
| 2024 January | 53 | 22 | 75 |
| 2023 December | 66 | 19 | 85 |
| 2023 November | 71 | 33 | 104 |
| 2023 October | 64 | 26 | 90 |
| 2023 September | 56 | 27 | 83 |
| 2023 August | 45 | 16 | 61 |
| 2023 July | 88 | 35 | 123 |
| 2023 June | 56 | 27 | 83 |
| 2023 May | 64 | 22 | 86 |
| 2023 April | 60 | 22 | 82 |
| 2023 March | 72 | 26 | 98 |
| 2023 February | 69 | 17 | 86 |
| 2023 January | 50 | 18 | 68 |
| 2022 December | 87 | 24 | 111 |
| 2022 November | 66 | 36 | 102 |
| 2022 October | 78 | 42 | 120 |
| 2022 September | 61 | 17 | 78 |
| 2022 August | 90 | 54 | 144 |
| 2022 July | 78 | 59 | 137 |
| 2022 June | 77 | 31 | 108 |
| 2022 May | 79 | 47 | 126 |
| 2022 April | 105 | 39 | 144 |
| 2022 March | 108 | 61 | 169 |
| 2022 February | 106 | 38 | 144 |
| 2022 January | 101 | 38 | 139 |
| 2021 December | 59 | 39 | 98 |
| 2021 November | 105 | 48 | 153 |
| 2021 October | 127 | 70 | 197 |
| 2021 September | 80 | 43 | 123 |
| 2021 August | 69 | 42 | 111 |
| 2021 July | 68 | 33 | 101 |
| 2021 June | 46 | 48 | 94 |
| 2021 May | 59 | 45 | 104 |
| 2021 April | 157 | 78 | 235 |
| 2021 March | 78 | 26 | 104 |
| 2021 February | 57 | 26 | 83 |
| 2021 January | 54 | 22 | 76 |
| 2020 December | 73 | 25 | 98 |
| 2020 November | 72 | 20 | 92 |
| 2020 October | 63 | 22 | 85 |
| 2020 September | 69 | 19 | 88 |
| 2020 August | 89 | 19 | 108 |
| 2020 July | 154 | 16 | 170 |
| 2020 June | 56 | 9 | 65 |
| 2020 May | 89 | 16 | 105 |
| 2020 April | 53 | 12 | 65 |
| 2020 March | 70 | 15 | 85 |
| 2020 February | 127 | 22 | 149 |
| 2020 January | 69 | 15 | 84 |
| 2019 December | 47 | 16 | 63 |
| 2019 November | 55 | 6 | 61 |
| 2019 October | 44 | 14 | 58 |
| 2019 September | 40 | 11 | 51 |
| 2019 August | 56 | 19 | 75 |
| 2019 July | 36 | 16 | 52 |
| 2019 June | 4 | 2 | 6 |
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