RESUMO
Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.
Assuntos
Eritroblastose Fetal , Imunoglobulinas Intravenosas , Incompatibilidade de Grupos Sanguíneos , Eritroblastose Fetal/tratamento farmacológico , Transfusão Total , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Recém-Nascido , FototerapiaAssuntos
Hiperbilirrubinemia Neonatal , Icterícia Neonatal , Bilirrubina , Feminino , Humanos , Recém-Nascido , Nomogramas , GravidezRESUMO
OBJECTIVES: To determine, as part of our Utah Newborn Nursery Bilirubin Management Program, whether end-tidal carbon monoxide concentration (ETCOc) measurements in all newborns in our nursery receiving phototherapy were associated with outcomes related to the management of hyperbilirubinemia, including time (hours after birth) when phototherapy was initiated, total duration of phototherapy during the nursery stay, repeat phototherapy treatments, and hospital readmission for phototherapy. STUDY DESIGN: We performed a planned interim analysis of a component of our program in which we measured ETCOc noninvasively using CoSense on each newborn in our nursery receiving phototherapy and recorded specific outcomes related to phototherapy management. RESULTS: Of 1856 newborns admitted to our nursery in a 6-month period in 2020, 170 (9.8%) were treated with phototherapy. An ETCOc reading was successfully obtained in 145 of 151 attempts (96%). Higher ETCOc values were associated with earlier institution of phototherapy and longer duration of phototherapy. For every 1-ppm increase in ETCOc, phototherapy was started 9 hours earlier (95% CI, 3.3-14.8; P = .002) and was administered for an additional 9.3 hours (95% CI, 4.1-14.6; P < .001). Three newborns were readmitted to the hospital for intensive phototherapy; while in the nursery, all 3 had an elevated ETCOc (2.2, 2.6, and 2.9 ppm). CONCLUSIONS: Our findings provide answers to questions raised in the 2004 American Academy of Pediatrics bilirubin guidelines. In our neonatal nursery, measuring ETCOc in all phototherapy recipients was feasible and safe, and the results were associated with multiple aspects of phototherapy management. Higher ETCOc values predicted earlier and longer phototherapy courses.
Assuntos
Monitorização Transcutânea dos Gases Sanguíneos/métodos , Monóxido de Carbono/análise , Hiperbilirrubinemia Neonatal/sangue , Fototerapia/métodos , Testes Diagnósticos de Rotina , Estudos de Viabilidade , Feminino , Humanos , Recém-Nascido , Masculino , Melhoria de QualidadeRESUMO
OBJECTIVE: To develop a statistically rigorous, hour-specific bilirubin nomogram for newborns based on a very large data set; and use it prospectively as a replacement for the 1999 Bhutani nomogram. STUDY DESIGN: This was a retrospective analysis of first total serum bilirubin (TSB) measurements from 15 years of universal bilirubin screening during birth hospitalizations at 20 Intermountain Healthcare hospitals. Hour-specific TSB values were assembled into a nomogram by percentile, and subgroups were compared. RESULTS: The information obtained included robust data in the first 12 hours after birth (which was not included in the 1999 nomogram), general agreement with the 1999 nomogram for values in the first 60 hours, but higher 75th and 95th percentile TSB values thereafter in the new version, no difference in TSB between male and female infants, higher TSB values among earlier gestation neonates (350/7-366/7 weeks vs ≥37 weeks, P < .0001), and lower TSB values in neonates of Black race (P < .0001) and higher values in neonates of Asian race (P < .001). CONCLUSIONS: An updated and more informative Bhutani neonatal bilirubin nomogram, based on 140 times the number of subjects included the 1999 version, is now in place in our health care system.
Assuntos
Bilirrubina/sangue , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/diagnóstico , Fatores Etários , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Triagem Neonatal , Nomogramas , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de TempoRESUMO
In order to reduce iron deficiency in neonates at-risk for iron deficiency, we implemented a guideline to increase the consistency of early iron supplementation in infants of diabetic mothers, small for gestational age neonates and very low birthweight premature neonates. Three years following implementation we performed a retrospective analysis in order to assess adherence to the guideline and to compare timing of early iron supplementation and reticulocyte-hemoglobin (RET-He) values at one month of life in at-risk infants. Adherence with early iron supplementation guidelines was 73.4% (399/543) with 51% (275/543) having RET-He values obtained at one month. Despite good adherence, 16% (44/275) had RET-He <25 pg (5th percentile for gestational age). No infants receiving red blood cell transfusion (0/20) had RET-He <25 pg vs. 26.1% (40/153) of those treated with darbepoetin (p < 0.001). There was no evidence of increased feeding intolerance (episodes of emesis/day) with early iron supplementation.
Assuntos
Unidades de Terapia Intensiva Neonatal , Deficiências de Ferro/tratamento farmacológico , Ferro/administração & dosagem , Feminino , Humanos , Recém-Nascido , Ferro/efeitos adversos , Deficiências de Ferro/sangue , Masculino , Estudos RetrospectivosRESUMO
In a two-part process, we assessed elements of the principal hormonal pathway regulating iron homeostasis in human neonates. Part 1: Quantifying erythropoietin (Epo), erythroferrone (ERFE), hepcidin, and relevant serum and erythrocytic iron-related metrics in umbilical cord blood from term (n = 13) and preterm (n = 10) neonates, and from neonates born to mothers with diabetes and obesity (n = 13); Part 2: Quantifying serum Epo, ERFE, and hepcidin before and following darbepoetin administration. Part 1: We measured Epo, ERFE and hepcidin in all cord blood samples. Epo and ERFE levels did not differ between the three groups. Preterm neonates had the lowest hepcidin levels, while neonates born to diabetic women with a very high BMI had the lowest ferritin and RET-He levels. Part 2: Following darbepoetin dosing, ERFE levels generally increased (p < 0.05) and hepcidin levels generally fell (p < 0.05). Our observations suggest that the Epo/ERFE/hepcidin axis is intact in the newborn period.
Assuntos
Eritropoetina/sangue , Hepcidinas/sangue , Hormônios Peptídicos/sangue , Transdução de Sinais , Eritropoetina/metabolismo , Feminino , Sangue Fetal/metabolismo , Hepcidinas/metabolismo , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Obesidade/sangue , Obesidade/metabolismo , Hormônios Peptídicos/metabolismo , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/metabolismo , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/metabolismo , Nascimento Prematuro/sangue , Nascimento Prematuro/metabolismoRESUMO
OBJECTIVE: To quantify the risk that transcutaneous bilirubin (TcB) screening would fail to recommend phototherapy for a neonate who would have qualified for it if total serum bilirubin (TSB) screening were used. STUDY DESIGN: We conducted a quality improvement project where simultaneous TcB and TSB were obtained on neonates ≥35 weeks of gestation during birth hospitalizations in our hospital system. Using our Utah bilirubin management algorithm, we quantified the risk that TcB screening would fail to identify the need for a confirmatory TSB when TSB screening alone would have revealed that phototherapy was indicated. RESULTS: In 3 hospitals, we obtained 727 paired TcB/TSB measurements. Two instances utilized a blood gas radiometer for TSB, and 725 utilized the clinical laboratory-based TSB method. One of the 727 instances had a TcB indicating NO PHOTOTHERAPY, when the simultaneous TSB indicated PHOTOTHERAPY NEEDED. The TSB from that instance was 1 of the 2 from the blood gas radiometer. We estimate the risk of such an error occurring is 1.4 per 1000 TcB measurements (95% CI 0.03-7.6 per 1000). When only the laboratory TSB is used, we estimate the risk of such an error occurring to be 0 per 1000 TcB measurements (95% CI 0.0-5.1 per 1000). CONCLUSIONS: Using TcB for screening at the birth hospital can identify those qualifying for phototherapy, using the Utah guidelines, with 1 of 727 neonates with a blood gas bilirubin and none of 725 with a laboratory-based analysis misidentified as not needing phototherapy when by TSB they did.
Assuntos
Bilirrubina/sangue , Atenção à Saúde/normas , Recém-Nascido Prematuro/sangue , Icterícia Neonatal/sangue , Triagem Neonatal/métodos , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Icterícia Neonatal/diagnóstico , Masculino , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare total serum bilirubin (TSB) levels, phototherapy usage, and hospital readmission for jaundice among neonates with Down syndrome vs controls. STUDY DESIGN: A retrospective cohort study using 15 years of multihospital data. We created control reference intervals (5th, median, and 95th percentiles) for initial TSB values hourly during the first days after birth, and determined the proportion of neonates with Down syndrome whose TSB exceeded the 95th percentile control interval. We determined the proportion with an initial TSB exceeding the upper control reference interval, the highest TSB recorded, the percentage of neonates receiving phototherapy, and the rate of hospital readmission for jaundice treatment. RESULTS: We compared 357 neonates with Down syndrome with 377 368 controls. Compared with controls, those with Down syndrome had 4.7 times the risk (95% CI, 3.9-5.7; P < .0001) of an initial TSB exceeding the 95th percentile control interval (23.5% vs 5.0%), 8.9 times (95% CI, 8.1-9.8; P < .0001) the phototherapy usage (62.2% vs 7.0%), and 3.6 times (95% CI, 1.6-8.2; P = .0075) the readmission rate for jaundice (17.4 vs 4.8 per 1000 live births). CONCLUSIONS: Neonates with Down syndrome have a substantial risk of early hyperbilirubinemia. The American Academy of Pediatrics currently advises obtaining an early screening complete blood count from neonates with Down syndrome. We submit that assessing their TSB is also advisable.
Assuntos
Síndrome de Down/complicações , Hiperbilirrubinemia Neonatal/complicações , Fatores Etários , Bilirrubina/sangue , Estudos de Coortes , Síndrome de Down/sangue , Feminino , Humanos , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/epidemiologia , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Masculino , Readmissão do Paciente/estatística & dados numéricos , Fototerapia , Valores de Referência , Estudos Retrospectivos , Medição de RiscoAssuntos
Eritroblastose Fetal/epidemiologia , Hiperbilirrubinemia Neonatal/diagnóstico , Fototerapia , Sistema ABO de Grupos Sanguíneos , Bilirrubina/sangue , Incompatibilidade de Grupos Sanguíneos , Prestação Integrada de Cuidados de Saúde , Registros Eletrônicos de Saúde , Eritroblastose Fetal/prevenção & controle , Humanos , Hiperbilirrubinemia Neonatal/epidemiologia , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Triagem Neonatal , Fototerapia/estatística & dados numéricos , UtahRESUMO
AIM: To identify neonates at risk of haemolytic hyperbilirubinaemia through near-concurrent measurements of total serum/plasma bilirubin (TB) or transcutaneous bilirubin (TcB) and end-tidal breath carbon monoxide (CO), corrected for ambient CO (ETCOc), an index of bilirubin production and haemolysis. METHODS: Paired TB/TcB (mg/dL) and ETCOc (ppm) measurements were obtained in newborns (n = 283) at 20 to <60 hours of age in five nurseries. TB/TcB values were assigned TB/TcB percentile risk values using the Bhutani hour-specific nomogram. In infants having two serial TB/TcB measurements (n = 76), TB rate of rise (ROR, mg/dL/h) was calculated. RESULTS: For the entire cohort (n = 283), 67.1% and 32.9% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.79 ± 1.84 vs 9.14 ± 2.25 mg/dL) and ETCOc (1.61 ± 0.45 vs 2.02 ± 1.35 ppm, p = 0.0002) were different between the groups. About 36.6% of infants with TB/TcB ≥75th percentile had ETCOc ≥ 2.0 ppm. In the subcohort of infants with serial TB/TcB measurements (n = 76), 44.7% and 55.3% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.28 ± 1.97 vs 9.53 ± 2.78 mg/dL), ETCOc (1.72 ± 0.48 vs 2.38 ± 1.89 ppm, p = 0.05) and TB ROR (0.011 ± 0.440 vs 0.172 ± 0.471 mg/dL/h) were different between the groups. CONCLUSION: The combined use of TB/TcB percentile risk assessments and ETCOc measurements can identify infants with haemolytic hyperbilirubinaemia. The addition of TB ROR can identify those infants with elimination disorders.
Assuntos
Bilirrubina/sangue , Monóxido de Carbono/análise , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/terapia , Triagem Neonatal/métodos , Fototerapia/métodos , Análise de Variância , Estudos de Coortes , Feminino , Idade Gestacional , Hemólise/fisiologia , Humanos , Recém-Nascido , Masculino , Berçários para Lactentes , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Volume de Ventilação Pulmonar , Resultado do TratamentoRESUMO
Various mutations in the genes encoding alpha spectrin (SPTA1) or beta spectrin (SPTB) are known to cause erythrocyte membrane disorders, sometimes associated with severe neonatal jaundice and anemia. We used a next-generation sequencing panel to evaluate 3 unrelated neonates who had puzzling cases of nonimmune hemolytic jaundice. In each case, we identified novel mutations in either SPTA1 or SPTB. Correlating erythrocyte morphology, clinical course, and computational analysis, we submit that each of the 3 variants is a probable pathogenic cause of the hereditary hemolytic conditions in these patients. We hope other pediatric practitioners caring for neonates with what appears to be idiopathic severe neonatal hyperbilirubinemia will look for spectrin variants as a possible cause, because additional cases with these specific variants along with this clinical phenotype are needed to confirm our postulate that these 3 cases are indeed pathogenic mutations.
Assuntos
Eliptocitose Hereditária/genética , Icterícia Neonatal/genética , Mutação/genética , Espectrina/genética , Esferocitose Hereditária/complicações , Adulto , Eliptocitose Hereditária/complicações , Feminino , Humanos , Recém-Nascido , Icterícia Neonatal/complicações , Icterícia Neonatal/terapia , Masculino , FototerapiaRESUMO
Professional societies have published recommendations for iron dosing of preterm neonates, but differences exist between guidelines. To help develop standardized guidelines, we performed a 10-year analysis of iron dosing in groups at risk for iron deficiency: IDM (infants of diabetic mothers), SGA (small for gestational age), and VLBW premature neonates (very low birth weight, <1500 g). We analyzed iron dosing after red cell transfusions and erythropoiesis-stimulating agents (ESA). Of IDM, 11.8% received iron in the hospital; 9.8% of SGA and 27.1% of VLBW neonates received iron. Twenty percent of those who received iron had it started by day 14; 63% by 1 month. Supplemental iron was stopped after red cell transfusions in 73% of neonates receiving iron. An ESA was administered to 1677, of which 33% received iron within 3 days. This marked variation indicates that a consistent approach is needed, and using this report and a literature review, we standardized our iron-dosing guidelines.
RESUMO
BACKGROUND: Our previous retrospective study suggested that red blood cell (RBC) transfusion of preterm neonates can be associated with an increase in bilirubin, but this has not been tested prospectively. STUDY DESIGN AND METHODS: We studied neonates before and after RBC transfusions, recording serial bilirubin levels and whether they qualified for phototherapy. Because lysed RBCs release plasma-free hemoglobin (Hb), a precursor to bilirubin, we also measured plasma free Hb and bilirubin from the donor blood. RESULTS: We studied 50 transfusions given to 39 neonates. Gestation ages of transfused neonates, at birth, were 26 (24-29) weeks (median [interquartile range]); birthweights were 750 (620-1070) g. The study transfusion was given on Day of Life 9.9 (3.4-19.2). In 20% (10/50) phototherapy was being administered at the beginning of and during the transfusion. In these patients neither the 4- to 6- nor the 24- to 36-hour-posttransfusion bilirubin levels were significantly higher than before transfusion. However, in 30% of the others (12/40) phototherapy was started (or restarted) after the transfusion and 15% had a posttransfusion bilirubin increase of at least 2.5 mg/dL. These neonates received donor blood with a higher plasma-free Hb (p < 0.05). CONCLUSIONS: Neonates commonly qualify for phototherapy after transfusion. A minority (15% in this series) have a posttransfusion bilirubin increase of at least 2.5 mg/dL. We speculate that neonates qualifying for a RBC transfusion, who are judged to be at high risk for bilirubin-induced neurotoxicity, might benefit from checking their serum bilirubin level after the transfusion and providing donor blood with low plasma-free Hb levels.
Assuntos
Bilirrubina/sangue , Transfusão de Eritrócitos/métodos , Fototerapia/estatística & dados numéricos , Feminino , Idade Gestacional , Hemoglobinas/análise , Hemólise , Humanos , Recém-Nascido , Masculino , Fototerapia/métodos , Estudos RetrospectivosRESUMO
Hemolysis can be an important cause of hyperbilirubinemia in premature and term neonates. It can result from genetic abnormalities intrinsic to or factors exogenous to normal to red blood cells (RBCs). Hemolysis can lead to a relatively rapid increase in total serum/plasma bilirubin, hyperbilirubinemia that is somewhat slow to fall with phototherapy, or hyperbilirubinemia that is likely to rebound after phototherapy. Laboratory methods for diagnosing hemolysis are more difficult to apply, or less conclusive, in preterm infants. Transfusion of donor RBCs can present a bilirubin load that must be metabolized. Genetic causes can be identified by next-generation sequencing panels.
Assuntos
Bilirrubina/metabolismo , Morte Celular , Eritrócitos , Hemólise , Hiperbilirrubinemia Neonatal/metabolismo , Transfusão de Sangue , Humanos , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Recém-Nascido Prematuro , FototerapiaRESUMO
BACKGROUND: It is not clear whether red blood cell (RBC) transfusions typically increase a neonate's total serum bilirubin (TSB) level or if so by how much. STUDY DESIGN AND METHODS: In this retrospective analysis, from 2009 through 2012, we collected TSB measurements before and after transfusions, recording blood types of mothers, neonates, and blood donors and whether phototherapy was used before, during, or after transfusion. RESULTS: Of 7272 neonates admitted during this period, 658 (9%) received 2597 RBC transfusions. TSB levels were drawn before and after 431 transfusions, 255 of which did not have phototherapy at the time the transfusion was administered. The mean increase in TSB was 2.2 mg/dL (95% confidence interval, 1.9-2.5 mg/dL). Seven percent of all transfusions and 12% of transfusions to very-low-birthweight (VLBW) infants (<1500 g) were followed by a TSB increase of at least 5 mg/dL. Transfusions with "universal donor" blood (O-) resulted in a higher TSB increase (p < 0.0001), but the magnitude was clinically insignificant (0.3 mg/dL). Older blood (days since donor draw) did not generate significantly higher posttransfusion TSB levels (p = 0.092). A focused study of the 10 neonates with the highest TSB increases revealed that six were unexplained other than transfusion related. CONCLUSIONS: We describe an association between RBC transfusion and TSB elevation, but we recognize that this does not establish a cause-and-effect relationship. However, the observation that an increase of at least 5 mg/dL occurs after 12% of transfusions to VLBW neonates suggests to us that clinicians will want to evaluate jaundice, or measure bilirubin, on VLBW neonates after transfusion.
Assuntos
Bilirrubina/sangue , Doadores de Sangue , Transfusão de Eritrócitos/efeitos adversos , Icterícia/sangue , Icterícia/etiologia , Adulto , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Fototerapia , Estudos RetrospectivosRESUMO
We cared for a neonate who had problematic hyperbilirubinemia born into a family where nine first-degree relatives had hereditary elliptocytosis (HE). As neonates, the nine relatives did not have any significant jaundice or anemia that was recognizable. Blood films on the proband suggested a diagnosis of pyropoikilocytosis. Analysis of the α-spectrin gene (SPTA1) in the proband revealed two previously reported low-frequency heterozygous polymorphisms of unknown clinical significance and the α(LELY) allele. In addition, a novel heterozygous mutation was identified in exon 2 of the ß-spectrin gene SPTB. No mutations were identified in ANK1 (ankyrin-1), SLC4A1 (band 3), EPB41 (band 4.1), or EPB42 (band 4.2).
Assuntos
Eliptocitose Hereditária/genética , Variação Genética/genética , Icterícia Neonatal/genética , Espectrina/genética , Comorbidade , Eliptocitose Hereditária/epidemiologia , Feminino , Humanos , Lactente , Icterícia Neonatal/epidemiologia , Icterícia Neonatal/terapia , Masculino , Mutação/genética , Linhagem , Fototerapia , Resultado do TratamentoRESUMO
We cared for a term male infant born to Burmese immigrants. At about 24 hours a total serum bilirubin (TSB) was 9.3 mg/dL, and phototherapy was begun. It was stopped 48 hours later, with a TSB of 10.9 mg/dL, and he was discharged from the hospital with an appointment for a repeat TSB check 48 hours later. A few hours before the appointment he became listless and apneic, and his parents took him to the emergency department of the regional children's hospital, where sepsis was suspected. The TSB was 41 mg/dL. He died 4 hours later, despite intensive care efforts, with opisthotonus and refractory hypotension. Blood drawn before the exchange transfusion had low glucose-6-phosphate dehydrogenase (G6PD) enzymatic activity, and sequencing of the G6PD gene revealed the G6PD Mahidol mutation (c.487G>A). Cultures and postmortem examination did not demonstrate an infectious process, but kernicterus was present. Acute kernicterus can mimic septic shock.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Kernicterus/diagnóstico , Sepse/diagnóstico , Diagnóstico Diferencial , Evolução Fatal , Deficiência de Glucosefosfato Desidrogenase/complicações , Humanos , Recém-Nascido , Kernicterus/etiologia , MasculinoRESUMO
We cared for a term female newborn, who at 108 hours of age, with a total serum bilirubin of 15.4 mg/dL, was discharged from the hospital on home phototherapy. At a return appointment 44 hours later, her total serum bilirubin was 41.7 mg/dL and signs of acute kernicterus were present. Maternal/fetal blood group O/B incompatibility was identified, with a negative direct antiglobulin test, which was positive on retesting. She had abundant spherocytes on blood smear, and these persisted at follow-up, but neither parent had spherocytes identified. A heterozygous SLC4A1(E508K) mutation (gene encoding erythrocyte membrane protein band 3) was found, and in silico predicted to result in damaged erythrocyte cytoskeletal protein function. No mutations were identified in other red cell cytoskeleton genes (ANK1, SPTA1, SPTB, EPB41, EPB42) and the UGT1A1 promoter region was normal. Neurologic follow-up at 2 and 4 months showed developmental delays consistent with mild kernicterus.