Unbound Bilirubin and Acute Bilirubin Encephalopathy in Infants Born Late Preterm and Term with Significant Hyperbilirubinemia.

OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

Evidence Suggests a Decrease in the Incidence of Kernicterus in California.

We identified children diagnosed with kernicterus in the California Department of Developmental Services and estimated an incidence of 0.42 per 100 000 births from 1988 to 2014, significantly decreasing to 0.04 per 100 000 births after 2009. We also examined national infant kernicterus mortality from 1979 to 2016 using CDC data. It did not decrease significantly.

Association between Hyperbilirubinemia and Hearing Screen Failure in the Neonatal Intensive Care Unit in Infants Born Preterm.

OBJECTIVE: To characterize the association between hyperbilirubinemia and a failed newborn hearing screen in infants born at 22-32 weeks of gestation. STUDY DESIGN: We included infants with gestational ages of 22-32 weeks who were discharged from neonatal intensive care units in the US from 2002 to 2017 with available newborn hearing screen results obtained after 34 weeks postmenstrual age. We excluded infants with severe birth asphyxia or craniofacial abnormalities. We identified 95 672 infants from 313 neonatal intensive care units. We used multivariable logistic regression to examine the association between maximum total bilirubin at <21 days postnatal age with failed hearing screen, adjusting for important demographic and clinical risk factors. RESULTS: The median gestational age and birth weight were 30 weeks (IQR, 28-32 weeks) and 1330 g (IQR, 1010-1630 g), respectively. The median maximum total bilirubin was 8.3 mg/dL (IQR, 6.7-10.0 mg/dL), and 5275 infants (6%) failed their newborn hearing screen. On adjusted analysis, each 1 mg/dL increase in maximum total bilirubin was associated with a small, but significant, increase in odds of a failed hearing screen (OR, 1.03; 95% CI, 1.02-1.04). CONCLUSIONS: An increased maximum total bilirubin level was independently associated with hearing screen failure. Further prospective studies are needed to understand whether this increased risk of hearing screen failure translates to increased risk of hearing loss.

Hyperbilirubinemia impact on newborn hearing: a literature review.

The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of hyperbilirubinemia in the hearing of newborns, relating audiological findings to serum levels of bilirubin. A literature review was conducted during October 2017, using the terms "hyperbilirubinemia", "jaundice", "infant", "newborn" and "hearing loss", on databases CAPES journals, MEDLINE and BIREME (SciELO, BBO). 827 studies were identified and 59 were selected for full-text reading, resulting in the selection of seven articles that met the inclusion criteria and were considered relevant to the sample of this study. All the reviewed studies performed brainstem auditory evoked potential as the main test for audiological evaluation. Changes in the audiological findings of neonates with hyperbilirubinemia were observed in all studies. There was no consensus on the serum bilirubin levels that may cause auditory changes; however, the relationship between hearing disorders and blood levels of bilirubin was positive. We identify the need to establish reference values for bilirubin levels considered critical for the occurrence of hearing disorders as well as the audiological follow-up of neonates with hyperbilirubinemia.

Hyperbilirubinemia impact on newborn hearing: a literature review

SUMMARY The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of hyperbilirubinemia in the hearing of newborns, relating audiological findings to serum levels of bilirubin. A literature review was conducted during October 2017, using the terms "hyperbilirubinemia", "jaundice", "infant", "newborn" and "hearing loss", on databases CAPES journals, MEDLINE and BIREME (SciELO, BBO). 827 studies were identified and 59 were selected for full-text reading, resulting in the selection of seven articles that met the inclusion criteria and were considered relevant to the sample of this study. All the reviewed studies performed brainstem auditory evoked potential as the main test for audiological evaluation. Changes in the audiological findings of neonates with hyperbilirubinemia were observed in all studies. There was no consensus on the serum bilirubin levels that may cause auditory changes; however, the relationship between hearing disorders and blood levels of bilirubin was positive. We identify the need to establish reference values for bilirubin levels considered critical for the occurrence of hearing disorders as well as the audiological follow-up of neonates with hyperbilirubinemia.

RESUMO O aumento nos níveis de bilirrubina no neonato pode provocar efeitos tóxicos no sistema auditivo, podendo levar à perda auditiva. O objetivo desta revisão foi verificar o impacto da hiperbilirrubinemia na audição de recém-nascidos, relacionando os achados audiológicos aos níveis séricos de bilirrubina. Realizou-se uma revisão sistemática de literatura durante o mês de outubro de 2017, utilizando-se os termos hyperbilirubinemia, jaundice, infant, newborn e hearing loss, nas bases de dados periódicos Capes, Medline e Bireme (SciELO, BBO). Foram identificados 827 estudos, dentre os quais 59 foram selecionados para leitura do texto na íntegra, resultando na seleção de sete artigos que atendiam aos critérios de inclusão e foram considerados relevantes para a amostra deste trabalho. Em todas as pesquisas revisadas, o potencial evocado auditivo de tronco encefálico foi o principal exame audiológico realizado. Em todos os estudos foram observadas alterações nos resultados audiológicos de neonatos com hiperbilirrubinemia. Não houve consenso quanto aos níveis séricos de bilirrubina que podem causar alterações auditivas, porém, a relação entre as alterações audiológicas e os níveis sanguíneos de bilirrubina foi positiva. Percebeu-se a necessidade de estabelecer valores de referência para os níveis de bilirrubina considerados críticos para a ocorrência de alterações audiológicas, assim como de acompanhamento audiológico dos neonatos com hiperbilirrubinemia.

[Neurodevelopment in patients with retinopathy of prematurity treated with intravitreal bevacizumab. Case series]. / Neurodesarrollo en pacientes con retinopatía del prematuro tratados con bevacizumab intravítreo. Serie de casos.

BACKGROUND: Retinopathy of prematurity (ROP) is an eye disease caused by an alteration in retinal vasculogenesis that may lead to partial or complete vision loss with a harmful impact in terms of neurodevelopment. The purpose of the present study was to determine the neurodevelopment in patients with type i retinopathy of prematurity treated with intravitreal bevacizumab. MATERIAL AND METHODS: Case series. The inclusion criteria were: patients with type I ROP treated with a dose of 0.625mg/0.025ml of intravitreal bevacizumab. Demographic data and comorbidities were documented. Neurodevelopment was evaluated with the screening test of the Bayley Scale of Infant Development (BSID) in all patients between 11 and 28 weeks of age. RESULTS: Seven patients were included in the study. Four patients showed normal neurodevelopment according to the overall scores of the BSID scale. The distribution of high risk for neurodevelopmental delay in the different areas evaluated were as follows: 3 patients presented it in the cognitive area, one in the receptive communication area, one in the expressive area, one in the fine motor skills and 3 patients in the gross motor skills area. CONCLUSIONS: In these case series, the majority of patients treated with intravitreal bevacizumab for ROP showed normal neurodevelopment scores.

Black race is not protective against hazardous bilirubin levels.

Although black race is considered protective against hyperbilirubinemia, black infants appear at increased risk of kernicterus. We found that although black infants have a lower risk of developing total serum bilirubin levels ≥ 20 mg/dL than white infants, they appear at greater risk of developing levels ≥ 30 mg/dL.

High rates of resolution of cholestasis in parenteral nutrition-associated liver disease with fish oil-based lipid emulsion monotherapy.

OBJECTIVE: To determine factors leading to resolution of cholestasis in patients with parenteral nutrition-associated liver disease treated with fish oil-based lipid emulsion (FOLE). STUDY DESIGN: Prospective observational study of 57 infants <6 months of age with parenteral nutrition-associated liver disease who received parenteral FOLE as monotherapy. RESULTS: Median gestational age of subjects at birth was 28 weeks (range 22.7-39.5). Median conjugated bilirubin level at initiation of therapy with FOLE was 7.5 mg/dL (range 2.1-25). Resolution of hyperbilirubinemia (conjugated bilirubin <2.0 mg/dL) and survival to hospital discharge occurred in 47 (82.5%) infants. Median number of days to resolution of cholestasis was 35 (range 7-129). Ten infants (17.5%) died. Non-survivors showed a trend towards being more premature than survivors at birth (25.9 vs 29.1 weeks, P = .056). Infants with higher conjugated bilirubin at initiation of therapy (>10.0 compared with <5.0 mg/dL) had longer times to resolution (98 vs 56 days, P < .005). Time to resolution correlated inversely with gestational age at birth (r(2) = 0.14, P = .02) and directly with time to receive 100% calories enterally (r(2) = 0.12, P = .03). CONCLUSIONS: Younger gestational age infants demonstrated higher degree of cholestasis, longer time to resolution of cholestasis, and increased mortality. Higher levels of cholestasis were associated with longer time to resolution. FOLE monotherapy led to resolution of cholestasis in all surviving infants.

Complicações neonatais do diabetes mellitus gestacional ­ DMG / Neonatal complications of gestacional diabetes mellitus ­ GDM

O diabetes mellitus gestacional (DMG) está associado a um risco aumentado de complicações fetais, neonatais e no desenvolvimento a longo prazo. As taxas de aborto espontâneo, natimorto, mal formações congênitas e morbidade e mortalidade perinatal são maiores em filhos de mães diabéticas. As principais complicações neonatais são: macrossomia, hipoglicemia neonatal, deficiência de ferro, alterações da função cardiorrespiratória, hiperbilirrubinemia, anormalidades neurológicas, hipocalcemia, hipomagnesemia e policitemia. A macrossomia predispõe a lesões do parto, especialmente distócia de ombro, maior risco de lesão do plexo braquial, fraturas de clavícula ou do úmero, asfixia perinatal, e, menos frequentemente, hemorragia subdural e paralisia facial. O controle glicêmico rigoroso pré-concepção e durante a gestação associa-se com menor morbimortalidade perinatal. Assim, o controle do DMG representa tarefa de fundamental importância para impedir sequelas em neonatais. (AU)

The gestational diabetes mellitus (GDM) is associated with an increased risk of fetal, neonatal, and possibly long-term complications. The rates of spontaneous abortion, stillbirth, congenital malformations, and perinatal morbidity and mortality are higher in infants of a diabetic mother than in pregnancies with normal glycemic control. The main neonatal complications are: macrosomia, neonatal hypoglycemia, iron deficiency, changes in cardiac and respiratory function, hyperbilirubinemia, neurological abnormalities, hypocalcemia, hypomagnesemia and polycythemia. Macrosomia predisposes to birth injury, especially shoulder dystocia, increased risk of brachial plexus injury, clavicular or humeral fractures, perinatal asphyxia, and, less often, subdural hemorrhage and facial palsy. Strict glycemic control preconception and during pregnancy is associated with lower perinatal morbidity and mortality. Thus, GDM control is of paramount importance to prevent neonatal harm. (AU)

Correlacionando icterícia, resultados de exames laboratoriais e diagnósticos de doenças / Correlating jaundice, laboratory test results and diagnosis of diseases

Para descobrir quais as doenças que mais comumente cursam com a icterícia em pacientes internados no Hospital Universitário Antônio Pedro (HUAP) e correlacioná-las com marcadores bioquímicos foram utilizados dados extraídos de prontuários de pacientes internados durante os anos de 2005 a 2007. 0s dados foram analisados usando métodos estatísticos como qui-quadrado e teste Z. Utilizamos a análise das dosagens de aspartato-aminotrans ferase (AST), alanina-aminotransferase (ALT), fosfatase alcalina (FA), gama-glutamiltransferase (gama-GT), bilirrubina (Bb) total e suas frações direta e indireta. Os sinais e sintomas mais comuns na amostra estudada foram: dor abdominal, vômitos e colúria, que estão presentes em cerca de 60% das queixas dos pacientes estudados. Na população entre nove e 85 anos de idade, a análise sugere que AST e ALT nos chamam atenção para uma possível lesão hepática associada aos casos de icterícia. Enquanto que FA e GGT são marcadores de colestase. A bilirrubina direta tem média mais elevada no grupo de pacientes entre nove e 85 anos e a bilirrubina indireta atinge níveis maiores no grupo com até dois meses de vida. As dosagens bioquímicas são armas muito importantes na pesquisa etiológica dos casos de icterícia.

To find out which diseases most commonly lead to jaundice in hospitalized patients in HUAP and correlate them with biochemical markers. We used data from medical records of patients hospitalized during the years 2005 to 2007. The data were analyzed using statistical methods to test and chi-square-Z. We used the analysis of the strengths of AST, ALI, FA, GGT, Bb and its fractions total direct and indirect. The most common signs and symptoms in the sample studied were abdominal pain, vomiting and choluria that are present in about 60% of complaints from patients. In the population between nine and 85 years of age, the analysis suggests that AST and ALT in calling attention to a possible liver damage linked to cases of jaundice. While FA and gamma-GT are markers of cholestasis. The direct bilirubin is highest average in the group of patients between nine and 85 years and indirect bilirubin levels higher in the group with up to two months of life. The biochemical doses are very important weapons in the etiological research of cases of jaundice.

Neuropatía auditiva, diagnóstico y manejo audiológico / Auditory neuropathy / dyssychrony, assessment and audiologic management

Los hallazgos clínicos que definen una neuropatía/des sincronía (NA/DA) son la integridad de las células ciliadas evidenciado, mediante la presencia de emisiones otoacústicas evocadas (EOAe) y/o la presencia de potenciales microfónicos cocleares (PMIC), junto con la ausencia de actividad neural evocada a nivel del VIII par craneano (potencial de acción compuesto) y tronco cerebral (potencial evocado auditivo de tronco (PEAT)). Las condiciones clínicas relacionadas con una NA/DA incluyen a la hiperbilirrubinemia, enfermedades neurovegetativas (ejemplo ataxia de Friedreich), síndrome de Charcot-Marie-Tooth así como otras neuropatías sensoriomotoras, desórdenes mitocondriales y neuropatías isquémica-hipóxicas como resultados de asfixia. El desarrollo de las habilidades auditivas y comunicacionales pueden estar comprometidas en forma importante en los niños con aparición prelingual de una NA/DA, mayor es aún este compromiso al no existir un perfil pronóstico preestablecido del desarrollo y resultados en el tratamiento de este desorden. En la actualidad existen múltiples estudios en donde se ha observado que hasta 50 por ciento de los pacientes con NA/DA presentan algún grado de beneficio al usar audífonos por lo que se sugiere que sistemas de amplificación como los audífonos o incluso implante coclear deberían ser el primer paso en el proceso de (re)habilitación.

The clinical findings that define an auditory neuropathy/dyssynchrony (AN/Dys) are the integrity of the outer hair cells demonstrated by the presence of evoked otoacoustics emissions (OAEe) and/or the presence of cochlear microphonic potential (CMP) along with the absence of neural activity evoked at level of VIII nerve (action potential compound) and brainstem (Auditory Brainstem Response, ABR). The clinical conditions related to an AN they include hiperbilirrubinemia, neurodegenerative diseases (eg ataxia of Friedreich), Charcot-Marie-Tooth syndrome as well as other sensoriomotor neuropathies, mitocondrial disorders and hypoxic neuropathy as perinatal asphyxia. The development of the auditory and communicational abilities can be compromise in children with prelingual onset of an AN/Dys, the development and results of treatment of this disorder is still this commitment when not existing a profile prognosis. At the present time multiple studies have been observed that until a 50 percent of the patients with AN present some degree of benefit using hearing aids, reason why it suggests amplification systems as the hearing aids or even cochlear implant would have to be the first step in the process of (re) habilitation of these patients.

Tooth pigmentation caused by bilirubin: a case report and histological evaluation.

Systemic disorders in pediatric patients, such as congenital biliary atresia, acute liver failure, and biliary hypoplasia, may be the indications for a need of liver transplantation. One of the manifestations of these disorders is the elevated serum levels of bilirubin (hyperbiliru-binemia), a product of hemoglobin degradation, which is deposited in different tissues, including mineralized and soft tissues. When hyperbilirubinemia occurs during the period of dental development, these teeth can develop a green coloration, which remains permanently, because, after maturation, these tissues loose their metabolic activity. This case report describes a 9-year-old girl who required a liver transplant due to biliary atresia when she was three years old. Some of her pigmented teeth needed extraction and afterwards were submitted for histological analysis and compared with sound teeth.

Apnea in infants.

OBJECTIVE: The main objective of this study was to describe frequency of risk factors in newborns who present different types of apnea in polysomnographic (PSG) recordings in neonatal care units. METHODS: The study was carried out in neonatal care units of a perinatal tertiary level institution in Mexico City between August 2002 and August 2003. Infants were selected from among 223 infants if they presented any type of apnea event in sleep PSG recordings. RESULTS: Nearly 25% of patients from a neonatal care unit presented apnea events. Infants with apnea showed lower values of age, weight, and cephalic perimeter at birth than infants without apnea, but did not show more neurologic risk factors. Central apnea events were more frequent in infants with preterm birth (birthweight < 1,500 g), obstructive apnea events were observed in infants with hyperbilirubinemia and gastro-esophageal reflux, while mixed events were seen in infants with sepsis, and hyperbilirubinemia. Sleep PSG recordings detected that 36% of infants with apnea have no previous clinic suspicion of the problem. CONCLUSION: Central events of apnea were found more frequent in infants with preterm birth, obstructive events in newborns with hyperbilirubinemia and gastroesophagic reflux, while infants mixed apnea had more frequent hyperbilirubinemia and sepsis.

Green pigmentation of deciduous teeth: report of two cases.

The purpose of this paper was to present 2 cases of green pigmentation in primary teeth caused by hyperbilirubinemia, from different pathologies during the neonatal period. Medical history revealed systemic problems during the neonatal period of an infectious, neurological, renal, respiratory, and cardiological nature, as well as a high amount of bilirubin in both cases and hepatitis in the first. The staining in the teeth was due to hyperbilirubinemia, caused by these systemic conditions. The clinical characteristics of teeth may help in the diagnosis of present current or past systemic diseases. The reported cases confirm the relevance of past medical history in establishing the diagnosis of the etiology of green pigmentation as a result of high levels of bilirubin serum.

Green teeth associated with cholestasis caused by sepsis: a case report and review of the literature.

Green stain is an uncommon condition associated with deposition of bilirubin in dental hard tissues. Prolonged hyperbilirubinemia has long been recognized as a frequent clinical manifestation of infection in the newborn, although the green staining of teeth caused by cholestasis associated with sepsis has not yet been reported. The purpose of this report is to present a case of green teeth of the primary dentition in a 3-year-old Brazilian girl. In addition, previously reported cases and their associated medical histories are analyzed.

Salud reproductiva y diabetes: nefropatía diabética y su efecto sobre el embarazo / Reproductive health and diabetes. Diabetic nephropathy and its effect on pregnancy

Se hizo una revisión para valorar los criterios actuales en relación con la repercusión del embarazo en las mujeres diabéticas con nefropatía diabética. En los últimos años hemos asistido a una disminución significativa de la mortalidad en estas pacientes. Cuando se logra un control metabólico óptimo y no existen complicaciones vasculares el índice de supervivencia es idéntico al de la embarazada no diabética, aunque no siempre se logra el control aspirado antes y durante el embarazo y, con frecuencia, coexisten en ellas complicaciones angiopáticas, lo que influye en la morbilidad y la mortalidad perinatal. El riesgo antes señalado se eleva aún más en las diabéticas con nefropatía. Muchos opinan que el embarazo no aumenta el riesgo subsecuente de nefropatía ni la aceleración de su progresión. Otros sin embargo, piensan que el embarazo puede elevar la morbilidad y la mortalidad perinatal. Se ha comprobado que el riesgo de preeclampsia, prematuridad y cesáreas es significativamente mayor en las diabéticas embarazadas con nefropatía. Otras complicaciones como: hipoglucemia, hiperbilirrubinemia, síndrome de distrés respiratorio, hipocalcemia y policitemia continúan presentando un índice alto en este grupo de mujeres. Un problema aún no resuelto del todo se relaciona con la incidencia elevada de malformaciones congénitas en esta mujeres. El control estricto del metabolismo y de la hipertensión arterial y la prevención del sufrimiento fetal son acciones que pueden contribuir a la reducción de la mortalidad de los hijos de madres diabéticas. El desarrollo de los cuidados intensivos de estos neonatos es otro proceder a tener en consideración(AU)

A review was made to evaluate the current criteria in connection with the repercussion of pregnancy on diabetic women with diabetic nephropathies. During the last years a significant reduction of mortality has been observed in these patients. When an optimum metabolic control is attained and there are no vascular complications the survival index is identical to that of the non-diabetic women, eventhough the desired control is not always obtained before and during pregnancy and angiopathic complications frequently coexist in them, which influences on perinatal morbidity and mortality. The above risk is even higher among diabetic patients with nephropathy. Many consider that pregnancy increases neither the subsequent risk of nephropathy nor the acceleration of its progression. However, others think that pregnancy may rise the perinatal morbi-mortality. It has been proved that the risk of preeclampsia, prematurity and cesarean sections is significantly higher in diabetic pregnant women with nephropathy. There is still a high index of complications such as hypoglucaemia, hyperbilirubinaemia, respiratory distress syndrome, hypocalcaemia and polycythaemia in this group of women. A problem that has not been solved yet is that related to the high incidence of congenital malformations in these women. The strict control of metabolism and arterial hypertension and the fetal suffering may contribute to the reduction of mortality of the children of diabetic mothers. The development of intensive care of these newborn infants is another procedure that should be taken into consideration(AU)

Influência da icterícia obstrutiva na cicatrização da pele e de anastomose jejunal em ratos / Influence of obstructive jaundice on wound and jejunal anastomosis healing in rats

A cicatrização da pele e do intestino podem ser influenciadas pela elevação da bilirrubina. Com o objetivo de avaliar o possível efeito da icterícia obstrutiva sobre a sutura da pele e de anastomose jejunal, foram estudados 32 ratos, divididos em quatro grupos (n=8) e acompanhados em períodos pós-operatórios de sete e 14 dias. Todos os animais foram submetidos a laparotomia e anastomose jejunal. Os grupos 1 e 2 serviam como controle dos grupos 3 e 4, os quais foram submetidos a ligadura do ducto biliopancreático. Os animais dos grupos 1 e 2 mantiveram o mesmo peso corporal durante todo o período de acompanhamento, enquanto os ictéricos apresentaram uma queda ponderal significativa após sete dias (p<0,05). Não houve diferença na resistência da sutura de pele entre os ratos ictéricos e não-ictéricos. Após duas semanas, a icterícia reduziu a resistência anastomótica jejunal (p<0,01). O exame histológico revelou menor grau de desenvolvimento da fibrose cicatricial nas anastomoses dos ratos ictéricos. Conclui-se que a icterícia obstrutiva pode atuar negativamente sobre a cicatrização tissular. Deve-se ressaltar a importância dos fatores associados à icterícia na gênese desse efeito