Clinical Study Hearing and Neurological Impairment in Children with History of Exchange Transfusion for Neonatal Hyperbilirubinemia

The objective was to determine frequency of sensorineural hearing loss (SNHL), identified by abnormal threshold in evoked potentials, absence of otoacoustic emissions and behavioral responses, auditory neuropathy (AN) (absence of evoked potentials, with preservation of otoacoustic emissions), and neurological comorbidity in infants with hyperbilirubinemia (HB) treated with exchange-transfusion (ET). From a total of 7,219 infants, ET was performed on 336 (4.6%). Inclusion criteria were fulfilled in 102; 234 children did not meet criteria (182 outside of the study period, 34 did not have complete audiological evaluation, and 18 rejected the followup). Thirty-five children (34%) were born at-term and 67 (66%) were preterm. Children had a mean age of 5.5 ± 3.9 years. Main causes of ET were Rh isoimmunization in 48 (47%), ABO incompatibility in 28 (27.5%), and multifactorial causes in 26 (25.5%). Fifteen (15%) children presented with SNHL. Preterm newborns presented more often with SNHL. Indirect bilirubin level was higher in children with SNHL (22.2 versus 18.7 mg/dL, = 0.02). No cases of AN were documented. An increased risk of neurologic sequelae was observed in children with SNHL. In conclusion, we disclosed a high frequency of SNHL in children with neonatal HB and ET and neurological alterations. No cases of AN were observed

Hearing and Neurological Impairment in Children with History of Exchange Transfusion for Neonatal Hyperbilirubinemia

The objective was to determine frequency of sensorineural hearing loss (SNHL), identified by abnormal threshold in evoked potentials, absence of otoacoustic emissions and behavioral responses, auditory neuropathy (AN) (absence of evoked potentials, with preservation of otoacoustic emissions), and neurological comorbidity in infants with hyperbilirubinemia (HB) treated with exchange-transfusion (ET). From a total of 7,219 infants, ET was performed on 336 (4.6%). Inclusion criteria were fulfilled in 102; 234 children did not meet criteria (182 outside of the study period, 34 did not have complete audiological evaluation, and 18 rejected the followup). Thirty-five children (34%) were born at-term and 67 (66%) were preterm. Children had a mean age of 5.5±3.9 years. Main causes of ET were Rh isoimmunization in 48 (47%), ABO incompatibility in 28 (27.5%), and multifactorial causes in 26 (25.5%). Fifteen (15%) children presented with SNHL. Preterm newborns presented more often with SNHL. Indirect bilirubin level was higher in children with SNHL (22.2 versus 18.7 mg/dL, P=0.02). No cases of AN were documented. An increased risk of neurologic sequelae was observed in children with SNHL. In conclusion, we disclosed a high frequency of SNHL in children with neonatal HB and ET and neurological alterations. No cases of AN were observed

Estado de la vacunación en prematuros menores de 1500 g nacidos entre 2004 y 2007 en una institución de tercer nivel de atención

Resumen: Antecedentes: La recomendación vigente de vacunación en prematuros es iniciar a la edad cronológica independientemente del peso y edad gestacional al nacer. Objetivo: Describir el estado de vacunación de los infantes prematuros menores de 1500 g pertenecientes al programa de seguimiento pediátrico del INPer. Material y métodos: Estudio de cohorte descriptico retrospectivo y transversal. Se incluyeron infantes que acudieron a consulta de junio del 2008 a junio del 2009 con fecha de nacimiento del 2004-2008, se obtuvo de la cartilla nacional de vacunación la fecha de la administración de la vacuna y se interrogó la causa del retraso de la administración del mismo de acuerdo al esquema vigente. Resultados: Se incluyeron 158 infantes. El 78.5% recibieron todas sus vacunas en el sector público. Transcurrieron 54.5 ± 30.2 días entre egreso y la primera aplicación de algún inmunógeno. La cobertura de vacunación contra influenza con dos dosis en el primer año de vida fue: 18.9%, contra rotavirus dos dosis: 59.5%, pentavalente acelular tres dosis: 73.5%, neumococo tres dosis: 28.2%, BCG: 98.1%, SRP: 100% y hepatitis B tres dosis: 77.8%. Todos los inmunógenos de administraron en forma atrasada. Las tres causas más frecuentes de rechazo en la vacunación fueron: peso bajo y/o prematurez, desabasto del biológico y antecedente de transfusión. Conclusiones: Los infantes prematuros mostraron retraso en la administración de todos los inmunógenos en relación con la recomendación del esquema nacional de vacunación, se debe de revisar las indicaciones vigentes para la administración de inmunógenos en esta población. Abstract: Background: The current recommendation for vaccination in preterm infants is to start it at the chronological age, regardless of their birthweight or gestational age. Objective: To describe the vaccination status of premature infants born under 1500 g, that were part of the INPer paediatric follow-up program. Material and methods: A retrospective, cross-sectional and descriptive cohort study, conducted on infants who attended their clinics from June 2008 to June 2009, and born between 2004 and 2008. The vaccination dates were obtained from their national immunisation record book and, where applicable, the cause of the administration delay was questioned. Results: The study included 158 infants, of whom 78.5% received all their vaccines in the public sector. A total of 54.5 ± 30.2 days elapsed between discharge and the first application of some immunogen. The vaccination coverage against influenza, with two doses in the first year of life, was: 18.9%, against rotavirus with two doses: 59.5%, acellular pentavalent, three doses: 73.5%, pneumococcus, three doses: 28.2%, BCG: 98.1%, MMR: 100%, and hepatitis B three doses: 77.8%. All immunogens were administered late. The three most frequent causes of immunisation rejection were: low weight and /or prematurity, lack of vaccines, and a history of transfusions. Conclusions: In premature infants there was a delay in the administration of all the immunogens as regards to the national vaccination recommendation. It is necessary to review the current indications for the administration of immunogens in this population. Palabras clave: Prematurez, Vacunación, Muy bajo peso al nacer, Keywords: Prematurity, Vaccination, Very low birth weig

Resultados maternos y neonatales de trillizos nacidos por diferentes métodos de embarazo

Resumen: Antecedentes: La incidencia de embarazos múltiples ha aumentando de manera constante desde hace más de 30 años. El objetivo fue analizar el comportamiento clínico de las madres y de los trillizos obtenidos por diferentes métodos de embarazo. Material y métodos: Estudio observacional, analítico de una cohorte longitudinal de trillizos de enero del 2000 a diciembre del 2010. Resultados: Se analizaron 82 conjuntos de trillizos, 246 (100%) neonatos, 12 (4.8%) fallecimientos. La distribución de las mujeres embarazadas según el método fue: 28 (34.1%) embarazo espontáneo, 20 (24.3%) inductores de ovulación, 13 (15.8%) inseminación artificial y 21 (25.6%) por FIVTE. La enfermedad más frecuente en general de todos los embarazos fue la infección de vías urinarias con un 13.4%, la media de la edad gestacional fue 32.6 ± 1.7 años, rango 25-36. El peso promedio fue de 1,561.52 ± 271.6, rango 620-2,460 g. Aunque el retardo en el crecimiento intrauterino se presentó en el 34% de todos los métodos, no existió diferencia estadística; las enfermedades respiratorias ocuparon el 34.6% de toda la muestra, p = 00014; el síndrome de dificultad respiratoria se presentó en todos los métodos, p = 0.00014; la sepsis para toda la muestra fue del 23.5% y se distribuyó de manera uniforme para todos los métodos; solo se presentaron 2 casos de enterocolitis 2A. Conclusión: El mayor porcentaje de embarazos fue espontáneo, todos los neonatos fueron prematuros con bajo peso al nacimiento, < 2,500 g, los problemas respiratorios fueron estadísticamente significativos (SDR, TTRN y SAP). Abstract: Background: The incidence of multiple pregnancies has been increasing steadily for more than 30 years. The aim of this study is to analyse the clinical outcomes of mothers and triplets born by different pregnancy methods. Material and methods: A longitudinal, observational, and analytical study conducted on a cohort of triplets born from January 2000 to December 2010. Results: The analysis included a total of 82 sets of triplets, 246 (100%) neonates, with 12 (4.8%) deaths. The distribution of pregnant women according to the method was: 28 (34.1%) spontaneous pregnancies, 20 (24.3%) ovulation inducers 13 (15.8%), artificial insemination, and 21 (25.6%) by IVF-ET. The most frequent pathologies, in general, of all pregnancies were urinary tract infection 13.4%. The mean gestational age was 32.6 ± 1.7, range 25-36. The mean weight was 1561.52 ± 271.6, range 620-2460 g. Although intrauterine growth retardation occurred in 34% of all methods, there was no statistical difference. Respiratory disease was present in 34.6% of the total sample, with a statistical difference, P=.00014, respiratory distress syndrome was present in all methods P=.00014. Sepsis for the entire sample was 23.5%, and was distributed evenly for all methods. Only 2 cases of enterocolitis 2A were seen. Conclusion: The highest percentage of pregnancies was spontaneous. All neonates were premature with low birth weight <2500 g. Respiratory problems (RDS, TTNB, and PAS) were statistically significant. Palabras clave: Embarazos de alto orden fetal, Prematurez, Métodos de embarazo, Keywords: Multiple pregnancies, Prematurity, Pregnancy method

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues

Two Novel FAM20C Variants in a Family with Raine Syndrome

Two siblings from a Mexican family who carried lethal Raine syndrome are presented. A newborn term male (case 1) and his 21 gestational week brother (case 2), with a similar osteosclerotic pattern: generalized osteosclerosis, which is more evident in facial bones and cranial base. Prenatal findings at 21 weeks and histopathological features for case 2 are described. A novel combination of biallelic FAM20C pathogenic variants were detected, a maternal cytosine duplication at position 456 and a paternal deletion of a cytosine in position 474 in exon 1, which change the reading frame with a premature termination at codon 207 and 185 respectively. These changes are in concordance with a negative detection of the protein in liver and kidney as shown in case 2. Necropsy showed absence of pancreatic Langerhans Islets, which are reported here for the first time. Corpus callosum absence is added to the few reported cases of brain defects in Raine syndrome. This report shows two new FAM20C variants not described previously, and negative protein detection in the liver and the kidney. We highlight that lethal Raine syndrome is well defined as early as 21 weeks, including mineralization defects and craniofacial features. Pancreas and brain defects found here in FAM20C deficiency extend the functional spectrum of this protein to previously unknown organs