Growth Patterns in Children With Congenital Cytomegalovirus Infection.

BACKGROUND: Congenital cytomegalovirus infection (CMVc) affects 0.7%-6% of recent births. Among its clinical manifestations are low weight and length at birth. OBJECTIVE: Describe the growth patterns of children with CMVc in their early years. METHODS: Observational, multicenter study of patients with CMVc. Anthropometric data were collected during the first 2 years of life and compared with World Health Organization standards. RESULTS: Anthropometric characteristics of 383 children with CMVc were studied, of which 198 (51%) were symptomatic at birth. At birth, 9% were small for gestational age (SGA) in terms of their weight and length and 17% had microcephaly. At 24 ± 3 months, 10% had a weight and length ≤2 SD, and 13% a head circumference ≤2 SD. Of those who were SGA at birth, at 24 ± 3 months >20% remained at ≤2 SD of their weight and length. Conversely, 75% of children with low weight or length at 24 ± 3 had not been SGA at birth. 20% of infants with microcephaly at birth remained with microcephaly, and 10% of those without microcephaly developed it at 24 ± 3 months. The average growth rate in length and weight was normal. Patients who were symptomatic at birth, premature and with motor and neurocognitive impairment had a significantly higher risk of low weight and length at 24 ± 3 months. CONCLUSION: Around 10% of children with CMVc are at ≤2 SD in weight, length and head circumference at 24 ± 3 months. The lack of adequate growth is associated with symptoms at birth, prematurity and motor and neurocognitive impairment. Growth impairment could be incorporated into the symptomatic spectrum of CMVc.

Is Polymerase Chain Reaction in Neonatal Dried Blood Spots Reliable for the Diagnosis of Congenital Cytomegalovirus Infection?

BACKGROUND: Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain reaction (rt-PCR) in dried blood spots (DBSs) collected for newborn screening has been assessed for retrospective diagnosis of congenital CMV (cCMV) infection, with variable results (sensitivities ranging from 34% to 100%). We aimed to assess the accuracy of this technique in Spain in a large patient series. METHODS: Ambispective, multicenter study including patients with confirmed cCMV from the Spanish Registry of cCMV patients. cCMV was established on the presence of CMV DNA in any body fluid, by positive culture findings or by molecular techniques during the first 2 weeks of life. Children in whom cCMV had been excluded were used as negative controls. Neonatal DBS samples were collected from both groups. The presence of CMV DNA was assessed by rt-PCR (RealStar CMV, Altona, Germany) in a central laboratory. RESULTS: One-hundred three patients and 81 controls from 10 hospitals were included. The performance of CMV DNA determination in DBS for the diagnosis of cCMV was as follows (95% confidence interval): sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood ratio 22.81 (5.74-90.58) and negative likelihood ratio 0.45 (0.36-0.56). Sensitivity increased with the birth viral load (bVL) log category. In cCMV patients, lower bVL was the single variable associated with a negative DBS rt-PCR result (P = 0.017). CONCLUSIONS: The sensitivity of CMV rt-PCR in DBS in our series was low and correlated with the bVL. Thus, a negative DBS result would not rule out cCMV infection, especially in patients with a low viremia level at birth.

Cytomegalovirus DNA Detection by Polymerase Chain Reaction in Cerebrospinal Fluid of Infants With Congenital Infection: Associations With Clinical Evaluation at Birth and Implications for Follow-up.

BACKGROUND: DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. METHODS: A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. RESULTS: A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P = .01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P = .04), although no association was found at 6 months of age. CONCLUSIONS: A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV.

¿Podemos descartar infección congénita por citomegalovirus cuando la reacción en cadena de la polimerasa viral es negativa en la prueba del talón? / Can we rule out a congenital cytomegalovirus infection when the result of polymerase chain reaction in dried blood spots is negative?

INTRODUCCIÓN: La determinación de la presencia de ADN de citomegalovirus (CMV) mediante técnicas de reacción en cadena de la polimerasa a tiempo real (rt-PCR) en la gota de sangre seca en el papel absorbente usado para la realización de la prueba de detección precoz neonatal ha sido validada para el diagnóstico retrospectivo de infección congénita por CMV (CMVc) en estudios realizados en otros países, pero no en el nuestro. El objetivo de este estudio es analizar el valor diagnóstico de esta técnica en nuestro centro. MÉTODOS: Estudio retrospectivo transversal observacional de todos los pacientes con diagnóstico confirmado de CMVc entre enero de 2007 y septiembre de 2012. Se ha determinado la presencia de ADN viral de CMV en las muestras de sangre seca de la prueba del talón de estos pacientes mediante rt-PCR. RESULTADOS: Se incluyeron 14 pacientes; 4/14 sintomáticos y 4/14 con secuelas. La detección de CMV por rt-PCR fue positiva únicamente en 7 de ellos. Se demostró una relación estadísticamente significativa entre la negatividad de la rt-PCR y cargas virales más bajas al nacimiento. CONCLUSIÓN: A pesar del pequeño tamaño muestral, nuestros datos ponen en evidencia la presencia de un número importante de falsos negativos en la detección de CMV por rt-PCR en este tipo de muestras en el diagnóstico de CMVc, especialmente en pacientes con cargas virales bajas al nacimiento

INTRODUCTION: The detection of cytomegalovirus (CMV) DNA by real time polymerase chain reaction (rt-PCR) in dried blood spots collected routinely for metabolic screening has been assessed for the retrospective diagnosis of congenital CMV (cCMV) infection in many studies, but not in Spain. The aim of this study is to analyze the diagnostic accuracy of this technique in our hospital. METHODS: A cross-sectional retrospective observational study was conducted including all patients born between January, 2007 and September, 2012 with confirmed cCMV infection. The assessment of CMV DNA was made by using rt-PCR in dried blood spots of these patients. RESULTS: Fourteen patients were included: 4/14 were symptomatic and 4/14 had sequelae. The detection of CMV DNA by rt-PCR was positive in only 7 patients. A statistically significant relationship between low viral load at birth and negative rt-PCR in dried blood spots was demonstrated. CONCLUSIONS: Despite the low number of patients included, our data highlight an important amount of false negative results in the DNA CMV detection by rt-PCR in these samples for the retrospective diagnosis of cCMV infection, especially in cases with low viral load at birth

[Can we rule out a congenital cytomegalovirus infection when the result of polymerase chain reaction in dried blood spots is negative?]. / ¿Podemos descartar infección congénita por citomegalovirus cuando la reacción en cadena de la polimerasa viral es negativa en la prueba del talón?

INTRODUCTION: The detection of cytomegalovirus (CMV) DNA by real time polymerase chain reaction (rt-PCR) in dried blood spots collected routinely for metabolic screening has been assessed for the retrospective diagnosis of congenital CMV (cCMV) infection in many studies, but not in Spain. The aim of this study is to analyze the diagnostic accuracy of this technique in our hospital. METHODS: A cross-sectional retrospective observational study was conducted including all patients born between January, 2007 and September, 2012 with confirmed cCMV infection. The assessment of CMV DNA was made by using rt-PCR in dried blood spots of these patients. RESULTS: Fourteen patients were included: 4/14 were symptomatic and 4/14 had sequelae. The detection of CMV DNA by rt-PCR was positive in only 7 patients. A statistically significant relationship between low viral load at birth and negative rt-PCR in dried blood spots was demonstrated. CONCLUSIONS: Despite the low number of patients included, our data highlight an important amount of false negative results in the DNA CMV detection by rt-PCR in these samples for the retrospective diagnosis of cCMV infection, especially in cases with low viral load at birth.

Parálisis braquial bilateral congénita en un prematuro extremo / Congenital bilateral brachial palsy in a 25-weel preterm infant with posthemorrahgic hydrocephalus

Introducción. La parálisis del plexo braquial congénita (o al nacimiento) normalmente ocurre por una lesión mecánica del plexo braquial, que tiene lugar en el momento del nacimiento, y su cuadro clínico depende de las raíces nerviosas que resulten lesionadas y de la extensión del traumatismo. En el caso de la parálisis del plexo braquial superior, se implican las raíces C5-C6 y en ocasiones C7, y también se denomina parálisis de Erb, que es la forma más frecuente de parálisis braquial 1. Caso clínico. Pretémino de 25 1/7 semanas gestacionales que a los 12 días de vida es derivado a nuestro centro para valoración neu- Paràlisi braquial bilateral congènita en un preterme de 25 setmanes gestacionals afectat d’hidrocefàlia posthemorràgica Yolanda Castilla Fernández 1, 2, Isabel Vives Oñós 1, Aurora Montoro Expósito 1, Margarita Arroyo Balaguer 1, Félix Castillo Salinas 1 1 Servei de Neonatologia. 2 SEM Pediàtric. Hospital Universitari Vall d’Hebron. Barcelona roquirúrgica por hemorragia intracraneal con hidrocefalia comunicante. En la exploración física destaca postura de extremidades superiores (EESS) en extensión y pronación (Fig. 1), y de extremidades inferiores (EEII) en flexión de caderas y rodillas. Se observa flexión dorsal activa de muñecas (C6) y flexión de dedos (C8-T1). Solamente se observa la contracción de bíceps (C5-C6) y tríceps (C7) al colocarlo en posición de ingravitación. No se observan reflejos osteotendionosos en EESS y se observa disminución del tono muscular en EESS. Se descartan lesiones óseas y se orienta como hidrocefalia posthemorrágica con parálisis braquial bilateral congénita superior C5 (tipo Erb). Comentarios. El propósito de este artículo es presentar el caso de una parálisis braquial bilateral congénita en un pretérmino extremo (25 semanas de gestación) con hidrocefalia post-hemorrágica y hacer énfasis en la importancia de la exploración física para realizar un diagnóstico correcto(AU)

Introduction. Congenital brachial plexus palsy is usually secondary to mechanical injuries occurring at birth; its clinical presentation depends on the affected nerve roots and the extent of the damage. In the case of upper brachial plexus palsy the C5-C6 nerve roots are affected; when C7 is also involved is known as Erb’s palsy, the most common type of brachial plexus palsy in newborns. Case Report. A preterm infant (25 1/7 weeks of gestational age) was referred to our center at 12 days of life for neurosurgery evaluation due to intracranial hemorrhage with communicating hydrocephalus. Physical examination revealed upper limbs in postural extension and pronation, and lower limbs in hip and knee flexion. Active wrist dorsiflexion (C6) and finger flexion (C8-T1) were observed. The infant showed biceps (C5-C6) and triceps (C7) contraction only in non-gravity position. No deep tendon reflexes were observed in the upper limbs, and there was decreased muscle tone in both lower limbs. Bone lesions were ruled out, and the infant was diagnosed with posthemorrhagic hydrocephalus and bilateral brachial plexus palsy C5 (Erb type). Comments. The purpose of this report is to describe a case of bilateral brachial plexus palsy in an extremely preterm infant with post-hemorrhagic hydrocephalus, and to emphasize the importance of physical examination to make a correct diagnosis(AU)