Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities.

OBJECTIVE: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). METHODS: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. RESULTS: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. CONCLUSIONS: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.

Perinatal hypoxic-ischaemic encephalopathy: a national survey of end-of-life decisions and palliative care.

OBJECTIVE: To explore end-of-life (EoL) decision-making and palliative care in hypoxic-ischaemic encephalopathy (HIE) nationwide. METHODS: A cross-sectional national study on moderate-to-severe HIE in newborns ≥35 weeks' gestational age in 2015, including all 57 level III units that offered hypothermia. Forty-one questions were included to explore how the prognosis is established, as well as timing of the decision-making process, and also how ongoing palliative care is offered. RESULTS: The main difficulties in EoL decisions lie in the scarce time to make an early, accurate prognosis. Only 20% shared the neurological prognosis with the parents within 72 hours of life, and in only a third of the centres is the nurse present when the prognostic information is given to the family. Almost 50% do not use protocols to order the EoL process. Practically, all centres (91%) reported taking into account the wishes of the parents. However, in 30% the team does not always reach consensus on how the withdrawal process. Specialised psychological support is available in 54% of the hospitals; in more than 50%, interviews are not arranged to examine the grieving process with parents. CONCLUSIONS: There are four areas for improvement in the comprehensive, multidisciplinary approach to the EoL decision in the patient with HIE: (1) the need for EoL and interdisciplinary palliative care protocols, (2) participation of nurses in the process and improvement in the nurse-physician communication, (3) psychological support for parents involved in the EoL decisions and (4) implementation of strategies to give support during the grieving process.

Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study

Abstract Objective We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly. Method This retrospective study utilized newborn participants in the Zika Cohort Study Jundiaí. Newborns from the Zika Cohort Study Jundiaí with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve. At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis. Results Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction; one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%). Conclusions Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby.

[Cerebral sinovenous thrombosis in a newborn with mutation of MTHFR C677T treated with enoxaparin]. / Trombosis senovenosa cerebral en un recién nacido con mutación MTHFR C677T tratado con enoxaparina.

INTRODUCTION: Neonatal cerebral sinovenous thrombosis (CSNT) is a rare and generally serious con dition about which there is little knowledge of the responsible pathophysiological mechanisms and, although controversial, it has been suggested that genetic thrombophilia may play a role in its patho genesis. Out of concern for intracranial bleeding, the anticoagulant treatment with low-molecular- weight heparin is controversial. CLINICAL CASE: Full-term newborn who presented at eight days of life breastfeeding rejection, clonic seizures, and locomotor hypoactivity. The MRI neuroimaging showed a CSNT involving multiple venous sinuses, a right thalamic hemorrhagic infarction, and venous con gestion in frontal white matter. Thrombophilia study highlighted a homozygous MTHFR C677T mutation. Treatment with low-molecular-weight heparin was associated with repermeabilization of the superior sagittal sinus after 23 days of starting therapy. CONCLUSIONS: The clinical presentation of CSNT in the neonate is nonspecific, probably related to the extent and severity of the injury and the development of associated complications, such as venous hemorrhagic infarctions and intraparenchymal or intraventricular hemorrhage. These complications are detected through ultrasound or MRI, and they should make us suspect a CSNT. In this experience, the anticoagulant treatment proved to be safe and prevents thrombus propagation.

Trombosis senovenosa cerebral en un recién nacido con mutación MTHFR C677T tratado con enoxaparina / Cerebral sinovenous thrombosis in a newborn with mutation of MTHFR C677T treated with enoxaparin

Resumen: Introducción: La trombosis senovenosa cerebral neonatal (TSVC), es una patología rara y generalmente grave, de la cual se conoce poco sobre los mecanismos fisiopatológicos responsables y, aunque controvertido, se ha sugerido que la trombofilia genética, puede desempeñar un rol en la patogénesis. Debido a los temores de un sangrado intracraneal el tratamiento anticoagulante con heparina de bajo peso mole cular es controvertido. Objetivo: presentar un recién nacido con una trombosis senovenosa cerebral neonatal, discutir los factores de riesgo trombofílico, y el manejo con heparina de bajo peso molecu lar de la trombosis venosa cerebral. Caso Clínico: Recién nacido de término que debutó a los 8 días de vida con convulsiones clónicas, rechazo al pecho más hipoactividad motora. La neuroimagen con RM mostró una TSVC involucrando múltiples senos venosos, un infarto hemorrágico talámico dere cho y congestión venosa de la sustancia blanca frontal. El estudio de trombofilia puso de relieve una mutación homocigota del gen MTHFR C677T. El tratamiento con heparina de bajo peso molecular se asoció a repermeabilización del seno sagital superior a los 23 días de iniciada la terapia. Conclusio nes: La presentación clínica de la TSVC en el neonato es inespecífica, probablemente en relación con la extensión y gravedad de la lesión y el desarrollo de complicaciones asociadas, como infartos he morrágicos venosos intraparenquimatosos o hemorragia intraventricular. Estas complicaciones son detectables mediante Ecografia o Resonancia Magnética, y deben hacer sospechar una TSVC. En esta experiencia el tratamiento anticoagulante mostró ser seguro y prevenir la extensión de la trombosis.

Abstract: Introduction: Neonatal cerebral sinovenous thrombosis (CSNT) is a rare and generally serious con dition about which there is little knowledge of the responsible pathophysiological mechanisms and, although controversial, it has been suggested that genetic thrombophilia may play a role in its patho genesis. Out of concern for intracranial bleeding, the anticoagulant treatment with low-molecular- weight heparin is controversial. Objective: To present a case of a newborn with neonatal CSNT, to analyze the thrombophilic risk factors, and the management of cerebral venous thrombosis with low-molecular-weight heparin. Clinical Case: Full-term newborn who presented at eight days of life breastfeeding rejection, clonic seizures, and locomotor hypoactivity. The MRI neuroimaging showed a CSNT involving multiple venous sinuses, a right thalamic hemorrhagic infarction, and venous congestion in frontal white matter. Thrombophilia study highlighted a homozygous MTHFR C677T mutation. Treatment with low-molecular-weight heparin was associated with repermeabilization of the superior sagittal sinus after 23 days of starting therapy. Conclusions: The clinical presentation of CSNT in the neonate is nonspecific, probably related to the extent and severity of the injury and the development of associated complications, such as venous hemorrhagic infarctions and intraparenchymal or intraventricular hemorrhage. These complications are detected through ultrasound or MRI, and they should make us suspect a CSNT. In this experience, the anticoagulant treatment proved to be safe and prevents thrombus propagation.

Variations in the number of births by day of the week, and morbidity and mortality in very-low-birth-weight infants / Variações no número de partos por dia da semana e morbidez e mortalidade em neonatos com muito baixo peso ao nascer

Abstract Objective: To know the distribution of births of very low birth weight infants by day of the week, and whether this distribution affects the morbidity and mortality in this group of patients. Methods: This was a retrospective analysis of data collected prospectively in the Spanish SEN1500 network (2002-2011). Outborn infants, patients with major congenital anomalies, and those who died in the delivery room were excluded. Births were grouped into "weekdays" and "weekends." A multivariate logistic regression analysis was conducted to evaluate the independent effect of the birth moment on outcomes, and Cox regression for survival. Results: Out of a total of 27,205 very low birth weight infants born at and/or admitted to the participating centers, 22,961 (84.4%) met inclusion criteria. A reduction of 24% in the number of births was observed during the "weekends" compared with "weekdays". In the raw analysis, patients born on weekends exhibited higher morbidity and mortality (mortality rate: 14.2% vs. 16.5%, p < 0.001), but differences were no longer significant after adjusting for confounding factors. Conclusions: The present results suggest that current care practices reduce the proportion of births during the weekends and tend to cluster some high-risk births during this period, increasing crude morbidity and mortality. However, after adjusting for confounding factors, the differences disappear, suggesting that overall care coverage in these centers is appropriate.

Resumo Objetivo: Conhecer a distribuição dos partos de neonatos com muito baixo peso ao nascer durante a semana e se essa distribuição afeta a morbidez e a mortalidade nesse grupo de pacientes. Método: Esta é uma análise retrospectiva de dados coletados prospectivamente na rede espanhola SEN1500 (2002-2011). Foram excluídos neonatos nascidos em outro local, pacientes com grandes anomalias congênitas e pacientes falecidos na sala de parto. Os partos foram agrupados em "Dias úteis" e "Final de semana". Foi realizada uma análise de regressão logística multivariada para avaliar o efeito independente do parto sobre os resultados e uma regressão de Cox para avaliar a sobrevida. Resultados: Do total de 27.205 neonatos com muito baixo peso ao nascer nascidos e/ou internados nos centros participantes, 22.961 (84,4%) atenderam aos critérios de inclusão. Houve uma redução de 24% no número de partos no "Final de semana" em comparação com os "Dias úteis". Na análise bruta, os pacientes nascidos em finais de semana apresentaram maior morbidez e mortalidade (Taxa de mortalidade: 14,2% em comparação a 16,5%, p < 0,001), porém as diferenças não eram mais significativas após o ajuste aos fatores de confusão. Conclusões: Nossos resultados sugerem que as práticas atuais de atendimento reduzem a proporção de partos em finais de semana e tendem a agrupar alguns partos de alto risco nesse período, aumentando a morbidez e mortalidade brutas. Contudo, após o ajuste aos fatores de risco, as diferenças desaparecem, sugerindo que a cobertura de atendimento geral em nossos centros é adequada.

Hyaline fibromatosis syndrome: Clinical update and phenotype-genotype correlations.

Hyaline fibromatosis syndrome (HFS) is the unifying term for infantile systemic hyalinosis and juvenile hyaline fibromatosis. HFS is a rare autosomal recessive disorder of the connective tissue caused by mutations in the gene for anthrax toxin receptor-2 (ANTXR2). It is characterized by abnormal growth of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular, and systemic involvement. We reviewed the 84 published cases and their molecular findings, aiming to gain insight into the clinical features, prognostic factors, and phenotype-genotype correlations. Extreme pain at minimal handling in a newborn is the presentation pattern most frequently seen in grade 4 patients (life-limiting disease). Gingival hypertrophy and subcutaneous nodules are some of the disease hallmarks. Though painful joint stiffness and contractures are almost universal, weakness and hypotonia may also be present. Causes of death are intractable diarrhea, recurrent infections, and organ failure. Median age of death of grade 4 cases is 15.0 months (p25-p75: 9.5-24.0). This review provides evidence to reinforce the previous hypothesis that missense mutations in exons 1-12 and mutations leading to a premature stop codon lead to the severe form of the disease, while missense pathogenic variants in exons 13-17 lead to the mild form of the disease. Multidisciplinary team approach is recommended.

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy / Eficácia da hipotermia passiva e eventos adversos durante o transporte de recém-nascidos asfixiados de acordo com a gravidade da encefalopatia hipóxico-isquêmica

Abstract Objective To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. Methods This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Results Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4 ± 1.4 °C and mean transfer time was 3.3 ± 2.0 h. Mean age at arrival was 5.6 ± 2.5 h. Temperature at arrival was between 33 and 35 °C in 41 (61%) infants, between 35 °C and 36.5 °C in 15 (22%) and <33 °C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature < 33 °C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p < 0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. Conclusion The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport.

Resumo Objetivo Determinar se a eficácia da hipotermia passiva e eventos adversos durante o transporte estão relacionados à gravidade da encefalopatia hipóxico-isquêmica neonatal. Métodos Estudo retrospectivo de 67 neonatos com encefalopatia hipóxico-isquêmica (nascidos entre abril de 2009 e dezembro de 2013) transferidos para hipotermia terapêutica e resfriados durante o transporte. Resultados Foram transportados 56 recém-nascidos (84%) sem fontes externas de calor e 11 (16%) precisaram de uma fonte externa de calor. A temperatura média na saída foi de 34,4 ± 1,4 °C e o tempo médio de transporte foi de 3,3 ± 2,0 horas. A idade média na chegada foi de 5,6 ± 2,5 horas. A temperatura na chegada ficou entre 33-35 °C em 41 (61%) neonatos, entre 35°-36,5 °C em 15 (22%) e < 33 °C em 11 (16%). Neonatos com encefalopatia hipóxico-isquêmica grave apresentaram maior risco de temperatura < 33 °C na internação (RC 4,5; IC de 95% 1,1-19,3). A gravidade da encefalopatia hipóxico-isquêmica e o pH da artéria umbilical foram fatores de risco independentes para uma baixa temperatura na internação (p < 0,05). Eventos adversos durante o transporte, principalmente hipotensão e sangramento do tubo endotraqueal, ocorreram em 14 neonatos (21%), sem diferenças entre neonatos com encefalopatia hipóxico-isquêmica moderada ou grave. Conclusão O risco de super-resfriamento durante o transporte é maior em recém-nascidos com encefalopatia hipóxico-isquêmica grave e naqueles com acidose mais grave no nascimento. Os eventos adversos mais comuns durante o transporte estão relacionados a deterioração fisiológica e sangramento do tubo endotraqueal. Essa observação fornece informações úteis para identificar neonatos asfixiados que exigem maior vigilância clínica durante o transporte.

A Prognostic Neonatal Neuroimaging Scale for Symptomatic Congenital Cytomegalovirus Infection.

BACKGROUND: Congenital cytomegalovirus (cCMV) can cause brain inflammation/destruction and teratogenic effects. The only validated neuroimaging prognostic categorization for symptomatic cCMV available is based on destructive lesions seen on computed tomography (CT). OBJECTIVE: The aim of this study was to establish the predictive ability of a comprehensive neonatal neuroimaging scale in symptomatic cCMV. METHODS: Twenty-six infants were studied by neonatal cranial ultrasound scans (US; n = 25), CT (n = 11) and magnetic resonance imaging (MRI; n = 9). A previously validated neuroimaging scale comprising calcifications, ventriculomegaly and atrophy was compared to a newly proposed system adding cerebral dysgenesis and white matter disease. The findings were graded from 0 to 3. Neurodevelopmental assessment included motor and cognitive functions, epilepsy, vision, hearing and behavioral disorders. RESULTS: Both scales showed a significant association with outcome (p < 0.005). Our scale was more accurate in predicting death or moderate-severe disability (area under the curve for scores ≥2, 0.88 ± 0.06 vs. 0.80 ± 0.08). All 5 infants with normal neuroimaging survived with intact neurological function. While our scale was highly associated with outcome in patients studied by MRI, it was unable to predict unfavorable outcomes in 2 patients with mildly abnormal US and/or CT. CONCLUSIONS: A comprehensive scale based on US and MRI predicts neurodevelopment in symptomatic cCMV. Significant destructive lesions are associated with a poor prognosis. While a strictly normal cranial US predicts a favorable outcome, in case of subtle US abnormalities, MRI is crucial for prognostication.

Microcephaly-lymphedema-chorioretinal dysplasia associated with pachymicrogyria and atrophy of the cerebellar vermis: an integration of brain-ocular migration disorders.

BACKGROUND: Microcephaly-lymphedema-chorioretinal dysplasia (OMIM 152950) is a rare malformative inherited disorder that can be associated with other systemic features. Other ocular and brain anomalies rather than microcephaly and chorioretinal dysplasia have been inconstantly reported in this syndrome. METHODS: We present a case of microcephaly-lymphedema-chorioretinal dysplasia with a dysmorphic facies, hypertonicity in the extremities and neuropsychomotor delay. Ophthalmological examination revealed bilateral nystagmus, microphthalmia, posterior subcapsular cataratacts, extensive chorioretinal dysplasia, optic nerve aplasia, persistent fetal vasculature, and absent retinal vessels. RESULTS: Magnetic resonance revealed pachymicrogyria and discrete atrophy of vermis cerebelosum and confirmed optic nerve hypoplasia. CONCLUSIONS: The developmental alterations observed in the retina of this patient could be analogous to central nervous system anomalies, reflecting a reduction in neural population. Ophthalmic examination of children with microcephaly is warranted.

Beta2-microglobulin concentrations in cerebrospinal fluid correlate with neuroimaging findings in newborns with symptomatic congenital cytomegalovirus infection.

OVERVIEW: In newborns with symptomatic congenital cytomegalovirus (CMV) infection, neuroimaging is the best available predictor of neurodevelopmental outcome. Cerebrospinal fluid (CSF) findings in congenital CMV infection have seldom been described. Neonates with central nervous system infections present high CSF Beta(2)-microglobulin (beta(2)-m) levels. OBJECTIVES: The objectives of this study were: (1) to determine whether CSF beta(2)-m is increased in newborns with symptomatic congenital CMV infection, and (2) to examine its correlation with neuroimaging findings. MATERIALS AND METHODS: Fourteen newborns with symptomatic congenital CMV infection admitted to La Paz Hospital from 1990 through 2004 underwent determination of CSF beta(2)-m. Ninety-three newborns, constituting the comparison group, underwent CSF beta(2)-m determination as part of a sepsis or meningo/encephalitis work-up, and at discharge had sterile cultures and normal neurological status. Neuroimaging findings were scored according to a semiquantitative system: (0) no abnormalities; (1) single punctate periventricular (PV) calcification and/or hyperechogenic areas in the thalamus and basal ganglia; (2) multiple discrete PV calcifications and/or ventriculomegaly; and (3) extensive PV calcifications and/or brain atrophy. DISCUSSION AND CONCLUSION: CSF beta(2)-m was increased in newborns with CMV infection (median 6.21 mg/L) compared with controls (1.68 mg/L) (P<.001). beta(2)-m showed a correlation with neuroimaging scores (r (s)=0.753, P=.002). beta(2)-m was higher in patients who scored 2-3 (12.83 mg/L) than in patients who scored 0-1 (5.52 mg/L) (P=.028). CSF beta(2)-m is increased in newborns with symptomatic congenital CMV infection and correlates with neuroimaging abnormalities. beta(2)-m appears to be an indicator of the severity of brain involvement in congenital CMV infection.

Intussusception in a preterm neonate; a very rare, major intestinal problem--systematic review of cases.

Intussusception is an extremely rare disorder in preterm infants and it is often misdiagnosed as necrotizing enterocolitis. We report a case of intussusception in a 30-day-old preterm infant of 26 weeks of gestational age and a birthweight of 610 g who was diagnosed via abdominal ultra sonography. A systematic review of the literature was performed and reports on 23 previous cases were found. The presence of recognizable causes of intussusception in preterms, such as Meckel's diverticulum, bowel polypus, etc. was very infrequent. Comorbidity before and after intussusception is heterogeneous and related to prematurity. The intussusception is predominantly located in the small bowel (91.6%)--ileal or jejunal. The condition is misdiagnosed as NEC and managed conservatively until clinical deterioration occurs. A definitive diagnosis is thus established during abdominal surgery, which is usually delayed an average of 9.5 days from the onset of symptoms. Our case illustrates the capability of abdominal ultrasonography to establish early diagnosis of intussusception in the premature newborn.

Peritoneal drainage as primary management in necrotizing enterocolitis: a prospective study.

BACKGROUND/PURPOSE: The use of peritoneal drainage (PD) in neonates with necrotizing enterocolitis (NEC) is controversial. The authors began to perform it successfully in infants with pneumoperitoneum, and subsequently they extended its use to infants with peritonitis and advanced NEC before radiologic evidence of peritoneal free air. To analyze the efficacy of PD they began a prospective study. METHODS: A prospective study was conducted in 6 neonatal intensive care units (NICU) in Spain: neonates with pneumoperitoneum or peritonitis and advanced NEC were all included, whatever the birth weight and gestational age (GA). RESULTS: PD was performed in 47 infants, but 3 of them were excluded because pneumoperitoneum was caused by pathologies other than NEC. In a cohort of 44 infants, 86% improved after PD, and 64% survived after only PD. After PD, 54% of infants needed delayed surgery. Overall survival rate was 82%; 57% infants with birth weight under 1,000 g, and 95% in infants over 1,000 g at birth. The main cause of mortality was massive NEC in the tiniest babies. Only one infant had a short bowel syndrome. CONCLUSIONS: From the authors' point of view, PD is the first step in treating neonates with pneumoperitoneum or overwhelming NEC, regardless of birth weight and GA. Laparotomy, if it is necessary, always must be performed after clinical stability is achieved. Mortality rates remain higher in the tiniest babies because of massive NEC.