Neurodevelopmental Correlates of Fetal Motor Behavior Assessed Using Cine MR Imaging.

BACKGROUND AND PURPOSE: Fetal motor behavior is widely used as a clinical indicator for healthy development; however, our understanding of its potential as a marker for neurologic integrity is underdeveloped. MR imaging allows complete views of the whole fetus, which, combined with brain imaging, may improve the characterization of this relationship. This study aimed to combine an analysis of fetal motor behavior, brain MR imaging, and postnatal outcome, to provide insight into neurodevelopmental correlates of motor behavior. MATERIALS AND METHODS: Cine MR imaging was used to acquire sequences of fetal motor behavior in subjects with normal and abnormal findings on conventional brain MR imaging between 18 weeks' gestation and term. General movement sequences were analyzed using established criteria. Brain MR imaging was reported by an expert fetal neuroradiologist. Subjects were followed for up to 4 years postnatally with standard postnatal assessments. RESULTS: Nineteen of 21 fetuses with normal brain MR imaging findings showed normal general movements, compared with 14 of 22 of the fetuses with abnormal brain MR imaging findings, which, when classified by severity of the malformation, showed a significant relationship with postnatal outcome (P = .021). There was a significant relationship among neurodevelopmental outcome, general movement quality, and MR imaging of the brain (P = .020). CONCLUSIONS: The findings from this study demonstrate that a combined structural and functional imaging approach to the fetus will improve the characterization of early neurologic integrity, with the potential to inform postnatal outcome. This also lays the groundwork for further in vivo research as advanced imaging techniques are developed to study fetal neurologic development.

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

The effects of hemorrhagic parenchymal infarction on the establishment of sensori-motor structural and functional connectivity in early infancy.

INTRODUCTION: The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. RESULTS: Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo-cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori-motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. CONCLUSION: Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy.

Seguimiento de los recién nacidos con encefalopatía hipóxico-isquémica / Follow-up of newborns with hypoxic-ischaemic encephalopathy

La introducción del tratamiento con hipotermia para la encefalopatía hipóxicoisquémica neonatal ha conseguido reducir el número de niños con esta enfermedad que fallecen o que sobreviven con secuelas neurológicas. A pesar de la generalización de esta terapia, la encefalopatía hipóxico-isquémica continúa siendo una causa importante de mortalidad y de discapacidad neurológica. Las consecuencias de esta enfermedad sobre el neurodesarrollo y la calidad de vida del recién nacido justifican que estos pacientes sean incluidos en programas de seguimiento específicos con el fin de identificar y tratar precozmente los problemas que puedan surgir, así como de ofrecer orientación y apoyo a las familias. En este artículo se describen las complicaciones más importantes que presentan los niños con encefalopatía hipóxico-isquémica después del alta hospitalaria y se propone un programa de seguimiento basado en el pronóstico neurológico, establecido este a partir del estado clínico del recién nacido y de otros indicadores pronósticos, principalmente los estudios de neuroimagen. Se exponen también brevemente algunos aspectos sociales de importancia durante el seguimiento

Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child’s neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programsin order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic ischaemic encephalopathy. We offer recommendations for follow-up based on the infant’s clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed

[Follow-up of newborns with hypoxic-ischaemic encephalopathy]. / Seguimiento de los recién nacidos con encefalopatía hipóxico-isquémica.

Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed.

Predicting motor outcome and death in term hypoxic-ischemic encephalopathy.

OBJECTIVES: Central gray matter damage, the hallmark of term acute perinatal hypoxia-ischemia, frequently leads to severe cerebral palsy and sometimes death. The precision with which these outcomes can be determined from neonatal imaging has not been fully explored. We evaluated the accuracy of early brain MRI for predicting death, the presence and severity of motor impairment, and ability to walk at 2 years in term infants with hypoxic-ischemic encephalopathy (HIE) and basal ganglia-thalamic (BGT) lesions. METHODS: From 1993 to 2007, 175 term infants with evidence of perinatal asphyxia, HIE, and BGT injury seen on early MRI scans were studied. BGT, white matter, posterior limb of the internal capsule (PLIC), and cortex and brainstem abnormality were classified by severity. Motor impairment was staged using the Gross Motor Function Classification System. RESULTS: The severity of BGT lesions was strongly associated with the severity of motor impairment (Spearman rank correlation 0.77; p < 0.001). The association between white matter, cortical, and brainstem injury and motor impairment was less strong and only BGT injury correlated significantly in a logistic regression model. The predictive accuracy of severe BGT lesions for severe motor impairment was 0.89 (95% confidence interval 0.83-0.96). Abnormal PLIC signal intensity predicted the inability to walk independently by 2 years (sensitivity 0.92, specificity 0.77, positive predictive value 0.88, negative predictive value 0.85). Brainstem injury was the only factor with an independent association with death. CONCLUSION: We have shown that in term newborns with HIE and BGT injury, early MRI can be used to predict death and specific motor outcomes.

Optimization and initial experience of a multisection balanced steady-state free precession cine sequence for the assessment of fetal behavior in utero.

BACKGROUND AND PURPOSE: The assessment of motor function is an essential component of neurologic examinations, which imaging studies have extended to the fetus. US assessment is hampered by a limited FOV, whereas MR imaging has the potential to be an alternative. Our objectives were to optimize a cine MR imaging sequence for capturing fetal movements and to perform a pilot analysis of the relationship between the frequency of movements and uterine spatial constrictions in healthy fetuses. MATERIALS AND METHODS: Initially, a bSSFP cine sequence was selected for optimization, and various compromises were explored in all acquisition parameters to achieve an effective balance between anatomic coverage of the fetus and the temporal resolution of cine data, with the aim of maximizing both. Subsequently, cross-sectional qualitative and quantitative analyses of fetal movements were performed prospectively by using a cohort of 37 healthy fetuses (median GA, 29 weeks; range, 20-37 weeks) with the optimized cine protocol. Two smaller subgroups were selected for representative sampling of overall behavior patterns by using cine data of longer duration and for volumetric quantification of free intrauterine space. RESULTS: The optimized cine sequence, with TR/TE of 3.21/1.59 ms, coupled with parallel imaging and partial-Fourier imaging, resulted in a section-acquisition time of 0.303 seconds. Anatomic coverage was enhanced by using a combination of thick sagittal sections (30-40 mm) and multisection acquisitions to display movements in all fetal limbs, head, and trunk simultaneously. All expected motor patterns were observed throughout this gestational period, and a significant decreasing trend in overall movement frequency with age was demonstrated (r = -0.514, P = .0011). Also a significant negative correlation was found between overall movement frequency and the total intrauterine free space (r = -0.703, P = .0001). Furthermore, a significant decrease in the frequency of leg movements was shown in fetuses older then 30 weeks' GA compared with those younger than that (P = .015). CONCLUSIONS: Cine MR imaging is effective for observing fetal movements from midgestation with near full-body coverage. Also, reductions in free space with increasing GA appear to be a factor in the gradual reductions in overall levels of fetal activity as well as in restrictions in movement within specific regions of the fetal anatomy.

Incidencia y prevalencia de la encefalopatía hipoxico-isquémica en la primera década del siglo XXI / Neonatal hypoxic-ischemic encephalopathy: Incidence and prevalence in the first decade of the 21st century

Objetivos: Examinar la magnitud del problema de la encefalopatía hipoxico-isquémica (EHI) en un hospital terciario en los últimos 9 años, con el fin de valorar la conveniencia y oportunidad de implementar un programa de hipotermia. Métodos: Se identificaron todos los recién nacidos (RN) ≥34 semanas con antecedentes de asfixia intraparto y encefalopatía neonatal, nacidos entre los años 2000 y 2008. La EHI se clasificó como leve, moderada o grave. Se realizó un joinpoint regression analysis para examinar la tendencia en la incidencia de EHI durante el período de estudio y los posibles cambios en ésta. Resultados: Entre el 1 de enero del año 2000 y 31 de diciembre del 2008 nacieron en el Hospital La Paz 90.963 RN vivos, de los cuales 21.228 (23,36%) ingresaron en Neonatología. Otros 200 neonatos ingresaron procedentes de extramuros. Un total de 110 neonatos presentaron EHI, de los cuales 99 (90%) nacieron intramuros. La incidencia global de EHI fue de 1,088 por cada 1.000 RN vivos, y se observó una tendencia decreciente (pendiente = -5,37; p<0,05), y la incidencia de EHI significativa (moderada y grave) fue de 0,49 por cada 1.000. Cincuenta y dos RN tuvieron EHI significativa y hubieran sido candidatos a entrar en un programa de hipotermia; esto supone una prevalencia de 2,42 por cada 1.000 neonatos ingresados y un promedio de 5–6 pacientes/año. Conclusiones: La EHI es un problema infrecuente, particularmente la EHI significativa. La baja prevalencia de esta entidad, aun en centros terciarios, hace necesaria la regionalización y, por tanto, la centralización de los programas de hipotermia, con el fin de garantizar una adecuada calidad asistencial y optimizar los recursos (AU)

Aim: To examine the incidence and the prevalence of neonatal hypoxic-ischemic encephalopathy (HIE) in a tertiary Spanish center over a 9-year period, before the implementation of a hypothermia program. Methods: All infants ≥34 weeks gestation, born between 2000 and 2008 with evidence of perinatal asphyxia and neonatal encephalopathy were identified. HIE was classified as mild, moderate or severe. Joinpoint regression model was used to identify changes in the trends of HIE incidences. Results: A total of 90,963 live infants were born in La Paz Hospital between 2000 and 2008, and 23.3% of them (21.228) were admitted to the Neonatal Unit. In addition, 200 infants were referred from other centers. A total of 110 infants had HIE, of which 90% were inborn. The overall incidence of HIE was 1.088 per 1,000 live births, and the incidence of clinically significant HIE (moderate and severe grades) was 0.49 per 1,000 live births. The incidence of HIE showed a linear downward trend throughout the study period (slope=−5.37; P<0.05). Fifty-two neonates had moderate or severe HIE, this represents a prevalence of 2.42 per 1,000 infants admitted to the Neonatal Unit and means that 5–6 infants a year would have been candidates for therapeutic hypothermia. Conclusions: Neonatal HIE, and in particular significant HIE, is an infrequent condition. The low prevalence of HIE requires that these infants are referred to regional centers with sufficient experience in the use of therapeutic hypothermia, and in the management of all the medical problems associated with HIE (AU)

[Neonatal hypoxic-ischemic encephalopathy: Incidence and prevalence in the first decade of the 21st century]. / Incidencia y prevalencia de la encefalopatía hipoxico-isquémica en la primera década del siglo xxi.

AIM: To examine the incidence and the prevalence of neonatal hypoxic-ischemic encephalopathy (HIE) in a tertiary Spanish center over a 9-year period, before the implementation of a hypothermia program. METHODS: All infants > or =34 weeks gestation, born between 2000 and 2008 with evidence of perinatal asphyxia and neonatal encephalopathy were identified. HIE was classified as mild, moderate or severe. Joinpoint regression model was used to identify changes in the trends of HIE incidences. RESULTS: A total of 90,963 live infants were born in La Paz Hospital between 2000 and 2008, and 23.3% of them (21.228) were admitted to the Neonatal Unit. In addition, 200 infants were referred from other centers. A total of 110 infants had HIE, of which 90% were inborn. The overall incidence of HIE was 1.088 per 1,000 live births, and the incidence of clinically significant HIE (moderate and severe grades) was 0.49 per 1,000 live births. The incidence of HIE showed a linear downward trend throughout the study period (slope=-5.37; P<0.05). Fifty-two neonates had moderate or severe HIE, this represents a prevalence of 2.42 per 1,000 infants admitted to the Neonatal Unit and means that 5-6 infants a year would have been candidates for therapeutic hypothermia. CONCLUSIONS: Neonatal HIE, and in particular significant HIE, is an infrequent condition. The low prevalence of HIE requires that these infants are referred to regional centers with sufficient experience in the use of therapeutic hypothermia, and in the management of all the medical problems associated with HIE.

[End-of-life care in a Spanish Pediatric Intensive Care Unit: staff and parental evaluation]. / Cuidados al final de la vida en una unidad de cuidados intensivos pediátricos: evaluación por parte del personal y de los padres.

OBJECTIVES: To evaluate end-of-life care in a Paediatric Intensive Care Unit (PICU). METHODS: Retrospective study developed in a PICU. SUBJECTS: 41 workers from the PICU and parents of 26 deceased children (from 2001 to 2005). A questionnaire was designed to investigate end-of-life care. RESULTS: An age < 1-year old and a chronic or congenital disease correlated with a perceived lack of consistency in information. Nearly 38 % parents were with their children at the time of death; 64 % of all parents consider this "positive", and 13 % consider it "negative". Forty per cent of staff stated that it is "positive" for parents to be by the side of their child at the time of death, and 52 % do not know. Seventy-three per cent of staff, but only 29 % of parents want further professional psychological support for parents. Twenty per cent of children died following withdrawal of life support. The most important factors for this decision were the possibility of survival and quality of life. The majority (73 %) of caregivers express the view that often, this decision should be taken earlier. CONCLUSIONS: Analysis of staff opinions underlines the importance of the way news is communicated, the timing of withdrawal of life support, and the need for psychological support. Parents emphasized the role of the family during time spent in a PICU and during the last moments.

Cuidados al final de la vida en una unidad de cuidados intensivos pediátricos: evaluación por parte del personal y de los padres / End-of-life care in a Spanish Pediatric Intensive Care Unit: staff and Parental Evaluation

Objetivos: Evaluar los cuidados al final de la vida en una unidad de cuidados intensivos pediátricos (UCIP). Métodos: Estudio retrospectivo desarrollado en una UCIP. Los sujetos fueron 41 trabajadores de la UCIP y los padres de 26 niños fallecidos entre 2001 y 2005. Se diseñó un cuestionario para evaluar los cuidados al final de la vida proporcionados en este período. Resultados: La edad inferior a 1 año y las enfermedades crónicas o congénitas son las variables que se correlacionaron con una mayor percepción de incoherencia en la información. Cerca del 38 % de los padres estuvieron junto a sus hijos en el momento del fallecimiento; el 64 % de ellos consideran estar presentes algo positivo, y el 13 %, algo negativo. El 40 % del personal declaró que es positivo para los padres estar al lado de sus hijos en el momento del fallecimiento, y el 52 % no sabía si era positivo o negativo. El 73 % del personal, pero sólo el 29 % de los padres, desearía apoyo psicológico profesional para los padres. El 20 % de los niños fallecieron tras la retirada del soporte vital. Los factores más importantes para esta decisión fueron la posibilidad de supervivencia y la calidad de vida. La mayoría de los sanitarios expresaron que, a menudo, esta decisión debería haber sido tomada antes. Conclusiones: El análisis del personal subraya la importancia del cómo las noticias son comunicadas, del momento de retirada del soporte vital y la necesidad del apoyo psicológico. Los padres enfatizan más el papel de la familia en la UCIP y durante los últimos momentos (AU)

Objectives: To evaluate end-of-life care in a Paediatric Intensive Care Unit (PICU). Methods: Retrospective study developed in a PICU. Subjects: 41 workers from the PICU and parents of 26 deceased children (from 2001 to 2005). A questionnaire was designed to investigate end-of-life care. Results: An age < 1-year old and a chronic or congenital disease correlated with a perceived lack of consistency in information. Nearly 38 % parents were with their children at the time of death; 64 % of all parents consider this "positive", and 13 % consider it "negative". Forty per cent of staff stated that it is "positive" for parents to be by the side of their child at the time of death, and 52 % do not know. Seventy-three per cent of staff, but only 29 % of parents want further professional psychological support for parents. Twenty per cent of children died following withdrawal of life support. The most important factors for this decision were the possibility of survival and quality of life. The majority (73 %) of caregivers express the view that often, this decision should be taken earlier. Conclusions: Analysis of staff opinions underlines the importance of the way news is communicated, the timing of withdrawal of life support, and the need for psychological support. Parents emphasized the role of the family during time spent in a PICU and during the last moments (AU)