Neonatal outcomes following early fetal growth restriction: a subgroup analysis of the EVERREST study.

OBJECTIVE: To quantify the risks of mortality, morbidity and postnatal characteristics associated with extreme preterm fetal growth restriction (EP-FGR). DESIGN: The EVERREST (Do e s v ascular endothelial growth factor gene therapy saf e ly imp r ove outcome in seve r e e arly-onset fetal growth re st riction?) prospective multicentre study of women diagnosed with EP-FGR (singleton, estimated fetal weight (EFW) <3rd percentile, <600 g, 20+0-26+6 weeks of gestation). The UK subgroup of EP-FGR infants (<36 weeks) were sex-matched and gestation-matched to appropriate for age (AGA) infants born in University College London Hospital (1:2 design, EFW 25th-75th percentile). SETTING: Four tertiary perinatal units (UK, Germany, Spain, Sweden). MAIN OUTCOMES: Antenatal and postnatal mortality, bronchopulmonary dysplasia (BPD), sepsis, surgically treated necrotising enterocolitis (NEC), treated retinopathy of prematurity (ROP). RESULTS: Of 135 mothers recruited with EP-FGR, 42 had a stillbirth or termination of pregnancy (31%) and 93 had live births (69%). Postnatal genetic abnormalities were identified in 7/93 (8%) live births. Mean gestational age at birth was 31.4 weeks (SD 4.6). 54 UK-born preterm EP-FGR infants (<36 weeks) were matched to AGA controls. EP-FGR was associated with increased BPD (43% vs 26%, OR 3.6, 95% CI 1.4 to 9.4, p=0.01), surgical NEC (6% vs 0%, p=0.036) and ROP treatment (11% vs 0%, p=0.001). Mortality was probably higher among FGR infants (9% vs 2%, OR 5.0, 95% CI 1.0 to 25.8, p=0.054). FGR infants more frequently received invasive ventilation (65% vs 50%, OR 2.6, 95% CI 1.1 to 6.1, p=0.03), took longer to achieve full feeds and had longer neonatal stays (median difference 6.1 days, 95% CI 3.8 to 8.9 and 19 days, 95% CI 9 to 30 days, respectively, p<0.0001). CONCLUSIONS: Mortality following diagnosis of EP-FGR is high. Survivors experience increased neonatal morbidity compared with AGA preterm infants. TRIAL REGISTRATION NUMBER: NCT02097667.

Intrinsic Functional Connectivity in Preterm Infants with Fetal Growth Restriction Evaluated at 12 Months Corrected Age.

Fetal growth restriction (FGR) affects brain development in preterm infants, but little is known about its effects on resting-state functional connectivity. We compared 20 preterm infants, born at <34 weeks of gestation with abnormal antenatal Doppler measurements and birth weights <10th percentile, with 20 appropriate for gestational age preterm infants of similar gestational age and 20 term infants. They were scanned without sedation at 12 months of age and screened for autistic traits at 26 months. Resting functional connectivity was assessed using group independent component analysis and seed-based correlation analysis. The groups showed 10 common resting-state networks involving cortical, subcortical regions, and the cerebellum. Only infants with FGR showed patterns of increased connectivity in the visual network and decreased connectivity in the auditory/language and dorsal attention networks. No significant differences between groups were found using seed-based correlation analysis. FGR infants displayed a higher frequency of early autism features, related to decreased connectivity involving the salience network, than term infants. These data suggest that FGR is an independent risk factor for disrupted intrinsic functional connectivity in preterm infants when they are 1-year old and provide more clues about the neurodevelopmental abnormalities reported in this population.

Measuring intellectual ability in cerebral palsy: The comparison of three tests and their neuroimaging correlates.

Standard intelligence scales require both verbal and manipulative responses, making it difficult to use in cerebral palsy and leading to underestimate their actual performance. This study aims to compare three intelligence tests suitable for the heterogeneity of cerebral palsy in order to identify which one(s) could be more appropriate to use. Forty-four subjects with bilateral dyskinetic cerebral palsy (26 male, mean age 23 years) conducted the Raven's Coloured Progressive Matrices (RCPM), the Peabody Picture Vocabulary Test-3rd (PPVT-III) and the Wechsler Nonverbal Scale of Ability (WNV). Furthermore, a comprehensive neuropsychological battery and magnetic resonance imaging were assessed. The results show that PPVT-III gives limited information on cognitive performance and brain correlates, getting lower intelligence quotient scores. The WNV provides similar outcomes as RCPM, but cases with severe motor impairment were unable to perform it. Finally, the RCPM gives more comprehensive information on cognitive performance, comprising not only visual but also verbal functions. It is also sensitive to the structural state of the brain, being related to basal ganglia, thalamus and white matter areas such as superior longitudinal fasciculus. So, the RCPM may be considered a standardized easy-to-administer tool with great potential in both clinical and research fields of bilateral cerebral palsy.

Correlation of quantitative texture analysis of cranial ultrasound with later neurobehavior in preterm infants.

The purpose of the study was to evaluate the association between a quantitative texture analysis of early neonatal brain ultrasound images and later neurobehavior in preterm infants. A prospective cohort study including 120 preterm (<33 wk of gestational age) infants was performed. Cranial ultrasound images taken early after birth were analyzed in six regions of interest using software based on texture analysis. The resulting texture scores were correlated with the Neonatal Behavioural Assessment Scale (NBAS) at term-equivalent age. The ability of texture scores, in combination with clinical data and standard ultrasound findings, to predict the NBAS results was evaluated. Texture scores were significantly associated with all but one NBAS domain and better predicted NBAS results than clinical data and standard ultrasound findings. The best predictive value was obtained by combining texture scores with clinical information and ultrasound standard findings (area under the curve = 0.94). We conclude that texture analysis of neonatal cranial ultrasound-extracted quantitative features that correlate with later neurobehavior has a higher predictive value than the combination of clinical data with abnormalities in conventional cranial ultrasound.

Correlation between a semiautomated method based on ultrasound texture analysis and standard ultrasound diagnosis using white matter damage in preterm neonates as a model.

OBJECTIVES: Diagnosis of white matter damage by cranial ultrasound imaging is still subject to interobserver variability and has limited sensitivity for predicting abnormal neurodevelopment later in life. In this study, we evaluated the ability of a semiautomated method based on ultrasound texture analysis to identify patterns that correlate with the ultrasound diagnosis of white matter damage. METHODS: The study included 44 very preterm neonates born at a median gestational age of 29 weeks 3 days (range, 26 weeks-31 weeks 6 days). Patients underwent cranial ultrasound scans within 1 week of birth and between 14 and 31 days of life. Periventricular leukomalacia was diagnosed by experienced clinicians on the 14- to 31-day scan according to standard criteria. To perform the texture analysis, 4 regions of interest were delineated in stored images: left and right periventricular areas and choroid plexuses. A classification algorithm was developed on the basis of the best combination of texture coefficients to correlate with the clinical diagnosis, and the ability of this algorithm to predict a later diagnosis of periventricular leukomalacia on the first scan was evaluated using a leave-one-out cross-validation. RESULTS: Periventricular leukomalacia was diagnosed by the standard procedure in 14 of 44 neonates. The texture classification algorithm performed on the first scan could identify cases with a later diagnosis of periventricular leukomalacia with sensitivity of 100% and accuracy of 97.7%. CONCLUSIONS: These data support the notion that semiautomated quantitative ultrasound analysis achieves early identification of changes in subclinical stages and warrant further investigation of the role of ultrasound texture analysis methods to improve early detection of neonatal brain damage.

Hipotermia inducida en los recién nacidos con encefalopatía hipóxico-isquémica (EHI). Un nuevo reto asistencial de la neonatología en Cataluña / Induced hypothermia in the newborn with hypoxic-ischemic encephalopathy. A new challenge in neonatal care in Catalonia

Fundamentos. La encefalopatía hipóxico-isquémica (EHI) perinatal en el recién nacido a término o casi a término es una importante causa de morbimortalidad en el periodo neonatal y de discapacidad ulterior en el niño 1-3. Las implicaciones médicas, sociales y legales que asocia la EHI son importantes y condicionan que ésta constituya un problema de salud pública. Durante todo el siglo XX no se ha dispuesto de ninguna aproximación terapéutica específica para prevenir o aminorar el daño cerebral asociado a esta agresión perinatal. Afortunadamente este panorama ha cambiado, ya que en los últimos años ha tenido lugar un importante avance terapéutico específico para la agresión hipóxico-isquémica del SNC: la hipotermia moderada sostenida. Diversos ensayos clínicos han mostrado que la reducción de la temperatura cerebral en 3-4ºC mediante un enfriamiento corporal total o selectivo del cabeza, iniciado antes de las 6 horas de vida y mantenido durante 72 horas, constituye una intervención eficaz para reducir la mortalidad y la discapacidad mayor en los supervivientes 7-9. Resultado. Este documento presenta las demostraciones que han conducido a que la EHI haya dejado de ser una condición huérfana de intervención terapéutica y examina brevemente los nuevos retos asistenciales que plantea(AU)

Background. Perinatal hypoxic-ischemic encephalopathy (HIE) in the term or near term newborn infant represents a major cause of morbidity and mortality during the neonatal period and subsequent disability in childhood. Medical, social, and legal implications of HIE are important and make this disease a public health problem. During the 20th century, measures aimed at preventing or ameliorating the brain damage associated with this perinatal aggression have been lacking. Fortunately, this situation seems to have changed in recent years with the use of moderate sustained hypothermia. Several clinical trials have shown that a reduction of cerebral temperature by 3-4oC via total body cooling or selective head cooling, initiated within the first 6 hours of life and maintained during 73 hours, is an effective intervention to decrease mortality and major disability among survivors. Result. In this manuscript we review the data that shows how HIE is no longer a disease with no therapeutic options, and we analyze the challenges that this new approach will pose on our healthcare system(AU)

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