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BACKGROUND: The ability to perceive and process visuospatial information is a condition for broader neurodevelopment. We examined the association of early visuospatial attention and processing with later neurodevelopmental outcome in very preterm infants. METHODS: Visuospatial attention and processing was assessed in 209 children (<30 weeks gestation) using an easy applicable eye tracking-based paradigm at 1 and 2 years. Average reaction times to fixation (RTF) on specific visual stimuli were calculated, representing time needed for overall attention (Cartoon stimuli) and processing (Motion and Form stimuli). Associations between RTFs and various measures of development at 2 years including cognitive and motor development (Bayley Scales of Infant and Toddler Development-Third edition; Bayley-III), language (Lexi test) and behavior (Child Behavior Checklist) were examined. RESULTS: At 1 year, 100 ms slower Cartoon and Motion RTFs were associated with lower cognitive Bayley-III scores (-4.4 points, 95%CI: -7.4; -1.5 and -1.0 points, -1.8; -0.2, respectively). A 100 ms slower Cartoon RTF was associated with a 3.5 (-6.6; -0.5) point decrease in motor Bayley-III score. CONCLUSIONS: Visuospatial attention and motion processing at 1 year is predictive of overall cognitive and motor development 1 year later. The nonverbal eye tracking-based test can assist in early detection of preterm children at risk of adverse neurodevelopment. IMPACT: Visuospatial attention and processing at 1 year corrected age is predictive for overall cognitive and motor development 1 year later in preterm infants. First study to relate early visuospatial attention and processing with later neurodevelopmental outcome in preterm children. Early detection of preterm children at risk of adverse neurodevelopment, which allows for more timely interventions.
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Atención , Sistema Nervioso Central/fisiopatología , Recien Nacido Extremadamente Prematuro , Percepción Espacial , Percepción Visual , Preescolar , Discapacidades del Desarrollo/fisiopatología , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is a rare lysosomal storage disorder in which the pathologic storage of glycosaminoglycans in various tissues can lead to severe symptoms, including cardiomyopathy. We report on a child with Maroteaux-Lamy syndrome whose cardiac condition deteriorated and eventually led to cardiac failure at the age of 7 years due to severe mitral regurgitation. She received a mitral valve replacement and tricuspid repair with successful outcome. Histologic examination of the mitral valve showed abundant "clear" cells in both the leaflets and chordae tendineae. In Hurler disease (MPS I), similar cells have been identified as activated valvular interstitial cells (VICs, a myofibroblast like cell type). Here we report that the "clear" cells are CD68 positive, a frequently used marker of macrophage lineage. The "clear" cells remained unstained with the more specific macrophage marker CD14 while persistent staining of other cells demonstrated macrophage infiltration. From these observations, we infer that macrophages are involved in mitral valve pathology in MPS VI.
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Macrófagos/patología , Válvula Mitral/patología , Mucopolisacaridosis VI/patología , Biopsia , Preescolar , Femenino , Humanos , Imagen por Resonancia Magnética , Mucopolisacaridosis VI/diagnóstico , Mucopolisacaridosis VI/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Children with intestinal failure (IF) receiving long-term parenteral nutrition (PN) have altered body composition (BC), but data on BC changes from start of PN onwards are lacking. OBJECTIVES: We aimed to assess growth and BC in infants after neonatal intestinal surgery necessitating PN and at risk of IF, and to explore associations with clinical parameters. METHODS: A prospective cohort study in infants after intestinal surgery. IF was defined as PN dependency for >60 d. SD scores (SDS) for anthropometry were calculated until 6-mo corrected age. In a subgroup, fat mass (FM) and fat-free mass (FFM) were measured with air-displacement plethysmography at 2- and 6-mo corrected age. SDS for length-adjusted FM index and FFM index were calculated. Associations between cumulative amount of PN and BC parameters were analyzed with linear mixed-effect models. RESULTS: Ninety-five neonates were included (54% male, 35% born <32 wk) and 39 infants (41%) had IF. Studied infants had compromised anthropometric parameters during follow-up. At 6-mo corrected age, they remained smaller (median weight-for-age SDS -0.9 [IQR -1.5, 0.1], P < 0.001) than the normal population. In 57 infants, 93 BC measurements were performed. FM index SDS was lower than in healthy infants at 2- and 6-mo corrected age (-0.9 [-1.6, -0.3], P < 0.001 and -0.7 [-1.3, 0.1], P = 0.001, respectively), but FFM index SDS did not differ. A higher cumulative amount of PN predicted a higher FM index in female infants but lower FM index in male infants. CONCLUSIONS: In this cohort of infants receiving PN after intestinal surgery, compromised anthropometrics, decreased FM, and adequate FFM were observed during the first 6 mo. Male and female infants seemed to respond differently to PN when it comes to FM index. Continuing growth monitoring after the age of 6 mo is strongly recommended, and further research should explore the benefit of incorporating ongoing BC monitoring during follow-up.
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Tejido Adiposo/fisiopatología , Antropometría , Índice de Masa Corporal , Insuficiencia Intestinal/fisiopatología , Nutrición Parenteral/efectos adversos , Composición Corporal , Femenino , Humanos , Lactante , Recién Nacido , Insuficiencia Intestinal/terapia , Masculino , Periodo Posoperatorio , Estudios Prospectivos , Factores SexualesRESUMEN
Background: Postnatal brain growth is an important predictor of neurodevelopmental outcome in preterm infants. A new reliable proxy for brain volume is cranial volume, which can be measured routinely by 3-D laser scanning. The aim of this study was to develop reference charts for normal cranial volume in newborn infants at different gestational ages starting from late preterm for both sexes. Methods: Cross-sectional cohort study in a German university hospital, including singleton, clinically stable, neonates born after 34 weeks of gestation. Cranial volume was measured in the first week of life by a validated 3-D laser scanner. Cranial volume data was modeled to calculate percentile values by gestational age and birth weight and to develop cranial volume reference charts for girls and boys separately. Results: Of the 1,703 included infants, 846 (50%) were female. Birth weights ranged from 1,370 to 4,830 grams (median 3,370). Median cranial volume ranged from 320 [interquartile range (IQR) 294-347] ml at 34 weeks to 469 [IQR 442-496] ml at 42 weeks and was higher in boys than in girls. Conclusions: This study presents the first reference charts of cranial volume which can be used in clinical practice to monitor brain growth between 34 and 42 weeks gestation in infants.
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BACKGROUND: Concerns are raised about the influence of rapid growth on excessive fat mass (FM) gain in early life and later cardiometabolic health of infants born preterm. OBJECTIVES: To study the association between postnatal weight gain trajectories and body composition in infancy in infants born very preterm. METHODS: In infants born <30 weeks gestation, we evaluated associations between weight Z-score trajectories for three consecutive timeframes (NICU stay, level-II hospital stay and at home) and body composition, measured at 2 and 6 months corrected age by air-displacement plethysmography. RESULTS: Of 120 infants included, median gestational age at birth was 27+5 (interquartile range 26+1 ;28+5 ) and birth weight 1015 g (801;1250). The majority of infants did not make up for their initial loss of weight Z-score, but growth and later body composition were within term reference values. Weight gain during NICU stay was not associated with fat mass (absolute, %FM or FM index) in infancy. Weight gain during NICU and level II hospital stay was weakly associated with higher absolute lean mass (LM), but not after adjustment for length (LM index). Weight gain in the level-II hospital was positively associated with fat mass parameters at 2 months but not at 6 months. Strongest associations were found between weight gain at home and body composition (at both time points), especially fat mass. CONCLUSIONS: Weight gain in different timeframes after preterm birth is associated with distinct parameters of body composition in infancy, with weight gain at home being most strongly related to fat mass.
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Trayectoria del Peso Corporal , Nacimiento Prematuro , Composición Corporal , Peso Corporal , Femenino , Humanos , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Pletismografía , EmbarazoRESUMEN
BACKGROUND: Breastfeeding is considered the most optimal mode of feeding for neonates and mothers. Human milk changes over the course of lactation in order to perfectly suit the infant's nutritional and immunological needs. Its composition also varies throughout the day. Circadian fluctuations in some bioactive components are suggested to transfer chronobiological information from mother to child to assist the development of the biological clock. This review aims to give a complete overview of studies examining human milk components found to exhibit circadian variation in their concentration. METHODS: We included studies assessing the concentration of a specific human milk component more than once in 24 h. Study characteristics, including gestational age, lactational stage, sampling strategy, analytical method, and outcome were extracted. Methodological quality was graded using a modified Newcastle-Ottawa Scale (NOS). RESULTS: A total of 83 reports assessing the circadian variation in the concentration of 71 human milk components were included. Heterogeneity among studies was high. The methodological quality varied widely. Significant circadian variation is found in tryptophan, fats, triacylglycerol, cholesterol, iron, melatonin, cortisol, and cortisone. This may play a role in the child's growth and development in terms of the biological clock.
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Relojes Biológicos/fisiología , Ritmo Circadiano/fisiología , Fenómenos Fisiológicos Nutricionales del Lactante , Lactancia/fisiología , Leche Humana/química , Adulto , Lactancia Materna , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: Very low-birth-weight (VLBW) infants are at risk for neurodevelopment impairment. This study assessed the effect of early aggressive parenteral nutrition (PN) on long-term outcome in VLBW infants. MATERIALS AND METHODS: Directly after birth, VLBW infants (birth weight <1500 g, n = 142) were randomized to 5 different PN regimes. Controls (n = 46) received glucose and standard-dose amino acids (AAs; 2.4 g/[kg·d]) from birth onward and pure soybean oil fat emulsion (SOY) on the second day of life. Two intervention groups received glucose, standard-dose AAs, and lipids from birth onward: SOY (n = 24) or mixed fat emulsion (MIX, n = 25). The 2 other intervention groups received glucose, high-dose AAs (3.6 g/[kg·d]), and lipids from birth onward: SOY (n = 24) or MIX (n = 23). The primary outcome of this follow-up study was the composite outcome of "death or major disability" at 2 years corrected age. Secondary outcomes were death, major disabilities, neurodevelopmental scores, and anthropometry. RESULTS: Follow-up rate was 92% (n = 134). Thirty-five (26%) infants had died or had a major disability, with no differences between intervention groups and controls. Increased odds for death were observed in the standard-dose AA-MIX group (odds ratio, 5.4; 95% confidence interval [CI], 1.1-27.0). Neurodevelopmental scores and incidence of major disabilities did not differ between groups. Growth in the high-dose AA-MIX group was enhanced compared with growth in controls at 2 years corrected age (+0.51 [0.01-1.02] weight SDS). CONCLUSION: This randomized controlled hypothesis-generating study demonstrated no beneficial effect of early high-dose AA administration and mixed fat emulsions on survival and neurodevelopmental outcome in VLBW infants, although growth was enhanced.
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Fenómenos Fisiológicos Nutricionales del Lactante , Nutrición Parenteral/métodos , Aminoácidos/uso terapéutico , Preescolar , Femenino , Estudios de Seguimiento , Glucosa/uso terapéutico , Humanos , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Lípidos/uso terapéutico , Masculino , Aceite de Soja/uso terapéutico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Aggressive parenteral nutritional practices were implemented in clinical practice over a decade ago to prevent early growth retardation in preterm infants. We aimed to study adherence to current nutritional recommendations in a population of very preterm infants, and to evaluate growth in early life. METHODS: Preterm infants (gestational age <30 weeks and birth weight <1500 g) were included in a prospective observational cohort study. Data on parenteral and enteral intake were collected on days 1-7, 14, 21 and 28 (d28) of life. Growth data were collected at birth, at moment of maximal weight loss (dip), and either at discharge from the neonatal intensive care unit or at d28, whichever came first. Nutritional intakes were compared to recommendations of current guidelines. The target growth rate was 15-20 g/kg/d. RESULTS: Fifty-nine infants (63% male) were included. Median gestational age was 27 3/7 (interquartile range 25 6/7;28 4/7), and birth weight was 920 g (720;1200). Median macronutrient intakes were within or above the targets on all study days, but energy targets were not met before day 5. Median growth rates were 9.5 and 18.1 g/kg/d, when calculated from respectively birth and dip to discharge/d28. Eight (14%) versus 46 (78%) infants met the growth targets, when evaluated from respectively birth and dip to discharge/d28. CONCLUSIONS: In this cohort, only energy intake up to day 5 was lower than recommended. Growth targets were achieved in the majority of the infants, but only when evaluated from dip onward, not from birth.
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Ingestión de Energía/fisiología , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Estado Nutricional , Nutrición Parenteral/métodos , Pérdida de Peso/fisiología , Peso Corporal , Estudios de Cohortes , Femenino , Humanos , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Environmental influences during pregnancy are able to affect off spring phenotype with lifelong effects. Clinical applicable markers are needed to identify foetuses at risk for neonatal adiposity. This systematic review aims to 1) review the current literature on prenatal markers of neonatal fat mass, and 2) appraise the clinical applicability of the assessed markers. METHODS: A systematic literature search was conducted to identify studies meeting the following inclusion criteria: 1) original research papers in English; 2) research on dynamic and measurable prenatal markers of neonatal fat mass; 3) neonatal fat mass measurement within one month after birth, using the four-compartment model, magnetic resonance imaging, dual-energy X-ray absorptiometry or air displacement plethysmography. Two reviewers independently performed study selection, assessment of methodological (QUADAS-II) and statistical quality and appraisal of clinical applicability. RESULTS: Of 2333 studies primarily identified by the search strategy, 16 studies were included. Four of these were both methodologically and statistically of moderate or high quality. Prenatal markers investigated were ultrasound parameters, maternal biochemical markers and maternal characteristics. Markers of predefined interest were maternal pre-pregnancy body mass index, fasting glucose and HbA1c, showing varying results. A meta-analysis was not possible due to substantial methodological heterogeneity. Clinically applicability of all markers was rated poor. CONCLUSIONS: Although associations were found, no useful marker was identified, due to lack of methodological and statistical quality, inconsistent results and poor clinical applicability. No markers were investigated in the periconceptional and embryonic period.
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Adiposidad , Composición Corporal , Absorciometría de Fotón , Biomarcadores/sangre , Glucemia/metabolismo , Índice de Masa Corporal , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Lactante , Pletismografía , Embarazo , Factores de Riesgo , Ultrasonografía PrenatalRESUMEN
BACKGROUND & AIMS: An anabolic state can be achieved upon intravenous amino acid administration during the immediate postnatal phase despite a low energy intake. The optimal dosing of amino acid and energy intake has yet to be established. The aim was to quantify the efficacy of early initiation of parenteral lipids and increased amounts of amino acids on metabolism and protein accretion in very low birth weight infants. METHODS: 28 very low birth weight infants were randomized to receive parenteral nutrition with glucose and either 2.4 g amino acids/(kg·d) (control group), 2.4 g amino acids/(kg·d) plus 2-3 g lipid/(kg·d) (AA + lipid group), or 3.6 g amino acids/(kg·d) plus 2-3 g lipid/(kg·d) (high AA + lipid group) from birth onward. On postnatal day 2, we performed a stable isotope study with [1-(13)C]phenylalanine, [ring-D4]tyrosine, [U-(13)C6,(15)N]leucine, and [methyl-D3]α-ketoisocaproic acid to quantify intermediate amino acid metabolism. RESULTS: The addition of lipids only had no effect on phenylalanine metabolism, whereas the addition of both lipids and additional amino acids increased the amount of phenylalanine used for protein synthesis. In addition, high amino acid intake significantly increased the rate of hydroxylation of phenylalanine to tyrosine, increasing the availability of tyrosine for protein synthesis. However, it also increased urea concentrations. Increasing energy intake from 40 to 60 kcal/(kg·d) did not increase protein efficiency as measured by phenylalanine kinetics. The leucine data were difficult to interpret due to the wide range of results and inconsistency in the data between the phenylalanine and leucine models. CONCLUSIONS: High amino acid and energy intakes from birth onwards result in a more anabolic state in very low birth weight infants, but at the expense of higher urea concentrations, which reflects a higher amino acid oxidation. Long-term outcome data should reveal whether this policy deserves routine implementation. This trial was registered at www.trialregister.nl, trial number NTR1445, name Nutritional Intervention for Preterm Infants-2.