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1.
J Pediatr ; 259: 113443, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37105408

RESUMEN

OBJECTIVE: To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm. STUDY DESIGN: This is a cohort study of infants born at 22-26 weeks of gestation in National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by 3 maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death postdischarge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and 2 SDOH (eg, group comparisons by education adjusted for insurance and race). RESULTS: Of 7438 children, 5442 (73%) had at least 1 risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% CL 0.06, 0.68) and readmission more likely (aOR 1.27, 95% CL 1.12, 1.43) for infants whose mothers had public/no insurance vs private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CL 1.86, 3.00) and death 5 times as likely (aOR 5.22, 95% CL 2.54, 10.73) for infants with 3 risk-associated SDOH compared with those with none. CONCLUSIONS: Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death postdischarge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.


Asunto(s)
Cuidados Posteriores , Recien Nacido Extremadamente Prematuro , Recién Nacido , Lactante , Embarazo , Femenino , Humanos , Niño , Estudios de Cohortes , Determinantes Sociales de la Salud , Alta del Paciente , Edad Gestacional
2.
Pediatr Res ; 94(5): 1720-1730, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-34686832

RESUMEN

BACKGROUND: Severe retinopathy of prematurity (ROP) is associated with adverse outcomes. Relationships between milder ROP and outcomes have not been defined. We hypothesized that children with ROP stage ≤3 who did not receive ophthalmologic intervention would have worse motor, cognitive, and language skills and more vision abnormalities than children without ROP. METHODS: This was a secondary analysis of a randomized trial evaluating the effects of myo-inositol on ROP in the NICHD Neonatal Research Network. Primary outcomes were Bayley Scales of Infant Development composite scores; secondary outcomes included behavioral difficulties and ophthalmologic measures. Outcomes were compared using adjusted linear or modified Poisson models. RESULTS: Of 506 children, 173 (34%) had no ROP, 262 (52%) had ROP stage ≤3 without intervention, and 71 (14%) had ROP with intervention. There was no difference in motor, cognitive, or language scores between children with ROP stage ≤3 without intervention and children without ROP. Children with ROP stage ≤3 without intervention had a higher rate of strabismus compared to children without ROP (p = 0.040). CONCLUSION: Children with ROP stage ≤3 without intervention did not have adverse neurodevelopmental outcomes at 2 years' corrected age compared to children without ROP but did have an increased incidence of strabismus. IMPACT: This study addresses a gap in the literature regarding the relationship between milder forms of retinopathy of prematurity (ROP) that regress without intervention and neurodevelopment and vision outcomes. Children with a history of ROP stage ≤3 without intervention have similar neurodevelopmental outcomes at 2 years' corrected age as children born extremely preterm without a history of ROP and better outcomes than children with a history of ROP with ophthalmologic intervention. Counseling about likely neurodevelopment and vision outcomes for children born extremely preterm with a history of ROP may be tailored based on the severity of ROP. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: Inositol to Reduce Retinopathy of Prematurity Trial: NCT01954082.


Asunto(s)
Enfermedades del Recién Nacido , Retinopatía de la Prematuridad , Estrabismo , Recién Nacido , Lactante , Niño , Humanos , Retinopatía de la Prematuridad/complicaciones , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/epidemiología , Recien Nacido Prematuro , Inositol , Estrabismo/complicaciones , Edad Gestacional
3.
Telemed J E Health ; 29(4): 531-539, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36036802

RESUMEN

Background: Remote infant viewing (RIV) uses a bedside camera to allow families to view a livestream video of their neonate 24/7 from anywhere with internet access. Objective: The aim of this study was to evaluate family use of RIV for infants in the neonatal intensive care unit (NICU) during the COVID-19 pandemic and whether RIV use varied by patient room type. Study Design: Use of RIV was evaluated for NICU patients between October 1, 2019, and March 31, 2021. The date, time, and duration of every RIV were exported from the RIV database and linked to the patient's room type. Results: Among 980 patients, 721 (73.6%) were viewed using RIV. The median (interquartile range) number of views per patient-days was 12.5 (5.4-26.0). Based on monthly aggregate data, the proportion of patients with at least one RIV increased during the pandemic from 71.6% in April 2020 to 94.3% in March 2021 (p < 0.001). The monthly number of views and view duration per patient-days also increased (p = 0.003; p = 0.029, respectively). When evaluating patient-level data by room type, the median number of views per patient-days was higher for open-bay than single-family rooms (13.5 vs. 10.5; p < 0.001) and median view duration (minutes) per patient-days was longer (21.8 vs. 12.1; p < 0.001). Conclusions: Use of RIV in the NICU increased during the COVID-19 pandemic. RIV was used more frequently and for longer duration by families with newborns in an open-bay room. RIV allows families to observe their newborn when visitor restrictions are in place or when in-person visits may be less private or do not allow for physical distancing.


Asunto(s)
COVID-19 , Unidades de Cuidado Intensivo Neonatal , Recién Nacido , Lactante , Humanos , Habitaciones de Pacientes , Pandemias , COVID-19/epidemiología , Pacientes
4.
J Pediatr ; 220: 175-183.e8, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32093932

RESUMEN

OBJECTIVE: To determine how gestational age relates to research-identified autism spectrum disorder (ASD-R) in the context of perinatal risk factors. STUDY DESIGN: This is a population-based cohort study using the 1994-2000 Olmsted County Birth Cohort. Children included were born and remained in Olmsted County after age 3 years. ASD-R status was determined from signs and symptoms abstracted from medical and educational records. Cox proportional hazards models were fit to identify associations between perinatal characteristics and ASD-R. RESULTS: The incidence of preterm birth (<37 weeks' gestation) was 8.6% among 7876 children. The cumulative incidence of ASD-R was 3.8% (95% CI 3.3-4.2) at 21 years of age. Compared with children born at full term, the risk of ASD-R appeared to be increased for children born preterm with unadjusted hazard ratios (HRs) of 2.62 (95% CI 0.65-10.57), 1.68 (95% CI 0.54-5.29), and 1.60 (95% CI 1.06-2.40) for children born extremely preterm, very preterm, and moderate-to-late preterm, respectively. In a multivariable model adjusted for perinatal characteristics, the associations were attenuated with adjusted HRs of 1.75 (95% CI 0.41-7.40), 1.24 (95% CI 0.38-4.01), and 1.42 (95% CI 0.93-2.15), for children born extremely preterm, very preterm, and moderate-to-late preterm, respectively. Among children with maternal history available (N = 6851), maternal psychiatric disorder was associated with ASD-R (adjusted HR 1.73, 95% CI 1.24-2.42). CONCLUSIONS: The increased risk of ASD-R among children born preterm relative to children born full term was attenuated by infant and maternal characteristics.


Asunto(s)
Trastorno del Espectro Autista/epidemiología , Edad Gestacional , Nacimiento Prematuro/epidemiología , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Embarazo , Factores de Riesgo , Adulto Joven
5.
J Pediatr ; 219: 152-159.e5, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32008764

RESUMEN

OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior. RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P < .001) and pervasive developmental problems (P < .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values < .05). CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.


Asunto(s)
Displasia Broncopulmonar/psicología , Cognición , Conducta del Lactante , Desarrollo del Lenguaje , Destreza Motora , Displasia Broncopulmonar/complicaciones , Preescolar , Femenino , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido , Masculino , Problema de Conducta , Estudios Prospectivos , Índice de Severidad de la Enfermedad
6.
J Pediatr ; 208: 156-162.e5, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30738658

RESUMEN

OBJECTIVE: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment. STUDY DESIGN: A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation. RESULTS: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids. CONCLUSIONS: Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment. TRIAL REGISTRATION: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).


Asunto(s)
Corticoesteroides/uso terapéutico , Enfermedades del Prematuro/terapia , Resucitación/métodos , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Enfermedades del Prematuro/mortalidad , Masculino , Análisis Multivariante , Nacimiento Prematuro , Estudios Prospectivos , Resultado del Tratamiento
7.
N Engl J Med ; 372(19): 1801-11, 2015 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-25946279

RESUMEN

BACKGROUND: Between-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth. METHODS: We studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%). RESULTS: Overall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and survival without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to 6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR, 78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26 weeks of gestation. Hospital rates of active treatment accounted for 78% and 75% of the between-hospital variation in survival and survival without severe impairment, respectively, among children born at 22 or 23 weeks of gestation, and accounted for 22% and 16%, respectively, among those born at 24 weeks of gestation, but the rates did not account for any of the variation in outcomes among those born at 25 or 26 weeks of gestation. CONCLUSIONS: Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients. (Funded by the National Institutes of Health.).


Asunto(s)
Discapacidades del Desarrollo/epidemiología , Mortalidad Infantil , Recien Nacido Extremadamente Prematuro , Terapéutica/estadística & datos numéricos , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Enfermedades del Prematuro/terapia , Masculino , Resucitación/estadística & datos numéricos , Tasa de Supervivencia , Resultado del Tratamiento , Estados Unidos/epidemiología
9.
Acta Paediatr ; 107(8): 1339-1344, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29333635

RESUMEN

AIM: To characterise the relationship between bronchopulmonary dysplasia (BPD) severity and cognition in the post-surfactant era. METHODS: This was a single-centre retrospective analysis of a cohort of infants born 2009-2012. Inclusion criteria were as follows: admission within 48 hours of birth, gestational age 22-0/7-31-6/7 weeks, birthweight 400-1500 g and Bayley Scales of Infant and Toddler Development-III testing at 18-26 months corrected age. Infants (n = 151) were classified by BPD severity with the NIH Workshop definition. Generalised linear modelling and multivariate logistic regression were performed. RESULTS: Bayley cognitive score was not associated with BPD severity in univariate (p = 0.053) or multivariate (p = 0.503) analysis. About 27% of infants with no/mild BPD, 33% of infants with moderate BPD and 40% of infants with severe BPD had a cognitive score <85. There was no difference in the odds of cognitive score <85 based on BPD severity in univariate (p = 0.485) or multivariate analysis (p = 0.225). All infants with cognitive score <70 had severe BPD, although the association between cognitive score <70 and BPD severity was not significant. CONCLUSION: We found no independent effect of BPD severity level on cognition. The likelihood of a cognitive score <85 was not associated with BPD severity.


Asunto(s)
Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/epidemiología , Desarrollo Infantil/fisiología , Trastornos del Conocimiento/epidemiología , Recién Nacido de muy Bajo Peso , Surfactantes Pulmonares/uso terapéutico , Análisis de Varianza , Displasia Broncopulmonar/tratamiento farmacológico , Trastornos del Conocimiento/diagnóstico , Estudios de Cohortes , Comorbilidad , Estudios de Seguimiento , Edad Gestacional , Hospitales Universitarios , Humanos , Lactante , Recién Nacido , Masculino , Análisis Multivariante , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo
11.
JAMA ; 318(16): 1550-1560, 2017 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-29067428

RESUMEN

Importance: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants: A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions: Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results: Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance: Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration: clinicaltrials.gov Identifier: NCT00614744.


Asunto(s)
Discapacidades del Desarrollo/etiología , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/terapia , Teorema de Bayes , Discapacidades del Desarrollo/prevención & control , Femenino , Edad Gestacional , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/mortalidad , Recién Nacido , Masculino , Embarazo , Complicaciones del Embarazo , Tiempo de Tratamiento
12.
JAMA ; 318(1): 57-67, 2017 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-28672318

RESUMEN

IMPORTANCE: Hypothermia for 72 hours at 33.5°C for neonatal hypoxic-ischemic encephalopathy reduces death or disability, but rates continue to be high. OBJECTIVE: To determine if cooling for 120 hours or to a temperature of 32.0°C reduces death or disability at age 18 months in infants with hypoxic-ischemic encephalopathy. DESIGN, SETTING, AND PARTICIPANTS: Randomized 2 × 2 factorial clinical trial in neonates (≥36 weeks' gestation) with hypoxic-ischemic encephalopathy at 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network between October 2010 and January 2016. INTERVENTIONS: A total of 364 neonates were randomly assigned to 4 hypothermia groups: 33.5°C for 72 hours (n = 95), 32.0°C for 72 hours (n = 90), 33.5°C for 120 hours (n = 96), or 32.0°C for 120 hours (n = 83). MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate or severe disability at 18 to 22 months of age adjusted for center and level of encephalopathy. Severe disability included any of Bayley Scales of Infant Development III cognitive score less than 70, Gross Motor Function Classification System (GMFCS) level of 3 to 5, or blindness or hearing loss despite amplification. Moderate disability was defined as a cognitive score of 70 to 84 and either GMFCS level 2, active seizures, or hearing with amplification. RESULTS: The trial was stopped for safety and futility in November 2013 after 364 of the planned 726 infants were enrolled. Among 347 infants (95%) with primary outcome data (mean age at follow-up, 20.7 [SD, 3.5] months; 42% female), death or disability occurred in 56 of 176 (31.8%) cooled for 72 hours and 54 of 171 (31.6%) cooled for 120 hours (adjusted risk ratio, 0.92 [95% CI, 0.68-1.25]; adjusted absolute risk difference, -1.0% [95% CI, -10.2% to 8.1%]) and in 59 of 185 (31.9%) cooled to 33.5°C and 51 of 162 (31.5%) cooled to 32.0°C (adjusted risk ratio, 0.92 [95% CI, 0.68-1.26]; adjusted absolute risk difference, -3.1% [95% CI, -12.3% to 6.1%]). A significant interaction between longer and deeper cooling was observed (P = .048), with primary outcome rates of 29.3% at 33.5°C for 72 hours, 34.5% at 32.0°C for 72 hours, 34.4% at 33.5°C for 120 hours, and 28.2% at 32.0°C for 120 hours. CONCLUSIONS AND RELEVANCE: Among term neonates with moderate or severe hypoxic-ischemic encephalopathy, cooling for longer than 72 hours, cooling to lower than 33.5°C, or both did not reduce death or moderate or severe disability at 18 months of age. However, the trial may be underpowered, and an interaction was found between longer and deeper cooling. These results support the current regimen of cooling for 72 hours at 33.5°C. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01192776.


Asunto(s)
Hipotermia Inducida , Hipoxia-Isquemia Encefálica/terapia , Trastornos del Neurodesarrollo/prevención & control , Teorema de Bayes , Femenino , Humanos , Hipotermia Inducida/mortalidad , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/mortalidad , Lactante , Recién Nacido , Masculino , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/etiología , Factores de Tiempo , Insuficiencia del Tratamiento
13.
Hum Mutat ; 37(7): 653-60, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26931382

RESUMEN

Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a ß1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder.


Asunto(s)
Trastornos Congénitos de Glicosilación/genética , Manosiltransferasas/genética , Mutación , Polisacáridos/metabolismo , Biomarcadores/metabolismo , Trastornos Congénitos de Glicosilación/metabolismo , Femenino , Genes Letales , Glicosilación , Humanos , Masculino , Análisis de Secuencia de ADN , Análisis de Supervivencia
14.
Pediatr Res ; 80(2): 197-203, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27064239

RESUMEN

BACKGROUND: Late preterm birth (34-36 wk gestation) is a common occurrence with potential for altered brain development. METHODS: This observational cohort study compared children at age 6-13 y based on the presence or absence of the historical risk factor of late preterm birth. Children completed a battery of cognitive assessments and underwent magnetic resonance imaging of the brain. RESULTS: Late preterm children (n = 52) demonstrated slower processing speed (P = 0.035) and scored more poorly in visual-spatial perception (P = 0.032) and memory (P = 0.007) than full-term children (n = 74). Parents of late preterm children reported more behavioral difficulty (P = 0.004). There were no group differences in cognitive ability or academic achievement. Imaging revealed similar intracranial volumes but less total tissue and more cerebrospinal fluid (P = 0.004) for late preterm children compared to full-term children. The tissue difference was driven by differences in the cerebrum (P = 0.028) and distributed across cortical (P = 0.051) and subcortical tissue (P = 0.047). Late preterm children had a relatively smaller thalamus (P = 0.012) than full-term children. Only full-term children demonstrated significant decreases in cortical tissue volume (P < 0.001) and thickness (P < 0.001) with age. CONCLUSION: Late preterm birth may affect cognition, behavior, and brain structure well beyond infancy.


Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Recien Nacido Prematuro , Adolescente , Antropometría , Niño , Cognición , Trastornos del Conocimiento , Estudios de Cohortes , Discapacidades del Desarrollo/etiología , Femenino , Edad Gestacional , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Destreza Motora , Tamaño de los Órganos , Factores de Riesgo
15.
Dev Sci ; 19(2): 221-34, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25873181

RESUMEN

Interest in monitoring long-term neurodevelopmental outcomes of children born moderate-to-late preterm (32-36 weeks gestation) is increasing. Moderate-to-late preterm birth has a negative impact on academic achievement, which may relate to differential development of executive function (EF). Prior studies reporting deficits in EF in preterm children have almost exclusively assessed EF in affectively neutral contexts in high-risk preterm children (< 32 weeks gestation). Disrupted function in motivational or emotionally charged contexts (hot EF) following preterm birth remains uninvestigated, despite evidence that preterm children show differential development of neural circuitry subserving hot EF, including reduced orbitofrontal cortex volume. The present study is the first to examine whether low-risk, healthy children born moderate-to-late preterm exhibit impairments in the development of hot EF. Preterm children at age 4.5 years were less likely to choose larger, delayed rewards across all levels of reward magnitude on a delay discounting task using tangible rewards, but performed more similarly to their full-term peers on a delay aversion task involving abstract rewards and on measures of cool EF. The relationship between gestational age at birth and selection of delayed rewards extended across the entire gestational age range of the sample (32-42 weeks), and remained significant after controlling for intelligence and processing speed. Results imply that there is not a finite cut-off point at which children are spared from potential long-term neurodevelopmental effects of PT birth. Further investigation of reward processing and hot EF in individuals with a history of PT birth is warranted given the susceptibility of prefrontal cortex development to early environmental variations.


Asunto(s)
Desarrollo Infantil , Descuento por Demora , Función Ejecutiva , Nacimiento Prematuro , Preescolar , Emociones , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Motivación
16.
Pediatr Int ; 58(8): 785-8, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27325525

RESUMEN

Congenital nephrotic syndrome (NS) in the newborn is most frequently related to mutations in genes specific for structural integrity of the glomerular basement membrane and associated filtration structures within the kidney, resulting in massive leakage of plasma proteins into the urine. Occurrence of congenital NS in a multi-system syndrome is less common. We describe the case of an infant with deteriorating neurological status, seizures, edema, and proteinuria who was found to have a mutation in gene ALG1 and a renal biopsy consistent with congenital NS. Furthermore, we briefly review rare existing case reports documenting congenital NS in patients with mutations in ALG1, and treatment strategies, including novel use of peritoneal dialysis.


Asunto(s)
Anomalías Múltiples , Trastornos Congénitos de Glicosilación/genética , ADN/genética , Manosiltransferasas/genética , Mutación , Síndrome Nefrótico/genética , Trastornos Congénitos de Glicosilación/metabolismo , Análisis Mutacional de ADN , Glicosilación , Humanos , Recién Nacido , Masculino , Manosiltransferasas/metabolismo , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/terapia , Diálisis Peritoneal
17.
Am J Perinatol ; 31(4): 305-14, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23775064

RESUMEN

OBJECTIVE: Very preterm birth (< 32 weeks' gestation) affects cognitive development. The impact of late preterm birth (34 to 36 weeks' gestation) on cognition, specifically executive function, is not fully characterized. The aim of this study was to assess whether late preterm children demonstrate impaired executive function compared with full-term children (38 to 42 weeks' gestation). STUDY DESIGN: This was a prospective cohort study of 4-year-old children. Preterm (n = 39) and full-term children (n = 44) completed a battery of executive function tasks and the Peabody Picture Vocabulary Test-4. Parents completed the Behavior Rating Inventory of Executive Function-Preschool version. RESULTS: Preterm children performed worse on the verbal inhibitory control (p = 0.02) and short-term verbal memory (p = 0.01) tasks. Gestational age predicted performance on the verbal inhibitory control (p = 0.02) and short-term verbal memory (p = 0.04) tasks. There was no group difference in nonverbal inhibitory control (p = 0.45) or spatial memory (p = 0.60). Parents of preterm and full-term children rated their children's behavior similarly (p = 0.79). CONCLUSION: Late preterm children demonstrated compromised verbal inhibitory control and short-term verbal memory compared with full-term peers. Late preterm children may not be spared from altered brain development. Further research is indicated to determine whether to screen late preterm children for executive function deficits.


Asunto(s)
Desarrollo Infantil/fisiología , Trastornos del Conocimiento/fisiopatología , Función Ejecutiva/fisiología , Edad Gestacional , Recien Nacido Prematuro/psicología , Inhibición Psicológica , Memoria a Corto Plazo/fisiología , Estudios de Casos y Controles , Preescolar , Estudios de Cohortes , Femenino , Humanos , Pruebas del Lenguaje , Masculino , Pruebas Neuropsicológicas , Estudios Prospectivos
18.
ATS Sch ; 5(1): 162-173, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38638918

RESUMEN

Background: Pediatric residents frequently manage critically ill neonates but have limited systematic training in mechanical ventilation (MV). Competing demands, varying learner levels, and topic complexity contribute to inconsistent education. A blended learning approach may be ideally suited to achieve meaningful learning but has not been described for this topic and learner. Objective: To design, implement, and evaluate a flipped classroom for pediatric residents in neonatal MV. Methods: We used Kern's six-step framework for curricular development to create a flipped classroom curriculum in neonatal MV. Individual prework included interaction with six prerecorded animated whiteboard videos, while in-person learning occurred in small groups at the bedside of a ventilated infant. A mixed-methods evaluation included surveys, quantitative knowledge test scores (before, immediately after, and six months after course completion), and qualitative analysis of participant focus groups. Results: Twenty-six learners participated in the curriculum. Mean knowledge test scores rose and were sustained after course completion (51% baseline, 82% immediate posttest, 90% retention; P < 0.001). Learners identified various design elements, technology affordances, and instructor factors as meaningful, and they identified unexpected impacts of the curriculum beyond knowledge acquisition, including effects on professional identities, interdisciplinary communication skills, and contribution to the culture of safety. Conclusion: This curriculum aligned with resident roles, was meaningful to learners, and led to long-term increases in knowledge scores and access to quality education; flipped classroom design using meaningful learning theory and leveraging animated whiteboard technology may be a useful strategy for other highly complex topics in graduate medical education.

19.
JAMA Pediatr ; 178(5): 454-464, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38466268

RESUMEN

Importance: Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding. Objective: To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm. Design, Setting, and Participants: This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks' gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic). Main Outcomes and Measures: The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks' gestation, death and neurodevelopmental impairment at 22 to 26 months' corrected age. Results: Of the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type. Conclusions and Relevance: For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.


Asunto(s)
Recien Nacido Extremadamente Prematuro , Determinantes Sociales de la Salud , Humanos , Femenino , Recién Nacido , Masculino , Estudios Retrospectivos , Estados Unidos , Adulto , Lactante , Estudios Prospectivos
20.
J Perinatol ; 43(3): 350-356, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36088494

RESUMEN

OBJECTIVE: We aimed to determine whether the use of remote infant viewing (RIV) in a neonatal intensive care unit (NICU) differed based on maternal sociodemographic factors. METHODS: The number of RIV camera views and view duration were obtained for NICU patients between 10/01/2019 and 3/31/2021 and standardized relative to patient days. Maternal sociodemographic and neonatal characteristics were obtained from institutional databases. RESULTS: Families in which mothers were unmarried (aOR 1.42, 95% CI 1.03-1.95), did not require an interpreter (aOR 2.86, 95% CI 1.54-5.32), were multiparous (aOR 1.56, 95% CI 1.16-2.10), delivered prior to 37 weeks' gestation (aOR 1.57, 95% CI 1.17-2.12), or resided ≥50 miles from the NICU (aOR 1.38, 95% CI 1.02-1.87) were significantly more likely to use RIV. CONCLUSION: Family use of RIV in the NICU varied by multiple sociodemographic factors. Further investigation to understand and to address potential equity gaps revealed or created by RIV are warranted.


Asunto(s)
Cuidado Intensivo Neonatal , Factores Sociodemográficos , Recién Nacido , Femenino , Lactante , Humanos , Edad Gestacional , Madres , Unidades de Cuidado Intensivo Neonatal
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