Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City.

Children's air pollution exposures are associated with systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The Apolipoprotein E (APOE) 4 allele is the most prevalent genetic risk for AD, with higher risk for women. We assessed whether gender, BMI, APOE and metabolic variables in healthy children with high exposures to ozone and fine particulate matter (PM2.5) influence cognition. The Wechsler Intelligence Scale for Children (WISC-R) was administered to 105 Mexico City children (12.32±5.4 years, 69 APOE 3/3 and 36 APOE 3/4). APOE 4v 3 children showed decrements on attention and short-term memory subscales, and below-average scores in Verbal, Performance and Full Scale IQ. APOE 4 females had higher BMI and females with normal BMI between 75-94% percentiles had the highest deficits in Total IQ, Performance IQ, Digit Span, Picture Arrangement, Block Design and Object Assembly. Fasting glucose was significantly higher in APOE 4 children p=0.006, while Gender was the main variable accounting for the difference in insulin, HOMA-IR and leptin (p<.05). Gender, BMI and APOE influence children's cognitive responses to air pollution and glucose is likely a key player. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5-2SD from average IQ). Young female results highlight the urgent need for gender-targeted health programmes to improve cognitive responses. Multidisciplinary intervention strategies could provide paths for prevention or amelioration of female air pollution targeted cognitive deficits and possible long-term AD progression.

Immunotoxicity and environment: immunodysregulation and systemic inflammation in children.

Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.

Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.

Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution.

BACKGROUND: Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. OBJECTIVES: The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O(3) that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. METHODS: We conducted a study of 81 children, 7.9 +/- 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O(3) levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. RESULTS: Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 mum in aerodynamic diameter (PM(2.5)) before endothelin-1 measurement (p = 0.03). CONCLUSIONS: Chronic exposure of children to PM(2.5) is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure.

Lung radiology and pulmonary function of children chronically exposed to air pollution.

We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala. In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S. National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters

Respiratory damage in children exposed to urban pollution.

Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.

Assessment of physical education time and after-school outdoor time in elementary and middle school students in south Mexico City: the dilemma between physical fitness and the adverse health effects of outdoor pollutant exposure.

Strategies to promote lifelong physical activity among children are needed to stem the adverse health consequences of inactivity. However, the health effects in growing children of long-term exposure to a polluted atmosphere are of deep concern. The atmosphere of south Mexico City (SMC) is characterized by a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Radiological evidence suggests that small-airway disease could be present in clinically healthy, tobacco unexposed SMC children. The aim of this study was to assess, by means of a self-reported questionnaire, the physical education class times, daily outdoor after-school exposure time, and tobacco exposure in students attending public elementary and middle schools in SMC. Additionally, the time each student spent viewing television was assessed, and the authors measured each student's weight and height to determine body mass index (BMI, weight in kg divided by height in m2). The survey included 1,159 students in grades 7-9. The authors identified 2 critical periods of outdoor exposure in SMC children that coincided with significant concentrations of both ozone and particulate matter with diameters less than 10 micrometers (PM10): during school time after 11:00 A.M. and in the after-school outdoor activity period, usually extending from 1:00 P.M. to 6:00 P.M. Thirty-two percent of elementary and 61% of middle school students have physical education classes after 11:00 A.M. Students in SMC spend an average of 19.6 hr/wk outdoors in the after-school period, during which time they are engaged in light to moderate physical activities. Half of the students are exposed to tobacco smoke at home, and 7% of middle school students smoke. On the basis of BMI, 60% of students were classified as undernourished, overweight, or obese. No correlations were found between BMI and time spent viewing TV, time outdoors (on weekdays and weekends), or exposure to environmental tobacco smoke. Children and adolescents in SMC are participating in physical activities that enhance multiple components of health-related fitness. However, their activities occur outdoors, where they are exposed to high concentrations of air pollutants throughout the year. The authors believe that SMC children and adolescents must be educated, through both the school and health systems, regarding ways to obtain the necessary exercise while protecting themselves from the high concentrations of pollutants. Individuals should instruct and encourage young people to be involved in lifetime fitness activities and to eat balanced diets, if the goal is to control health-care costs, reduce disease incidence, and improve the overall quality of life of the Mexico City population.

Exposure to urban air pollution and bone health in clinically healthy six-year-old children.

Air pollution induces systemic inflammation, as well as respiratory, myocardial and brain inflammation in children. Peak bone mass is influenced by environmental factors. We tested the hypothesis that six-year-olds with lifetime exposures to urban air pollution will have alterations in inflammatory markers and bone mineral density (BMD) as opposed to low-polluted city residents when matched for BMI, breast feeding history, skin phototype, age, sex and socioeconomic status. This pilot study included 20 children from Mexico City (MC) (6.17 years ± 0.63 years) and 15 controls (6.27 years ± 0.76 years). We performed full paediatric examinations, a history of outdoor exposures, seven-day dietary recalls, serum inflammatory markers and dual-energy X-ray absorptiometry (DXA). Children in MC had significantly higher concentrations of IL-6 (p=0.001), marked reductions in total blood neutrophils (p= 0.0002) and an increase in monocytes (p=0.005). MC children also had an insufficient Vitamin D intake and spent less time outdoors than controls (p<0.001) in an environment characterized by decreased UV light, with ozone and fine particulates concentrations above standard values. There were no significant differences between the cohorts in DXA Z scores. The impact of systemic inflammation, vitamin D insufficiency, air pollution, urban violence and poverty may have long-term bone detrimental outcomes in exposed paediatric populations as they grow older, increasing the risk of low bone mass and osteoporosis. The selection of reference populations for DXA must take into account air pollution exposures.

Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology.

Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.

Arrinia congénita / Congenitalarrhinia

Introducción. La arrinia congénita es una anomalía craneofacial rara, la cual se presenta en forma aislada o asociada a otros defectos, o bien puede ser componente de un síndrome o alteración genética. El tratamiento dependerá de la extensión y gravedad del defecto, pero es fundamental establecer una vía aérea permeable.Caso clínico. Se presenta el caso de un recién nacido de 37 semanas de edad gestacional, de 8 horas de vida extrauterina y con arrinia congénita, sin antecedentes heredo-familiares de importancia y que cursó con dificultad respiratoria grave que requirió de traqueostomía. Como defecto asociado presentó agenesia del cuerpo calloso.Conclusión. El tratamiento primario de los pacientes con arrinia congénita consiste en establecer una vía aérea permeable, siendo la traqueostomía el procedimiento quirúrgico de elección. La corrección definitiva del defecto dependerá de la gravedad del mismo y debido a la escasa frecuencia de estos defectos aún no existen lineamientos bien definidos; sin embargo, es importante que el abordaje sea integral y que se proporcione apoyo psicológico tanto a la familia como al paciente.

Evolución del manejo del niño prematuro e incremento de su sobrevida / Progress in the management of premature children and increase in survival rate

Se hace una relación histórica comentada de la participación que los avances científicos y tecnológicos en Perinatología a nivel internacional, han tenido en el manejo del niño pretérmino para mejorar su sobrevida y se mencionan las contribuciones significativas que en este campo de la investigación se han realizado en los últimos 25 años en el Instituto Nacional de Pediatría

Gemelos unidos heterópagos. Presentación de cinco casos / Conjoined twins heteropagus. Presentation of five cases

Se describen cinco casos de gemelos unidos variedad heterópagos, de acuerdo a la clasificación de Potter. Contrario a la literatura, predominó el sexo masculino (3/5), la mortalidad fué de 40% (2/5). El primer caso presentó al parásito con extremidades y cráneo malformados, así como una porción del abdomen unidos al esternón y epigastrio. El segundo caso, el más raro de todos, incluso en la literatura internacional, mostraba una cabeza supernumeraria unida a la región occipito-parietal del autósito. Falleció por complicaciones no relacionadas a la cirugía. Los tres casos restantes presentaron al parásito unido a cara posterior del tórax, sacro o pelvis. Se presentan los resúmenes de los tres casos más representativos. En la actualidad, los tres pacientes sobrevivientes se encuentran en buenas condiciones. Se revisan las teorías sobre su embriogénesis y se analizan errores comunes de clasificación.

Enfermedad por membranas hialinas: epidemiología en el Instituto Nacional de Pediatría / Hyaline membrane disease: epidemiology at the national Institute of Pediatrics

Se estudiaron 134 recién nacidos con enfermedad por membranas hialinas en la unidad de Cuidados intensivos Neonatales del Instituto Nacional de Pediatría (INP) de 1989 a 1991; 59.70 por ciento correspondieron a varones y 40.30 por ciento a mujeres; la edad gestacional promedio fue 32.4 semanas y el peso al nacer de 1,715 g. Las complicaciones más frecuentes fueron icteriacia, trastornos metabólicos, anemia, sepsis, persistentcia de conducto arterioso y hemorragia intracraneana. La mortalidad fue de 54.47 por ciento; las secuelas de los sobrevivientes, de 72 por ciento, principalemente neurológicas. Se concluye que el principal factor es la prematurez y que podría ayudarse a disminuir su frecuencia con un buen control médico prenatal

Traslado del recién nacido de alto riesgo / Transportation of high risk newborn infant

Breve análisis sobre la justificación y los recursos que se requieren para el funcionamiento de un programa de transporte de recién nacidos de alto riesgo. Se presenta una opción para la organización y funcionamiento de un sistema coordinado de referencia y transporte de niños recién nacidos de alto riesgo en nuestro medio (país en vías de desarrollo)

Eficacia de un analizador de bilirrubina no invasivo en neonatos / Utility of a non-invasive bilirubin transcutaneous analyzer in neonates

Introducción. La ictericia es una causa frecuente de consulta en el recién nacido. Se han intentado métodos para determinar su intensidad en forma no invasiva. Se realizó el presente estudio para evaluar la utilidad de un analizador no invasivo de bilirrubina. Material y métodos. Se estudiaron 22 neonatos con ictericia, a quienes se les determinó bilirrubina sérica total y bilirrubina transcutánea en la piel de la frente, tórax y abdomen con el método de espectrofotometría de reflectancia (Bilichek de Spectrx). Se realizó comparación de resultados en los diferentes sitios contra la bilirrubina sérica total. Para el análisis estadístico se realizó prueba de correlación de Pearson. Resultados. La mejor correlación fue en la piel de la frente con un coeficiente de pearson de 0.958 (P<0.001) con error estándar estimando de 1.87 mg/dL. Conclusión. La determinación predictiva transcutánea es eficaz cuando se usa dentro de los límites de funcionamiento del analizador no invasivo de bilirrubina

Hipocalcemia en prematuros / Hypocalcemia in premature infants

Se estudiaron prospectivamente 56 recién nacidos prematuros que ingresaron al Departamento de Cuidados Intensivos Neonatales del I.N.P. durante un año. Se encontró hipocalcemia en 24 casos (0.43 por ciento). La patología más frecuentemente asociada a hipocalcemia, al momento de la hospitalización, fue dificultad respiratoria, 20 de 24 paciantes (0.8 por ciento); asfixia, 14 a 24 (0.6 por ciento) septicemía, 10 de 24 (0.4 por ciento) y hemorragia intracraneana, 8 de 24 (0.3 por ciento). La asociación hipocalcemia/sexo femenino fue de 13 a 24 (0.5 por ciento) y ayuno/hipocalcemia 17 de 24 (0.7, cifras altamante significativas con p<0.05 y p<0.01, respectivamente. El temblor fino y la hipotensión fueron más frecuentes en hipocalcémicos que en normocalcémicos. Los niños que recibieron furosemide requirieron aporte terapéutico de calcio por más tiempo que los que no lo recibieron (p<0.001)

Retinopatía del prematuro. Conceptos actuales / Retinopathy of the premature: current concepts

La retinopatía del prematuro es de tipo vasoproliferativo. Se caracteriza por diversos grados de afectación de la vasculatura retiniana en desarrollo; se presenta sobre todo en recién nacidos prematuros y afecta en especial a los de menor edad gestacional y bajo peso al nacer. Se han propuesto varias hipótesis etiopatogénicas de la retinopatía del prematuro. La hiperoxia es una de las principales. Sin embargo es probable que el espectro de la enfermedad depende dela interacción de varios factores más como las transfusiones de sangre, la deficiencia de vitamina E, la hipercarbia, la PCA, etc. En base a los hallazgos clínicos, y mediante la oftalmoscopía indirecta, se clasifica la retinopatía del prematuro en estadios clínicos que tienen gran valor práctico desde el punto de vista terapéutico y pronóstico. En esta revisión hacemos notar la importancia de la prevención, de la búsqueda, de la detección temprana, del tratamiento y seguimiento a largo plazo de esta enfermedad

Retinopatía del prematuro. Frecuencia en el Servicio de Neonatología del Instituto Nacional de Pediatría del 1o. de marzo de 1988 al 28 de febrero de 1989 / Retinopathy of the premature: frequence in the Service of Neonatology of Instituto Nacional de Pediatría from march 1st of 1988 to february 28 of 1989

Se examinaron los ojos de 25 niños recién nacidos prematuros que ingresaron al Servicio de Neonatología del Instituto Nacional de Pediatría en el período comprendido entre 1o. de marzo de 1988 al 28 de febrero de 1989. Todos pesaron menos de 2000 g al momento del nacimiento; llegaron al servicio en sus primeras 24 horas de vida; recibieron oxígeno y fueron dados de alta por mejoría. Cinco de estos niños desarrollaron retinopatía del prematuro en su fase aguda. Cuatro de ellos presentaron una retinopatía grado I y uno, retinopatía grado II de acuerdo a la clasificación Internacional de la Retinopatía del Prematuro publicada en 1984. Los niños que desarrollaron retinopatía, fueron pacientes con peso y una edad gestacional menor al nacimiento; fueron trasfundidos un mayor número de veces; recibieron FIO2 entre 80 y 100% por más tiempo, con una duración total de oxigenoterapia mayor que los niños que no la desarrollaron

Etiología, frecuencia, tratamiento y secuela de ictericia neonatal patológica en el Instituto Nacional de Pediatría de la SS, México, D.F.: revisión de casos de 1988 / Etiology, frecuency, treatment and secuelae of pathologic neonatal jaudince in the National Institute of Pediatrics of the Ministry of Health, Mexico, D.F.: 1988 cases review

Se estudiaron retrospectivamente 89 casos de ictericia patológica de entre los 200 pacientes con este diagnóstico tratados en la Unidad de Cuidados Intensivos Neonatales del Instituto Nacional de Pediatría de la ciudad de México, durante 1988. Todos reunieron las variables propuestas. En 31.5 por ciento, la ictericia fue unifactorial, y multifactorial en el 68.53 por ciento; las causas más frecuentes fueron: isoinmunización materno fetal al sistema ABO en 44/89 (49.43 por ciento); al sistema Rh 5/89 (5.62 por ciento); al sistema LEA 1/89; hipoxia 19.10 por ciento; cefalohematoma 5.6 por ciento; oxiticina 4.50 por cietno, y con menor frecuiencia infecciosas, metabólicas, por leche materna y malformación congénta de atresia intestinal. Los niveles de bilirrubina indirecta al ingreso fuerno de 35 mg por ciento como máximo con media de 22 mg por ciento. El tratamiento fue con fototerapia en todos los casos y en el 56.18 por cietno se efectuó exanguinotransfusión. No hubo mortalidad, y las secuelas neurológicas evaluadas al año de edad fueron leves en el 35 por ciento, moderadas el 4 por ciento, graves en el 6 por ciento y sin secuelas 55 por ciento.

El recién nacido potencialmente infectado: evaluación de factores de riesgo / The potentially infected newborn: risk factors evaluation

Dado que la información del neonato potencialmente infectado es escasa, en el Instituto Nacional de Pediatría se estudiaron retrospectivamente 136 pacientes atendidos durante un período de 46 meses. Se estableció su perfil clínico-bacteriológico y se encontró que éste y los factores maternos, no modificaron la frecuencia de infección o mortalidad secundaria a ésta. Todos los pacientes contaron con hemocultivo, siendo positivos en 21 neonatos (15.4%); 17 en prematuros y 4 en neonatos de término. La mortalidad se presentó en 6/21 (28.6%), todos pretérmino. Además de la prematurez, las patologías más frecuentemente asociadas fueron el síndrome de dificultad respiratoria, hemorragia intracraneana y persistencia del conducto arterioso. De los hemocultivos positivos, 13 fueron Gram-negativos (61.9%) y 8 por Gram-positivos (38.1%); de los Gram-negativos, Klebsiella enterobacter fue la más común con 4/13, entre los Gram-positivos, el Staphilococcus aureus con 7/8. La mortalidad por Gram-negativos se presentó en 5/13, contra 1/8 por Gram-positivos. En menores de 2 000 g, la frecuencia de infección fue mayor. Se justifica la toma de hemocultivo para diagnóstico, así como doble esquema antibiótico (ampicilina-aminoglucósido).