[In-utero antiretroviral exposure and mitochondrial toxicity in a cohort of uninfected infants born to HIV-1-infected women]. / Exposición a antirretrovirales y toxicidad mitocondrial en una cohorte de niños no infectados hijos de madres VIH positivas.

INTRODUCTION: In this study, we attempt to find out the percentage of uninfected infants born to HIV-infected women and exposed in-utero and perinatally to Antiretroviral Treatment (ART) that show high lactate levels, or any other mitochondrial damage markers (such as hypertransaminasaemia or hyperamylasaemia), during the first three months of age. We shall also establish whether certain drugs used in-utero are associated with higher lactate, transaminase or amylase levels. METHODS: We analysed the available data from 623 uninfected infants born in the Spanish FIPSE cohort that were born in the period 2000-2005. The normal values for lactate, transaminases and amylase were set according to AIDS Clinical Groups Trials toxicity tables for infants. RESULTS: The percentages of children with high lactate levels at 0.5; 1.5 and 3 months of age were 48%, 51.4% and 43% among those infants with available data. Respectively, the percentages of children with high AST values were 13.2; 10.4 and 17.2%. The values for high ALT were 3.3%; 3.4% and 5%. The percentages for hyperamylasaemia were 0%; 0.6% and 2.6%. We found no significant difference among the drugs used in utero for the four analysed biochemical markers along the first three months of age. CONCLUSIONS: We have found a high proportion of hyperlactataemia among infants exposed in-utero to ART, as shown in other cohorts of similar characteristics. No morbidity or mortality was communicated to the cohort analysis group. No ART drug among those used in-utero was statistically associated with a higher proportion of high lactate levels in these infants.

Exposición a antirretrovirales y toxicidad mitocondrial en una cohorte de niños no infectados hijos de madres VIH positivas / In-utero Antiretroviral exposure and mitochondrial toxicity in a cohort of uninfected infants born to HIV-1-infected women

Introducción: En el presente trabajo, pretendemos definir el porcentaje de lactantes, hijos de madre VIH−+, pertenecientes a la cohorte prospectiva madrileña Fundación para la Investigación y la Prevención del SIDA en España y expuestos a tratamiento antirretroviral intraútero y perinatal, que presentan hiperlactacidemia u otros marcadores de posible daño mitocondrial, como hipertransaminasemia, o hiperamilasemia, durante los 3 primeros meses de vida, así como establecer una correlación entre los fármacos usados y el porcentaje de lactantes con dichos efectos adversos. Métodos: Se realizó el análisis de las analíticas disponibles de 623 niños no infectados nacidos en el periodo 2000–2005, fijándose los límites para hiperlactacidemia, hipertransaminasemia e hiperamilasemia de las tablas de toxicidad pediátrica para ensayos relativos al VIH (tablas ACTG), de manera global y para cada fármaco usado durante la gestación. Resultados: Los porcentajes de niños con hiperlactacidemia a los 0,5, 1,5 y 3 meses fueron del 48, 51,4 y 43%, de entre los lactantes con analítica disponible el porcentaje de niños con elevación de GOT a los 0,5, 1,5 y 3 meses fue del 13,2, 10,4 y de 17,2%. Respectivamente, la proporción de lactantes con elevación de GPT fue del 3,3, 3,4 y 5%. No se encontró hiperamilasemia en ningún niño en el análisis de los 15 días de vida. La proporción de niños con hiperamilasemia a las 6 semanas y a los 3 meses fue de 0,6 y 2,6%. No hubo diferencias significativas al realizar la comparación de los porcentajes de hiperlactacidemia, hipertransaminasemia o hiperamilasemia según el fármaco usado intraútero. Conclusiones: Hemos encontrado un alto porcentaje de lactantes expuestos a tratamiento antirretroviral intraútero con hiperlactacidemia, acorde con los resultados de otras series, sin que se haya comunicado morbimortalidad asociada a este fenómeno y no hemos podido asociar mayor prevalencia de hiperlactacidemia, hipertransaminasemia o hiperamilasemia a ninguno de los fármacos usados en la gestación (AU)

Introduction: In this study, we attempt to find out the percentage of uninfected infants born to HIV-infected women and exposed in-utero and perinatally to Antiretroviral Treatment (ART) that show high lactate levels, or any other mitochondrial damage markers (such as hypertransaminasaemia or hyperamylasaemia), during the first three months of age. We shall also establish whether certain drugs used in-utero are associated with higher lactate, transaminase or amylase levels. Methods: We analysed the available data from 623 uninfected infants born in the Spanish FIPSE cohort that were born in the period 2000–2005. The normal values for lactate, transaminases and amylase were set according to AIDS Clinical Groups Trials toxicity tables for infants. Results: The percentages of children with high lactate levels at 0.5; 1.5 and 3 months of age were 48%, 51.4% and 43% among those infants with available data. Respectively, the percentages of children with high AST values were 13.2; 10.4 and 17.2%. The values for high ALT were 3.3%; 3.4% and 5%. The percentages for hyperamylasaemia were 0%; 0.6% and 2.6%. We found no significant difference among the drugs used in utero for the four analysed biochemical markers along the first three months of age. Conclusions: We have found a high proportion of hyperlactataemia among infants exposed in-utero to ART, as shown in other cohorts of similar characteristics. No morbidity or mortality was communicated to the cohort analysis group. No ART drug among those used in-utero was statistically associated with a higher proportion of high lactate levels in these infants (AU)

Opportunistic infections and organ-specific diseases in HIV-1-infected children: a cohort study (1990-2006).

OBJECTIVES: Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ-specific diseases in HIV-infected children. METHODS: An observational study of a cohort of 366 vertically HIV-infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990-1996: no patients on HAART), CP2 (1997-1999: <60% on HAART) and CP3 (2000-2006: >60% on HAART). RESULTS: Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ-specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV-associated encephalopathy) were lower in CP2 and CP3 than in CP1. CONCLUSIONS: This study provides evidence of improved clinical outcomes in HIV-infected children over time and shows that mortality, AIDS, opportunistic infections and organ-specific diseases declined as HAART was progressively instituted in this population.

Exposición a antirretrovirales y crecimiento en una cohorte de niños no infectados, hijos de madre con VIH positivo / Growth of uninfected infants exposed to antiretrovirals born to HIV-infected woman

Introducción: Existen datos que aseguran que la exposición al tratamiento antirretroviral (TAR) durante la gestación en la mujer infectada por VIH no afecta al posterior desarrollo ponderoestatural del lactante. El propósito de este estudio es realizar un análisis antropométrico de los niños no infectados de la cohorte de la Fundación para la Investigación y la Prevención del Sida en España (FIPSE) durante los primeros 18 meses de vida, así como analizar los posibles factores que influyen en el peso al nacimiento. Métodos: La cohorte de la FIPSE incluye 8 hospitales públicos de Madrid y sigue prospectivamente a los niños de madre infectada por VIH que haya dado a luz en estos hospitales. Se recogieron los datos de 601 niños no infectados de los que se disponía el peso al nacimiento, según los protocolos estandarizados durante los 2 primeros años de vida. Se consideraron estadísticamente significativos los valores de p menores de 0,05. Se usaron las tablas de la Fundación Pablo Orbegozo para comparar las medidas antropométricas y hallar los valores z. Resultados: La media de peso fue de 2.766g (±590) y la media de peso con exclusión de los prematuros fue de 2.967g (±427). La proporción de los niños no prematuros con crecimiento retardado intrauterino fue del 19,8% (IC del 95%: 16,3–23,8). Los hijos de madre adicta a drogas pesaron menos: 2.752(±325) versus 3.002g (±435) (p<0,001), así como los hijos de madre fumadora: 2.842(±363) versus 3.018g (±444) (p<0,001). La anemia materna no influyó en el bajo peso en la población de los niños no prematuros. No se encontraron diferencias significativas en el peso al nacimiento, de acuerdo con el tipo de TAR. Los niños de madre que presentaba CD4>500cel/mm pesaron más (2.834g [±503]) que aquéllos de madre que presentaba CD4<200cel/mm (2.565g [±702]; p=0,008). Estas diferencias no se mantienen al excluir los prematuros. En la población general, los niños de madre con cargas virales indetectables pesaron más (2.866g [±532] versus 2.704g [±588]; p=0,005), pero estas diferencias tampoco se mantuvieron en la población al excluir a los prematuros. La media de peso, talla y perímetro craneal (PC) al nacimiento de la población estudiada (con exclusión de los prematuros) es ligeramente menor al de la población española (peso z=−0,83; talla z=−1,02; PC z=−1,00), pero estas diferencias no son significativas y estas medidas son equiparables entre sí a los 18 meses de vida (peso z=−0,08; talla z=−0,32; PC z=−0,31). El tipo de tratamiento no influyó de manera significativa (AU)

Introduction: Recent reports show that Antiretroviral Treatment (ART) during pregnancy does not affect somatic growth of children born to HIV-infected mothers, are reassuring. The aim of this study is to perform an anthropometric analysis of the uninfected children followed in the Spanish FIPSE cohort during their first 18 months of life, and to describe the possible risk factors during pregnancy that may influence low birth weight. Methods: The FIPSE cohort includes 8 public hospitals in Madrid, and prospectively follows children born to HIV-infected women at these hospitals. We collected data on 601 uninfected children, following standardised protocols, during their first 2 years of life. A P value<0.05 was considered statistically significant. Data from the Pablo Orbegozo Foundation were used to compare the means of our population with the standard weight, longitude an occipitofrontal circumference (OFC) of the Spanish population during the first 18 months of life. Results: The mean weight was 2766g (+/−590), and 2967g (+/−427) when premature neonates were excluded. The proportion of Intrauterine Growth Restriction among non- premature neonates was 19.8% (95% CI: 16.3–23.8). Children born to mothers that used illicit drugs weighed less: 2752g (+/−325) vs. 3002g (+/ 435), P<0.001, as did children born to mothers who smoked during pregnancy: 2842g (+/−363) vs. 3018g (+/−444), P>0.001. Maternal anaemia did not influence the low birth weight of the children when premature neonates were excluded. We found no statistically significant differences depending on the ART received during pregnancy. Children born to mothers who had CD4 > 500 cell /mm were heavier (2834g +/−503) than those whose mothers had CD4 of less than 200 cell/mm (2565g +/−702), P=0.008. These differences disappeared when premature neonates were excluded. Children born to mothers with undetectable viral load were heavier (2866g +/−532 vs. 2704g +/−588, P=0.005), but these differences also disappeared when the prematures were excluded from the analysis. Mean weight, length, and OFC of our population at birth (excluding premature neonates) were lower than the Spanish standards. (z for weight=−0.83; z for length =−1.02; z for OFC=−1.00), but these differences are not statistically significant and disappear at 18 months of age (z for weight=−0.08; z for height=−0.32; z for OFC=−0.31). The type of ART did not have any significant influence (AU)

[Growth of uninfected infants exposed to antiretrovirals born to HIV-infected woman]. / Exposición a antirretrovirales y crecimiento en una cohorte de niños no infectados, hijos de madre con VIH positivo.

INTRODUCTION: Recent reports show that Antiretroviral Treatment (ART) during pregnancy does not affect somatic growth of children born to HIV-infected mothers, are reassuring. The aim of this study is to perform an anthropometric analysis of the uninfected children followed in the Spanish FIPSE cohort during their first 18 months of life, and to describe the possible risk factors during pregnancy that may influence low birth weight. METHODS: The FIPSE cohort includes 8 public hospitals in Madrid, and prospectively follows children born to HIV-infected women at these hospitals. We collected data on 601 uninfected children, following standardised protocols, during their first 2 years of life. A P value<0.05 was considered statistically significant. Data from the Pablo Orbegozo Foundation were used to compare the means of our population with the standard weight, longitude an occipitofrontal circumference (OFC) of the Spanish population during the first 18 months of life. RESULTS: The mean weight was 2766g (+/-590), and 2967g (+/-427) when premature neonates were excluded. The proportion of Intrauterine Growth Restriction among non- premature neonates was 19.8% (95% CI: 16.3-23.8). Children born to mothers that used illicit drugs weighed less: 2752g (+/-325) vs. 3002g (+/ 435), P<0.001, as did children born to mothers who smoked during pregnancy: 2842g (+/-363) vs. 3018g (+/-444), P>0.001. Maternal anaemia did not influence the low birth weight of the children when premature neonates were excluded. We found no statistically significant differences depending on the ART received during pregnancy. Children born to mothers who had CD4 > 500 cell /mm were heavier (2834g +/-503) than those whose mothers had CD4 of less than 200 cell/mm (2565g +/-702), P=0.008. These differences disappeared when premature neonates were excluded. Children born to mothers with undetectable viral load were heavier (2866g +/-532 vs. 2704g +/-588, P=0.005), but these differences also disappeared when the prematures were excluded from the analysis. Mean weight, length, and OFC of our population at birth (excluding premature neonates) were lower than the Spanish standards. (z for weight=-0.83; z for length =-1.02; z for OFC=-1.00), but these differences are not statistically significant and disappear at 18 months of age (z for weight=-0.08; z for height=-0.32; z for OFC=-0.31). The type of ART did not have any significant influence. DISCUSSION: There is a very significant difference between the weight of the children born to mothers addicted to illicit drugs and the rest of the children. Similarly, the weight of the children born to smoking mothers is significantly lower. There was no association between maternal anaemia and the type of ART. The children of our population have lower weights, length and OFC at birth, but this may due to the high number of scheduled caesarean births, practised at 38 weeks of pregnancy (54.5%). Our children catch-up with anthropometric measurements during the first and second year of life, and these are similar to Spanish standards at 18 months old.

Malformaciones congénitas en una cohorte de niños no infectados, hijos de madres infectadas por el virus de la inmunodeficiencia humana / Birth defects in a cohort of uninfected children born to HIV-infected women

Introducción: a causa de las medidas de prevención de la transmisión perinatal del virus de la inmunodeficiencia humana (VIH), la tasa de transmisión vertical es cercana al 1%. Los fármacos antirretrovíricos usados no están exentos de efectos adversos; el más observado es el efecto mielosupresor de la cidovudina. En este estudio se pretende analizar la tasa, la distribución y los factores asociados a las malformaciones congénitas (MC) observadas en una cohorte madrileña integrada por pares de madres infectadas por el VIH y sus hijos. Métodos: se analizó según protocolo estandarizado a 623 niños no infectados seguidos en la cohorte FIPSE (2000–2005), que agrupa a 8 hospitales públicos de la Comunidad de Madrid, así como también se analizaron las características sociosanitarias, biológicas y el tratamiento antirretrovírico (TAR) de las madres infectadas por el VIH. Se definieron las MC según el EUROCAT, organismo europeo de registro, y se eliminaron del análisis los errores leves de la morfogénesis. Se clasificó a los niños según prematuridad, peso, origen étnico, presencia de síndrome de abstinencia y tratamiento recibido intraútero. Se compararon las variables categóricas mediante el test de la χ2 o el test exacto de Fisher. Resultados: cuatrocientas ochenta y seis madres (78%) eran caucásicas; 117 madres (18,8%) tomaron alguna droga durante la gestación; 55 madres (8,8%) no recibieron tratamiento; 10 madres (1,6%) recibieron monoterapia, y 469 madres (75,3%) recibieron tratamiento antirretrovírico de gran actividad (TARGA). Cincuenta y dos niños (8,4%) presentaron MC; las más frecuentes fueron las genitourinarias y las cardiológicas. La anemia materna en el primer trimestre (17,9 frente a 1%; p=0,04) y el uso de metadona u otras drogas (13,8 frente a 7,6%; p=0,04) fueron los únicos parámetros asociados. No se observó aumento del riesgo de MC de manera significativa para ningún fármaco en concreto, aunque se observó cierto efecto protector significativo con el uso de nevirapina (NVP) intraútero. La tasa de MC en niños que habían recibido TAR en el primer trimestre de la gestación (8,8%) fue igual a la tasa de los que no lo habían recibido (7,4%; p=0,67). Conclusiones: en este estudio se ha obtenido una tasa de MC superior a la que muestran otros estudios con población general o con población infantil expuesta a TAR, debido a que este estudio es del tipo ®de seguimiento activo» (búsqueda activa mediante seguimiento y ecografías). Las características inmunovirológicas maternas parecieron no influir en la tasa de MC, pero sí la anemia materna del primer trimestre y la ingesta de drogas. No se ha encontrado teratogénesis relacionada con ningún fármaco antirretrovírico, aunque la nevirapina podría ejercer cierto efecto protector. En este estudio, las madres que empezaron el tratamiento en el primer trimestre parecen no tener en su descendencia más MC que las madres que lo suspenden en ese momento o lo inician más tarde (AU)

Introduction: Mother-to-Child HIV transmission is now just 1% in western countries, due to prevention measures. Antiretroviral Treatment (ART) drugs do have adverse effects, anaemia and myelosupression caused by cidovudina being the most commonly observed effects. In the present study, we have analysed the proportion and characteristics of congenital malformations (CM) or birth defects (BD) in a cohort of uninfected children born to HIV-infected women. Methods: A total of 623 uninfected children belonging to the FIPSE cohort were followed up according to standardised protocols. This cohort includes 8 public hospitals from Madrid and follows up HIV-infected pregnant women and their children. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment. Birth defects were described and defined according to the EUROCAT, the European registry for BD. Mild errors of morphogenesis were excluded from the analysis. Categorical variables were compared with the X2 or the Fisher test. Results: A total of 78% (486) of the mothers were of Caucasian origin; 18.8% (117) used some illicit drug (heroine, cocaine or methadone) during gestation; 51 mothers (8.1%) received no ART, 10 (1.6%) received monotherapy and 469 (75.3%) received HAART. BD were seen in 52 children, with the most frequent being genitourinary and cardiological. Anaemia in the first trimester was an associated risk for BD (17.9% vs. 8.1%, P=0,04). Similarly, mothers who used any illicit drug (plus methadone), had a slightly higher risk for BD in their offspring (13.8% vs. 7.6%, P=0,04) There was no increased risk for BD significantly associated with any of the in-utero used antiretrovirals, although Nevirapine use in-utero showed a protective effect. Children born to mothers who received ART in the first trimester had the same rate of BD (7.4%) as those whose mothers started ART in the second trimester (8.8%), P=0,67. Conclusions: The proportion of BD that we have observed seems higher than those shown in other European teratogenicity studies and also higher than those shown in cohorts with HIV and antiretroviral exposed infants. This may be due to the fact that our series show the results of an active surveillance system (that includes ultrasound), where BD classically appear in a higher proportion. Immunovirological characteristics of the mother did not influence the proportion of BD, but anaemia in the first trimester and the use of illicit drugs (or methadone) did. No specific antiretroviral drug was associated with an increase in BD, although Nevirapine showed a possible protective effect in the statistical analysis. Mothers who started antiretrovirals in the first trimester do not have more BD in their offspring than mothers who started on antiretrovirals later on (AU)

[Birth defects in a cohort of uninfected children born to HIV-infected women]. / Malformaciones congénitas en una cohorte de niños no infectados, hijos de madres infectadas por el virus de la inmunodeficiencia humana.

INTRODUCTION: Mother-to-Child HIV transmission is now just 1% in western countries, due to prevention measures. Antiretroviral Treatment (ART) drugs do have adverse effects, anaemia and myelosupression caused by cidovudina being the most commonly observed effects. In the present study, we have analysed the proportion and characteristics of congenital malformations (CM) or birth defects (BD) in a cohort of uninfected children born to HIV-infected women. METHODS: A total of 623 uninfected children belonging to the FIPSE cohort were followed up according to standardised protocols. This cohort includes 8 public hospitals from Madrid and follows up HIV-infected pregnant women and their children. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment. Birth defects were described and defined according to the EUROCAT, the European registry for BD. Mild errors of morphogenesis were excluded from the analysis. Categorical variables were compared with the X(2) or the Fisher test. RESULTS: A total of 78% (486) of the mothers were of Caucasian origin; 18.8% (117) used some illicit drug (heroine, cocaine or methadone) during gestation; 51 mothers (8.1%) received no ART, 10 (1.6%) received monotherapy and 469 (75.3%) received HAART. BD were seen in 52 children, with the most frequent being genitourinary and cardiological. Anaemia in the first trimester was an associated risk for BD (17.9% vs. 8.1%, P = 0,04). Similarly, mothers who used any illicit drug (plus methadone), had a slightly higher risk for BD in their offspring (13.8% vs. 7.6%, P = 0,04) There was no increased risk for BD significantly associated with any of the in-utero used antiretrovirals, although Nevirapine use in-utero showed a protective effect. Children born to mothers who received ART in the first trimester had the same rate of BD (7.4%) as those whose mothers started ART in the second trimester (8.8%), P = 0,67. CONCLUSIONS: The proportion of BD that we have observed seems higher than those shown in other European teratogenicity studies and also higher than those shown in cohorts with HIV and antiretroviral exposed infants. This may be due to the fact that our series show the results of an active surveillance system (that includes ultrasound), where BD classically appear in a higher proportion. Immunovirological characteristics of the mother did not influence the proportion of BD, but anaemia in the fist trimester and the use of illicit drugs (or methadone) did. No specific antiretroviral drug was associated with an increase in BD, although Nevirapine showed a possible protective effect in the statistical analysis. Mothers who started antiretrovirals in the first trimester do not have more BD in their offspring than mothers who started on antiretrovirals later on.

Anemia y neutropenia en una cohorte de niños no infectados hijos de madres positivas para el virus de la inmunodeficiencia humana / Anaemia and neutropenia in a cohort of non-infected children of HIV-positive mothers

Introducción: Gracias a las medidas de prevención de la transmisión perinatal del virus de la inmunodeficiencia humana (VIH), la tasa de transmisión vertical actual se sitúa en torno al 1%. Los fármacos antirretrovirales usados no están exentos de efectos adversos, el más observado de los cuales es el efecto mielosupresor de la zidovudina (AZT). En este estudio pretendemos analizar la prevalencia de la anemia y la neutropenia en una cohorte de niños no infectados hijos de madres positivas para el virus de la inmunodeficiencia humana (VIH). Material y métodos: Se analizaron según protocolo estandarizado 623 niños no infectados controlados prospectivamente en la cohorte FIPSE (Fundación para la Investigación y la Prevención del Sida en España), que agrupa a 8 hospitales de la Comunidad de Madrid, así como las características y el tratamiento de las madres positivas para el VIH. Se definieron la anemia y la neutropenia según las tablas de toxicidad de los ACTG (AIDS Clinical Trails Group). Se clasificó a los niños según prematuridad, peso, origen étnico, presencia de síndrome de abstinencia y tratamiento recibido intraútero y como profilaxis en las primeras 4-6 semanas de vida. Se compararon las variables categóricas usando el test de chi al cuadrado o el test exacto de Fisher. Resultados: Un total de 188 niños (30,1 %) presentaron anemia, y 161 (25,8 %) tuvieron anemia de toxicidad de grado 2 o superior. La prematuridad (p < 0,001), el bajo peso al nacer (p = 0,005) y el tratamiento antirretroviral de gran actividad (TARGA) con inhibidores de la proteasa (p = 0,016) se asociaron con una mayor proporción de anemia. Las cifras de hemoglobina alcanzaron un nadir a las 6 semanas y se normalizaron en torno a los 6 meses. La prevalencia de neutropenia fue del 41,9 % (261 niños), y la de neutropenia moderada-grave fue del 22,7 %. La prematuridad (p = 0,01) se asoció con riesgo de neutropenia y el bajo peso influyó en la proporción de lactantes con neutropenia moderada-grave (p = 0,023). Existe una tendencia a una mayor proporción de neutropenia en los lactantes subsaharianos (el 50 % frente al 44 %), aunque esto no fue estadísticamente significativo (p = 0,12). El tipo de tratamiento recibido intraútero no influyó en el desarrollo de neutropenia. El 12,5 % de los lactantes aún presentaron neutropenia a los 18 meses de vida. El desarrollo de citopenias no se asoció con el tipo de profilaxis recibida (monoterapia, doble terapia o triple terapia). Conclusión: En nuestra serie de hijos de madres positivas para el VIH, expuestos a antirretrovirales intraútero, la proporción de casos de anemia es elevada, del 30,1 %. La prematuridad, el bajo peso al nacer y el TARGA se asociaron con una mayor proporción de anemia, que es transitoria y clínicamente poco relevante. La tasa de niños con neutropenia fue mayor (41,9 %), y se asocia con prematuridad, bajo peso y origen subsahariano. El tipo de profilaxis de la transmisión vertical empleada en los neonatos no parece influir en el desarrollo de anemia ni de neutropenia. Se observó la persistencia de la neutropenia a los 18 meses de edad, sin relevancia clínica, en un pequeño porcentaje de los niños (12,5%) (AU)

Introduction: Mother-to-child HIV transmission is currently around 1% in western countries, due to prevention measures. Antiretroviral drugs do have adverse effects, anaemia and myelosupression caused by AZT being the most observed effects. In the present study, we analyse the prevalence of anaemia and neutropenia in an uninfected children cohort born to HIV-infected women. Material and methods: We followed up 623 uninfected children belonging to the FIPSE cohort according to standardised protocols. This cohort groups 8 hospitals from Madrid and follows up HIV infected pregnant women and their children. Anaemia and neutropenia were defined according to the ACTG (AIDS Clinical Trails Group) toxicity tables. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment and neonatal prophylaxis. Categorical variables were compared with the X2 or the Fisher tests. Results: Anaemia was observed in 188 (30.1 %) children during follow-up and 161 (25.8 %) had anaemia grade 2 or higher. Prematurity (p < 0.001), low birth weight (p = 0.005) and Highly Active Antiretroviral Treatment (HAART) with Protease Inhibitors (p = 0.016) were associated with higher percentages of anaemia in children. Nadir haemoglobin values were reached by 6 weeks of life and anaemia was transient and disappeared by six months of age. Neutropenia was present in 41.9 % (261 children) and 22.7% of the children had moderate-severe neutropenia. Prematurity was again associated with neutropenia (p = 0.01) and low birth weigh was associated only with moderate severe neutropenia (p = 0.023). African infants had a higher percentage of neutropenia than the rest of the children (50 % vs. 44 %), although the differences were not significant. The type of in-utero treatment did not appear to influence the neutropenia. Neutropenia was still present in 12.5 % of infants at 18 months of age. The type of neonatal prophylaxis to prevent mother-to-child transmission (monotherapy, dual therapy or triple therapy) did not influence either cytopenia. Conclusion: In our series, the proportion of children with anaemia is high: 30.1 % Prematurity, low birth weight and HAART with IP were associated with a higher proportion of anaemia, which was transient and had little clinical relevance. The proportion of children with neutropenia was higher (41.9 %) and was associated with prematurity, low birth weight and African origin. The type of neonatal prophylaxis does not seem to influence the development of cytopenias. Persistence of neutropenia (without clinical significance) was observed in a small percentage of the children 12.5 %, at 18 months of age (AU)

[Anaemia and neutropenia in a cohort of non-infected children of HIV-positive mothers]. / Anemia y neutropenia en una cohorte de niños no infectados hijos de madres positivas para el virus de la inmunodeficiencia humana.

INTRODUCTION: Mother-to-child HIV transmission is currently around 1% in western countries, due to prevention measures. Antiretroviral drugs do have adverse effects, anaemia and myelosupression caused by AZT being the most observed effects. In the present study, we analyse the prevalence of anaemia and neutropenia in an uninfected children cohort born to HIV-infected women. MATERIAL AND METHODS: We followed up 623 uninfected children belonging to the FIPSE cohort according to standardised protocols. This cohort groups 8 hospitals from Madrid and follows up HIV infected pregnant women and their children. Anaemia and neutropenia were defined according to the ACTG (AIDS Clinical Trails Group) toxicity tables. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment and neonatal prophylaxis. Categorical variables were compared with the chi2 or the Fisher tests. RESULTS: Anaemia was observed in 188 (30.1%) children during follow-up and 161 (25.8%) had anaemia grade 2 or higher. Prematurity (p < 0.001), low birth weight (p = 0.005) and Highly Active Antiretroviral Treatment (HAART) with Protease Inhibitors (p = 0.016) were associated with higher percentages of anaemia in children. Nadir haemoglobin values were reached by 6 weeks of life and anaemia was transient and disappeared by six months of age. Neutropenia was present in 41.9% (261 children) and 22.7% of the children had moderate-severe neutropenia. Prematurity was again associated with neutropenia (p = 0.01) and low birth weigh was associated only with moderate-severe neutropenia (p = 0.023). African infants had a higher percentage of neutropenia than the rest of the children (50% vs. 44%), although the differences were not significant. The type of in-utero treatment did not appear to influence the neutropenia. Neutropenia was still present in 12.5% of infants at 18 months of age. The type of neonatal prophylaxis to prevent mother-to-child transmission (monotherapy, dual therapy or triple therapy) did not influence either cytopenia. CONCLUSION: In our series, the proportion of children with anaemia is high: 30.1% Prematurity, low birth weight and HAART with IP were associated with a higher proportion of anaemia, which was transient and had little clinical relevance. The proportion of children with neutropenia was higher (41.9%) and was associated with prematurity, low birth weight and African origin. The type of neonatal prophylaxis does not seem to influence the development of cytopenias. Persistence of neutropenia (without clinical significance) was observed in a small percentage of the children 12.5%, at 18 months of age.

Estimation of complex refractive index of polydisperse particulate systems from multiple-scattered ultraviolet-visible-near-infrared measurements.

A method to extract the complex refractive index of spherical particles from a polydisperse suspension at concentrations where multiple light-scattering effects are significant is presented. The optical constants are estimated from total diffuse reflectance and transmittance measurements and inverting the measurements using the radiative transfer equation (RTE) and the Mie theory for scattering by polydisperse spherical particles. The method is tested by applying it to three different polydisperse polystyrene suspensions and extracting the optical constants of polystyrene particles in the wavelength range of 450-1200 nm. The effect of particle size, concentration, and polydispersity on the estimated values of the optical constants is also discussed.

Scaling law for the transient behavior of type-II neuron models.

We study the transient regime of type-II biophysical neuron models and determine the scaling behavior of relaxation times tau near but below the repetitive firing critical current, tau approximately or equal to C(I(c)-I)(-Delta). For both the Hodgkin-Huxley and Morris-Lecar models we find that the critical exponent is independent of the numerical integration time step and that both systems belong to the same universality class, with Delta=1/2. For appropriately chosen parameters, the FitzHugh-Nagumo model presents the same generic transient behavior, but the critical region is significantly smaller. We propose an experiment that may reveal nontrivial critical exponents in the squid axon.

Mucosal immune response of spotted sand bass Paralabrax maculatofasciatus (Steindachner, 1868) orally immunised with an extracellular lectin of Aeromonas veronii.

To assess the immunogenic and immunoprotective role of the extracellular lectin from Aeromonas veronii (MCBP), which has affinity for mucosal constituents such as mucin, lactoferrin, immunoglobulins and collagen, spotted sand bass (Paralabrax maculatofasciatus) were orally immunised either with soluble MCBP, adjuvant-conjugated MCBP or immobilised MCBP on latex microspheres. The results suggest that the MCBP is capable of eliciting protective immunity against A. veronii infections when administered orally. The highest mucosal immune response was elicited in fish immunised with MCBP covalently linked to cholera toxin B subunit (CTB) or to Escherichia coli heat-labile toxin (hLT). MCBP-CTB was found to elicit immunoprotection against a challenge with live Aeromonas cells with a relative percent survival of almost 70% and without the expression of the severe histopathological alterations induced by A. veronii.

[Adult respiratory distress syndrome in childhood]. / Síndrome del "distress" respiratorio del adulto en la infancia.

Adult respiratory distress syndrome is becoming more frequent in pediatric age. There are several factors involved in its' etiology. Sepsis is almost invariably present in all patients. Basic mechanism is an increase of pulmonary capillary permeability with production of acute non cardiogenic oedema. The decrease in compliance and functional residual capacity produce a respiratory failure with hypoxemia non-responsive to the increase in FiO2. Pulmonary hypertension and low cardiac output appear once the syndrome has developed. In its' management, cardiorespiratory monitoring is essential. Prophylaxis is based on early treatment of the essential pathological process. Corticoids are only effective if they are administered before development of pulmonary oedema. The treatment is based on: a) Moderate water restriction. b) Early respiratory assistance using PEEP or CPAP. c) Maintenance of adequate oxygen transport. The extracorporeal oxygenation guarantees the oxygen exchange but it does not affect survival. Mortality is 95%. Patients who survive have minimal pulmonary sequelae.