Efectividad y seguridad de inhibidores de integrasa en la gestante con infección VIH en la Cohorte de embarazadas de la Comunidad de Madrid / Effectiveness and safety of integrase inhibitors in HIV-infected pregnant women followed up in the Madrid Cohort

INTRODUCCIÓN: El riesgo de transmisión vertical (TV) del VIH depende fundamentalmente de la edad gestacional de inicio del tratamiento antirretroviral y la carga viral materna al parto. Son crecientes las pautas con inhibidores de integrasa (INI) en embarazadas con situaciones de riesgo. Nuestro objetivo fue revisar la experiencia con INI en la Cohorte de Madrid de madres-niños. PACIENTES Y MÉTODOS: Estudio retrospectivo, multicéntrico, observacional, de gestantes con infección por VIH-1 expuestas a INI de 9 hospitales públicos durante 2000-2017. RESULTADOS: Hubo 67 gestantes (cohorte: 1.423) y 68 neonatos (el 17,6% prematuros, el 34,3% con profilaxis combinada). No hubo casos de TV. Veinte mujeres se diagnosticaron en la gestación actual. De 43 con tratamiento antirretroviral previo a gestación, el 65% recibía INI preconcepcional. El más empleado fue raltegravir (80,5%). Aumentó significativamente (p = 0,02) la proporción de madres con carga viral indetectable al parto. La tolerancia a INI fue adecuada. Hubo anomalías congénitas menores en el 11,7% de los niños. CONCLUSIONES: Los INI parecen seguros y eficaces como prevención de TV. Nuestros hallazgos refuerzan su utilidad como intensificación en gestantes que llegan al tercer trimestre con pauta no supresora

INTRODUCTION: The risk of HIV-1 mother-to-child transmission (MTCT) is associated mainly with gestational age at which antiretroviral therapy begins and the HIV-1 RNA plasma viral load at delivery. Regimens with integrase inhibitors (INI) are increasing in high-risk pregnant women. The objective was to review the experience with INI in a Madrid Cohort of mother-infant pairs. PATIENTS AND METHODS: Retrospective, multicentric, observational study, of HIV-infected pregnant women exposed to INI. Patients of 9 hospitals were included (2000-2017). RESULTS: Sixty-seven pregnant women exposed to INI (cohort: 1,423) and 68 children (17.6% premature babies, 34.3% with combined postexposure prophylaxis). There were no cases of MTCT. Of 24 women with no previous antiretroviral therapy, 20 were diagnosed in current pregnancy. Of 43 women with antiretroviral therapy before pregnancy, 65% received INI before conception. Raltegravir was the most used (80.5%). There was a statistically significant increase (p = 0,02) of mothers with undetectable viral load at delivery. INI were well tolerated. In 11.7% of exposed children minor congenital anomalies were detected. CONCLUSIONS: INI seem safe and effective in the prevention of MTCT. Our findings support their use as intensification regimens in pregnant women with high risk of MTCT

Effectiveness and safety of integrase inhibitors in HIV-infected pregnant women followed up in the Madrid Cohort. / Efectividad y seguridad de inhibidores de integrasa en la gestante con infección VIH en la Cohorte de embarazadas de la Comunidad de Madrid.

INTRODUCTION: The risk of HIV-1 mother-to-child transmission (MTCT) is associated mainly with gestational age at which antiretroviral therapy begins and the HIV-1 RNA plasma viral load at delivery. Regimens with integrase inhibitors (INI) are increasing in high-risk pregnant women. The objective was to review the experience with INI in a Madrid Cohort of mother-infant pairs. PATIENTS AND METHODS: Retrospective, multicentric, observational study, of HIV-infected pregnant women exposed to INI. Patients of 9 hospitals were included (2000-2017). RESULTS: Sixty-seven pregnant women exposed to INI (cohort: 1,423) and 68 children (17.6% premature babies, 34.3% with combined postexposure prophylaxis). There were no cases of MTCT. Of 24 women with no previous antiretroviral therapy, 20 were diagnosed in current pregnancy. Of 43 women with antiretroviral therapy before pregnancy, 65% received INI before conception. Raltegravir was the most used (80.5%). There was a statistically significant increase (p = 0,02) of mothers with undetectable viral load at delivery. INI were well tolerated. In 11.7% of exposed children minor congenital anomalies were detected. CONCLUSIONS: INI seem safe and effective in the prevention of MTCT. Our findings support their use as intensification regimens in pregnant women with high risk of MTCT.

Jóvenes y VIH. Conocimiento y conductas de riesgo de un grupo residente en España / Young adults and HIV. Awareness and risk behaviour of a group living in Spain

Introducción: El contacto sexual es actualmente en España la primera vía de contagio de VIH. Pese a los descensos en el número de nuevas infecciones en mujeres y consumo de drogas, en hombres se mantiene estable. El presente estudio pretende evaluar conductas de riesgo y conocimientos sobre VIH en una muestra de jóvenes en España. Métodos: Se realizó un estudio observacional descriptivo transversal utilizando un cuestionario sobre salud sexual y conocimiento sobre el VIH adaptado del Instituto Nacional de Estadística. El grupo estuvo compuesto por jóvenes no infectados por VIH. Se incluyó la variable riesgo sexual (alto y bajo), siendo de riesgo alto los sujetos que habían tenido tres o más parejas y no utilizaban preservativo en todas las relaciones. Resultados: Se encuestaron 243 jóvenes (65,6% mujeres) de entre 16 y 36 años (media = 25,7; DE = 4,1) (16-24 años: 134 sujetos; 25-29 años, 60 sujetos; más de 30 años, 47 sujetos). El 40,9% contestaron que utilizaban el preservativo en todas sus relaciones y el 61% que no perciben ningún riesgo de infección. De forma mayoritaria no se encuentran diferencias significativas en conocimiento sobre vías de transmisión entre los grupos de alto y de bajo riesgo. Los métodos de protección que se asociaron significativamente con las diferencias en riesgo sexual fueron lavarse tras las relaciones sexuales, tener pocas parejas, uso de espermicidas y carga viral indetectable (p < 0,05). Conclusiones: El principal resultado del estudio es la infravaloración personal de riesgo indicado según las diferencias encontradas entre la valoración personal y el índice de riesgo sexual. Se encuentran resultados tanto positivos como negativos en cuanto al conocimiento sobre el VIH

Introduction: Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in new infections among women and drug users, the rate remains stable in men. The aim of this study was to assess risk behaviour and HIV awareness in a sample of young adults in Spain. Methods: A cross-sectional, observational, descriptive study was performed on a non-HIV infected sample, using a questionnaire on sexual health and HIV awareness adapted from the Spanish National Institute of Statistics. A sexual risk variable was included (high and low), which was classified as high if subjects had had three or more sexual partners and did not always use a condom in all their sexual encounters. Results: 243 subjects were included (65.6% women) aged between 16 and 36 years (mean = 25.7; SD = 4.1) (16-24 years: 134 subjects; 25-29 years: 60 subjects; over 30 years: 47 subjects). Approximately 40.9% said that they used a condom in all sexual relations and 61% did not perceive any risk of infection. There were no significant differences in awareness of infection routes between the high and low risk profiles. Washing after sex, having few partners, spermicide use and having undetectable viral load were protective measures significantly associated with differences in sexual risk (P < .05). Conclusions: The main finding of the study was the underestimation of risk of infection, analysed after differences found between self-assessment and sexual risk. Both positive and negative results were found concerning HIV awareness

Young adults and HIV. Awareness and risk behaviour of a group living in Spain. / Jóvenes y VIH. Conocimiento y conductas de riesgo de un grupo residente en España.

INTRODUCTION: Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in new infections among women and drug users, the rate remains stable in men. The aim of this study was to assess risk behaviour and HIV awareness in a sample of young adults in Spain. METHODS: A cross-sectional, observational, descriptive study was performed on a non-HIV infected sample, using a questionnaire on sexual health and HIV awareness adapted from the Spanish National Institute of Statistics. A sexual risk variable was included (high and low), which was classified as high if subjects had had three or more sexual partners and did not always use a condom in all their sexual encounters. RESULTS: 243 subjects were included (65.6% women) aged between 16 and 36years (mean=25.7; SD=4.1) (16-24years: 134 subjects; 25-29years: 60 subjects; over 30years: 47 subjects). Approximately 40.9% said that they used a condom in all sexual relations and 61% did not perceive any risk of infection. There were no significant differences in awareness of infection routes between the high and low risk profiles. Washing after sex, having few partners, spermicide use and having undetectable viral load were protective measures significantly associated with differences in sexual risk (P<.05). CONCLUSIONS: The main finding of the study was the underestimation of risk of infection, analysed after differences found between self-assessment and sexual risk. Both positive and negative results were found concerning HIV awareness.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis]. / Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (I): epidemiología y diagnóstico. Tuberculosis congénita.

Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment]. / Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (ii): profilaxis y tratamiento.

In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended.

Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

[Emergence of invasive pneumococcal disease caused by non-vaccine serotypes in the era of the 7-valent conjugate vaccine]. / Serotipos no vacunales emergentes causantes de enfermedad neumocócica invasora en la era de la vacuna 7-valente.

INTRODUCTION: There has been an increased incidence in invasive pneumococcal disease (IPD) produced by non-vaccine serotype (NVS) of Streptococcus pneumoniae after the introduction of PCV7. Our objective was to describe the epidemiological, clinical and microbiological characteristics of IPD caused by NVS in a tertiary hospital in Madrid. PATIENTS AND METHODS: Retrospective (1998-2004) and prospective (2005-2009) study evaluating IPD caused by NVS in children. The study was divided into three periods: P1 (1998-2001) when PCV7 was not commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. RESULTS: We analyzed 155 cases of IPD. One hundred and fifty of these isolates were serotyped (100 were NVS). There was an increase in the prevalence of IPD from P1 (31%) to P2 (54%) and P3 (91%). The most relevant emerging serotypes were 19A, 7F, 1, 5, 3 and 15C. The most significant clinical syndromes produced by some specific serotypes were as follows: lower respiratory tract infection (LRTI) by serotypes 1, 3, 5 and 15C; LRTI, primary bacteremia and meningitis by serotype 19A; and primary bacteremia by serotype 7F (66%). The large majority (83.8%) of NVS were sensitive to penicillin. CONCLUSIONS: There has been an increased prevalence of IPD caused by NVS since the introduction of PCV7. These changes should prompt the introduction of new pneumococcal vaccines, which include most of the NVS, in the childhood immunization calendar to prevent IPD in children.

[Increase in the incidence of invasive pneumococcal disease caused by serotype 19A prior to the implementation of the expanded pneumococcal vaccines]. / Aumento de la incidencia de enfermedad neumocócica invasora producida por el serotipo 19A previo a la introducción de las vacunas neumocócicas ampliadas.

OBJECTIVE: To describe the epidemiology, clinical syndromes and microbiological characteristics of serotype 19A as the main cause of invasive pneumococcal disease (IPD) in children admitted to a tertiary hospital in Spain. METHODS: A retrospective (1998-2004) and prospective (2005-2009) study was conducted on children with IPD produced by serotype 19A. The study was divided into three periods (P): P1 (1998-2001) when PCV7 had not been commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. RESULTS: A total of 155 isolates of Streptococcus pneumoniae (SP) producing IPD were analysed, with 21 of them being serotype 19A (14%). An increased prevalence of serotype 19A was found: 2/45 cases (4.4%) in P1, 3/41 cases (7.3%) in P2 and 16/69 cases (23.2%) in P3. It occurred mostly in children younger than 2 years (16/21; 76%). This serotype was the main cause of meningitis (5/20; 25%), pleural empyema (3/22; 14%) and bacteraemic mastoiditis (2/4; 50%). Thirteen isolates (61.5%) had an MIC ≥ 0.12µ/ml for penicillin in extra-meningeal infections, and 3 of the 5 isolates causing meningitis (60%) had an MIC ≥ 1µ/ml for cefotaxime. CONCLUSIONS: Serotype 19A was the main causal agent of IPD in the PCV7 era (P3), with high antibiotic resistance rates. This serotype was responsible for all types of IPD, being the main cause of meningitis.

[Consensus document by the Spanish Society of Paediatric Infectious Diseases and the advisory committee on vaccines of the Spanish Paediatrics Association on vaccination in immunocompromised children]. / Documento de consenso de la Sociedad Española de Infectología Pediátrica y el Comité Asesor de Vacunas de la Asociación Española de Pediatría para la vacunación en inmunodeprimidos.

Vaccination in immunocompromised infants, children and adolescents is a major aspect in the follow-up of this complex pathology in specific Paediatric Units. Vaccination is also an important prevention tool, as this can, to a certain extent, determine the morbidity and mortality in these patients. This consensus document was jointly prepared by Working Groups of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Paediatric Association, who are usually involved in updating the management of vaccinations in immunocompromised children, and reflects their opinions. The consensus specifically summarises indications for vaccination in the following special paediatric populations: Solid organ and haematopoietic transplant-recipients; primary immunodeficiency; asplenic children; non-previously transplanted immunocompromised patients; chronically ill patients; HIV-infected children and also the vaccines recommended for immunodeficient children who travel.

2011 Año Europeo del Voluntariado: el voluntariado en cuidados paliativos / The European Year of Voluntary Service: voluntary service in Palliative Care

No disponible

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)

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.