Clinical Outcomes of a Zika Virus Mother-Child Pair Cohort in Spain

BACKGROUND: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. METHODS: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. RESULTS: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4-6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4-39.6%). CONCLUSIONS: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit

En niños sanos, el ácido ascórbico parece facilitar la absorción del hierro contenido en los alimentos de consumo habitual en forma de fumarato ferroso

Authors� conclusions: The administration of orange juice, which contains a modest dose of ascorbic acid, provides a significant increase in the absorption of ferrous fumarate in children without prior iron deficiency. Reviewers� commentary: The absorption of ferrous fumarate appears to be enhanced when it is administered together with ascorbic acid. It is not possible, however, to provide a direct comparison between ferrous fumarate and sulfate to know if the facilitating effect of the ascorbic acid absorption is similar for both forms of iron presentation. Studies in healthy children comparing the absorption of ferrous fumarate and ferrous sulfate administered with ascorbic acid are needed in order to determine which method of administration is the most effective and cost-effective.Conclusiones de los autores del estudio: la administración de zumo de naranja, que contiene una modesta dosis de ácido ascórbico, proporciona un incremento significativo de la absorción de fumarato ferroso en niños sin déficit de hierro previo. Comentario de los revisores: la absorción del fumarato ferroso parece verse aumentada cuando se administra junto a ácido ascórbico. No es posible, sin embargo, establecer una comparación directa entre fumarato y sulfato para conocer si el efecto facilitador de la absorción del ácido ascórbico es similar para ambas formas de presentación del hierro. Se necesitan estudios realizados en niños sanos que comparen la absorción de fumarato ferroso y sulfato ferroso administrado con ácido ascórbico para determinar cuál es la forma de administración más eficaz y coste-efectiva

La vacuna acelular de la tos ferina, administrada al nacimiento y al mes de vida, es eficaz para obtener títulos detectables de anticuerpos antitoxina pertussis a los dos meses de edad

Authors� conclusions: acellular pertussis vaccine administered at birth and one month produces a detectable immune response at two months of age. Reviewers� commentary: the results of this pilot trial are encouraging because they demonstrate seroconversion when acellular vaccine against pertussis is administered at birth and at two months old. However, these results should be confirmed in a clinical trial to solve the methodological limitations of this study.This trial should determine whether the seroconversion is clinically protective and if the pattern of administration interferes with seroconversion against other vaccine antigens.Conclusiones de los autores del estudio: la vacuna acelular contra la tos ferina, administrada al nacimiento y al mes de vida, es eficaz para producir una respuesta inmunológica detectable a los dos meses de edad. Comentario de los revisores: los resultados de este ensayo clínico piloto son esperanzadores al demostrar una seroconversión cuando la vacuna acelular frente a la tos ferina se administra al nacimiento y a los dos meses de edad. Sin embargo, estos resultados deben ser confirmados por un ensayo clínico que solvente las limitaciones metodológicas de este estudio. Este ensayo clínico debería determinar si la seroconversión obtenida es clínicamente protectora y si la pauta de administración interfiere con la seroconversión frente a otros antígenos vacunales

No parece existir asociación entre la incidencia de cáncer infantil precoz y la exposición de las madres a estaciones de telefonía móvil durante el embarazo

Conclusiones de los autores del estudio: no existe asociación entre la exposición a estaciones de telefonía móvil durante el embarazo y la aparición de cáncer durante los primeros cuatro años de vida. Comentario de los revisores: la amplitud geográfica del estudio, su emplazamiento comunitario utilizando registros de base poblacional y la utilización de técnicas de análisis multivariante en el análisis de los resultados refuerzan la conclusión principal de los autores. Para conocer el posible riesgo a largo plazo (más de cuatro años de edad) o el posible riesgo de la exposición postnatal a fuentes de radiación electromagnética son necesarios estudios diseñados específicamente para tal fin

Los corticoides administrados durante la gestación no parecen asociarse a mayor riesgo de hendiduras orofaciales

Conclusiones de los autores del estudio: no parece existir un aumento del riesgo de hendiduras orofaciales asociado al uso de corticoides durante el embarazo. La asociación entre hendidura labial con/sin hendidura palatina y el uso de corticoides dermatológicos durante el embarazo puede ser producto del azar, como consecuencia de las múltiples comparaciones estadísticas realizadas, sin implicar una relación causal. Comentario de los revisores: los resultados de este estudio podrían permitir la utilización de corticoides en aquellas gestantes en las que, por el padecimiento de determinadas enfermedades que lo requirieran, fuera totalmente imprescindible su uso. La presencia de otros posibles efectos indeseables de los corticoides durante la gestación (por ejemplo, retraso del crecimiento fetal-bajo peso al nacimiento) recomiendan máxima prudencia con el uso de estos medicamentos

En niños con cólico del lactante, los probióticos no parecen disminuir la duración del llanto

Conclusiones de los autores del estudio: Lactobacillus reuteri (L. reuteri), comparado con simeticona o placebo, parece eficaz para disminuir las horas de llanto de los niños con cólico del lactante (CL). Comentario de los revisores: las limitaciones metodológicas de los estudios revisados no permiten establecer actualmente una recomendación firme para administrar preparados de L. reuteri como tratamiento del CL. Se recomienda proporcionar información a los padres sobre el CL con el objeto de tranquilizarlos acerca de su evolución. El consejo adecuado proporcionado por un profesional sanitario es eficaz para disminuir la sintomatología clínica del niño

Las pruebas que relacionan la diabetes tipo 1 con infección previa por enterovirus son actualmente insuficientes

Conclusiones de los autores del estudio: existe una asociación clínica significativa entre la infección por enterovirus, detectada por métodos moleculares, y la autoinmunidad/diabetes tipo 1. Comentario de los revisores: parece existir una asociación entre la detección de enterovirus y la presencia de prediabetes/diabetes tipo 1. Esta asociación no puede interpretarse como causal debido a las limitaciones del diseño de los estudios individuales. Para establecer la existencia de causalidad será necesaria la realización de un estudio prospectivo de cohortes de base poblacional

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed