Impacts on prenatal development of the human cerebellum: a systematic review.

PURPOSE: The cerebellum is essential for normal neurodevelopment and is particularly susceptible for intra-uterine disruptions. Although some causal prenatal exposures have been identified, the origin of neurodevelopmental disorders remains mostly unclear. Therefore, a systematic literature search was conducted to provide an overview of parental environmental exposures and intrinsic factors influencing prenatal cerebellar growth and development in humans. MATERIALS AND METHODS: The literature search was limited to human studies in the English language and was conducted in Embase, Medline, Cochrane, Web of Science, Pubmed and GoogleScholar. Eligible studies were selected by three independent reviewers and study quality was scored by two independent reviewers. RESULTS: The search yielded 3872 articles. We found 15 eligible studies reporting associations between cerebellar development and maternal smoking (4), use of alcohol (3), in vitro fertilization mediums (1), mercury (1), mifepristone (2), aminopropionitriles (1), ethnicity (2) and cortisol levels (1). No studies reported on paternal factors. CONCLUSIONS: Current literature on associations between parental environmental exposures, intrinsic factors and human cerebellar development is scarce. Yet, this systematic review provided an essential overview of human studies demonstrating the vulnerability of the cerebellum to the intra-uterine environment.

Influenza vaccination in children being treated with chemotherapy for cancer.

BACKGROUND: Influenza infection is a potential cause of severe morbidity in children with cancer; therefore vaccination against influenza is recommended. However, data are conflicting regarding the immune response to influenza vaccination in children with cancer, and the value of vaccination remains unclear. OBJECTIVES: 1. To assess the efficacy of influenza vaccination in stimulating an immunological response in children with cancer during chemotherapy, compared with control groups.2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or in stimulating immunological response in children with cancer treated with chemotherapy, compared with placebo, no intervention or different dosage schedules.3. To identify the adverse effects associated with influenza vaccines in children with cancer treated with chemotherapy, compared with other control groups. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2012) and EMBASE (1980 to 2012) up to August 2012. We also searched reference lists of relevant articles and conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Infectious Diseases Society of America (IDSA), the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Paediatric Oncology (SIOP). SELECTION CRITERIA: We considered randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which the serological response to influenza vaccination of children with cancer was compared with that of control groups. We also considered RCTs and CCTs that compared the effects of influenza vaccination on clinical response and/or immunological response in children with cancer being treated with chemotherapy, compared with placebo, no intervention or different dosage schedules. DATA COLLECTION AND ANALYSIS: Two independent review authors assessed the methodological quality of included studies and extracted the data. MAIN RESULTS: We included 1 RCT and 9 CCTs (total number of participants = 770). None of the included studies reported clinical outcomes. All included studies reported on influenza immunity and adverse reactions to vaccination. In five studies, immune responses to influenza vaccine were compared in 272 children receiving chemotherapy and 166 children not receiving chemotherapy. In four studies, responses to influenza vaccine were assessed in 236 children receiving chemotherapy compared with responses in 142 healthy children. Measures used to assess immune responses included a four-fold rise in antibody titre after vaccination, development of a haemagglutination inhibition (HI) titre > 32 and pre- and post-vaccination geometric mean titres (GMTs). Immune responses in children receiving chemotherapy were consistently weaker (four-fold rise of 38% to 65%) than those in children who had completed chemotherapy (50% to 86%) and in healthy children (53% to 89%). In terms of adverse effects, 391 paediatric oncology patients received influenza vaccine, and the adverse effects described included mild local reactions and low-grade fever. No life-threatening or persistent adverse effects were reported. AUTHORS' CONCLUSIONS: Paediatric oncology patients receiving chemotherapy are able to generate an immune response to the influenza vaccine, but it remains unclear whether this immune response protects them from influenza infection or its complications. We are awaiting results from well-designed RCTs addressing the clinical benefit of influenza vaccination in these patients.

Influenza vaccination in children being treated with chemotherapy for cancer.

BACKGROUND: Influenza infection is a potential cause of severe morbidity in children with cancer, therefore vaccination against influenza is recommended. However, there are conflicting data concerning the immune response to influenza vaccination in children with cancer and the value of vaccination remains unclear. OBJECTIVES: 1. To assess the efficacy of influenza vaccination in stimulating immunological response in children with cancer during chemotherapy, compared to control groups. 2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or stimulating immunological response in children with cancer treated with chemotherapy, compared to placebo, no intervention or different dosage schedules. 3. To determine the adverse effects associated with influenza vaccination in children with cancer. SEARCH STRATEGY: We searched CENTRAL, MEDLINE (1966 to 2007) and EMBASE (1980 to 2007) up to February 2007. We also searched reference lists of relevant articles and conference proceedings of ICAAC, IDSA, MASCC and SIOP. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which the serologic response to influenza vaccination of children with cancer was compared to other control groups. We also considered RCTs and CCTs comparing the effects of influenza vaccination on clinical response and/or immunological response in children with cancer, with placebo, no intervention or different dosage schedules. DATA COLLECTION AND ANALYSIS: Two independent authors assessed the methodological quality of included studies and extracted data. MAIN RESULTS: We included 1 RCT and 8 CCTs ( total number of participants=708). None of the included studies reported on clinical outcome. All included studies reported on influenza immunity and adverse reactions to vaccination. In five studies, immune responses to influenza vaccine were compared in 272 children on chemotherapy with 166 children not on chemotherapy. In three studies, responses to influenza vaccine were assessed in 204 children on chemotherapy compared with responses in 112 healthy children. The measures used to assess immune responses were: a four-fold rise in antibody titre after vaccination, development of haemagglutination inhibition (HI) titre > 32, and pre- and post-vaccination geometric mean titres (GMT). Immune responses in children receiving chemotherapy were consistently weaker (four-fold rise of 25% to 52%) than in those children who had completed chemotherapy (50% to 86%) and in healthy children (71% to 89%). Concerning adverse effects, 359 paediatric oncology patients received influenza vaccine and the side effects described were mild local reactions and low grade fever. No life-threatening or persistent adverse effects were reported. AUTHORS' CONCLUSIONS: Paediatric oncology patients receiving chemotherapy are able to generate an immune response to the influenza vaccine, but it remains unclear whether this immune response protects them from influenza infection or its complications. We are awaiting results from well-designed RCTs addressing the clinical benefit of influenza vaccination in these patients.