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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Perinatal outcomes and childrens health after prenatal exposure to influenza and influenza vaccination

Awarded: NOK 17.7 mill.

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2013 - 2017


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In 2009 the world was exposed to a new pandemic strain of influenza A (H1N1) resulting in young people becoming sick, including pregnant women. To explore possible consequences of influenza infection during pregnancy, the Norwegian Institute of Public Health initiated the research project NorFlu. The aim is to address both short and long term effects of influenza infection on maternal health and child development. The effect of influenza vaccination in pregnancy will also be studied. Influenza vaccination is generally considered safe, but reports of narcolepsy after vaccination have alerted both the public and scientific community of possible side-effects of the central nervous system. The NorFlu cohort consists of 4400 women who were pregnant during the pandemic and their children. Data from questionnaires, health registries, clinical assessments and blood samples provide the basis for the analyses. According to these data, approximately 20 % of NorFlu- participants had influenza during pregnancy whereas 57 % were vaccinated. 2 % took anti-viral (influenza) medication during pregnancy. Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality, but the immunological mechanisms are not well understood. We explored the relation between the severity of disease and different parts of the immune system: the humoral (antibody) response and the cellular (so-called T-cell) response. Analysis of the mothers blood samples taken at birth indicated sufficient levels of antibodies to protect against influenza A (H1N1) infection in almost half of the samples. Amongst the women who had influenza during pregnancy, the antibody titers at birth were higher amongst the most ill women in comparison to those who were less ill. Further, we found that the presence of certain immune cells ("T cells and NK cells") protect against influenza symptoms in pregnant women which indicates that cellular immunity may effect disease progression. As part of this research, we developed a method for measuring specific cellular immune responses against influenza in collaboration with La Jolla Institute of Allergy and Immunology in the USA (Savic et al., 2016). In addition we have together with Columbia University, New York, developed a method for distinguishing between influenza infected and vaccinated individuals. This is a useful tool when an individuals information on previous influenza infections and vaccinations is not available, and the tool has been applied in a large epidemiological study (Mahic et al., 2017). Maternal antibodies are important for protection of the newborn against infection. For women who underwent infection during pregnancy, we found a good correlation between the amounts of antibody against the pandemic virus in the mother and child samples taken at birth. We are in the process of studying the correlation of antibody levels between mother and child also for pregnancies where the mother was vaccinated, and at age 4. How does influenza during pregnancy affect the fetus? Our results indicate that mild influenza illness during pregnancy is not associated with an increased risk of pre-eclampsia, lower birth weight or premature birth. Analyses have also been done on child development, as to whether exposure to influenza or influenza vaccine during pregnancy affects child temperament and psychomotor development at 6 months. So far the results show that children exposed to influenza virus during the first few weeks of pregnancy score somewhat lower in psychomotor development at 6 months of age, than children of uninfected mothers. To further study the association between pandemic influenza and vaccination during pregnancy and the cognitive development of children, we carried out clinical assessments of 614 children aged 4 years during 2014/2015. The children were assessed for 3,5 hours using standardized tools to map cognitive and motor skills. Analyzes of the clinical data and blood samples are ongoing.

The Norwegian Influenza Cohort (NorFlu), was established during the influenza A H1N1pdm09 pandemic.The cohort comprises about 3200 mother and child pairs, 2600 with biological samples from mother and cordblood, questionnaire data and linked registry expos ure and outcome data available.Using the combined potential of data from these sources, we will study perinatal outcomes and childrens mental and cognitive development after prenatal exposure to influenza A H1N1pdm09 virus infection or influenza immunizat ion, as well as risk factors for severe influenza in pregnancy. Pandemic influenza has many health effects related to the complications of the acute infection, and to brain damage with long-term consequences.Influenza vaccination is largely safe, but sign als of narcolepsy have alerted public and scientific communities to serious side effects affecting the central nervous system-especially in young children.Prenatal exposure to immunization and infection will be established through immune status analyses o f maternal- and cord blood at birth, questionnaire- and register data.Outcomes will be studied according to four maternal exposure groups: 1) vaccinated and infected, 2) only vaccinated, 3) only infected and 4) neither vaccinated nor infected.Clinical ass essment of a sample of 3-year old children focusing on developmental health will be performed and additional maternal and child blood samples will be drawn. NorFlu questionnaires cover exposure to vaccination, influenza infection and anti-viral medication as well as maternal and child development and health. Cohort data will be linked to national health registries for selected outcomes and exposures:the Medical Birth Registry of Norway on perinatal health, the Norwegian Patient Registry on childhood devel opmental disorders and maternal health outcomes, the Norwegian Immunisation Register for vaccination data and the Surveillance System for Infectious Diseases for data on confirmed maternal influenza infection.

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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering