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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Causal pathwaus for asthma

Awarded: NOK 11.5 mill.

Project Number:

221097

Application Type:

Project Period:

2013 - 2018

Subject Fields:

Partner countries:

The cause of the development of asthma and allergy is unknown. The goal of the project was to increase the knowledge of how different types of exposures in pregnancy can affect the risk of asthma and allergies The project has contributed with new knowledge about the effect of smoking in pregnancy, intake of vitamins, including vitamin A, D and folic acid, fatty acids, intake of alcohol, and maternal use of paracetamol, maternal body mass index and the development of asthma in the child. Some of our latest results show that high intake of vitamin A in pregnancy above the recommendations increase the risk of asthma by 7 years of age, while a moderate intake of vitamin D in line with the recommendations reduces the risk. Furthermore, we have shown that children of women, who take folic acid, and that have a high intake of folic acid through their diet have an increased risk for asthma. We found no clear relationship between preeclampsia, or the mother's stress in pregnancy and asthma in the child. Growth rate in early infancy can also have an effect on asthma. A possible underlying explanation of this finding is that growth rate is a measure of conditions that may have occurred in fetal life, and that epigenetics may be one of several possible underlying mechanisms. For example, we have shown that epigenetic changes can predict gestational length. The project aimed to explore whether epigenetics could be an underlying mechanism that explains the effects of exposures in pregnancy and asthma. We can define epigenetics as changes in genetic material that does not include the actual DNA code, but which, nevertheless changes the function of the genes. Typical changes is DNA methylation. Simplified, we can say that genes can be turned ?on and off? in fetal life because of environmental exposures. We therefore studied whether it is epigenetic changes in cord blood, so-called DNA methylation, in children who are exposed to risk factors for asthma in a fetal life compared to children who are not exposed. In the project period there has been an extensive development of new methods in the epigenetic research area. We have therefore participated in a large international network, Pregnancy And Childhood Epigenetics (PACE) Consortium, to address some of the epigenetic research questions. We have contributed with new knowledge that shows that exposure to smoking in pregnancy is associated with changes in DNA methylation in cord blood, which also can be found among children with asthma later in life. The changes also seem to be able to be transferred to the next generation. In contrast to folic acid, which seems to affect cord blood DNA methylation, the project has shown that there is no association between vitamin D level of the mother during pregnancy and DNA methylation, while it may be that the mother's fatty acid level of Omega 3 measured during pregnancy can give epigenetic changes. In contrast to another study, we did not find that the mother's weight gain in pregnancy was associated with cord blood DNA methylation. Finally, we found differentially methylated regions in new borns for development of asthma by school age. There was also differentially methylated regions in older children related to current asthma, which may reflect both risk for and effects of disease. We still need more studies to show that epigenetics may be an underlying mechanism that explains the effects of exposures in pregnancy and asthma. Our study was based on the extensive ongoing collaboration that was established between the Norwegian Institute of Public Health (NIPH), the National Institute of Environmental Health Sciences (NIEHS) in US and several other national and international collaborators within The MoBa Asthma Group.

The present study is based on The Norwegian Mother and Child study (MoBa), which is a pregnancy cohort study that enrolled 90,706 women, during 108,859 pregnancies, between 1999 and 2009. This grant proposal based on MoBa is designed to take advantage of the potential for research on human biological material in biobanks, by coupling analysis results with data from health surveys, health registers and the health services. Our study is based on the extensive ongoing collaboration that is established betwee n the Norwegian Institute of Public Health (NIPH), the National Institute of Environmental Health Sciences (NIEHS) in US and several other national and international collaborators within The MoBa Asthma Group. The groups have received grants from Norway, US and the European Union (EU). These grants include funding for 1) a follow-up questionnaire of the children at age 7 yr, 2) measures of maternal plasma levels of several exposures during pregnancy including methyl donors, cotinine (a tobacco smoke metab olite) and vitamin A, D and E in mothers of approximately 3,500 children, 3) methylation of child DNA as measured in cord blood in a sub sample of about 2000 children. The present grant application applies for additional funding to extend the unique scien tific possibilities of these data by including; 1) similar measures of exposures also in the children after age 7 yr. 2) Measures of omega-3 fatty acids in both maternal plasma and the children, and 3) measures of objective markers of asthma and allergies in children to distinguish between different asthmatic and allergic phenotypes after age 7 yr. This project takes advantage not only of the basic MoBa samples and infrastructure including links to other national registries, but also this new study that i ncludes measures of prenatal exposures in maternal plasma believed to have epigenetic influences on asthma/atopy development, data on methylation of cord blood DNA, and measures of early life exposures in the child.

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Funding scheme:

BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering