NorFlu - a study of influenza A(H1N1) and vaccination in pregnancy

Approximately 4,500 mothers and their children from the Oslo and Bergen areas are taking part.

Most women who have influenza when pregnant complete their pregnancy without problems. However, they are at greater risk of complications such as pneumonia and pulmonary failure. Severe complications may lead to a miscarriage or premature birth. The Norwegian health authorities recommended that pregnant women in their 2nd and 3rd trimester should be vaccinated against swine influenza because the risk of serious illness and death among pregnant women outweighed the risk of possible unwanted effects from the vaccine. The same advice was given by WHO and other countries with access to the vaccine.

For many years, the seasonal influenza vaccine has been recommended to pregnant women in USA. No evidence of foetal harm has been found.

Several hundred thousand pregnant women in Europe were vaccinated with Pandemrix in autumn 2009. To date, there are no reports of unwanted effects for either the women or their children.

A registry study of Norwegian women who were pregnant during the swine influenza pandemic in 2009 showed that pregnant women who were vaccinated did not have an increased risk of stillbirth. However, pregnant women who had influenza did have an increased risk of stillbirth. The study was published in the New England Journal of Medicine (Håberg et al, 2013). 

Who is participating?

NorFlu participants are women from Bergen and Oslo who were pregnant during the influenza pandemic of 2009-2010 were invited to take part in the project, and their children. Approximately 3 200 pregnant women accepted the invitation to participate in NorFlu. In addition, 1,300 women and their children agreed to take part in a collaborative project between NorFlu and the Norwegian Mother and Child Cohort Study (MoBa). Approximately 4,500 mothers and their children are participating. In addition, 300 women who were not pregnant were recruited as controls.

Women who did or did not have influenza and who did or did not take the vaccine during the swine influenza pandemic are participating. Participtaion is voluntary.  

What does participation in NorFlu involve?

• Participation in NorFlu involves answering questionnaires and giving a blood sample. Participants were asked to fill out a questionnaire before birth, and again when the child is 6 months, 18 months and 3 years. Data collection for the 7 year form is ongoing. The next questionnaire is planned when the children are 9 years old. The mothers were also asked for a blood sample in connection with childbirth and a blood sample from the umbilical cord after separation from the baby. 
• Consent gives NorFlu permission to obtain information about the mother and child from the Medical Birth Registry of Norway. Information can also be obtained from other registers for Norwegian Surveillance System for Communicable Diseases (MSIS), the Norwegian Immunisation Registry (SYSVAK), the Norwegian Patient Registry, the Cancer Registry, the Cause of Death Registry and the Norwegian Prescription Database. If the woman is also participating in the Norwegian Mother and Child Cohort Study (MoBa) information can be obtained from there too. The extent to which information is obtained from these registers depends on the health conditions that are relevant to study. 
• Information from hospital records, registers in Statistics Norway or social security records requires NorFlu to gain specific approval from the Regional Committee for Medical and Health Research Ethics in each case.
• Participants in NorFlu may also be asked to take part in projects which involve the collection of new data directly from the mother or child. Such surveys are voluntary and will require a new consent and approval from the Regional Committee for Medical and Health Research Ethics. In 2013, NorFlu was given support from the Research Council of Norway for a new subproject, the clinical study of 3-4 year-olds.

Data protection

Only anonymous material will be made available to researchers. Participants in NorFlu cannot be identified when research results are published.

Participants are entitled to access all health information recorded about them and have the right to amend any errors. At any time, and without stating a reason, participants can withdraw from the study and request the deletion of their information or biological samples, which then cannot be used for further research.

All participants signed a consent form that applies for both mother and child until the child reaches 16 years of age. At this point, the child must give their autonomous consent to any further participation.

Safe storage of information

Blood samples will be stored in the Biobank at the Norwegian Institute of Public Health, and then analysed in an anonymous form. Data from the questionnaires are stored in a similar way without name or personal identity number. A code number links the participant to the information through a coupling key. This key is stored separately from the rest of the data, and only a few authorised project team members can access it. Information and samples will be destroyed upon completion of the project, provisionally set for 2025. A continuation of approvals may occur.

Withdrawal from the study and disposal of data

The study is voluntary and participants can opt out whenever they wish. They can choose to stop receiving further questionnaires but the samples and data they have already supplied will still be used and they will continue to receive newsletters about research. Alternatively, participants may request disposal of all information and samples collected by the study for themselves and their children.

Responsibility for the study

The Norwegian Institute of Public Health is responsible for NorFlu. Recruitment to the study was carried out in collaboration with Haukeland University Hospital in Bergen, Oslo University Hospital and Vestre Viken Asker and Bærum Hospital. NorFlu has been approved by the Regional Committee for Medical and Health Research Ethics. Blood samples and information will only be used for research as approved by the Regional Committee for Medical and Health Research Ethics.

The study has been financed by the Ministry of Health and Care Services.