The Norwegian Institute of Public Health (NIPH) intends to follow the families for years to come and to collect more new material to create a Norwegian research database of high quality
There is good evidence that conditions in pregnancy and early childhood can have a major impact on a child's later health. Causal knowledge is necessary for prevention. For example we need to know if toxins, infections, dietary factors, work stress or other factors (exposures) are responsible for impaired health. We are also interested in genetic factors.
The research must be carried out in a way that can give good answers. We do this by asking about causal factors before any disease has developed. Thus, we get more reliable information than if we ask the participants after a disease has developed. We need to include a large cohort because some important environmental factors and some diseases are rare.
There is growing focus on paternal impact on child health. This is due to concerns that fathers, through their professional situation or in other ways, are subjected to exposures that lead to gamete changes with subsequent damage (congenital malformations, cancer) in the child.
The study relies on maternal and paternal consent and benevolence. In return, we promise that the information supplied will be managed properly - privacy will be stringent, and analyses will be carried out to the highest standards by Norwegian and international experts in their various research fields.
The reason for the project is our lack of knowledge about the causes of serious diseases. Poliomyelitis and diphtheria are no longer feared in Norway, partly because specific knowledge about the causes (micro-organisms) laid the foundation for the development of vaccines and antibiotics.
There are few who would disagree that suffering can be prevented if children and young adults can avoid serious injury and disease. Experience from medical causal research after World War II shows that prospective investigations give the most reliable results, i.e. those that start with healthy people and record potential causal factors before diseases develop. The studies must be large because many of the serious diseases are relatively rare. The research is specific and is based on defined problems that take into account the prevalence and diversity of causal factors and the incidence of disease. When we add together the prevalence of many of the serious conditions (cancer, stillbirth, severe congenital malformations, diabetes, arthritis, severe psychiatric and neurological diseases), many people are affected, even at a young age. For all diseases, there will be a causal chain, with many elements. There is no contradiction between our understanding of multifactorial diseases or our perception of health as a concept with many dimensions, and the specific causal research. The lessons learned from the diseases we have been able to treat means that we can come a long way if we find the critical points in the causal chain.
Knowledge of the causes is important for three reasons:
1. Specific knowledge can lead to direct prevention
If we know that a toxin or a drug is a direct cause, we can prevent this by removing the causal factor. If it is due to an infection, we can give infectious disease control advice and develop vaccines.
2. The research could lead to curative or palliative treatment.
This also applies in those cases where we cannot prevent disease. An example is phenylketonuria, a hereditary condition which can be treated with diet. It is important to find out whether a disease is hereditary and to identify the causal genes because this will lead to further laboratory research that can produce effective medicines. There are analogies to infectious diseases here.
For example, epidemiological studies in the 19th century showed that water supply and sewerage had significance for the spread of cholera. The next step was to detect the bacterium that caused the disease. However, there was little they could do before effective drugs and vaccines could be developed. For cholera, it is necessary to know the detail of the body's defence mechanisms and bacterial molecular structure to create vaccines and drugs, and even now not enough is known.
3. Knowledge is essential to avoid unnecessary concern, even if it does not lead to prevention or cure
We want to dispel suspicions about the causal relationships. For example in a situation where we do not know the reasons for severe congenital malformations, we tend to blame ourselves or factors in the environment or dietary and lifestyle habits.
Causal research related to the mother and child has been of low priority. In recent decades, cardiovascular disease and cancer, with prospective studies of adult participants have dominated the medical research arena.
The cause of many diseases and complications arising in pregnancy is largely unknown. One example is the cause of stillbirth and another is the cause of severe congenital malformations. We know little about the causes of premature birth. For many diseases that can occur in childhood and require significant resources in treatment, e.g. diabetes, autism, arthritis and allergy, knowledge of the causes is lacking. Many of the conditions and illnesses that affect women during pregnancy and after birth are also not understood. Examples include morning sickness, pre-eclampsia, pelvic girdle pain, and depression.
We believe that if we can help to understand the causes of some of the diseases that will be studied in this project, it will be worth the effort. This knowledge will in most cases be generalisable, meaning that it will be valid for the future and for women and children outside Norway. From a scientific theoretical perspective, we realise that we can never prove that a certain amount of exposure is a cause. Nevertheless, it is appropriate to think in concrete causal models (rather than more diffuse risk models) and therefore we choose to use the word causal factor to make the issues precise and more focused.
Pre-natal care was introduced to combat pre-eclampsia. We still do not know the causes of pre-eclampsia, although the incidence and mortality is drastically reduced due to significant improvements in treatment.
Prevention is the only right approach if we are to make progress in combating a number of diseases of both mother and child. The road to prevention needs research-based knowledge of the type that MoBa may provide.
About 20 years ago, a Norwegian researcher, Anders Forsdahl, in Finnmark, found a striking correlation between the mortality of adult men and infant mortality in their home county around their birth date. His theory was that the mortality in adulthood was "pre-determined" already as a foetus. Today’s theories suggest that many diseases, particularly of a cardiovascular nature are determined by early influences in foetal life or early childhood. Forsdahl's study, and most of the current research is retrospective, i.e. they are based on data that can be extracted from old records and registers. We will obviously get more reliable and better data if we can follow the development from foetal life onwards. No one has conducted follow-up studies which also include foetal life. This is one of the reasons why MoBa intends to follow the cohorts into adulthood. Several experts believe that research will not progress by studying the existing risk factors, but that one must take into account early influences in life.
It is also important to identify the environmental factors that cause disease. In the years to come there will be suspicion about several factors believed to cause disease, but which in reality do not. We therefore need a safe way to disprove such alleged false causes.
In the years ahead, we will increasingly encounter questions like:
- Do power lines cause cancer?
- Do mobile phones destroy the brain?
- Does high chlorine content in water damage human health in ways we do not know?
- Should pregnant women avoid computer screens in the interests of the child?
- Should pregnant women be protected from noisy jobs for the sake of the foetus?
- Has the new motorway caused the children who live nearby to develop asthma?
- Can pregnant women work on oil platforms?
- Are there more allergies after the chemical industry adopted the new "miracle oil"?
- Is the hormone-treated meat that agriculture now produces safe, or does it damage health?
- Are there substances in farmed fish that can harm the foetus?
Individuals and society should be given a reliable answer to these questions. For questions to be answered reliably data must be provided where one can see if there actually was a higher frequency of illness among children of pregnant women who worked in particular conditions. This study can provide these types of answers.
Norway is in an excellent situation to follow such a study well. Norway is a well-ordered society, the individuals are likely to provide reliable information about themselves, and there is great social stability. Moreover, we have the advantage of having some good health registers.
How is the study designed?
This study is a cohort study. This means that we recruit people from the population who are healthy, and request regular follow-up contact. In this case it means that we invited all pregnant women over a period of time to participate. We wanted to recruit 100,000 women in the study and follow them and their children for a long time to come.
Such a prospective study is considered to provide the most reliable information about illness and health and factors that may have influenced them. This is because once a disease has already occurred, it is far harder to remember what happened beforehand. We can also connect the prospective study with case-control studies, where healthy people (controls) are selected from the main study. This is considered to make the best of both designs.
What are we measuring?
We seek to determine what factors that pregnant women have been exposed to during pregnancy. There may be exposure from the environment, from dietary and lifestyle habits and from diseases they have recovered from. We can only find out by asking. Therefore, the study is based on questionnaires, in which pregnant women, and subsequently the mother and child will provide answers in the questionnaire. Apart from this, we collect blood samples and freeze them until they will be analysed. We can determine the factors that are linked with infections, environmental toxins, medicines and other environmental factors in blood samples.
Blood samples are important for two reasons:
- Blood samples can reveal some important environmental exposures. For example we can see if the pregnant woman has had an infection, or if we can find toxins in the blood. We do not have methodology for everything today but this is under rapid development.
- By extracting genetic material (DNA) from blood samples from both mother and child, genetic disposition to disease can be studied. This is especially valuable when these can be compared with environmental exposure to look at the gene-environment interaction.
How do we select the questions?
Most questions are based on certain hypotheses for the relationship between health/ disease (as outcomes) and exposures. Some questions are fairly general, others are aimed at specific issues, and will be a "project within the project," or a sub-project. All sub-projects will have to use the same information about background factors, but some questions are intended to answer specific hypotheses.
There are several researchers who have expressed interest in specific issues and we will provide a list of such sub-projects later.
Are there any ethical problems linked to the project?
The basis document for ethical issues in medical research is the Declaration of Helsinki. The guidelines refer primarily to clinical research, and it has been necessary to have specific guidelines for epidemiological research, given by CIOMS - Council for International Organizations of Medical Sciences. The difference is that within epidemiology, primarily observational studies are made, for example through questionnaires as in this project. In the meantime, blood samples will also be collected, which involves very little physical intervention for the participants, but there has been discussion about the use of blood samples. The following points are reviewed and discussed in relation to the implementation of the project:
- Will the questions we ask participants seem provocative and create anxiety?
- Is privacy sufficiently protected? The project requires regular follow-up so data cannot be totally anonymous. However, the link between personal identification and results is not performed by scientists, and access to personal data is strictly limited.
- Participants do not receive feedback on the results of the study other than through publications on a group level, even though there may be desire for such feedback from participants.
- Analyses of blood samples will apply to both genetic and environmental factors. New questions will arise during the project, so that one can not foresee what can be done in the future.
- The questions are evaluated by the agencies and institutions that exist for such assessments. Within medicine, there are ethics committees for each health region, and the Norwegian Data Inspectorate evaluates privacy. For this project, the Data Inspectorate granted the licence for the establishment of the various registers related to the project. Ongoing ethical re-evaluations may be needed when new applications such as sub-projects associated with the main study are considered.
Professor Per Magnus is the project manager with daily responsibility for the project's progress. A project team in Oslo and Bergen shares the tasks.
Approximately 100 subprojects with specific research questions have been proposed. The questions cover environmental factors, such as medication, nutrition, infection and work exposure. Genetic factors and the interplay between genes and the environment will be studied. Blood samples from as many fathers as possible will also be collected, enabling association studies between genes and diseases.
- MoBa Magazine(pdf)