Memorandum by the Avon Longitudinal Study
of Parents and Children (ALSPAC)
1. The ALSPAC study is designed to look
at the ways in which different aspects of the environment impact
on the development and health of the child and parents, and the
ways in which such influences are affected by genetic susceptibility.
The study was designed therefore to collect
blood samples for extraction of DNA from the very beginning. Women
who were pregnant with an expected date of delivery between 1
April 1991 and 31 December 1992 were enrolled in the study if
they were resident in Avon. The bulk of the information is collected
from questionnaires completed by the parents, and more recently
the children, as well as medical and other record extraction.
From the age of seven years onwards children have been invited
to visit the study and undertake a number of different tests on
a one to one basis.
A brochure outlining the types of data to be
collected was given to mothers at the very start of the study
and this included information on the analysis of DNA. Women were
told that being part of the study was purely optional, and that
they could withdraw at any time they wanted. At the same time
they were informed that biological samples would only be analysed
with their signed permission.
The study is based within the University of
Bristol and all data and biological samples belong to the University.
It is governed by a Scientific Advisory Committee which is in
turn advised by an Ethics and Law Sub-committee, a Genetic Advisory
Committee, a Cognitive, Educational and Social Development Advisory
Committee and a Biomarker Advisory Group.
The overall aim of the study is to continue
following up the children and their parents, monitoring the changes
in the environment (which we define as all aspects of exposure
whether physical, psychological or social) throughout the rest
of their lives.
Full details of the study can be found on the
study website at www.ich.bristol.ac.uk/alspac.html.
2. Funding for this study has come from
a wide variety of sources including the Medical Research Council,
UK Government Departments such as MAFF, Department of Health,
Department for Education and the Health and Safety Executive.
Other sources of funds include Medical Research Charities such
as the Wellcome Trust, the National Asthma Campaign, American
sources such as the National Institutes of Health and the March
of Dimes charity. Commercial funding has been provided to enable
the study to look at the safety of specific products such as Coca
Cola or electric blankets. Such projects are always undertaken
on the understanding that the study has the right to publish the
results regardless of what is found.
3. Biological samples were obtained from
the mother during pregnancy by asking community midwives to take
an extra sample of blood for the study at each time point at which
they were taking blood from the pregnant woman. This blood sample
was sent to the study laboratory, and in addition the study went
to the local laboratories and acquired any blood from the women
that was left over after clinical assays had been undertaken.
At the time of delivery a sample of blood from the umbilical cord
was collected specifically for the study, a piece of the cord
was frozen and the placenta was kept in formalin. As already indicated,
we have promised mothers that we would not analyse these samples
without their signed permission. There are to date 14,000 women
who have signed permission forms out of a total sample of 14,500.
DNA is being extracted from the mother's blood
and the child's blood. This provides a variable amount of DNA,
which will certainly be insufficient for the number of assays
that will be requested over time.
With the human genome project being able to
identify many hundreds of thousands of genes, there is more pressure
to have an extensive stock of DNA. It has therefore been decided
to investigate the possibilities of immortalised cell lines on
fresh samples of blood to be taken from parents and their children.
Whilst this has received the approval of the ALSPAC Ethics Committee,
it has yet to go through the local NHS Ethics Committees. In approaching
parents for permission to create immortalised cell lines, the
option always to be able to opt out will be emphasized. No pressure
will be put on parents or the children to take part in this aspect
of the study, but it is hoped that a large proportion of the families
will want to do so.
4. The consent forms signed by the mother
in respect of the biological samples have always stipulated that
no results from any of the assays to be carried out would be linked
back to the name of either the mother or child. We occasionally
stipulate at the time of taking the sample that we are going to
carry out a particular assay and feed the results back. In such
an instance we carry out the assay prior to complete anonymisation
of the sample. For all genetic assays, no feedback of results
to the family will be undertaken. We always present specific problems
to the ALSPAC Ethics Committee for discussion.
Collaboration with scientists in a variety of
different fields is important. This is carried out with due care,
taking full account of the confidential and sensitive nature of
the data involved. A balance has to be carefully made between
making the information as freely available as possible to the
research community in general, and preserving the confidentiality
of the study. Up until now, geneticists have received aliquots
of DNA from a group of ALSPAC participants, which they have genotyped
and the data has then been linked back into the overall database.
Unused DNA is returned to the study centre. Statistical analysis
of such data, linked to the other information held on these parents
and children is then carried out within the ALSPAC offices, either
with the ALSPAC statisticians carrying out the statistical analyses
under the guidance of the geneticists, or vice versa. In this
way it is intended that the confidentiality and inability to link
genetic information with other identifying details will be preserved.
The Scientific Advisory Committee has overall
control of which projects are undertaken. For this they take advice
from experts in the field. This safeguards the scientific integrity
of the projects carried out.
Professor Jean Golding,
Scientific and Executive Director of the ALSPAC Study, University
Professor Marcus Pembrey, Director of Genetics within the
Professor Michael Furmston, Professor of Law and Chair
of the Ethics and Law Sub-Committee.