The Aim of the Study

The aim of this study is to develop better ways of detecting genetic causes of structural anomalies observed on ultrasound scan within pregnancy. To do this we will use next generation sequencing technology, a new 'molecular' laboratory method, which allows us to pick up very small changes in the baby's genes. Our genes act as instructions for passing on inherited characteristics such as eye colour and height from parent to child. Sometimes changes in our genes cause certain diseases or conditions. To find out more about genes and the genome, please follow this link: What is a genome?

In order to diagnose certain chromosomal problems in pregnancy, a procedure known as amniocentesis (a sample taken from the fluid surrounding the baby) or chorionic villus sampling (CVS) (a sample taken from the placenta) is needed.

We are developing new molecular methods that look at a baby's genes in much more detail when women have a CVS or amniocentesis. We would like to find out if the molecular methods give us as much or more information than the current methods do. In this study we will not be able to give any results from the new laboratory method within the pregnancy. We hope to be able to do this for future parents.

Before we can offer any new tests routinely it is important to ensure they work well and are accurate. To do this we need the help of parents with complicated pregnancies to collect samples that will allow us to compare these new tests with those in current use.

Apart from exploring the technical aspects of these new tests, the study will also look at any ethical questions relating to the new tests and the personal experience of the patients during the study.

Participation in PAGE

We know that the particular appearance on your baby's ultrasound scan may be associated with changes in your baby's chromosomes or genes. Therefore you will have been offered an amniocentesis or CVS to test for certain genetic changes such as trisomies (extra copy of an entire chromosome).

You can participate in the PAGE study if the testing of your amniocentesis or CVS sample did not detect any trisomies and if the ultrasound scan showed a nuchal translucency (fluid at the back of the baby's neck) of larger than 4 mm, or one or more structural anomalies at any time in pregnancy after 11 weeks gestation. Your partner (the father of your baby) should also consent to the PAGE study; both of you must be at least 16 years of age and you should both be able to understand the study patient information provided by your clinical team.

We know that it can be a distressing time for you when a scan shows that your baby is not developing as expected. We are grateful to you for thinking about participating in the PAGE Study.

What will happen to me if I take part?

If you agree to take part we will ask you and your partner to donate an additional blood or saliva sample (blood sample is preferable). We are not asking permission to take any extra CVS or amniocentesis samples, we will use DNA left over after the standard clinical tests have been performed.

These new tests are very sensitive and may also detect minor changes that won't affect the health of your baby. These changes can be inherited from either parent. For this reason we need to test you and your partner's DNA at the same time as testing your baby's DNA so that we know which changes are new in your baby, and so might be important, and which are inherited from you or your partner. We also seek permission to ask your doctor, or check your hospital notes to confirm the outcome of the pregnancy and the results of any tests done. With your agreement we may contact you when your baby is around 2 years old to arrange a follow-up to find out how he/she is developing.

These new tests are still in development and the results of this research will not be available during the course of your pregnancy. If we find any information that explains your baby's problems, we will inform your doctor who will contact you. This research study is designed to improve the diagnosis of unexpected problems in the developing baby, so we will not seek or feed back any findings not related to your pregnancy.

In some cases you may be asked if you would like to share your thoughts about your genetic testing experience with fetal medicine specialists. Your views as a parent will be very valuable, helping us to shape clinical services and tests in the future. See also: Social Science section.

What happens to the samples in the PAGE study?

1. CVS, Amniocentesis or fetal blood samples are collected and in addition blood samples are taken from both parents.

2. At the NHS diagnostic laboratories the samples will be anonymised and DNA is purified from all samples.

3. DNA arrives at Sanger Institute. After an initial quality control, analysis will look for genetic causes of the observed fetal anomalies (exome and whole-genome sequencing).

4. Results fed back to families by local clinical genetics service.

5. Results from consenting families deposited in secure databases for further research.

Confidentiality

We will follow ethical and legal practice and all your information will be handled in confidence. Any information you give us will only be used in the course of the research to develop these new tests. Any samples and data stored will be stored securely.

They will be coded, and no personal data (for example name and address) will be available to the researchers. In the event that we identify specific gene changes that might explain your baby's condition we will deposit these changes and the anonymised information in large international databases containing similar information to allow us to identify babies anywhere else with similar problems and a similar change in their genes.

This helps us understand which gene changes might explain your baby's problems and which are more likely to be minor changes that are unlikely to affect health.

To advance research and maximise our understanding of the effect of any gene changes on the health of babies, all the anonymised data will be shared with other medical researchers in a secure manner, but only if these researchers commit to keep these anonymised data secure.

Researchers can request access to anonymised information on variants likely to explain the structural anomalies (via the DECIPHER database) or the anonymised genomic dataset containing all genetic information (via the European Genome-phenome Archive, EGA). Publications of anonymised study results in scientific journals will also be a way of communicating new findings to a wider research and clinical community, paving the way for further progress in diagnosing and understanding of genetic conditions causing developmental problems during pregnancy.

 
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