Frequently asked questions

This study aims to improve understanding of how being born early affects the brain and learning in children. We are seeking to understand what makes a premature baby more or less likely to have problems when s/he is older, including clinical, biological, environmental and social factors. We hope to be able to continue this study into the teenage years and adulthood to find out about long-term effects too.

Your baby is invited to participate in this research study because

• he or she was born early, at less than 32 weeks, or
• he or she was born near their due date (after 36 weeks of gestation).   We hope to study healthy babies born near their due date so that we can compare them with the preterm group.

We want to understand the effect of being born early on long-term outcomes for the child. From previous studies, we know that babies born early sometimes have different brain development and later difficulties – for example, in school. But we do not know why some babies develop problems while others do not. We think there are a number of factors that may have an effect and we want to investigate these in this study so that we can work out how to improve the lives of babies in the future.

Medical and family information. We will ask about your pregnancy and the health and well-being of your family because this information may be relevant for understanding risk and protection, and for predicting the outcomes of newborn babies and young children.

Placenta and cord blood. Looking at the placenta under the microscope and running blood tests on umbilical cord blood can provide information about your baby’s development in the womb. All babies make their own stem cells (the type of cell that gives rise to specialist cells eg brain cells) and these are present in umbilical cord blood. We may ask to use some of these to test new treatments that might help brain cells survive.

Genetic tests. A person’s “genetic make-up” may be defined as the molecules in our bodies that we inherit from our parents, which help determine who we are, and how our body grows and develops. This information is held in a ‘code’ that exists in the cells of our body, called DNA. The exact way in which that code works is influenced by another set of molecules in each cell called the epigenome. Both types of genetic information can be obtained from cells that are present in baby saliva.

Pictures of brain development from MRI. Magnetic resonance imaging (MRI) of the brain provides very detailed pictures that cannot be obtained in any other way (figure 1). It is safe and does not involve radiation.

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We are collecting brain scans from MRI from premature babies and babies born at full term so that we can find out what leads to altered brain development for some babies. In this way we hope to develop ways of helping children in the future.

MRI can show us how the nerve pathways cells in the developing brain connect to each other. By using images such as this we can study how connections are changed by premature birth. If you take part in this study, we will be able to create a picture like this one of your baby’s brain.

Metabolic responses and sleep rhythms. The body can respond to physical or mental stressful events by changes in hormone levels and these may influence long term outcomes. Very little is known about normal baby metabolic responses, which can be measured in saliva and blood.

Stool samples. Stool (meconium and faeces) contain lots of bacteria. The number and type of bacteria in stool is important for long term health. There is some evidence that early life events, such as type of delivery, type of milk feed and the need for antibiotics can change the bacteria in the stool. We want to find out the effect of preterm birth on these bacteria, and whether it matters for babies in the long run.

Nasal samples. Preterm infants are in general more susceptible to infections of the breathing system in infancy and childhood. This may be due to differences in ability to fight infection in nasal secretions. We plan to test whether immunity in the nose is altered by sampling nasal secretions using an absorbent strip of paper.  We also plan to test with a swab of the mucosal surface of the nose whether preterm infants have altered bacterial communities in their noses that might be less capable of fighting ill-making bugs.

Eye-movements in response to pictures. The project is using an eye-tracker to measure what babies and young children prefer to look at.  This can give us an insight into how their brain works and what they are learning. We’re interested in whether the information we get relates to other information, like brain scans.  We also want to know whether we can tell the difference at this young age between babies who later do, or don’t, develop learning problems.

Eye-tracking means recording where a person is looking using a specially-designed machine. From your baby’s point of view, it will be just like looking at pictures on a TV while they sit on your knee.  The tracker is completely non-invasive – it uses invisible light and nothing touches the eyes – so the baby can’t feel or see anything unusual.

No, it is up to you to decide whether or not to take part. We know this is a difficult time so take as long as you need, you won’t be rushed into anything.  If you do decide to take part you will be given this information sheet to keep and be asked to sign two  consent forms, one for you and one for your baby.  The consent forms asks you for permission to collect information at the time of your child’s birth and shortly afterwards while they are in hospital.  If that all goes well and you’re enjoying helping us out with this important research, we will also give you two more consent forms when you leave hospital. Again, one consent for you and one for your baby.  These forms will check that you are happy to continue to take part in the study as your baby grows up. Even if you sign the forms, you are still free to withdraw at any time in the future and without giving a reason.  Deciding not to take part or withdrawing from the study will not affect the healthcare that you receive, or your legal rights.

During the study we are hoping your family will take part in a number of different appointments as your baby gets older. We will keep in touch with you by email, letter or phone – you can let us know what you prefer. We will have a website, Facebook page and twitter account for the study. We will send all of our families information about the study and other interesting news about every six months. We are grateful to you for your contribution to science and understanding and we will do our best to make your experience interesting and fun.

We will collect different types of information about your baby at seven time points from pregnancy to age 5 years. For every appointment, your travel costs will be reimbursed.  There will be light refreshments available where appropriate and we hope that you and your baby will feel comfortable and happy with us. In each case, when we get back in touch we will send you a reminder of what the next appointment involves and there will be a chance to ask questions again.

1.  Antenatal

We will ask to collect information about you and your pregnancy from your medical records. We will also talk to you (for no longer than 30 minutes) to collect information that may not be recorded in your medical records.

2.  Birth

Samples of placenta, umbilical cord blood and an extra blood spot (the “Guthrie card”) will be collected when your baby is born. These samples will be taken when other blood tests are being done as part of usual NHS care – no extra needle episodes are involved.  If your baby is born unexpectedly or overnight you may not have agreed to take part in the study at that point.  If this happens we will ask your permission to use some of the placenta that was collected as part of your usual NHS care for the study. If you decline then the placenta would only be used for tests carried out as part of standard care and will not be used for research. We will also ask to collect information about the birth of your baby from your and your baby’s medical records and in discussion with you.

3.  Neonatal (birth to when you leave hospital)

A blood sample will be collected from your baby. This sample is timed to coincide with a blood test that is needed as part of your baby’s usual NHS care and no extra procedure is involved.  We will ask to collect a saliva sample from your baby. The saliva sample will take 5 to 10 minutes and is collected using a mouth swab sample kit, similar to a cotton wool bud being placed just inside the cheek.  We will also ask to collect up to three nasal secretion samples from some babies but not all. Each sample will take not more than 5 minutes and is collected using an absorbent strip of paper placed in the nostril or by taking some mucus from the back of the nose by a small soft swab.   A sample of your baby’s first stool will be collected and again before your baby leaves hospital.  We do this by keeping a dirty nappy.

Also, sometime near to their due date, your baby will be invited for an a MRI scan at the Brain Research Imaging Centre in the hospital or the Clinical Research Imaging Centre situated near this hospital, in Little France Crescent. When you arrive you and your baby will be greeted by a member of the research team who will take you to the MRI suite

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Before the scan, one of the research team will carry out a routine check and examination of your baby. We will confirm that your baby is well with no signs of coughs or colds, and that he / she is fit for MRI scanning. We ask that your baby does not wear any jewellery, religious artefacts or clothing with metal ‘poppers’ because the presence of metallic objects can affect the quality of the images.

The MRI scanner is a cylinder-shaped tube surrounded by a circular magnet. Your child will be wrapped in a blanket and placed on the examination table whilst asleep. We make sure your baby is secure by using a special wrap, which helps to swaddle him or her. This table slides on runners into the centre of the circular magnet. Next to the scanner is the control room where the radiographer taking the pictures sits. This has clear views into the scanner. You will be able to be with your baby until the scan starts and immediately when it finishes.

The scan will last about 60 minutes. Your baby’s oxygen levels and heart rate will be monitored during the scan. A paediatric doctor and paediatric nurse will be present in the control room observing your baby.

We try to make sure that babies go to sleep naturally, as they need to be as still as possible for the scan to work. We achieve this by letting your baby have a feed and swaddling him / her. If your baby likes a dummy we can also use this during the scan. We have found that these simple methods allow the baby to sleep through the whole scan in the majority of cases.

We will ask you to complete six questionnaires about you and your baby before you leave hospital and will take about one hour in total to complete. This will include a short reading questionnaire for yourself because this is a good way to learn about abilities that children inherit from parents.

Finally, we may ask that your baby comes for an eye test because we want to investigate whether pictures of the back of the eye tell us useful information about the brain. This will take about 20 minutes and uses equipment that resembles that used by opticians.

4.  4.5 months

We will ask you to complete four questionnaires. You can choose to do this by post, online or over the telephone.  They will take 25 minutes in total.  For those babies who provided a nasal swab at the neonatal stage, we will ask to collect the same sample again.  A research nurse would arrange to visit you and your baby at home to collect the sample.

5.  9 months

We will write to you to ask if you would be willing to visit the University for your baby to take part in an eye-tracking assessment, to complete some questionnaires, talk about your baby, and play with your baby while we film you. For babies who provided saliva and nasal secretions and/or nasal swabs at the neonatal and 4.5 month stage, we will ask to collect the same samples again. You do not have to take part in this part of the study but we are asking now for your permission to contact you at that time.

The assessment room is as family friendly as we can get it. We have some baby toys, a changing mat and wipes, comfy chairs, sippy cups and snacks available. There’s tea, coffee and biscuits for parents too. We can provide hot water to warm bottles up and if you want some privacy to feed your baby we can leave you alone, of course. There is access by a lift, and somewhere to leave your buggy too.

The eye-tracking will involve your baby sitting on your lap while different pictures and cartoons are presented on a computer screen about 40cm away. A remote camera will follow how your baby’s eyes respond to the different pictures, which are of everyday shapes and images. We believe that this is one of the earliest possible ways of assessing learning and memory and we wish to investigate whether newborn brain scans are related to these abilities. Before the eye-tracking we will also check your baby’s vision by showing them black and white pictures – this is a baby version of an eye-test like you might have at an optician.

We will ask you to complete 4 questionnaires about you and your baby, they will take 30 minutes to complete. The questionnaires will ask you about your mood and stress levels and your baby’s personality.  We will also ask you for a general update on how things are going for you as a parent, and ask you to fill in a form to find out what you think about our research study. Finally, we will also ask to talk to you about your baby’s development and this will take 35 minutes.

The third thing we will do at this visit is ask you to play with your baby for about ten minutes while we record this on a video camera. Having a record of how your baby behaves in a more natural setting is incredibly useful. We can look back at these videos later and explore all sort of things, like early signs of language (i.e. babbling), play skills and motor behaviour – the way your baby moves.

During your visit, we will aim to do about thirty minutes of eye-tracking, about thirty minutes of interview and about thirty minutes of other activities, but we’ll book you in for two hours so there’s plenty of time to fit in around your baby’s preferences on the day. We will try to book your appointment at a time when you think your baby will be feeling awake, but if they are sleeping when you arrive we can do the interview first! If the eye-tracking is going well, we can do it all in one go, or we can break it up into smaller bits if you prefer.

6.  2 years

We will write to you to ask if you would be willing to visit the University for your toddler to take part in an eye-tracking assessment, to complete some questionnaires, talk about your toddler, and play with your toddler while we film you. For families who provided saliva and nasal secretions and/or a nasal swab at the neonatal stage, we will ask to collect the same samples again. You do not have to take part in this part of the study but we are asking now for your permission to contact you at that time.

This appointment will be really similar to the appointment at 9 months old and about the same length in total (2 hours). We will repeat many of the same questionnaires, and the same (or similar) eye-tracking session. Instead of a detailed interview about your child’s development, we will do a slightly shorter questionnaire which should take about 25 minutes. We will also film you playing with your toddler again.

7.  5 years

We will write to you to ask if you would be willing to visit the University for your child to take part in an eye-tracking assessment, to complete some questionnaires, and play with your child while we film you. For families who provided saliva and nasal secretions and/or a nasal swab at the neonatal stage, we will ask to collect the same samples again. We will ask to carry out an eye test, to measure blood pressure, height and weight. You do not have to take part in this part of the study but we are asking now for your permission to contact you at that time.

This appointment will be really similar to the appointment at 2 years old, but with some new things. It should still take about 3 hours. We will ask you to complete 8 questionnaires about you and your child, they will take 1 hour 30 minutes to complete. We will also ask you tell us how satisfied you are with the project up to now, this questionnaire will take 5 minutes. We will also film you playing with your child again.

Because your child will be a bit older at this appointment, we will do eye-tracking with him or her at the same time as you complete the questionnaires. This will prevent the appointment getting too long. We will also do some direct assessments with your child – these will feel like games and allow us to find out how your child’s skills are developing in ‘the real world’.

Finally, we will ask if we can send two questionnaires to your child’s teacher about your child’s development at school. They will take 10 minutes in total to complete and we will post them out direct to the school, with your permission.

At the end of this visit, we will ask your child to complete a “mock scan”, which involves lying down in a pretend MRI scanner. This allows us to teach your child about MRI and to determine your and your child’s interest in completing the MRI visit. You and your child will be provided with information about the MRI visit and will be given the opportunity to ask questions. This session will typically be scheduled within a few weeks of the initial five-year visit. You will be asked to sign a separate consent form for the scan visit.

If you agree for your child to participate, we will ask your child to try the following tasks:

1. MRI Scan (up to 60 mins).  Before entering the magnet room, we will make sure your child’s clothing does not contain any metal. If necessary, your child can change clothes before entering the scanner room.

During the MRI scan, your child will watch movies on a screen. Your child may listen to voices and music through headphones. Your child will be inside the MRI scanner for up to 60 minutes, as long as he or she is comfortable. A researcher will stand next to your child during the scan.

2. Behavioural Testing (up to 2 hours). During these tasks, we try to understand how your child acts, thinks, or solves a problem. Behavioural testing does not involve brain imaging. Your child will complete this testing on a computer or seated at a table. Your child will be asked to complete social and non-social tasks. These tasks will involve paying attention to pictures, stories, toys, or videos. Your child may be asked to remember or think about the material and answer questions about it.

For your participation in this part of the study you will receive a £20 gift card and a book about the brain.

Yes. You are free to change your mind at any point. Your baby’s medical care would not be affected if you withdraw from the study. If you change your mind we ask that you contact one of our team so that we can re-assign any appointments to another baby. You can also change your mind at any point about allowing us to store your baby’s samples.  If you change your mind we will destroy the samples.

The study is designed to answer questions that will help babies in the future. It will help us understand more about the effect of premature birth on brain growth and learning outcome. In future, we hope to develop treatments to improve the outcome of babies born too early or too small because we know that some of them have problems with development in childhood. This study will help us work out what to treat, how to treat it, when to offer treatment and who needs this extra help. Some families enjoy the extra focus given to assessing the neurodevelopmental outcome of their baby that study participation brings.

There are no known risks from MR imaging: it does not involve ionising radiation. The MR scanner makes a loud knocking noise during the scan, so ear plugs and muffs are used to prevent discomfort due to noise, and to encourage your baby to sleep. As MR scanners use a strong magnet, care must be taken to ensure that metallic objects are kept away.

A consultant radiologist will review your baby’s scan. The scan is unlikely to show any problems that are known to affect your baby. Rarely, there may be a finding that requires further assessment or treatment. If this is the case we will tell you and your general practitioner and refer your baby to appropriate NHS services.

The DNA is collected from saliva with a special mouth swab sampling kit. This is like a cotton bud which we use to rub along the gum – in our experience babies don’t seem to mind. The type of genetic analysis we are planning provides information that is relevant for large groups of babies: we do not expect to identify genetic problems that are of direct clinical relevance for your baby.

This is a difficult time for you and your family and some people may become upset when they are completing the questionnaires or speaking to the research team. If this happens you can stop at any time without giving a reason.

If any findings such as post-natal depression, are identified for you from the questionnaires we will discuss this with you, ask your permission to let your general practitioner know and refer you to appropriate NHS services.

Having a baby can be a stressful time, especially if s/he is preterm. If you are having difficulty coping then please don’t hesitate to mention this to a member of the research team, who would, with your permission, let your nurse / doctor / midwife know because the clinical team will be able to provide you with the support you need.

We do not envisage risks or disadvantages from any other form of assessment proposed by this study.

If you have a concern about any aspect of this study please contact Dr James Boardman (0131 242 2567) who will do his best to answer your questions. If you remain unhappy and wish to complain formally, you can do this by contacting the NHS Lothian Complaints Service at Patient Experience Team, NHS Lothian, 2^nd Floor, Waverley gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG.  Tel: 0131 536 3370.  Email: feedback@nhslothian.scot.nhs.uk

In the unlikely event that something goes wrong and you are harmed during the research and this is due to someone‘s negligence then you may have grounds for a legal action for compensation against NHS Lothian but you may have to pay your legal costs. The normal National Health Service complaints mechanisms will still be available to you (if appropriate).

All data collected about your baby will be kept confidential and there are strict codes of practice to safeguard privacy at every stage. Data will be stored at the University of Edinburgh and anonymised to remove identifying information (e.g. names, dates of birth) before being reviewed by researchers. The anonymised data (including samples) may be used for future studies related to brain development. Examples of this include: contribution to data-sharing initiatives, whereby data that is collected as part of single centre study, is stripped of all identifying information, and shared with the research community to build large research databases. This is a well recognised way of ensuring maximal value is obtained from samples and data that research participants have contributed.  Another example is to use the data to answer as yet unknown questions about the effects of prematurity that arise as medical science progresses. Under no circumstances will research data be used in a future study unless that proposed study has received approval from the appropriate UK regulatory bodies, and there are no circumstances when participant identifiable information will leave the research team.

All data will be anonymised (identifiable only by a code number, not your name or any other details) and will be stored securely (in a locked filing cabinet, or in password-protected digital files) at the University of Edinburgh. Only members of the research team will have access to the data.

All data will be stored on and analysed on University of Edinburgh IT system, which is protected.

The film data will be analysed by psychologists with expertise in child development to explore how your child interacts with others. Due to the nature of the film recording of you playing with your child it cannot be fully anonymised.  With your permission, we will keep the film data securely stored for 10 years and use it for future studies related to child development.  At that point we may ask you and your child for permission to retain the data.

With your consent we will inform your GP that you are taking part.

To ensure that the study is being run correctly, we will ask your consent for responsible representatives from the Sponsor and NHS Institution to access your medical records and data collected during the study, where it is relevant to you taking part in this research. The Sponsor is responsible for overall management of the study and providing insurance and indemnity.

Results from the study will be published in scientific journals and presented at scientific meetings, thereby making them available to researchers who study brain development and learning. It will not be possible to identify any participant from the results.

This study has been organised/sponsored by the University of Edinburgh and NHS Lothian and is funded by the children’s charity Theirworld, which is interested in deepening understanding of the causes and consequences of premature birth.

All research in the NHS is looked at by an independent group of people, called a Research Ethics Committee. A favourable ethical opinion has been obtained from South East Scotland Research Ethics Committee 01. NHS management approval has also been obtained.