In this summary we explain the background to newborn blood spot screening, and the rationale for this study; the methods we employed; an overview of our findings and our recommendations for policy and practice.
Expanded newborn screening
A national newborn screening programme was introduced for phenylketonuria (PKU) in 1969, based on a blood sample collected from a baby’s heel around a week after birth. In 1981 this programme was expanded to include screening for congenital hypothyroidism (CHT). More recently the NHS Plan, published in 2000, announced the development of a ‘new national linked antenatal and neonatal screening programme for haemoglobinopathy and sickle cell disorders’ for England and Wales. In 2001 the English and Scottish health ministers announced the introduction of screening for cystic fibrosis (CF).
Whilst the roll-out of newborn screening for sickle cell disorders and cystic fibrosis is a gradual process, there is now a commitment to newborn screening for four conditions based on the blood spot sample.
The addition of sickle cell disorders and cystic fibrosis to the newborn screening programme brings new challenges, in particular the identification of carriers of these conditions. The conditions and the identification of carriers is explained in more detail below.
Background on the conditions: sickle cell disorders
What are sickle cell disorders?
The term sickle cell disorder, includes sickle cell disease and sickle cell anaemia, as well as some other related conditions. Around 1 in 2500 people in the UK have a sickle cell disorder.
Haemoglobin enables oxygen to be carried in our blood. There are several different types of haemoglobin, usually called by different letters of the alphabet, for example haemoglobin A, or haemoglobin E. In short hand these are written HbA, or HbE etc Some types of haemoglobin can cause illness.
Everyone has two copies of the gene for haemoglobin: one from their mother and one from their father. These two genes determine a person haemoglobin type. Mutations on this gene can cause your body to produce unusual forms of haemoglobin.
If both copies of the gene instruct cells to make HbA then the person will be healthy (HbAA). If both copies of the gene instruct cells to make HbS then that person has a sickle cell disorder called sickle cell anaemia (HbSS), and will become sick. If one copy of the gene instructs that person to make HbA and the other instructs them to make HbS, then that person is a carrier of a sickle cell disorder. They are ‘HbAS’.
As well as HbS, there are other types of haemoglobin which cause similar health problems, such as HbC. Someone with HbSC is said to have a sickle cell disorder. Someone with HbAC is a carrier of a sickle cell disorder.
Sickle cell anaemia (HbSS) is the most serious of the sickle cell disorders. Our red blood cells are usually shaped like doughnuts. However, HbS can cause red blood cells to become rigid and sickle or crescent shaped. These sickle shaped red cells can’t squeeze through small blood vessels easily and get blocked. This means oxygen can not reach all parts of the body. People with sickle cell disorders experience pain, and damage to their body tissues and organs. They are more likely to get serious infections and can die of the condition. Some children with sickle cell disorders will get seriously ill and may die of the condition before anyone is able to do anything to prevent it.
Tests to identify people with sickle cell disorders are usually based on haemoglobin appearance rather than looking for mutations on the gene for haemoglobin. These tests based on haemoglobin appearance can identify people with the disorders and also carriers of sickle cell disorders.
What can be done for people with sickle cell disorders?
People with sickle cell disorders need to have access to appropriate health care when they become ill. This includes pain relief, blood transfusions, social support, and special arrangements for operations and childbirth. There is good evidence that early identification of people with sickle cell disorders and early treatment can prevent death in young children. Newborn screening can identify babies before they first become ill. Their treatment includes immunisiations against infection, regular antibiotics, and education for parents, so they can help identify early symptoms.
Couples can also be tested during pregnancy. This can help identify fetuses at risk of having a sickle cell disorder (or other haemoglobin disorder) and can enable termination of affected fetuses.
What does it mean to be a carrier of a sickle cell disorder?
Sickle cell carriers have enough healthy haemoglobin (HbA) to keep their red blood cells flexible, preventing their small blood vessels from becoming blocked. They do not become sick in the way in which people with the disorders do. It is thought that being a carrier for sickle cell disorders can help protect against malaria.
Carriers of HbS are more common in certain ethnic groups, and are most common in London and in the Midlands. Carriers need to be careful during activities where they might not have enough oxygen, such as scuba diving and climbing at high altitude, or if they have a general anaesthetic.
If someone who carries the mutation for HbS, has a baby with another carrier there is a risk their child will inherit two mutations for HbS (one from each parent). The child will then have a sickle cell disorder (HbSS). If both parents are carriers, there is a one in four risk that their baby will have the condition. If one parent has a sickle cell disorder and the other is a carrier, there is a one in two risk that the child will also have a sickle cell disorder.
What can it mean if newborn screening finds that a baby is a carrier of a sickle cell disorder?
Little is known about the implications of identifying babies who are carriers for sickle cell disorders. Some people argue that this information is helpful for the parents when planning future pregnancies, and even that it will be helpful for the baby when they grow up and want to have babies of their own. Revealing the genetic status of sickle cell carriers reveals the genetic status of one of their parents. This has implications for the parents’ reproductive choices, and raises issues about the purpose and ethics of disclosing genetic information.
There are some concerns about what this information might mean for families. It is thought that parents do not always understand that being a carrier is not the same as having a sickle cell disorder. This might change the way they treat their baby, as well as causing them considerable anxiety.
If a baby is found to be a carrier, they must have inherited the mutation for a sickle cell disorder from either their mother or their father. Often mothers are tesed in pregnancy so will know whether or not their baby could have inherited this mutation from them. If the mother knows she is not a carrier, or affected with a sickle cell disorder then it is clear that the sickle gene has been inherited from the father.
There can be a problem if the father is tested and is not a carrier, nor has a sickle cell disorder. This implies that the child has actually has a different father. The potential for newborn screening to instigate a train of events that might to reveal that the supposed father is not actually the biological father is of great concern.
This study set out to explore the implications of telling parents that their baby is a carrier of sickle cell following newborn screening.
Background on the conditions: cystic fibrosis
What is cystic fibrosis?
Around 1 in 2500 people in the UK have cystic fibrosis. People with cystic fibrosis produce thick sticky mucus, especially in the lungs and pancreas. They also have very salty sweat. They can have a range of different symptoms. Newborn babies often have blocked bowels. Young children often have get chest infections, or diarrhoea and fail to gain weight. Men with cystic fibrosis can be infertile. About half of people with cystic fibrosis will die by the time their in their mid-forties, usually due to lung damage.
Cystic fibrosis is inherited in a similar way to sickle cell disorders. You inherit two genes, one from each parent. If both genes contain a CF mutation, you will develop cystic fibrosis. If you only inherit one gene with a CF mutation you will be a carrier of the condition.
There are a number of different tests for cystic fibrosis. These include a sweat test (testing the saltiness of the sweat), and DNA tests for the many different mutations on the CF gene. Newborn babies can also be tested using an IRT test, which tests the levels of a substance called immunoreactive trypsin. Newborn babies with cystic fibrosis have higher than normal levels of IRT.
What can be done to help people with cystic fibrosis?
Treatment for cystic fibrosis includes physiotherapy and antibiotics for chest infections, enzymes, vitamins and high calorie diets, as well as social support. There is some evidence that early diagnosis and treatment for people with cystic fibrosis, before they become sick, can improve their health. Increased pressure for a newborn screening programme led to a decision by the health ministers for England and Scotland to introduce a national screening programme.
Identifying couples who are at risk of having a baby with cystic fibrosis, before pregnancy, or early in pregnancy can enable them to chose whether or not to terminate the pregnancy. However very few couples in the UK are offered this screening during pregnancy.
What does it mean to be a carrier of CF?
Carriers of mutations for CF are not affected by the condition and do not become ill in the way that people with CF do. There is no recognised advantage of being a carrier for cystic fibrosis.
Cystic fibrosis is more common in people from northern Europe.
If someone who is a carrier of cystic fibrosis has a baby with another carrier there is a risk their child will inherit two mutations for CF (one from each parent). If they inherit two mutations the child will have CF. If both parents are carriers, there is a one in four risk that their baby will have the condition. If one parent has cystic fibrosis and the other is a carrier, there is a one in two risk that the child will also have CF.
How are CF carriers recognised?
Cystic fibrosis carriers are identified in the course of care given to affected people: because cystic fibrosis is an inherited condition relatives of someone with CF will often be carriers. The biological parents of an affected person are by definition both carriers (or are affected with CF themselves). Siblings of an affected person have a 1 in 2 chance of also being carriers.
Carriers can also be identified following newborn screening if a DNA test is used as part of the screening process. Some laboratories in the UK use IRT tests to identify babies at high risk of CF. Babies with persistently high IRT are then tested using a sweat test. This type of screening process will not identify carrier babies, but it does require a second heel prick.
However, other laboratories use IRT and DNA tests to identify babies at high risk of CF. Introducing DNA early in the screening pathway speeds the identification of affected babies but also identifies carrier babies.
Policy options are to:
- employ tests that do not identify carrier status, if available;
- identify acceptable ways of disclosing carrier status; or
- identify acceptable ways of not disclosing carrier status.
What can it mean if newborn screening finds that a baby is a carrier of cystic fibrosis?
The implications of telling parents their babies are carriers for CF are not fully understood. Antenatal testing for cystic fibrosis is very rare, so it is unlikely that the mother will know whether she is a carrier for CF before she has her baby.
Although using DNA testing in newborn screening identifies carriers, only babies with a high IRT will have their DNA tested, so not all CF carriers will be identified. Babies who are found to be carriers will need further tests to find out whether they do only carry one mutation, or two. This is because there are over 1200 mutations for CF and the screening programme can only ever test for a small number of these. It is therefore difficult to say for certain that someone is only carrying one mutation, and not two. In addition, because there are so many mutations, it is not clearly understood what some mutations mean, and some people with two mutations might not actually be very ill.
Although most babies with one identified mutation do not require medical treatment, revealing their genetic status reveals the genetic status of one of their parents. This has implications for the parents’ reproductive choices, and raises issues about the purpose and ethics of disclosing genetic information. (If one parent is known to be a carrier, their risk of a subsequent pregnancy being affected is 1 in 200.)
As with sickle cell screening, identifying babies who are carriers of cystic fibrosis can, in some circumstances, suggest that the man thought to be the father of the child, is actually not the biological father. Although with hardly any antenatal carrier testing for cystic fibrosis, fewer women know their genetic status in relation to cystic fibrosis.
Screening for cystic fibrosis can also be a lengthy process, with some babies needing a more than one test over a number of weeks, and then further diagnostic testing, before reaching a confirmed result.
Rationale for this project
Identification of infants who are not affected but who carry gene for sickle cell disorders or for cystic fibrosis is an unintended consequence of newborn screening. It is unknown what the implications are for families of this unintended information. It is not clear how it should be communicated, or what follow up services should be provided.
Furthermore, whilst there is currently no available alternative test for sickle cell disorders, there is a question over whether DNA testing should be included in screening protocols for cystic fibrosis, as the identification of carriers could technically be avoided.
The aims of this research
The aim of this project was to inform policy and practice for newborn screening in advance of expanding universal screening to embrace sickle cell disease and cystic fibrosis. This project addressed existing uncertainty about the detection of carrier newborns and the optimal methods of communicating screening results, including those relating to carrier status to parents.
This study included a systematic review of the available research evidence; a survey of current practice in England and Wales; and a primary study of parents experiences.
Survey of current practice
In order to understand better the different practices for identifying carriers, and telling parents these results we planned to survey all newborn screening laboratories in England and Wales which screened newborns for cystic fibrosis. We developed a questionnaire, which was circulated to all the relevant laboratories. We asked what tests laboratories were using, how and when carrier results were identified, and how these were then communicated to record systems and to parents themselves.
We were able to draw on an existing map of London haemoglobinopathy services (due to be extended throughout the UK) undertaken by the NHS Sickle Cell and Thalassaemia programme. More detailed information could not be accessed through laboratories because laboratories were already under pressure with changes in screening policy and, with the roll out of newborn screening for sickle cell disorders, the situation was constantly changing. Nevertheless, the laboratory in Birmingham kindly provided additional information regarding their policy and practice with regard to communication about disclosing carrier status for sickle cell disorders.
Whilst a number of published systematic reviews have addressed whether or not to introduce screening programmes for cystic fibrosis and sickle cell disorders on the basis of economics and the potential to improve the health of affected children, there are no published reviews which consider directly the identification of carrier babies.
We developed a protocol for this part of the study, which was peer-reviewed by experts in the field. We then searched the research literature for studies about: newborn screening, cystic fibrosis or sickle cell disorders, carriers, communication of results to parents, and possible implications of these results. All studies identified by these searches were screened and only the most relevant studies included in the review. We collected full reports of potentially relevant studies, and again screened these so only the relevant papers were considered.
All relevant studies were coded according to the type of research, the type of communication and the potential implications of telling parents their babies were carriers, as well as the quality of the research. These codes were entered into a specialist database. This database was then used to provide an overview of the available research literature. From this ‘map’ of the literature we were then able to identify which studies could tell us more about the effectiveness of telling parents their babies are carriers, and which studies could tell us more about parents views of these results.
This systematic approach to the research literature allowed us to summarise with confidence, what is known about telling parents their babies are carriers for sickle cell disorders and cystic fibrosis. It also allowed us to identify gaps in the research and make recommendations for policy and practice.
Primary study of parents experiences
Firstly we gained ethics approval from both multi and local centre ethics research committees. We identified seven regional screening laboratories (six for CF, two for sickle cell disorders) with a range of different screening protocols for identifying and reporting carrier results for these two conditions. We then sent invitation packs to parents asking them to contact us to talk about their experience of receiving results after newborn bloodspot screening. These parents were identified on our behalf by screening laboratories and counselling centres. Invitations were sent via general practitioners, to insure that it was not inappropriate to approach these families. Parents of both unaffected and carrier babies were invited to contact us. Parents who sent back replies took part in a short telephone interview. Those parents who told us that their babies had been found to be carriers of the conditions were then invited to take part in longer face-to-face interviews. These took place in the parent’s home and included open ended questions about their views and experiences of being told their baby was a carrier.
All in-depth interviews were transcribed. These were coded independently by two researchers. Themes were identified from the interviews and findings and recommendations drawn from these themes.
In addition to interviewing parents, we also approached a small number of health professional involved in communicating with parents about carrier results. We carried out in-depth interviews with a small number of health professionals. These were also transcribed and coded. Findings from the parents and health professional interviews were compared.
Synthesis of findings
Findings from the three parts of this project were mapped out on a screening timeline from pregnancy to results. This enabled us to compare different findings, as well as identify priorities for further research (see figure 1).
The survey of policy and practice
The survey of communication policy for the varied newborn bloodspot screening protocols for cystic fibrosis identified aspects of the screening pathway that may make parents vulnerable, and deserve further investigation: incomplete information provision and consent procedures; repeated contact with the NHS service by ultimately healthy newborns, which may medicalise early life and parenthood; waiting times following the initial heel prick for the test results of unaffected and carrier babies to parents, which range between 10 days and 6 weeks, with most parents never being told the result; waiting time between the second heel-prick test and subsequent contact, which is currently 2 – 21 days if a sweat test is required, otherwise parents may not receive results at all; different health care providers communicating with parents along the screening pathway, which might undermine establishing and maintaining relationships; non-reporting of carrier results to parents when this information is held on Child Health Records and may be subsequently accessed and disclosed by health professionals unaware that parents do not already have this information; reporting the test results of carrier newborns, as this has implications for other family members; and inconsistent terminology for reporting results, which may cause confusion if parents records are accessed and discussed with them by different health professionals.
Newborn screening for sickle cell disorders was similarly varied, although standardised policies are being introduced. In some areas there is no official policy for screening newborns for sickle cell and thalassaemia; and where there is a policy the timing of the screening test itself varies, with some areas using cord bloods collected at time of delivery and some areas screening on the Guthrie sample taken at about 5-8 days. Related communication policies also varied. In some areas parents are not told of their baby is thought to be unaffected by sickle cell disorders. Other areas notify parents of ‘normal’ results, and some specify that what they report is that sickle cell disorders are not suspected but that there is still a possibility of the child having Beta thalassaemia (this is not identified in newborn screening). Similarly, in some areas carrier results are also not reported to parents. In at least one area this is the case even if one of the parents was identified as a carrier through antenatal screening (and therefore may have been alerted to their baby’s results). Alternatively, in some areas all carrier results are notified to parents whereas elsewhere normal results and/or carrier results are only reported to parents if both the parents’ status is known. Policies vary in terms of who tells the parents of their baby’s carrier result (the health visitor, a specialist nurse counsellor, a consultant haemotologist, the GP, the laboratory, the midwife, or a paediatrician), how (by letter or a home visit) and whether parents are only given literature or are also offered counselling. At least one area issues parents with a haemoglobinopathy card. In some areas carrier newborns are re-screened between 2 and 6 months. Some are also tested again at one year.
The systematic review of research literature
The systematic review found that despite potential difficulties, parents of cystic fibrosis carriers favoured newborn screening and knowing the carrier status, and anticipated telling their child in due course. However, Cystic Fibrosis carrier status led to problems with insurance companies with some families in the USA. A minority of parents used carrier status to inform reproductive planning, although when results were withheld parents were angry at being denied the opportunity to do so. Discovering their own carrier status could also be an emotional event for parents. Few parents appeared to change their behaviour towards their carrier child. Discussing carrier status with the wider family was perceived as difficult, but necessary.
Studies in the systematic review that addressed extended screening pathways confirmed that waiting times following requests for repeat tests are extremely stressful for parents. The risk of ‘medicalising’ early parenthood materialised in some screening pathways and parents expressed a preference for having familiar, non-specialists report test results to them; with these non-specialists being sufficiently briefed and not alarmist. Indeed, the presence of cystic fibrosis specialists to discuss raised IRT results alarmed parents, as did being giving information about cystic fibrosis at that stage.
The systematic review found little or no evidence about how outcomes are influenced by: parents’ previous knowledge of the screened conditions; the methods of communicating test results; or follow-up support; and no reliable evidence about the implications for parents of an unclear diagnosis for cystic fibrosis. These issues were addressed in the qualitative study.
The qualitative study of parents’ and health professionals’ views
The qualitative study confirmed some of the findings of earlier literature and filled some gaps. Parents favoured disclosing carrier status following newborn screening and emphasised three issues in relation to knowing their baby’s genetic status: retaining the knowledge of genetic status for future information; their own status, whether known or not known, in relation to reproductive planning; discussing screening results with the wider family, particularly close family members expecting a baby. Parents of babies who had been through diagnostic sweat testing had received clear test results as well as genetic counselling and appeared to have come to terms with their baby’s health status. However, parents of babies who had had a repeat request in a screening area where normal results are not routinely communicated, grappled with understanding their baby’s health status in light of an unresolved screening result ‘scare’.
This study provided more detail about communication during extended screening pathways, when the repeat samples are requested. At the time of a request for a second blood sample, three aspects of this communication influenced parents either positively or negatively: the method of communication and the behaviour of the health professional; the level of information provided, whether verbal or written; and compounding factors relating to parent’s experience or aspects of services. In relation to this difficult stage in the screening pathway, health professionals believed that parents require health professionals to be: trustworthy, knowledgeable and reliable listeners with an ability to help parents maintain a sense of normality in the absence of a confirmed health problem.
None of the studies illuminated the difficulties posed by the implications of revealing misattributed paternity.
For policy and practice
Successful communication along the screening pathway with parents depends largely on a combination of technical knowledge, accurate reporting of test results and health professionals’ listening and support skills. This needs health professionals to have appropriate training and a prior relationship with the family.
- We recommend that parents, other family members and health professionals be involved in:
- the development and evaluation of parent information to accompany disclosure of carrier status and false positive screening test results.
- the development and evaluation of information to support parents wishing to discuss screening test results with their wider family.
- the development and evaluation of training for non-specialist health professionals such as midwives and health visitors who have responsibilities for requesting repeat blood samples.
- the evaluation of pre-screening parent information that addresses openly the limitations of newborn screening, such as false positive results and identifying newborn carriers.
- an evaluation comparing the impact of disclosing carrier status by non-specialists (e.g. midwives, health visitors or GPs) and specialists (e.g. genetic counsellors, sickle cell counsellors, CF nurses), including consideration of revealing misattributed paternity.
Synthesis of findings from three parallel studies of disclosing carrier results following newborn screening
This report should be cited as: Oliver S, Lempert T, Stewart R, Kavanagh J, Dezateux C. (2004). Disclosing to parents newborn carrier status following routine blood spot screening. London: EPPI Centre, Social Science Research Unit, Institute of Education, University of London.