new disso draft UPDATED SAN

Genetic Screening and Counselling for
Haemoglobinopathiesin Enfield, North
London
A Review of the literature
9/23/2011
Universityof Bedfordshire
SifumaAndrewNjenga1026086
21,290 words
THIS DISSERTATION IS SUBMITTED IN PART FULLFILLMENT OF THE DEGREE OF MASTER OF SCIENCE
IN PUBLIC HEALTH

Sifuma Andrew Njenga 1026086
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Table of Contents
Abstract....................................................................................................................................viii

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Acknowledgements ...................................................................................................................... x
CHAPTER 1...................................................................................................................................1
INTRODUCTION............................................................................................................................ 1
1.1 Purpose of the study..........................................................................................................1
1.2 Backgroundinformation on Haemoglobinopathies.............................................................. 2
1.2.2 Inheritance of Haemoglobinopathies: Carriers VS Sufferers .................................................... 3
1.2.3 Clinical symptoms of the Haemoglobinopathies.....................................................................8
1.2.4 Treatment for the Haemoglobinopathies............................................................................... 9
1.2.5 Prevalence of the haemoglobinopathies.............................................................................. 11
1.2.6 Diagnosis of Haemoglobinopathiesin secondary care........................................................... 12
1.3 Screening for Haemoglobinopathies................................................................................. 13
1.4 Background information on Enfield........................................................................................ 15
1.5 The Problem.................................................................................................................... 20
1.6 Significance........................................................................................................................... 21
1.7 Aim and Objectives of the study............................................................................................. 22
Chapter 2................................................................................................................................... 23
Preliminary literature review....................................................................................................... 23
2.1 A Recent History of Haemoglobinopathy screening in the UK................................................... 23
2.2 Diversity and screening.......................................................................................................... 25
2.3 Screening policyworldwide ................................................................................................... 26
2.4 Universal vs. selective screening ............................................................................................ 27
2.5 Economic evaluations of screening for Haemoglobinopathies in the UK ................................... 28
2.6 Ethical issues associatedwith genetic screening...................................................................... 29
2.7 Current screening protocols in the UK .................................................................................... 31
2.8 Screening services in Enfield and surrounding areas................................................................ 34
Chapter 3................................................................................................................................... 36
Methodology & Methods............................................................................................................ 36
3.1 Initial research design............................................................................................................ 36
3.1.2 SAMPLE INFORMATION...................................................................................................... 37
3.1.3 INCLUSION CRITERIA .......................................................................................................... 37
3.1.4 EXCLUSION CRITERIA.......................................................................................................... 38
3.1.5 Recruitment of Participants ................................................................................................ 38
3.1.6 TIMESCALE/RESOURCES NEEDED FOR STUDY....................................................................... 41
3.1.7 ETHICAL CONSIDERATION................................................................................................... 41

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3.1.8 ANALYSIS OF RESULTS......................................................................................................... 42
3.2 Change of methodology, deciding to perform a systematic review........................................... 42
3.2.1 Systematic reviews as a methodology.................................................................................. 43
3.2.2 Critical aspects of the systematic review.............................................................................. 45
3.2.3 Search Terms ..................................................................................................................... 47
3.2.4 Critical appraisal of identified articles – inclusion/exclusion criteria....................................... 48
3.2.5 Drawing a conclusion.......................................................................................................... 52
3.2.6 Ethical Problems................................................................................................................. 52
3.3 Method................................................................................................................................ 53
3.3.1 Defining the review question .............................................................................................. 53
3.3.2 Search strategy and sources................................................................................................ 53
3.3.3 Determining the selection, inclusion and exclusion criteria................................................... 61
3.3.4 Determining quality assessment criteria .............................................................................. 63
3.3.5 Thematic Analysis............................................................................................................... 63
Chapter 4................................................................................................................................... 64
Results....................................................................................................................................... 64
4.1 summary of articles used for review....................................................................................... 64
4.2 Methodological summary of results ....................................................................................... 85
Chapter 5................................................................................................................................... 87
Data Analysis.............................................................................................................................. 87
5.1 Themesemerging from the literature..................................................................................... 87
Chapter 6..................................................................................................................................103
Discussion.................................................................................................................................103
6.1 Themes in context................................................................................................................103
6.1.2 Information and consent ...................................................................................................104
6.1.3 Perceivedrisk,decisionmakinginparentsconsultedaboutscreeningforHaemoglobinopathies
& other diseases........................................................................................................................105
6.1.4 Communication of screening results...................................................................................106
6.1.5 Responses/Outcomes to genetic screening & counselling....................................................106
6.2 Relationship of themes to chapter 2......................................................................................107
6.3 Implications and link to practice in Enfield.............................................................................110
Chapter 7..................................................................................................................................111
7.1 Challenges met by the researcher .........................................................................................111
7.2 Limitations of the study........................................................................................................112

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7.3 Recommendations...............................................................................................................113
7.4 Conclusion...........................................................................................................................113
7.5 Plans for dissemination ........................................................................................................114
7.6 Reflection on Learning..........................................................................................................114
References................................................................................................................................116
Appendix 1................................................................................................................................120
Cover letter sent to schools and nurseriesin Enfield....................................................................120
Appendix 2 Sample Supplementaryletter sent to schools in Enfield..............................................122
Appendix 3................................................................................................................................123
Interview topic guide/schedule ..................................................................................................123

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Abstract
Screening is defined as “the systematic application of a test or inquiry, to identify individuals
at sufficient risk of a specific disorder to warrant further investigation or direct preventative
action, amongst persons who have not sought medical attention on account of symptoms of
that disorder”. The NHS Sickle Cell and Thalassaemia (SC&T) Screening Programme was set
up in England in 2001 following Government commitment in the NHS Plan (2000) which
offers universal screening for haemoglobinopathies for all expectant mothers. As well as
antenatal and neonatal screening, genetic counselling is offered to carrier mothers, at risk
parents and at request from healthcare practitioners
Purpose: The aim and objectives of the study were to; explore theme(s), shared patterns
and/ or issues pertaining to parent attitudes and experiences towards antenatal, neonatal
screening and genetic counselling for haemoglobinopathies and its relation to service
provision in the London borough of Enfield.
Method: This study reviews the literature in 10 selected articles regarding parents who have
experienced genetic screening and counselling for haemoglobinopathies and other genetic
disorders
Results: Findings from the collated studies suggest that the main issues regarding screening
for haemoglobinopathies are; information and consent, risk perception and reproductive
decisions, communication of screening results , and response/outcomes to screening and
counselling.

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Conclusion: For screening to be successful, healthcare practitioners must take into
consideration the personal values, information needs, reproductive decisions and responses
to screening and counselling to provide equitable services to people from ethnic minorities.

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Acknowledgements
The researcher would firstly like to thank God for allowing me to reach this stage of my
personal and professional development and taking me through this Master’s course.
I would secondly like to thank my supervisor Ron Driver for his guidance and assistance
while i have been undertaking this dissertation and to my course leader Susan Sapsed for
her availability and quick correspondence to any questions that I had regarding the
dissertation.
Last but not least I would like to thank my family and in particular my mother Ruth Njenga
for taking time out to teach me the correct methodology of conducting a systematic review
and constant encouragement.

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CHAPTER 1
INTRODUCTION
1.1 Purpose of the study
The purpose of this study is to review selected papers on screening for
haemoglobinopathies.
The initial study attempted to assess patient attitudes and satisfaction towards antenatal,
newborn screening and genetic counselling for haemoglobinopathies in Enfield by using
qualitative approach. The reasons for the change in methodology are described in section
3.3 and explained further in section 6.2.
The rationale for selecting this topic was for the author to gain a deeper understanding and
appreciation of the literature on this topic in order to provide information to colleagues,
relevant authorities and policy makers in North London working in Maternity services and
Haematology. The information will serve as a knowledge base to hopefully assist policy and
practice within these areas.
Background information on haemoglobinopathies, their inheritance, diagnosis and
treatment are described below in section 1.2

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1.2 Background information on Haemoglobinopathies
The Haemoglobin molecule is made up of four polypeptide chains, each of which has a
single haem group consisting of an iron atom located at the centre of a porphyrin ring
(Bragg and Perutz, 1952) (Bragg and Perutz, 1952 in Njenga, 2010). The molecule retains its
quaternary structure through hydrogen bonds between the opposite polarized polypeptide
chains and the structure changes with the addition of oxygen molecules is by each haem
group. The structure of haemoglobin is shown in fig 1.1 below
Fig. 1.1 Quaternary configuration of a single haemoglobin molecule
Manning & Russell (2007) cited by Njenga (2010) describes that the genes that code for
haemoglobin in humans are found in two clusters on an α or α-like complex on chromosome
16 and a β complex on chromosome 11.(Manning et al., 2007)
Adult human haemoglobin (Hb A) consists of 2 α-Globin and 2β-globin chains of 141 and 146
amino acid chains each and also consists of a small percentage of Hb A2 chains which has 2
δ-globins and 2 α-globins.

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As described by Paul (1976),the Synthesis of Globin chains is a complex genetic process
where firstly transcription of Globin genes produces a messenger RNA precursor which is
then processed post-transcription with 5’ end capping and methylation. Translation of the
resultant tRNA then produces the 2 α and β globins, and finally the ionic interaction
between the haemoglobin chains to form mature active haemoglobin. Because of this
myriad of active processes and their complex nature, errors can occur during processing
causing haemoglobin disorders (Paul, 1976) in (Njenga, 2010). When these errors in
haemoglobin processing cause a clinical presentation, they are known as
haemoglobinopathies.
Haemoglobinopathies are the most common single gene disorders in man. They are passed
on to generation to generation and these conditions are more prevalent in the tropical and
malarial regions of the world and in that are populations of African, Afro-Caribbean,
Mediterranean, Middle Eastern, Asian and Hispanic descent (Modell and Darlison, 2008).
Haemoglobinpathies are described as any blood disorder caused by defects in Globin gene
chain synthesis. Classified into two broad categories; those which cause a quantitative
reduction in haemoglobin synthesis (the Thalassaemias), and structural
haemoglobinopathies where there is a qualitative loss of haemoglobin synthesis, causing
haemoglobin variants cause the disorder (Sickle cell disease)(WHO., 2007).
1.2.2 Inheritance of Haemoglobinopathies: Carriers VS Sufferers
People possess two copies of the β Globin gene, on homologous chromosomes. In most
people, the two Globin gene copies are identical. A person with two identical gene copies is
said to be homozygous.

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In some people, the two copies of the β globin gene are not identical. People who possess
two non-identical alleles of the β Globin gene are known as being heterozygous for that
gene. The β Globin allele that leads to sickle cell disease is called the Haemoglobin S (HbS)
allele and is the most commonly occurring recessive variant of regular adult human
haemoglobin gene (HbA)(Frenette and Atweh, 2007).
As detailed by the European Haemoglobinopathy registry (2003), each time a couple is
expecting a child, the child will inherit one haemoglobin gene from each parent according to
Mendelian genetics. In each pregnancy there are always four possible allele combinations
the child can be born with, also known as chances.
If both parents possess the most common combination of haemoglobin genes (HbAA) this
couple’s children have a 100% chance of inheriting the usual combination of Globin genes
and will therefore produce normal haemoglobin at birth(registry, 2003). This is shown in
figure 1.2 overleaf.

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Father (HbAA) Mother (HbAA)
Fig 1.2 inheritance of normal globin genes
When one parent has homologous normal haemoglobin, and the other is heterozygous
possessing one abnormal globin allele, the chances of having a child who is homologous for
the normal gene is 75% and they have a 25% chance of having a child who is heterozygous
(HbAS) and is therefore a carrier of abnormal haemoglobin. HbS is a recessive gene however
so it will most likely not produce a clinical presentation.
When both parents possess a trait condition i.e. One normal haemoglobin allelle and one
abnormal haemoglobin such as sickle trait (HbAS) or β thalassaemia trait (Hb AbThal) there

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is a chance that their children will inherit the abnormal haemoglobin gene from either one
or both. The inheritance of abnormal haemoglobins is depicted in Figure 3. In these couples
there is a 25% chance of having a child with the disease, a 50% chance of having a child with
the heterozygous trait condition and a 25% chance that the child will inherit a normal
homozygous gene from both parents, and so will be completely normal. This is shown fig 1.3
below.
Father (HbAS) Mother (HbAS)
Children: HbSS HbAS HbAS HbAA
Fig 1.3. Inheritance of abnormal haemoglobins in parents who are both carriers

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Thalassaemia is caused by a deﬁciency of α-Globin chain synthesis, mostly occurring due to
deletion of one or both of the contiguous α-Globin genes. This mutation occurs due to
unequal cross-over between homologous allelle sequences in the α-Globin gene
cluster(Young, 2010).
Due to the high gene frequencies of Globin chains, and the existence on two separate
chromosomes, there is a possibility of interactions of genes and pseudo genes which can
cause of different forms of haemoglobinopathy, especially in those with mixed ethnic
background. Individuals are often encountered who have inherited two or more mutations
on the α and/or β-Globin gene clusters(Young, 2010).
An individual who is a carrier for both α-thalassaemia and β-thalassaemia is referred to as a
double heterozygote and are generally healthy however those who are compound
heterozygotes for α-thalassaemia and Hb S have a severe disorder similar to sickle-cell
disease(Young, 2010).
As mentioned before, haemoglobinopathies are autosomal recessive defects. Carriers only
have one affected locus on the gene and because of the recessive nature of abnormal Hb
genes they generally remain healthy throughout life although they are at risk of transmitting
the disease to children and successive generations. People who are homozygous and have
inherited a defective Hb gene from both parents gene suffer the disorder with varying
severity depending on the specific point mutation existing on the gene. Over 600
haemoglobin variants have been identified however most manifestations of abnormal
haemoglobins do not have a clinical presentation(Higgs and Weatherall, 1993).
Due to advances in technology and genetics, it is possible to screen for many genetically
linked diseases and conditions.

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1.2.3 Clinical symptoms of the Haemoglobinopathies
Sickle cell anaemia and the Thalassaemias exhibit some clinical similarities between the two
conditions. Both are expressed as a direct result of a defect in the Globin chain and patients
suffer chronic haemolysis throughout their life(Njenga, 2010).
Carriers are described as having the sickle cell trait and for the most part are entirely
healthy, although they can develop clinical problems, such as vaso-occlusive episodes in
conditions of very low oxygen saturation such as those encountered in deep-sea diving, high
altitude situations, air travel, or when under general anaesthesia (Young, 2010).
In regards to sickle cell, onset of the condition begins in infancy as β-Globin gene expression
overtakes generation of foetal haemoglobin(Bank, 2006). When this happens, affected
children present symptoms such as anaemia and jaundice, due to haemolysis of red blood
cells. Haemolysis occurs throughout life and red blood cells in sickle cell patients break
down much faster than in normal people.
The most common symptom of sickle cell disease is recurrent painful sickle cell crises which
are a result of anaemia, vaso-occlusive Ischaemia and haemolysis of red cells. Damage to
the spleen due to haemolysis can result in increased susceptibility to infection with bacteria
such as Streptococcus pneumonia and Haemophilus influenza(Young, 2010).
Young (2010) illustrates that individuals with α-thalassaemia trait are usually asymptomatic,
with only a mild anaemia and haemoglobin levels of 10–12 g/100 ml (normal range 12–14
g/100 ml). In contrast, individuals with Hb H disease where there is a loss of 3 of the α-
Globin genes have a more severe anaemia with haemoglobin levels of 7–10 g/100 ml,
associated with increased rates of bacterial infection, haemolysis, and Splenomegaly.

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Children with β- thalassaemia (thalassaemia major) usually start having symptoms at 6
months during the transition of foetal to adult haemoglobin. Symptoms include poor
feeding, recurrent infection, and poor development. If left untreated the child will
eventually die due to general ill health and recurrent infections. Regular blood transfusion
from a suitable donor will reverse symptoms of anaemia and malaise, but leads to excess
iron deposition in the heart, pancreas, and liver(Young, 2010). This accumulation of ferric
ions can be a cause of death in early adult life unless prevented by adherence to a strict
regime of iron chelation therapy.
1.2.4 Treatment for the Haemoglobinopathies
For acute sickle cell crises, it has been suggested that Paracetamol (1000 mg ) and NSAIDs
(for example, Diclofenac 100 mg), either dosed singly or in combination for one patient to
experience at least 50% decrease in pain from acute sickle cell crises (McQuay, 1999).
More severe pain may require analgesia using opioids such as intravenous morphine (10 mg
in saline). Opioids are widely accepted as the treatment of choice for acute severe painful
crises and that there is a variation in the type of opioids utilised for treatment, as well as the
route and the mode of administration. Some drugs, especially strong Opioids are associated
with liver and kidney toxicity and so clinical benefit must be weighed against the
risks(Dunlop and Bennett, 2006).
There is also considerable clinical interest in the prevention of sickle pain through
modiﬁcation of the underlying pathophysiology. Examples of preventative strategies include
the use of exchange blood transfusions, Hydroxyurea therapy and prophylactic penicillin to

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reduce the amount of sickled haemoglobin and susceptibility to infection (Dunlop and
Bennett, 2006).
Treatment of chronic pain caused by Sickle cell disease takes a multidisciplinary approach,
including the use of analgesic drugs, nerve block, physiotherapy, orthopaedic intervention
or surgery, and cognitive behaviour therapy (Okpala et al., 2002). Mild chronic pain can be
alleviated by dihydrocodeine or co-proxamol. Okpala et al (2002) also goes on to mention
that any pain not controlled by two tablets 4-hourly is considered moderate/severe, and is
then treated using morphine. Slow-release oral morphine, taken 12-hourly, is used for long-
term analgesia, with smaller doses of rapid-release oral morphine for breakthrough pain.
NSAIDS are discouraged due to liver toxicity. A switch from morphine to hydromorphone
may be required due to development of tolerance to the opioids.
Supplementary approaches may be used to treat the pain of avascular necrosis of the hip,
shoulder or intervertebral joints using nerve block which can last for up to 12 weeks.
Physiotherapy can significantly reduce joint pain, prevent muscle spasming and contraction
and lessen joint stiffness which can reduce mobility and cognitive function(Ballas, 1990).
Cognitive behaviour therapy and counselling enables the sufferer to develop ways of
overcoming the frustration and acute depression that can accompany painful episodes.
Patients who are homozygous for β-thalassaemia usually exhibit some form of anaemia and
ineffective creation of red cells and so to prevent this regular blood transfusions with a
suitable donor is required (Lee et al., 2006).In patients where yearly transfusion
requirements exceed 200 mL packed cells per kilogram body weight, splenectomy(removal
of the spleen) is usually performed so as to reduce Red Blood Cell requirements
accumulation of iron in essential organs (Modell, 1977). Because of the risk of

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postsplenectomy infection, splenectomy is normally delayed until the patient has past the
age of 5. Excessive blood transfusions and hypersplenism can result in deposition of excess
iron from transfused blood to the heart, pancreas, and liver of the patient. This causes
toxicity to these organs and can prove fatal in later life.
Iron chelation therapy with a drug such as desferrioxamine prevents iron overload through
the ability of iron chelators to complex with iron and promote its excretion.
The only true cure for the haemoglobinopathies that has so far been developed is Bone
marrow transplantation using HLA-compatible unaffected related donors and has
been carried out in children with success rates of over 90% (Young, 2010). The procedure is
however very intrusive, painful and recovery occurs over a long time in quarantine because
patients will be immunocompromised and very weak during recovery.
1.2.5 Prevalence of the haemoglobinopathies
At present, about 5% of the world’s population are carriers of a potentially pathological
haemoglobin gene (i.e. healthy people who have inherited only one mutant gene from one
parent), and that each year approximately 300 000 infants worldwide are born with
thalassaemia syndromes (30% of cases) or sickle-cell anaemia (70% of cases)(WHO, 2006).
The percentage of carriers of thalassaemia is greater than that of carriers of sickle-cell
anaemia, but because of the higher frequency of the sickle-cell gene in certain regions, the
number of affected births is higher than with thalassaemia(WHO, 2006).
β thalassaemia is the most common haemoglobin disorder in the Mediterranean basin, the
Middle East and Asia. Severe α-thalassaemia is common in south-east Asia, and sickle-cell
anaemia predominates in Africa. Increasing global migration, however, has introduced
haemoglobin disorders into many areas where they were not originally endemic.

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In the United States of America, 10% of the population is at risk of sickle-cell anaemia, and
in north-western Europe between 2% and 9% belong to the ethnic minorities at risk of
haemoglobin disorders. In some south-east Asian countries up to 40% of the population
may carry significant haemoglobin mutations, resulting in increased rates of infants born
with thalassaemia(WHO, 2006).
According to the National Health Service of the UK, an estimated one in 300 babies of
African-Caribbean parents and one in 60 of West African parents are born with sickle cell
disease each year. An estimated 8,000-10,000 people with sickle cell disease and 600 with β
Thalassaemia live in the UK. Approximately 1 in 4 West African, 1 in 10 African-Caribbean, 1
in 50 Asian and 1 in 100 Northern Greek have sickle cell trait (carrier state). Whilst 1 in 7
Greek, 1 in 10-20 Asian, 1 in 50 African and African-Caribbean and 1 in 1000 English people
have beta thalassaemia trait. Worldwide α thalassaemia carrier states are commoner than ß
thalassaemia carrier states(registry, 2003) in (Njenga, 2010).
1.2.6 Diagnosis of Haemoglobinopathies in secondary care
The detec(Trent, 2006)tion and characterisation of a haemoglobinopathy involves a 3 tier
work up. (1) Full blood count (2) Special haematological tests and (3) DNA testing (Trent,
2006).
Trent (2006) describes that “The key to successful detection and characterisation of the
haemoglobinopathies, particularly the thalassaemias, is the initial haematological data”.
Diagnosis presents a number of analytical complexities and a diagnosis is not always as
straightforward as simply looking at laboratory results. The clue for a thalassaemia comes
with a low MCV (mean corpuscular volume) or MCH (mean corpuscular haemoglobin).
Although iron deficiency is the other explanation for a low MCV or MCH, the first step after

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the initial abnormal blood count as described above, is to exclude iron deficiency and if
present, to treat it. The blood count is then repeated, and if the MCV / MCH remain low, a
thalassaemia is most likely.
Trent (2006) also mentions that if only MCV or MCH is used for the initial screen, the HbS
allele will not be able to be identified. Therefore, health professionals or laboratories
dealing with populations in which HbS occurs should always include a HbEPG(Haemoglobin
electrophoregram) which is a DNA test that can identify Haemoglobin variants.
Once a haemoglobinopathy is suspected, the next tier of investigation requires a number of
special haematological tests known as a haemoglobinopathy screen which include a variety
of assays such as electrophoresis of the various globins, red blood cell staining, and
chromatography.
1.3 Screening for Haemoglobinopathies
Screening is defined as “the systematic application of a test or inquiry, to identify individuals
at sufficient risk of a specific disorder to warrant further investigation or direct preventative
action, amongst persons who have not sought medical attention on account of symptoms of
that disorder” (Davies et al., 2000).
First use of the term "Inborn Errors of Metabolism" was coined by Archibald Garrod, who in
1902 showed insight into the inheritance of specific chemical defects in metabolism and
demonstrated that an enzyme deficiency can be inherited and lead to a manifested
condition that can cause morbidity and mortality.
In the case of antenatal screening, two methods are the most widely utilised to perform
antenatal screening for haemoglobinopathies and other genetic defects and these are
Amniocentesis and Chorionic villus sampling. Analysis and tapping of amniotic fluid has been

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practised for over a 100 years. transabdominal amniocentesis in the third trimester has
been reported by Prochownick, Von Schatz and Lambl in 1877 and Schatz in the 1890s. The
first use of amniotic fluid examination in the diagnosis of genetic disease was reported
byFuchs and Riis in 1956 in their seminal article in "Nature" describing how analysis of
amniotic cells can be used to determine sex of a fetus. John Edward (1956) also discussed
the possibility of the "antenatal detection of hereditary disorders".
In the 1960’s, Dr. Robert Guthrie yielded a breakthrough in screening for genetic conditions
when he developed a test to detect Phenyl Ketonuria (PKU) before it becomes clinically
symptomatic. The test consisted of a culture of Bacillus subtilis and B-2-thienylalanine(a
bacterial growth inhibitor). Once a blood sample from the newborn was added to this
culture, the bacteria would leach the phenylalanine from the blood spot, overcome the
inhibition caused by the B-2-thienylalanine, and grow (Guthrie and Susi, 1963). Growth of
the bacteria beyond a normal range indicated that there were elevated levels of
phenylalanine present within the blood sample and therefore the presence of PKU in the
newborn. By the late 1960s, newborn screening for rare genetic diseases using the Guthrie
test had become a permanent part of infant health care in the United States. There was
however an issue in collection of blood from the neonate as there was a need for a
relatively large sample. Dr Guthrie developed a method of blood collection known as a “heel
prick” which collected a smaller sample which reduced pain and discomfort in neonates.
In the 1970’s, screening for PKU for newborns using dried blood spots onto a filter paper
card(Guthrie card) at around 1 week of age was put in place throughout the United Kingdom
(Pollitt, 2006). It became possible to screen for a further range of disorders with the advent
of radio-immunoassay in the 1970s. Local programmes for SCD newborn screening began in
London and Birmingham in the early 1970s. Electrophoresis (citrate agar and cellulose

15
acetate) were the early methods but these have been superseded by High Performance
Liquid Chromatography (HPLC) and isoelectric focussing (IEF) (Levy, 1998).
1.4 Background information on Enfield
The London Borough of Enfield is the most northerly borough of London and forms part of
the greater London area. It borders the London Boroughs of Haringey to the south, Barnet
to the west and Waltham Forest to the east. Enfield also borders the Hertfordshire districts
of Welwyn Hatfield to the North and the Essex district of Epping Forest to the North East.
The current geographical area of the borough was formed in 1965, combining the three
municipal boroughs of Southgate, Enfield and Edmonton.
The Population of Enfield according to the Office for national statistics (2006) was 285,300.
Enfield, similar to other London boroughs is multicultural, with people from all ethnic
backgrounds and there is a mix of urban, rural, affluent and deprived communities (Enfield
P.C.T, 2003). Table 1.1 overleaf shows the percentage split of different ethnic groups as of
the 2001 census(Council, 2010).
Ethnic Group Number % split
White: British 167,394 61.2%
White: Irish 8,398 3.1%
White: Other White 35,157 12.9%
Mixed: White and Black Caribbean 2,549 0.9%
Mixed: White and Black African 1,068 0.4%

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Mixed: White and Asian 2,278 0.8%
Mixed: Other Mixed 2,199 0.8%
Asian or Asian British: Indian 10,887 4.0%
Asian or Asian British: Pakistani 1,717 0.6%
Asian or Asian British: Bangladeshi 3,524 1.3%
Asian or Asian British: Other Asian 5,121 1.9%
Black or Black British: Caribbean 14,590 5.3%
Black or Black British: African 11,884 4.3%
Black or Black British: Other Black 2,117 0.8%
Chinese or other ethnic group: Chinese 2,011 0.7%
Chinese or other ethnic group: Other 2,665 1.0%
Table 1.1 percentage spread of ethnic groups in Enfield (Enfield.gov.uk, 2010)
The Other White group is made up primarily of Greek, Turkish and Cypriots and Enfield is
known for having a high population of these peoples. A Further one percent of the
population, approximately 1,911 people, are asylum seekers (Hughes et al., 2003).
In the same census, performed in 2001, Social Grades of the people of Enfield between the
ages of 16 and 74 was detailed and this is shown in table 1.2 below.
Grade Number % Description
AB 47,897 22.5% Professional/ Managerial

17
C1 70,214 33.0% Intermediate & Junior Non-Manual
C2 28,562 13.4% Skilled Manual
DE 65,858 31.0% Semi-Skilled and Unskilled Manual
Table 1.2 Social grades of Enfield population 16-74 (Enfield.gov.uk, 2010)
It was found by the census that 26.4% of the population in Enfield is aged 19 and under,
which is above the London average, and was predicted to grow over the coming years
(Mason, 2010).
Mason (2010) also describe that in Enfield, educational results are close to or above the
national averages, with 79% of pupils achieving level 4 or above in English at Key Stage 2,
compared to a national average of 80% and 78% of pupils achieving level 4 or above in
Maths at Key Stage 2, compared to a national average of 79%.
In terms of deprivation, GLA figures show that, in May 2010, 7.2% of the labour force in
Enfield is unemployed (claiming Jobseeker’s Allowance or National Insurance credits). This
figure represents the tenth highest figure for a London borough, and is above both the
Greater London (5.9% average) and Great Britain overall(5.3% average)(Mason, 2010).Nine
wards in Enfield have labour force claimant count rates higher than the overall borough
average, with Edmonton Green being the worst affected ward, where 14.1% of the labour
force is claiming Jobseeker’s Allowance or National Insurance credits. Figure 1.4 below
shows a map of Enfield showing deprivation score by ward showing the large variations in
the borough

18
Fig 1.4 Map of Enfield showing deprivation score by ward
Life expectancy at birth for Enfield residents was higher than the national average between
2007 – 2009 for both males and females, and this is shown diagrammatically in fig 1.5
overleaf. Male life expectancy is 78.8 years and female life expectancy is 82.7 years.
However, there are large disparities between life expectancy in different parts of the
borough, with a ten year difference between life expectancy in the south eastern and north
western parts of the borough (Mason, 2010).

19
Fig 1.5. Life expectancyfor malesandfemalesin Enfield as compared to the national average with margins of error
(Mason, 2010)
In general, the health of Enfield residents is similar to the England average. Mortality rates
from serious illnesses such as cancer and heart disease have fallen over the past 10 years,
and remain below the England average (Mason, 2010).
Two major NHS hospitals, North Middlesex Hospital and Chase Farm Hospital serve the
population. Enfield Primary Care NHS Trust is responsible for primary care of the local
population. Another hospital in the borough, Highlands, was closed in 1993 and the area
was converted into middle level residential area.

20
1.5 The Problem
Currently some areas of Enfield have limited access to rail and bus services. There is poor
public transport accessibility along the Lee Valley Corridor despite the presence of the West
Anglia Main Line, which suffers from low service frequencies and poor station access,
particularly at Angel Road station.
As an outer London borough, it is acknowledged that many people in Enfield will continue to
rely on the use of the car for travel. However, according to 2001 Census data, 29% of the
Borough’s households have no access to a car and in some wards in the east of the borough
up to 50% of households do not have a car. These are generally the areas with higher rates
of deprivation and unemployment such as Edmonton and Ponders End. This may cause
problems with accessibility to NHS services and as such may discourage mothers from fully
accessing all maternity services available to them.
It has been noted by the Enfield Primary Care Trust that there still exists a need for outreach
between GP surgeries and specific black and minority ethnic groups, more training for
frontline staff in cultural awareness and sensitivity regarding service provision to these
peoples, recruitment within statutory bodies to ensure representation for the diverse
communities and ethnic monitoring of health service use in hospital and primary care. It had
also been highlighted that there is a need for signage and translated material including
pictorial information for non-readers(Hughes et al., 2003).
There are significant numbers of young people living in poverty; 20% of all children living in
Enfield live with lone-parents on benefits (Mason, 2010).

21
In September 2006 Primary Care Trusts in Barnet, Enfield and Haringey decided to look into
options for improving the way health care is to be delivered for people in these three
Boroughs (Tyrell, 2010). The debate around proposals for change in local health services
began in 2006 with the identification of 10 possible Scenarios for changing hospital services
within these areas. After Deliberation, reviews and conferences to see which option would
be the most feasible. It was decided that maternity and A&E at Chase farm hospital would
be transferred to the new site at North Middlesex Hospital. These moves will allow the
consolidation of emergency and consultant-led obstetric and neonatal specialist services on
the Barnet and North Middlesex University Hospital sites and the development of Chase
Farm Hospital (Tyrell, 2010).
The NHS Enfield Board decided in 2010 that changes to Women’s and Children’s services
would be the first to be implemented and have been completed as of summer 2011. Work
on A&E services, urgent care, emergency inpatients and planned care developments, are
underway and are hoped to be completed by 2013(Tyrell, 2010).
It has been argued by lobbying groups such as the save chase farm hospital group, that are
against the transfer of services in Enfield that this option reduces accessibility for Women
and Children from the most deprived communities in Enfield and that the plans being made
by the P.C.T are unsustainable and may lead to a decline in quality of care.
1.6 Significance
North London, consisting of the boroughs of Enfield, Harringay, Waltham Forest and Barnet
are some of the most diverse boroughs within the greater London area and has a high
proportion of inhabitants of West African, Afro-Caribbean, Cypriot, Greek, Turkish, Middle

22
Eastern and South Asian descent. These are all at risk groups in relation to
haemoglobinopathies and so an investigation into their attitudes, satisfaction and feeling
towards screening and genetic counselling services would be important.
There is insufficient information about family values and expectations with regard to SCD
screening. It is important to consult high-risk populations to understand if identified infants
are being enrolled in a programme for treatment and care, if certain types of services or
programs are deemed necessary to prevent the birth of children with the disease, and if
there is a need for community education, couples counselling, and/or carrier screening to all
high-risk populations of childbearing age.
1.7 Aim and Objectives of the study
The study will be a review of relevant literature to identify common themes covering the
topics of haemoglobinopathy screening services and genetic counselling in relation to the
London borough of Enfield.
The objectives in the study would be to:-
 to understand and add to his personal knowledge base relating to
neonatal/antenatal screening for haemoglobinopathies and genetic counselling
including those detailing patient satisfaction and inequalities
 to identify the common themes critique and appraise the strengths of the studies,
and then conduct a thematic analysis of the research findings
 Find out the feelings, attitudes and information needs of the participants towards
neonatal and antenatal screening.

23
Chapter 2
Preliminary literature review
The NHS Plan for England made a commitment in 2001 to establish ‘a linked antenatal and
newborn screening programme for haemoglobinopathies and sickle cell disease’(Streetly,
2006). The Programme is under the management of the UK National screening committee.
Internationally, screening for haemoglobinopathies is mostly done on an Ad-hoc basis but in
some southern European countries such as Greece, Italy and Cyprus there is a more
systematic screening model and in Iran there is mandatory testing for carrier status prior to
marriage(Saadallah and Rashed, 2007).
2.1 A Recent History of Haemoglobinopathy screening in the UK
The NHS Sickle Cell and Thalassaemia (SC&T) Screening Programme was set up in England in
2001 following Government commitment in the NHS Plan. It is the world’s first linked
antenatal and newborn screening programme which means that results from antenatal tests
taken by parents-to be are linked with their babies test result which allows reduction of
anxiety in parents, easy access to information, avoid unnecessary repeat testing and
ensuring accuracy in interpretation of results(Streetly, 2000).
Initially, there were a variety of models of screening existing in the UK, which were not
always effective in their functioning. It was first thought that due to the varied distribution
of the “at risk” population that there was a need for different service models according to
the prevalence of the conditions, based on cost effectiveness, but this brought about the
issue of equity and access to health care for those at risk in non “at risk” areas (Zeuner et al.,

24
1999). Also, it is known that ethnicity is not always a good predictor of risk as Afro-
Caribbeans, Cypriots and Italians frequently marry outside their ethnic group which can
cause a risk to the population(DOH., 1993). As different alleles for haemoglobinopathies can
interact, and an increase in mixed parenting in the UK it was decided that screening would
become a universal incentive by the NHS’ programme (Streetly et al., 2009). A universal
programme is deemed better than being selective as a selection process can be costly and
not identify all at risk pregnancies which can attract litigation in some cases (Lane et al.,
1992). A universal screening protocol also assists in raising awareness of the
haemoglobinopathies among communities and as well as health service providers. A
universal screening programme is therefore more instrumental in satisfying the aims of the
national screening programme which are to
 Save lives through prompt identification of affected babies
 Offer informed choice to couples expecting a baby
 Support the development of a managed clinical care network such that people
have fair access to quality services throughout England
 Raise public awareness of the disorders and challenge stigma
(Streetly et al., 2009)
As well as neonatal and antenatal screening, genetic counselling is offered to carrier
mothers, at risk parents and at request from healthcare practitioners.

25
2.2 Diversity and screening
In regards to haemoglobinopathies, the first indicator that can identify an “at risk” couple is
ethnicity and/or ancestry i.e. whether the individuals are descended from people’s who
originate in the parts of the world where haemoglobinopathy genes are most prevalent.
This information can only be obtained by questioning the individual. Classification based on
skin colour or the 2001 census categories 11 has been seen to be inappropriate. This is due
to the fact that Census categories simply attempt to classify an individual by “ethnic group”
as opposed to their ethnic origin. These classifications do not equate to ancestral origin and
do not identify ‘white’ individuals from those descended from Mediterranean populations
where there is a high prevalence of thalassaemia and sickle cell genes. The futility of census
classifications is further shown in the fact that the prevalence of haemoglobinopathy genes
are expressed significantly in nearly all populations except those with northern European
ancestry/origin(Aspinall et al., 2003).
To make informed choices about screening, all individuals require good quality information
from health practitioners, given to them in presented in a form that is sensitive to their level
of literacy as well as sensitive to their culture and way of life. In the past the NHS has been
slow to act on its lack of informational and public relational needs of its diverse populations.
It has been argued by some researchers (Khattab et al., 2005, Spencer and Jordan, 2001),
that the training of biological sciences in nurse and midwife education has caused many of
them to have insufficient knowledge of health behaviours and health needs of ethnic
minorities which in turn may lead to inequalities in the health care provision of these
peoples. Indeed, in terms of knowledge of haemoglobinopathies, researchers have
concluded that midwives are under-educated in issues relating to management of

26
haemoglobinopathies in pregnancy and inheritance of haemoglobinopathies(Dyson et al.,
1996).
The NHS has responded to these claims however, and with the introduction of the NHS
national sickle cell and thalassaemia screening program in 2001 has brought about a clear
benchmark in standards of screening, training to midwives, GP’s and Lab staff, as well as
information about screening to prospective mothers in 30 languages.
2.3 Screening policy worldwide
In most western countries, (U.K, U.S.A, Canada, Australia etc), newborn screening for
haemoglobinopathies has been accepted as a worthwhile and effective intervention.
However, an important drawback is the lack of consistent policies for SCD screening. For
example, it has been reported that in the United States (Wertz et al., 1994) that where there
are programmes for haemoglobinopathies exist, differences exist among primary care
physicians in the acceptability and commitment to screen all newborns with 71 percent of
paediatricians, 46 percent of obstetricians, and 40 percent of family practitioners agreeing
that only “at risk groups” should be screened.
France has chosen to offer SCD screening to all high-risk infants (Frezal et al., 1990,
Bardakjian et al., 2000) by adopting a targeted screening approach in metropolitan areas,
where infants are offered sickle cell screening if they fall under one of the 5 criteria defined
by the Association Française pour le Dépistage et la Prévention des Handicaps de l’Enfant
.The 5 criteria are as follows: 1) if one of the two parents is originally from a country where
the incidence of SCD is significant; 2) if one of the parents is from one of the above countries

27
and the other is from Asia; 3) if the mother is at risk and the father is not known; 4) if a
parent suffers from a haemoglobin disorder or is aware of any family history in this regard;
and 5) if there is any doubt with regard to the 4previous points.
In Cyprus, Greece and Italy, premarital screening for thalassaemia has been normal practice
for a long time because consanguinity is high. Similar preventive programmes have been
introduced in Bahrain, China, India, the Islamic Republic of Iran, Indonesia, Malaysia, the
Maldives, Singapore and Thailand, and recently in Saudi Arabia and the United Arab
Emirates(Avard et al., 2006).
2.4 Universal vs. selective screening
Guidelines and reviews of screening programmes have been published by various agencies
around the world. Some have recommended universal screening for all newborns, while
others, such as Avard et al (2006) have suggested that screening strategies, whether
universal or selective, should depend on the proportion of high-risk individuals in a
community.
For instance, researchers in Georgia, U.S.A, compared the number of black newborns
screened for haemoglobinopathies between 1981 and 1985 with black birth figures for the
same period, and estimated that approximately 20 percent of black newborns were not
screened. Results of a study of universal screening in multiethnic California also indicated
that an approach of targeting certain groups in that state would have missed at least 10
percent of those whose sickle cell disease was actually diagnosed at birth.66 Indeed, the US
experience suggests that adequate targeting strategies are difficult to define and the criteria
used to identify ethnic origin in relation to risk of sickle carrier status are likely to vary

28
between and within countries, thus making the generalisability of such analyses difficult to
interpret(Harris and Eckman, 1989 ).
2.5 Economic evaluations of screening for Haemoglobinopathies in
the UK
Economic evaluations are generally categorised into four main types of analyses, namely:
cost minimisation, cost-effectiveness analysis, cost–benefit analysis and cost–utility analysis.
As Explained in Zeuner et al (1999) Cost–benefit analysis “measures and values the
outcomes, or non-resource-use consequences, of the options under consideration in
monetary terms”. Measuring outcomes explicitly in terms of monetary units is however
known to be notoriously difficult. Hence, cost benefit analysis in the last century were more
tailored to hypothesizing that financial savings for healthcare organizations were the sole
benefit of screening and not take into consideration the non resource consequences
(Modell and Kuliev, 1991). Methods such as using ‘willingness to pay’ to obtain monetary
outcome values do exist and have been used in the context of antenatal screening for cystic
fibrosis, but are generally considered to be experimental (Pollitt et al., 1997).
Zeuner et al (1999) also note that Cost–utility analysis measures outcome in terms of
‘utility’, most commonly expressed in terms of quality adjusted life years (QALY). The quality
of life associated with a health state is measured on a scale of zero to one, where death is
assigned a value of zero and good health is assigned a value of one.
Techniques have been developed (McGuire et al., 1988), such as the time trade-off and
standard gamble, to give a standard representation of such values. The duration of each
health state is multiplied or weighted by its utility value. Where an option leads to a series
of health states, the weighted durations are summed to give the QALY.

29
In the case of antenatal screening it has been argued by researchers (Ganiats, 1996, Karnon
and Brown, 1998), that the use of cost–utility analysis is made more complex due to the
implications of it to the pregnant woman, her family and the fetus (or child-to-be).
The effect on their utility is likely to be contingent and/or flexible, depending on the
experience of screening, pathways to screening and their own individual reproductive
decisions(Karnon et al., 2000). The process of delivering a programme may also be utility- or
disutility-bearing, such as the manner by which results are delivered (e.g. in person, by
telephone or by letter), or the accessibility of the individual to services.
It has been concluded that in terms of laboratory diagnosis for haemoglobinopathy screens
that Iso Electric Focussing and HPLC are very similar in terms of average cost per test and
that it is mainly up to the managers to decide which should be used based on technicians
expertise and skill set(Cronin et al., 1998). They also remark that the decision whether to
use a universal or targeted strategy should not be based on ethnicity, but on the number of
births, the prevalence and resulting cost per extra SCD identified with universal screening
(Cronin et al., 2000).
2.6 Ethical issues associated with genetic screening
The WHO considers that newborn screening should be mandatory if early diagnosis and
treatment will benefit the newborn(WHO, 2006).
In order to assess the effectiveness of the linkage between antenatal and newborn
screening, and to know whether the newborn screening standards are being achieved and
babies who require clinical care are receiving appropriate follow up, named patient data is
required. The collection of named patient data is a very sensitive issue and the screening
programme centre applied for, and obtained, permission from the Ethics and Confidentiality

30
Committee (ECC) of the National Information Governance Board (NIGB) to obtain named
data without parental consent
However, it has been argued by some researchers (Avard et al., 2006) that identifying
carriers raises a number of ethical dilemmas for the family. First, while identification of
carriers may be beneficial for the parents, birth is generally considered a poor time for
communicating carrier screening information. Moreover, this information is of minimal
benefit to the child; indeed, it may not be useful until the child reaches adolescence or
reproductive age.
Additional disadvantages of knowing carrier status have been argued by the American
Society of Human Genetics (1995) such as alteration of self-esteem, and impacting on a
parents’ perception of the child. It has also been argued that genetic screening can have
negative implications on the foetus, as there is a lack of choice to be tested, increased
anxiety of the condition once they are aware of it, blaming oneself for the condition and
possible discrimination against the child in education, insurance and employment(Wertz et
al., 1994).
In the absence of proper public education, social support and parental counselling,
confusion about the significance of carrying the common sickle cell trait and sickle cell
anaemia (with a frequency of 1 in 600) can lead to unnecessary discrimination and stigma
(Frezal et al., 1990). Consequently, with the establishment of a newborn SCD program, the
detection of carriers (both parents and children) should be accompanied by adequate
counselling.

31
It has been argued by Aksoy (2001) that the availability of antenatal screening and
diagnostic testing has changed the experience of pregnancy. Before the development of
antenatal testing for foetal abnormality, the foetus was assumed to be healthy, unless there
was evidence to the contrary. The presence of antenatal testing and monitoring shifts the
balance towards having to prove the health or normality of a foetus(Aksoy, 2001).
2.7 Current screening protocols in the UK
In the UK, the screening programme is a multi stage process with involvement of different
health professionals during each stage. The main reason for screening for
haemoglobinopathies is to let couples make decisions on the pregnancy based on the
results of screening, and to give informed choice to the mother on termination of the
pregnancy depending on the results of the screening (Streetly, 2006). Screening policy is
defined into two policies in areas of high prevalence, and areas of low prevalence based on
a benchmark of more than 1.5 babies displaying a haemoglobinopathy born per 10,000
births(Zeuner et al., 1999). In high prevalence areas, all pregnant women are offered the
test for haemoglobinopathies and all partners of identified carrier mothers are offered
screening. In low prevalence areas all women are offered the screening using routine red
blood cell indices and a family origin questionnaire is used to assess the risk of the woman
and/or her partner being a carrier. Women identified in high risk groups are offered the
screen for their baby. Partners of mothers who are carriers for haemoglobinopathies are
offered the test irrespective of their ethnicity(Streetly et al., 2009).
During the first trimester of pregnancy, leaflets are given to expectant mothers to educate
them on haemoglobinopathies. In most settings however leaflets are only available in

32
English and so language may be a possible barrier to understanding in this instance. Offering
of Antenatal screening is normally conducted by midwives and specialist nurses however it
has been argued by some researchers (Dyson et al., 1996) that midwives show a lack of
awareness on the topic of haemoglobinopathies and of “at risk” groups in some cases it has
also been argued by them that the women being screened are not given adequate
information about screening and its implications and also in some cases screened without
consent. It has been seen from programmes where there is a high prevalence of
haemoglobinopathies that screening for thalassaemias more often results in a termination
of affected foetus and is in general more acceptable (Davies et al., 2000). However it has
been noted in some studies that practice and turnover time of tests can identify couples
who are at risk too late to offer first trimester prenatal diagnosis and informed choice for a
termination (Petrou et al., 1992).
Newborn screening is performed for the primary reason of identifying babies with SCD and
to get affected babies on an active early penicillin prophylaxis and pain management. The
test also serves to be able to permit for beginning of counselling and dissemination of
management information to parents of affected or carrier newborns. The screening
pathway involves a pre-screening leaflet given antenatally during the 3rd trimester of the
pregnancy and informed choice for the mother to do the test once the baby has been born.
If the mother consents, the blood test involves a small heel prick to the baby to obtain a
bloodspot and the sample is then sent for laboratory analysis(Streetly, 2006). If there is a
suspected abnormal result there is a repeat analysis and a result is obtained. Results are
then sent to the GP and then relayed to the parents. Best standards and high quality
screening services must be offered to all parents and these are supported by the
implementation and reporting guidance. It has been noted that results of tests are normally

33
sent in the post and this has lead to some parents becoming anxious and unsure of the
implications of a positive result and parents would rather have results of neonatal tests
given to them in person and explained fully by a health professional(Ryan et al., 2010).
In the event of a detection of carrier status or a haemoglobinopathy, parents of affected
babies are referred to a genetic counsellor as well as clinical services. Genetic counsellors
may be a health professional who has undertaken training at master’s level to enable them
to develop the skills to occupy the role, or may be a health professional who has specialised
in genetics (ENGNC., 2010). The role of a genetic counsellor is:
 To identify the needs of the individual or family and use an empathic, client centred
approach to the provision of genetic counselling
• To collect, select, interpret, confirm and analyse information (including family and medical
history, pedigree, laboratory results and literature) relevant to the delivery of genetic
counselling for individuals or families
• To help people understand and adapt to the medical, psychological, social and familial
implications of genetic contributions to disease
• To assess the chance of disease occurrence or recurrence
• To provide diagnostic information to clients based on family and/or medical history and/or
genetic testing
• To provide education about inheritance, testing, management, prevention, resources and
research to relevant individuals or families
• To promote informed choices and psychological adaptation to the condition or risk of the
condition.
Indeed, most genetic counselling takes place during the pregnancy and neonate stages.
These are the periods of time however when the mother is at the most psychologically

34
vulnerable (Green et al., 2004). In general, genetic counsellors will work with families with a
pre-established diagnosis or in a general setting under the supervision of a clinical doctor.
Genetic counsellors however will not be responsible for conducting any physical
examinations and so there must be expert collaboration between the counsellor and other
members of staff and in accordance with the code of practice for genetic counsellors in
Europe (ENGNC., 2010). Outcomes of genetic counselling ideally should be an increase in
knowledge of haemoglobinopathies, their inheritance and management, without addition of
anxiety or any other negative psychosocial effects in the parents of the child. Studies have
noted that in the past that learning during genetic counselling is sometimes below
expectations as the significance of being a carrier may not be clear to the counselee,
counselees being unable to remember information given through counselling, and simply
the fact that counselling is initiated by healthcare practitioners and not the parents in
question (Loader et al 1991). Even more recently it has been discovered that there is an
inadequacy of current procedures for achieving informed consent and although there is
attainment of knowledge there is a difference between that and understanding
(Linnenbringer et al., 2010). Anxiety of a positive result occurs in most women however
studies are yet to conclude on whether there is a positive reassuring effect after counselling.
People whose first language is not English, it is understood that there is an additional barrier
to understanding their screening results as they cannot be presented results in their own
language and there is a possibility of interpreter bias.
2.8 Screening services in Enfield and surrounding areas
The George Marsh centre for sickle cell and thalassaemia at St Ann’s Hospital in nearby
Tottenham provides genetic counselling for haemoglobinopathies to parents who are at risk

35
of having a child affected by a haemoglobinopathy and the hospital also handles analysis of
blood samples from Enfield Haringey and Barnet. Affected infants are seen at home after
initial diagnosis and then attend the joint paediatric haematology clinic held weekly on a
Wednesday.
The department at George Marsh centre is well known for its expertise in the management
of haemoglobinopathy disorders and the multi-disciplinary team including medical staff,
social workers and a clinical psychologist care for around 1000 patients in Haringey Enfield
and Barnet and act as the centre of a network of services for these patients.

36
Chapter 3
Methodology & Methods
The following chapter details the methodological development of the project and the
methods used by the researcher to gain data to accomplish the aims and objectives of the
study. The researcher had initially chosen to use qualitative methods to get data however
due to challenges experienced by the researcher in conducting the study it was decided that
a systematic review of relevant literature would still be appropriate in addressing the
research question. The methodological development of the initial qualitative study remains
in this section as the researcher believes it is still relevant to the research study and he
hopes that it can be conducted in a future project.
3.1 Initial research design
To meet the aims and objectives of the study, the research was initially to be achieved using
qualitative methods. The method of data collection that was at first chosen to carry out this
research was face to face open ended interviews with women/couples that have undergone
screening for haemoglobinopathies and genetic counselling. It was decided that open ended
interviewing would be the best method to fully obtain the opinions, attitudes and feelings of
participants. The advantages of face to face interviews are that interviewers can probe fully
for responses and clarify any ambiguities; more complicated and detailed questions can be
asked; more information of greater depth can be obtained and inconsistencies and
misinterpretations can be checked (Bowling, 2009).

37
The disadvantages are that interviews can be expensive and time consuming, there is
potential for interviewer bias and additional bias can exist if interpreters are needed for
participants (Bowling, 2009).
3.1.2 SAMPLE INFORMATION
Once ethical approval has been granted, permission will be asked for access to patient
records for mothers who have gone through screening for haemoglobinopathies for
themselves and their children and genetic counselling. The sample population must
represent the population of interest in order for results to be generalisable (Bowling, 2009
p.) and seen to be able to apply to the population at large. 100 participants will be sought
out hopefully there will be enough positive responses for 30 interviews to be conducted
with mothers, with or without their partners.
3.1.3 INCLUSION CRITERIA
The inclusion criteria for the study will be Mothers/Parents with at least one child who have
undergone neonatal or antenatal screening. The participants do not necessarily have to be
in an “at risk” ethnic group but should have gone through the screening and/or counselling
for a pregnancy occurring within the past 5 years. This is because haemoglobinopathies are
more common in ethnic minorities as detailed above. White mothers who have had mixed
race children will be considered but will have to fill the criteria of having a child who is a
carrier for a haemoglobinopathy
Participants can either have been born in the UK or in the country of origin but it will noted
in the interview.

38
Participants will be between the ages of 18 and 40. Level of education will not be taken into
account.
3.1.4 EXCLUSION CRITERIA
Women who have been through screening and produced a negative result for being carriers
for haemoglobinopathies or their children being afflicted with a disorder or being carriers.
Women who have haemoglobinopathies but have no children will not be considered.
Women who are not considered to be in the “at risk” racial groups (i.e. Caucasian women)
who have not had children with men in at risk groups will not be considered.
Non-English speakers will not be included for reason of possible interpreter bias.
3.1.5 Recruitment of Participants
After creation of the interview schedule, the researcher had to identify prospective sites
where mothers/couples could be recruited from to participate in the study. As a resident of
Enfield, the first point of call was the researcher’s local GP surgery (highlands surgery),
which serves the residents of highlands village to attempt to get assistance in recruitment.
After meeting with the practice manager and discussing the research, it was seen that
although it would be feasible to gain some participants from the surgery, it only served a
small, almost homogenous community within Enfield and so gaining participants from this
area alone would not give a generalisable sample population. It was decided therefore that
the researcher would reach out to other GP surgeries and hospitals in different wards of
Enfield however was met with many issues of bureaucracy and gate-keeping at these NHS
services preventing the researcher from communicating with the relevant managers to

39
make it possible to gain participants from these institutions. These issues, coupled with the
need for ethical approval from managers of these institutions and the REC of Enfield, which
can take a significant time.
Since the mothers/couples to be used in the study were users of NHS services and not
necessarily NHS patients per se, it was decided that to eliminate the oft cumbersome
requirements of going through the NHS ethics system, it would be more feasible to instead
try and recruit participants through nurseries and primary schools in the Enfield area. This is
because these institutions provide a way to recruit parents from a mix of cultural
backgrounds, from Enfield, who have undergone screening within the past 7 years,
therefore satisfying them under the inclusion criteria detailed in section 3.1.3. A covering
letter was drafted to communicate the agenda of the researcher to schools to gain
authorisation from them before vetting/recruiting of participants would be done. A copy of
the covering letter drafted to be presented at the schools is given in appendix 1. The
researcher also requested supplementary letters to be drafted in support of the covering
letter detailing that the research was ethically sound and that the researcher was indeed a
student of University of Bedfordshire. An example of this supplementary letter is given in
appendix 2. The schools identified for communication and their various locations in Enfield
are listed in table 3.1 overleaf.

40
Name of School/Nursery Address Ward
Cornerstone day nursery 2 Napier Road
Ponders End, Enfield,
Middlesex EN3 4QW
Ponders End
Platform one nursery ltd Grange Park Railway Station,
Vera Avenue, London N21
1RE
Grange
Highlands village pre-school Village Hall, 5 Florey Square,
London N21 1UJ
Highlands
Busy bees nursery Enfield 2 Florey Square, London N21
1UJ
Highlands
Happy days nursery
Oakwood
Westpole Avenue
EN4 0BD
Cockfosters
Bright stars nursery Tristram Drive, London
N9 9TQ
Lower Edmonton
Asquith Nursery 2 Queen Anne's Place,
Enfield, Middlesex EN1 2PX
Bush hill park
Eversley primary school Chaseville Park Road,
London, London N21 1PD
Highlands

41
Tara’s kindergarten nursery, 98 High Street, Ponders
End Enfield EN3 4EZ
Ponders End
Woodberry Day Nursery 63 Church Hill, London N21
1LE
Winchmore Hill
Table 3.1 schools identified for recruitment of participants for the study
3.1.6 TIMESCALE/RESOURCES NEEDED FOR STUDY
As mentioned above face to face interviews are some of the more time consuming and
expensive methods of research and the researcher will be financing all travel and other
resources. Since the study will be conducted within the borough and neighbouring boroughs
of the researcher it will be relatively easy to plan and conduct travel to and from interviews.
If plans are successful and 30 interviews are conducted it would cost the researcher
approximately £250 to conduct the interview minus any incentive offered to the
interviewees. Incentives would take the form of book tokens or coupons for school
equipment for participants’ children. All interviews were planned to be completed by July
2011.
3.1.7 ETHICAL CONSIDERATION
Ethical consideration was obtained from the University’s health and social care ethics
committee. As it was approved by the committee, the study is in accordance with the
standards and guidelines set for research that involves human participants.
During the research, certain fundamentals of ethics must be adhered to considering it will
be primary research. Confidentiality, informed consent, and protection of the human rights

42
of participants must be taken into account at all times. Participants will not be referred to by
their names and will instead be referred to as “patient” in accordance with the Nursing and
Midwifery protocol (NMC, 2009). The researcher must be a neutral party at all times, be non
judgemental and make the participants feel valued and kept in a positive frame of mind
towards the study. Participants will be notified that they can exit the study at any stage if
they feel uncomfortable or no longer want to participate. All recorded interviews and notes
from interviews will be kept on the researcher’s person or locked and/or password
protected if kept electronically. A copy of the interview schedule/topic guide is shown in
appendix 3.
3.1.8 ANALYSIS OF RESULTS
Analyses of interviews, which are a qualitative methodology, are not quite as
straightforward. The researcher will identify common themes existing in interview data and
notes confer units of meaning such as specific words and sentences as participants express
them and therefore code them in this way (Burnard, 1991). The coded information will then
be reformulated and a constructed in more theoretical terms to make a model of
understanding using coherence, differences and hierarchies of data (Bowling, 2009).
3.2 Change of methodology, deciding to perform a systematic review
Due to challenges the researcher experienced in recruitment of participants, finding a site to
perform interviews and some issues with gate keeping from the schools, he decided to
instead undertake a systematic review. He had to update his research question as well as

43
the aim and objectives of the study. The principles of systematic reviews and the framework
used to conduct the review are described in section 3.3.2 and 3.3.3 respectively.
3.2.1 Systematic reviews as a methodology
People are more aware of research as a source of knowledge, viewing a piece of research in
a contextual view of other research acts to keep professionals updated with information. As
the volume of data in the healthcare field is constantly expanding with increased emphasis
on evidence based practice, literature reviews are key tools that can be used to identify
information, conceptual frameworks and summarized ideas (Hart, 1998, Aveyard, 2006,
Depoy and Gitlin, 2005). Before considering to undertake reviewing the literature, certain
factors ought to be considered such as ones topic, regulations and expectations that apply,
the size of the topic, the time, expense and resources available and the accessibility
(Denscombe, 2007). Contextually, the main reasons for conducting a literature review can
be summed up as;
 Determine previous research on the topic of interest
 Determine the level of theory and knowledge development
 Determine the relevance of current knowledge base to problem area
Provide rationale for selection of research strategy.
Methodology is defined as:
“a system of methods and rules to facilitate the collection and analysis of
data...provides a starting point for choosing an approach made up of theories, ideas,
concepts, and definitions of the topic; therefore the basis of a critical activity
consisting of making choices…” (Hart, 1998).

44
Systematic reviews aim to provide an overview of work in specific areas by searching,
finding, evaluating and synthesising evidence employing specific terms, rules and
expectations about process that follow key principals are listed below.
Principals of a systematic review (Hart, 2005)
 Well focused research question
 Focused searching strategy
 Rigorous methods of appraisal and synthesis
 Explicit and replicable methods of review
 Detailed and determined presentation and synthesis
Reviewing literature systematically becomes a methodology when one bases ones
information on the criteria above (Aveyard, 2007). The study therefore sees the researcher
reviewing the literature around the subject of patient outcomes for screening and genetic
counselling for haemoglobinopathies.
Systematically reviewing the literature was seen to be the best methodology to use for the
study for the following reasons (a) enabled him to further familiarize himself with the multi
faceted nature of the research question (b) enabled him to determine the development of
knowledge and theory relating to screening and genetic counselling for
haemoglobinopathies (c) enabled him to form a framework by which his study findings
would be interpreted, (d) add to his knowledge base from the available literature and (e) to
enable the researcher to see if his initial study plan would have produced generalisable,
reliable and quality data.

45
3.2.2 Critical aspects of the systematic review
Defining the review questions was based on the chapter 2 which acted to direct the search
and final analysis of the selected papers. The review questions were:
 What were the contextual views of parents who had undergone antenatal and
neonatal screening for haemoglobinopathies in a universal screening setting?
 What were the outcomes for parents who had received genetic counselling after
receiving a carrier or affected foetus diagnosis?
(a) Limiting the scope of the study is necessary to answer defined research questions.
According to Hart (2005) for a research question to be answerable it should follow
the principles of the acronym PICO: Population/problem of interest, intervention or
investigation, comparison of interest and the outcomes considered most important.
In the case of this study, the PICO parameters are detailed in table 3.2 below
P-Population – parents experiencing prebirth screening for haemoglobinopathies
I-Investigation – investigate attitudes, perceptions, communications, experiences and
expectations of screening
C- comparison of evidence focusing on different methodologies/populations as well as
outcomes considered most important in assessing results
O- Outcomes – outlines in the aim and objectives of the study
Table 3.2 principles outlining an answerable research question
Reading abstracts is a fundamental aspect of modification of research questions and
reducing the scope of a study. The assessment of associated studies and literature available

46
on the topic at hand provides visual representation of the historical records, decisions and
processes that lead a researcher to understanding the theory, practice and methodological
debates surrounding a chosen topic. Summarizing abstracts in a table enables one to
identify the articles relevant content and specialized features (Aveyard, 2006, Hart, 2005).
(b) Concepts underpinning search Because of the multi-faceted nature of the research
questions and multiple topics to be explored dealing with haemoglobinopathy
screening, an organizational strategy was employed to select the most important
points in each article to highlight in the review, thus building a search strategy where
all possible relevant literature is searched and appraised. Systematic Reviews may
combine methodological, chronological or thematic searches (Greenlagh, 2006).
Those reviews following a chronological method are written according to when
articles to be studied were published. Articles by publication chronology may be used
if they demonstrate important trends in the development of the current knowledge
(Rosen and Behrens 2007). For example, for the topic of screening for
haemoglobinopathies, some articles would focus on targeted screening and
therefore the ethnicity question, some on universal screening outcomes, others
would focus on neonatal screening and its outcomes, and yet others focusing on
counselling when a carrier or disease diagnosis was made.
Thematic approach search strategies are organized around topics or issues rather
than the progression of time, although progression of time may still be an important
factor (Depoy and Gitlin, 2005). In this study the key themes and frameworks
associated with antenatal & neonatal screening experience were to be explored.

47
A methodological approach on the other hand differs from thematic analysis and
chronological analysis in the respect that the focal area of the review is not the data that has
been gathered but in the methods and/or interventions used by researchers within the
literature. A methodological scope influences the type of articles in the review and the way
in which they were discussed. A Methodological approach is crucial in the assessment of
articles to be reviewed so as to identify any methodological failings or redundancies
(Greenlagh, 2006).
3.2.3 Search Terms
The establishment of search terms and key words used to identify prospective articles for
review is fundamental in systematic reviews and enables the researcher to determine the
number of relevant studies on the topic to be studied (Churchill, 2005). The terminology
used to search for the articles for review were varied due to the nature of the study and the
review question to be addressed e.g ‘neonatal screening’, ‘patient outcomes for neonatal
screening’ ‘genetic counselling’ ‘genetic testing for haemoglobinopathies’. Boolean logic was
used as a strategy for searching for articles as it enables a researcher to identify and manage
articles in a logical and systematic way to ensure that all databases and journals are
searched. The exact terms and key words used to locate articles are described fully in
section 3.3.2 and 3.3.3.

48
3.2.4 Critical appraisal of identified articles – inclusion/exclusion
criteria
Critical appraisals are routes for closing the gap between practice and research and are tools
that help researchers understand the methods/results of research and assess their quality
(Aveyard, 2006) and is an integral process in Evidence based practice (EBP) that aims to
identify methodological flaws in the literature and provide researchers’ with the opportunity
to make informed decisions about the quality of research evidence. Strong evidence is based
on hierarchal ranking of evidence which (Aveyard 2006) stated was not always feasible to
apply to ones question. There are numerous study designs available that have caused much
debate as each have their unique strengths and limits that could distort ones conclusions
(Creswell, 2003). (Popay et al., 1998) described this as judgement that requires the
invocation of criteria tailored to the particular features of the topic in question. In this
regard, the assessment criteria emphasizes the reporting structure, methodology, data
analysis among other criteria such as sample, intervention, response and outcome measures
utilized that enabled the author clarify and classify with better understanding the results of
the articles (Cormack, 2006). Asking oneself the following questions determined the
selection of the critical analysis tool (s) utilized:
 It is sensible to group various populations together and why?
 It is sensible to combine various interventions together and why? `
 What outcomes are relevant that work to answer ones question?
 What study designs should be included /excluded and why?

49
Stating the inclusion and exclusion criteria is vital as the information was used in the final
selection of articles for review. The inclusion and exclusion criterion determines the primary
markers, research aims, context and sampling strategy. In order to find a focus criterion for
the inclusion and exclusion of articles on staff haemoglobinopathy screening, the author
considered the following questions in relation to the review question.
 Do the studies present one or different solutions on the topic area?
 Are there different aspects that influence the topic area that are different or missing?
 How well do the articles present the material and do they portray a methodology
that is appropriate?
 What trends in the field are revealed and the current situation?
 What is the criterion of selecting the articles?
Quality assessment criteria (CASP 2008) were applied on the articles in order to qualify for
inclusion in the study as described in section under methods. The search strategies
employed in this study were selected as to be inclusive of the wider context of
haemoglobinopathy screening and genetic counselling.
In this regard, consideration was made as to the aims and objectives of this study, bearing in
mind that the protocols existing regarding haemoglobinopathy screening and genetic
counselling differ. Thirdly, research designs either quantitative or qualitative would serve to
inform him on different aspects of haemoglobinopathy screening and genetic counselling
which would result in rich, diverse and strong evidence for the study.
In seeking criteria for assessing studies, the debates on critiquing of qualitative papers and
quantitative papers in relation to the terms used was noted. For instance, in quantitative

50
studies ‘validity and reliability’ while qualitative studies use the terms ‘trustworthiness and
authenticity that is further made up of four criteria (Popay et al., 1998, Bryman, 2008)
shown in table 3.3 below.
Qualitative - Trustworthiness Qualitative – Authenticity Quantitative
Credibility Fairness Internal validity
Transferability Educative authenticity External validity
Dependability Catalytic authenticity Reliability
Confirmability Tactical authenticity Objectivity
Table 3.3 criteria for assessing research articles
Quantitative researchers rely on data collection techniques such as questionnaires,
interviews and observations where the data is presented in quantifiable form; being aware
of the following: peer reviewed articles; research question and the reasons the study was
conducted; a summary of the research process; sample size and whether random or non-
randomly selected; data collection methods and analysis and measurement tools.
Qualitative researchers typically rely on methods such as observations, field notes, and
reflexive journals, structured / unstructured interviews presented in descriptive form.
Similar to quantitative questions; one ought to be aware whether articles were peer
reviewed, whether the research question and method were appropriate; whether the right
research method was used, whether the sample was purposive rather than random
sampling; theoretical aspects (Holliday, 2007). The size of the sample in contrast to
quantitative research, although (Gregory, 2003) argues that phenomenological studies have

51
smaller samples than grounded theory studies); data collection (in-depth interviews and
focus groups) although there is debate on the benefits of interviews (Barbour 2001).
In assessing articles, the author applied, Critical Appraisal Skills Program (CASP, 2006) which
integrate Oxman and Guyatt (1988) and Law et al (1988), Popey et al (1998) and
(Greenhalgh, 2006).
A thematic analysis is a process that essentially involves the detection of patterns and
inconsistencies and is geared towards developing themes systematically using either and/or
three approaches a) theory; b) prior research and c) inductive driven(Boyatzis, 1998). Coding
or categorizing is an interpretive technique that both organizes the data and provides a
means to introduce the interpretations by reading the data and separating themes within it.
Each theme is labelled with a “code” word(s) or short phrase(s) that suggests how the
associated data themes inform the research objectives (Bowling, 2006). When coding is
complete, scoring of the results is prepared that consists of summarizing the prevalence of
codes, discussing similarities and differences in related codes across original
context/sources, or comparing the relationship between one or more codes (Boyatzis, 1998).
The author employed the prior research driven (b) approach which meant that most of the
codes applied to the themes in his study were themes that had been introduced in previous
research in his topic area. Categorization of themes on individual and environmental
stressors led to specific revelations(s), gap(s) and relationships (Boyatzis 1998, Hart 2006,
Aveyard 2007) that exist within the literature. This process enabled the author gain a better
understanding of the content of each article before combining the results although the
technique has been criticized for seeking to transform qualitative data into quantitative data
(Boyatzis, 1998).

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