2. CRUCE DE VARIABLES
2.1 Prueba del coágulo al ingreso con las demás variables del hospital “Dr. Gustavo
Following a short socio-history of Down’s syndrome and screening/testing for the condition, I begin this section by describing the origins and possible symptoms of the condition itself. I subsequently outline current screening and testing practices in Freymarsh and Springtown and how maternal age is implicated in an increased chance of having a baby with Down’s syndrome. To conclude, I contextualise my study and draw attention to current practices establishing Down’s syndrome as a critical site of sociological attention.
Down’s syndrome: the condition
The human body is made up of cells containing genes. Genes are enclosed within thread-like structures referred to as chromosomes, that is, the packages of genetic material or deoxyribonucleic acid (DNA) stored within the nucleus of each cell. These contain instructions of how the body’s cells develop, eye colour, and the sex of the unborn baby (NHS 2013). A human usually has forty-six chromosomes organised into twenty-three pairs (twenty-two autosomal pairs and one pair of sex chromosomes) inherited from the mother-to-be and father-to-be. Genetic diversity
among different people is generated via the exchange of genetic material between homologous chromosomes (meiosis I) and the separation of chromosome pairs (meiosis II). When an egg becomes fertilised to create a new cell called a zygote, new pairs of chromosomes are created in which each parent-to-be contributes one chromosome to each pair. On occasions, an error in meiosis (non-disjunction) occurs in which there is a failure of the chromosomal pairs to separate. This causes an imbalance of chromosomes in the gamete (‘aneuploidy’). A cell losing a chromosome (‘monosomy’) is likely to be lethal. This may not always be the case when a cell gains a chromosome (‘trisomy’), causing three copies of a chromosome instead of a usual pair (CARIS 2012).
According to CARIS (2012), trisomies are the most common anomaly in which there are more or less than forty-six chromosomes. One such trisomy is Down’s syndrome (or Trisomy 21) caused by the presence of an extra chromosome on the twenty-first pairing. It is the most common aneuploidy detected during pregnancy
followed by Edward’s syndrome (Trisomy 18)22 and Patau’s syndrome (Trisomy
13)23. Down’s syndrome is an incurable chromosomal condition which occurs in
one to two of every 1,000 live births in the UK (NHS 2013). It is one of the most common genetic causes of learning disability and the National Down Syndrome Cytogenetic Register (NDSCR) reports most people with the condition (94% of all cases) have Full Trisomy 21 Down’s syndrome, whilst 4% of cases have Translocation Down’s syndrome and 2% of cases have Mosaic Down’s syndrome. Children with Translocation Trisomy 21 have extra chromosome 21 material attached to another chromosome (Buckley and Bird 2002). Only Translocation Down’s syndrome can be hereditary. Some people do not have symptoms of Translocation Down’s syndrome but they can be a ‘carrier’, meaning they have
22 Edward’s syndrome (Trisomy 18) is a chromosomal condition affecting three of every 10,000 live
births. It is caused by an extra copy of chromosome 18 in each cell. There are three forms of Edward’s syndrome: complete trisomy, mosaic trisomy, and partial trisomy. According to NHS FASP (2012), complete trisomy 18 is fatal. Babies with partial and mosaic trisomy 18 may survive to adulthood but this is rare. The condition is associated with intellectual disability and physiological impairment, although the prognosis of a partial or mosaic trisomy 18 is less clear.
23 Patau’s syndrome (Trisomy 13) is a chromosomal condition affecting two of every 10,000 live
births. It is caused by an extra copy of chromosome 13 in each cell. There are three forms of Patau’s syndrome: complete trisomy, mosaic trisomy, and partial trisomy. According to NHS FASP (2012), complete trisomy 13 is fatal. Babies with partial and mosaic trisomy 13 may survive to adulthood but this is rare. The condition is associated with intellectual disability and physiological impairment, although the prognosis of a partial or mosaic trisomy 13 is less clear.
altered genes triggering the condition in their unborn children (NHS 2013). The risk of ‘passing on’ the condition depends on the sex of the carrier (with mothers- to-be more likely to ‘pass’ the condition onto a child). Mosaic Down’s syndrome is caused by the mis-division of chromosomes after fertilisation during early cell division. Whilst children with Full Trisomy 21 have an extra copy of chromosome 21 in every cell, children with Mosaic Trisomy 21 have forty-six chromosomes and some cell lines with an extra chromosome and some cells lines which are not similarly affected (Buckley and Bird 2002).
Whilst symptoms of the condition vary between each case, common symptoms of Down’s syndrome include an upward eye slant, large tongue, clinodactyly of the fifth finger, single or transverse palm crease, sandal gap toe, excess skin on the back of the neck, a flat profile of the face, brushfield spots, hypotonia, and umbilical hernia (CARIS 2012). People with condition may also have impaired cognitive abilities, a reduced IQ, learning difficulties, shortened limbs, poor muscle tone, and restricted physical growth. They may also be susceptible to colds, ear infections, bronchitis, and pneumonia. Females with Down’s syndrome can have fertility problems and males with the condition are frequently infertile (CARIS 2012). The outlook of life for a person with Down’s syndrome can vary widely depending on if a child develops other serious health conditions such as sight and hearing loss, intestinal problems, hearing and vision problems, thyroid complications, dementia, Alzheimer’s disease, and leukaemia (Buckley and Buckley 2008; NHS 2013). Around 50% of children with Down’s syndrome have a congenital heart defect and around 60% of this group require treatment in hospital. By contrast, the condition appears to offer protection against some cancers and cardiovascular disease (Buckley and Buckley 2008). Importantly, people with Down’s syndrome may experience few or several of these complications (NHS 2013).
There is no ‘cure’ for the condition but Down’s syndrome is frequently demarcated as ‘not lethal’ (Ivry 2009), meaning individuals with the condition are likely to survive childbirth and can enjoy a good ‘quality of life’ (Buckley and Buckley 2008; CARIS 2012; NHS FASP 2012). NHS (2013) reports there are a number of ways in which children with the condition can develop into ‘healthy and fulfilled
individuals’ who can achieve independence and enjoy access to healthcare and early intervention programmes. Similarly, Buckley and Buckley (2008) suggest support for people with the condition is much better than in earlier years and their current medical needs are largely understood; several healthcare professionals may monitor and treat people with Down’s syndrome including physiotherapists, speech and language therapists, ophthalmologists, occupational therapists, general practitioners, audiologists, dieticians, paediatricians, and cardiologists (NHS 2013). Adults with Down’s syndrome can pursue further education, gain employment, and live independently (Buckley and Buckley 2008). Additionally, according to Buckley and Buckley (2008: 84), people with the condition are rarely anti-social or violent and whilst they can experience challenges, they can ‘make positive contributions to family and community life and often form loving and caring relationships’.
However, whilst the progress of people with the condition has been remarkable in the past fifty years, the prognosis of the condition is uncertain and it is impossible to predict how a child will be affected (NHS 2013). Nonetheless, due to medical advancements and better knowledge regarding treatment and care, children born with Down’s syndrome – most of which are diagnosed postnatally – are likely to survive beyond sixty years today (CARIS 2012). This has significantly increased from nine years old in 1929, twelve years old in 1946, twenty-five years old in 1983, and forty-nine years old in 1997 (Penrose 1949; Yang et al. 2002).
The object of screening at Freymarsh and Springtown
In the UK, all parents-to-be are offered prenatal screening for Down’s syndrome which cannot establish a diagnosis but can assist reproductive decision-making regarding diagnostic testing (NHS 2013). Screening should take place in a window of ten to twenty weeks during a pregnancy although the preferred period of time is by the end of the first trimester (thirteen weeks and six days gestation). During my fieldwork at two institutions – Freymarsh (NHS hospital) and Springtown (privately-funded clinic) – two screening methods were used: quadruple screening (Freymarsh) and combined screening (Springtown). The quadruple screen, using a risk threshold of 1 in 150, can detect approximately 75% of affected pregnancies with a 3% false-positive rate. In contrast, combined screening, also using a risk
threshold of 1 in 150, can detect around 85% of affected pregnancies with a lower false-positive rate (CARIS 2012).
Irrespective of the screening method, parents-to-be receive a ‘risk factor’, namely a numerical ratio establishing the odds of an unborn baby having the condition. Both screening methods are based on the same mathematical principle and work by combining a prior probability – maternal age at expected date of delivery – with a likelihood ratio based on a range of factors such as blood proteins, hormones, and a nuchal translucency measurement (Reynolds 2010). Taken together, these create an estimate of whether the unborn baby has Down’s syndrome. At Freymarsh and Springtown, this is calculated using computer software combining a risk factor with other characteristics including maternal age, weight, gestation, ethnicity, pregnancy history, smoking habits, the number of unborn babies, and whether it is an assisted conception. At Springtown, these factors are combined with the size of
a nuchal translucency24. Parents-to-be receive three risk factors at Freymarsh: a
background risk (based on age, ethnicity, previous history, etc.), a biochemistry risk (based on measurements of four biochemical markers), and an adjusted risk (based on combining a background risk and biochemistry risk). At Springtown, parents-to-be receive these three risk factors alongside an ultrasound risk (based on the nuchal translucency size alone). In Freymarsh and Springtown, only the adjusted risk factor is referred to when delivering a result. In addition, whilst only a risk factor for Down’s syndrome is given to parents-to-be in Freymarsh, parents- to-be in Springtown also receive risk factors for Edward’s syndrome and Patau’s syndrome. This reflects a shift in modern biomedical practice from the actual to the potential, redefining the idea of ‘the patient’ to include those ‘at risk’ alongside those who are ‘sick’ (Gross and Shuval 2008; Scott et al. 2005).
In Freymarsh and Springtown, the cut-off point for this categorisation is 1:150 (a 1 in 150 risk of having a baby with Down’s syndrome). If parents-to-be receive a risk factor numerically higher than 1:150 (e.g. 1:250), they are categorized as ‘lower- risk’ and receive a letter notifying them of this information (at Springtown, they
24 Some institutions will also take account of the presence/absence of a nasal bone, another marker
of Down’s syndrome and other genetic conditions (Cicero et al. 2001). However, Springtown do not usually offer this service owing to a lack of training among sonographers.
receive a telephone call). At this point, parents-to-be are not offered or advised to have further treatment other than an ultrasound scan at twenty weeks to check for potential problems (an ‘anomaly scan’). In contrast, if parents-to-be receive a risk factor numerically lower than 1:150 (e.g. 1:100), they are categorised as ‘higher- risk’ and diagnostic testing (amniocentesis/CVS) is offered to prove or refute a suspected diagnosis. Around three to five percent of pregnant women in England and Wales consenting to screening receive a higher-risk result (NHS FASP 2012) and according to Buckley and Buckley (2008), between 1 in 20 and 1 in 30 higher- risk (screen-positive) results detect an unborn baby with Down’s syndrome. For a timeline and flowchart of Down’s syndrome screening in Freymarsh/Springtown
and the UK more generally, see Appendices 1-325.
The object of testing at Freymarsh and Springtown
Diagnostic testing for Down’s syndrome involves undertaking an amniocentesis or CVS. During CVS, a small sample of placenta is taken either by passing a small needle through the abdomen of a mother-to-be or by passing a small tube through a vagina and the neck of a womb (NHS 2013). During an amniocentesis, a small sample of amniotic fluid is taken by passing a fine needle through the abdomen of a mother-to-be and drawing the fluid out using a syringe. CVS is carried out in the first trimester after ten weeks of a pregnancy and an amniocentesis is commonly carried out in the second trimester between fifteen and twenty weeks gestation (NHS 2013). An amniocentesis can also be carried out late in a pregnancy to check the unborn baby’s wellbeing and potentially diagnose a condition (although not for the purpose of termination). Amniocentesis and CVS provide an accurate diagnosis but have a few possible complications including miscarriage, infection, heavy bleeding, premature labour, and postural deformities. The risk of miscarriage following amniocentesis is 1% and is 2% following CVS (Buckley and Buckley 2008). The move toward first trimester screening, together with detecting more unborn babies who may not have naturally survived to term than biochemical serum screening, may trigger an increase in the miscarriage of unborn babies who do not have Down’s syndrome since CVS, which has a higher-risk of miscarriage
25 Suspicions of Down’s syndrome can also be established during an ‘anomaly scan’ performed at
twenty weeks gestation. The absence of a nasal bone, an increased nuchal translucency, cardiac defects, or an echogenic bowel can indicate a potential diagnosis of the condition.
than amniocentesis, can also be performed in the first trimester (Buckley and Buckley 2008). Diagnostic testing is offered because of an indication of a condition, previous pregnancy complications, a family history of a particular condition, and an advanced maternal age (although this last option is currently not common in UK medicine).
After diagnostic testing is completed, samples are sent to a cytogenetic laboratory. Cytogenetics is concerned with the function and structure of cells, especially chromosomes. Two results are possible following testing: a QF-PCR (quantitative fluorescence polymerase chain reaction) result and a full karyotype. A QF-PCR result includes amplification, detection, and analysis of chromosome-specific DNA sequences. This provides a conclusive diagnosis for Down’s syndrome, Edward’s syndrome, Patau’s syndrome, and sex chromosome ‘aneuploidies’ such as Turner
syndrome26 or Klinefelter’s syndrome27. A diagnosis of cystic hygroma might also
be possible via QF-PCR testing. Since QF-PCR misses some chromosomal conditions, it is followed by a full karyotype which involves analysing all chromosomes in detail at the microscopic level including deletions and duplications, translocations, mosaicisms, and inversions and insertions. This reveals chromosomal conditions other than those specified above together with any abnormal genes. Although a QF-PCR result is usually available in less than two days following a procedure, a full karyotype is available approximately two weeks after this period.
After a result is established, this information is returned to professionals who must deliver this news to parents-to-be. If a diagnosis is established, counselling is offered to parents-to-be before a decision is made about whether to continue or terminate a pregnancy. The main objective of screening is to identify women in whom a risk factor is deemed high enough to warrant offering them diagnostic testing.
26 Turner syndrome is a genetic disorder which only affects females. A female with the condition
will have all or part of one X chromosome missing.
Maternal age and Down’s syndrome
While it is not fully understood why some babies are conceived with abnormal copies of chromosomes, maternal age is the only clear factor which increases the chance of having a baby with Down’s syndrome (NHS 2013). Whilst the reason for this relationship remains unclear, what is observable is despite higher pregnancy rates among mothers under thirty-five years old (ONS 2011), more babies with Down syndrome are born to mothers aged thirty-five and above (CARIS 2012). This could reflect the increasing numbers of women delaying childbearing for reasons including increased participation in higher education and the labour force, the rising opportunity costs of childbearing, labour market uncertainty, housing factors, and instability of partnerships (ONS 2011). Nevertheless, according to a handbook published for professionals at Freymarsh, a mother-to-be who is sixteen years old has a maternal age risk of 1:1509, that is, there is a 1 in 1509 chance the unborn baby has Down’s syndrome. This increases to 1:1476 at the maternal age of twenty, 1:1339 at twenty-five, and 1:937 at thirty. At the age of thirty-five, a maternal age risk prior to any form of screening is 1:352. This increases to 1:266 at thirty-six, 1:199 at thirty-seven, 1:148 at thirty-eight, 1:111 at thirty-nine, and 1:85 at forty. At the age of forty-five, the maternal age risk is 1:35.
A report conducted by the National Down’s Syndrome Cytogenetic Register (NDSCR) claims in 2011 in England and Wales, 119 mothers-to-be aged twenty- four and below (6% of all cases) received a prenatal or postnatal diagnosis of Down’s syndrome (Morris and Springett 2013). This increased to 183 for mothers- to-be aged twenty-five to twenty-nine (10% of all cases), 331 for mothers-to-be aged thirty to thirty-four (18% of all cases), 622 for mothers-to-be aged thirty-five to thirty-nine (33% of all cases), 450 for mothers-to-be aged forty to forty-four (24% of all cases), and 50 for mothers-to-be aged forty-five and above (3% of all
cases)28. The mean age of mothers with a prenatal diagnosis was 36.7 compared to
34.4 of mothers with a postnatal diagnosis. According to the NDSCR report, 64% (N=1122) of mothers with a known age and who received a diagnosis of Down’s syndrome were thirty-five years old and above (Morris and Springett 2013).
Summary
In this section of the chapter, I have described Down’s syndrome, its (possible) symptoms, how it is screened and testing for at Freymarsh and Springtown, and how maternal age is associated with the condition. Alongside the socio-history provided at the beginning of the chapter, this section has identified how screening for the condition has become a routine practice in NHS medicine. By outlining the history and recent developments regarding Down’s syndrome and its intersection with medical and scientific worlds, I have recognised how a mundane procedure has been widely accepted and embraced by the public and medical communities, particularly Freymarsh and Springtown. After identifying how Down’s syndrome screening represents a key site for sociological attention, I spend chapter four situating the study by discussing my entry to the field, how data was collected, fieldwork, data analysis, and both ethnographic and my study’s limitations.