How many people have sickle cell disease in the UK?

Background: Sickle Cell Disease (SCD) is now one of the most common serious genetic condition in England. There is no reliable estimate of the total number of people living with SCD in the UK, to support commissioners and providers of services for people with SCD. Aim: To obtain reliable data on the total number of people living with SCD in the UK in 2016. Method: Information was requested from all national databases known to hold information on the number of people living with SCD in the UK. The information from each data source was first reviewed to estimate likely inaccuracies and then combined to provide a best estimate of people living with SCD in the UK. Conclusion: This process indicated there are are about 14000 people living with SCD in the UK. This is equivalent to 1 in 4600 people.

Offering antenatal sickle cell and thalassaemia screening to pregnant women in primary care: a qualitative study of women's experiences and expectations of participation.

OBJECTIVE: To describe the acceptability to women of being offered antenatal Sickle cell and Thalassaemia (SC&T) screening in primary and secondary care at the visit to confirm pregnancy; and to explore the implications of their views for participating in decisions about their health care. METHODS: Qualitative semi-structured interviews were conducted with twenty-one ethnically diverse women registered at twenty-five general practices in two English inner-city Primary Care Trusts. The material was analysed thematically, using the method of constant comparison. RESULTS: Women generally welcomed the opportunity of early diagnosis, although they expected screening to confirm they were carrying a healthy child. Women felt general practitioners did not present antenatal screening as a choice, but they did not necessarily see this as a problem. Doctors were believed to be acting out of concern for the women's well being. CONCLUSIONS: Women were generally positive about being offered screening in primary care at the first visit to confirm pregnancy. To this extent it was acceptable to them, although this was largely informed by assumptions associated with being a 'good mother' rather than a straightforward enactment of informed choice, assumed by health-care policy. This represents the context in which women participate in decisions about their health care.

Improving Screening Programmes for Sickle Cell Disorders and Other Haemoglobinopathies in Europe: The Role of Patient Organisations.

This discussion paper has been written to show the unique contribution and added value that Patient Organisations can give to the development and improvement of newborn screening programmes for sickle cell disorder (SCD) and other haemoglobinopathies in Europe. As an example, the action of the Sickle Cell Society (SCS) in partnership with statutory organisations in the U.K., such as the National Health Service (NHS) Sickle Cell and Thalassaemia Screening Programme (NHS SCT SP), will be described.

Towards socially inclusive research: an evaluation of telephone questionnaire administration in a multilingual population.

BACKGROUND: Missing data may bias the results of clinical trials and other studies. This study describes the response rate, questionnaire responses and financial costs associated with offering participants from a multilingual population the option to complete questionnaires over the telephone. DESIGN: Before and after study of two methods of questionnaire completion. PARTICIPANTS AND SETTING: Seven hundred and sixty five pregnant women from 25 general practices in two UK inner city Primary Care Trusts (PCTs) taking part in a cluster randomised controlled trial of offering antenatal sickle cell and thalassaemia screening in primary care. Two hundred and four participants did not speak English. Sixty one women were offered postal questionnaire completion only and 714 women were offered a choice of telephone or postal questionnaire completion. OUTCOME MEASURES: (i) Proportion of completed questionnaires, (ii) attitude and knowledge responses obtained from a questionnaire assessing informed choice. RESULTS: The response rate from women offered postal completion was 26% compared with 67% for women offered a choice of telephone or postal completion (41% difference 95% CI Diff 30 to 52). For non-English speakers offered a choice of completion methods the response rate was 56% compared with 71% for English speakers (95% CI Diff 7 to 23). No difference was found for knowledge by completion method, but telephone completion was associated with more positive attitude classifications than postal completion (87 vs 96%, 95% CI diff 0.006 to 15). Compared with postal administration the additional costs associated with telephone administration were pound3.90 per questionnaire for English speakers and pound71.60 per questionnaire for non English speakers. CONCLUSION: Studies requiring data to be collected by questionnaire may obtain higher response rates from both English and non-English speakers when a choice of telephone or postal administration (and where necessary, an interpreter)is offered compared to offering postal administration only. This approach will, however, incur additional research costs and uncertainty remains about the equivalence of responses obtained from the two methods.

Delay between pregnancy confirmation and sickle cell and [corrected] thalassaemia screening: a population-based cohort study.

BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. AIM: To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. METHOD: Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated.

Evaluation of newborn sickle cell screening programme in England: 2010-2016.

OBJECTIVE: To evaluate England's NHS newborn sickle cell screening programme performance in children up to the age of 5 years. DESIGN: Cohort of resident infants with sickle cell disease (SCD) born between 1 September 2010 and 31 August 2015 and followed until August 2016. PARTICIPANTS: 1317 infants with SCD were notified to the study from all centres in England and 1313 (99%) were followed up. INTERVENTIONS: Early enrolment in clinical follow-up, parental education and routine penicillin prophylaxis. MAIN OUTCOME MEASURES: Age seen by a specialist clinician, age at prescription of penicillin prophylaxis and mortality. RESULTS: All but two resident cases of SCD were identified through screening; one baby was enrolled in care after prenatal diagnosis; one baby whose parents refused newborn screening presented symptomatically. There were 1054/1313 (80.3%, 95% CI 78% to 82.4%) SCD cases seen by a specialist by 3 months of age and 1273/1313 (97%, 95% CI 95.9% to 97.8%) by 6 months. The percentage seen by 3 months increased from 77% in 2010 to 85.4% in 2015. 1038/1292 (80.3%, 95% CI 78.1% to 82.5%) were prescribed penicillin by 3 months of age and 1257/1292 (97.3%, 95% CI 96.3% to 98.1%) by 6 months. There were three SCD deaths <5 years caused by invasive pneumococcal disease (IPD) sensitive to penicillin. CONCLUSION: The SCD screening programme is effective at detecting affected infants. Enrolment into specialist care is timely but below the programme standards. Mortality is reducing but adherence to antibiotic prophylaxis remains important for IPD serotypes not in the current vaccine schedule.

Undergoing prenatal screening for Down's syndrome: presentation of choice and information in Europe and Asia.

To date, studies assessing whether the information given to people about screening tests facilitates informed choices have focussed mainly on the UK, US and Australia. The extent to which written information given in other countries facilitates informed choices is not known. The aim of this study is to describe the presentation of choice and information about Down's syndrome in written information about prenatal screening given to pregnant women in five European and two Asian countries. Leaflets were obtained from clinicians in UK, Netherlands, Spain, Italy, Czech Republic, China and India. Two analyses were conducted. First, all relevant text relating to the choice about undergoing screening was extracted and described. Second, each separate piece of information or statement about the condition being screened for was extracted and then coded as either positive, negative or neutral. Only Down's syndrome was included in the analysis since there was relatively little information about other conditions. There was a strong emphasis on choice and the need for discussion about prenatal screening tests in the leaflets from the UK and Netherlands. The leaflet from the UK gave most information about Down's syndrome and the smallest proportion of negative information. By contrast, the Chinese leaflet did not mention choice and gave the most negative information about Down's syndrome. Leaflets from the other countries were more variable. This variation may reflect cultural differences in attitudes to informed choice or a failure to facilitate informed choice in practice. More detailed studies are needed to explore this further.

Development of a measure of informed choice suitable for use in low literacy populations.

OBJECTIVE: To assess the reliability and validity of a simplified questionnaire-based measure of informed choice in populations with low literacy. The measure comprises (a) knowledge about the test and (b) attitudes towards undergoing the test. Responses to (a) and (b) together with information on test uptake, are used to classify choices as informed or uninformed. METHODS: A cross-sectional study of 79 pregnant women (46 women with higher, and 33 with lower education levels) completed a simplified questionnaire, a standardised questionnaire and a semi-structured interview about antenatal sickle cell and thalassaemia (SCT) screening. The measures used were: (a) informed choice, based on knowledge about the test, attitudes towards undergoing the test, and uptake of the test and (b) ease of completion measures. RESULTS: The simplified measures of knowledge and attitudes were able to distinguish between women classified according to interview responses as having good or poor knowledge (knowledge scores 6.8 versus 3.2, p<0.001), and positive or negative attitudes towards undergoing the test (attitude scores 20.6 versus 16.2, p=0.023). There was no difference in rates of informed choice derived from the simplified or standardised measures (54% versus 51%, 95% CI difference -11 to 19). Women with lower levels of education found the simplified questionnaire easier to complete than the standardised version (11.0 versus 9.6, p=0.009). Those with higher levels of education found no difference in ease of completion between the two versions of the questionnaire (11.8 versus 11.6, p=0.54). CONCLUSION: A simplified questionnaire-based measure of informed choice in antenatal SCT screening is as reliable and valid as a more complex standardised version and for those with less education, easier to complete. PRACTICE IMPLICATIONS: The simplified questionnaire-based measure of informed choice is suitable for use in populations with low and high levels of education.

Informed choice in antenatal Down syndrome screening: a cluster-randomised trial of combined versus separate visit testing.

OBJECTIVE: Building upon the results of an observational study, this clinical trial aimed to test the hypothesis that conducting antenatal Down syndrome screening (DSS) at the same time as other tests result in higher rates of informed choice to accept DSS, than when it is conducted separately from other tests. METHODS: The trial used a cluster-randomised controlled design, with informed choice as the outcome measure. The post of midwife was randomised to offer DSS at the same time as other tests (combined visit) or separately from other tests (separate visit). RESULTS: Overall 43.5% of women made an informed choice about DSS. There was no difference in rates of informed choice for women accepting DSS according to the method of conducting testing (23.7% at combined visit versus 22.5% at separate visit, OR = 1.1, 95% CI: 0.70-1.7, p = 0.67). CONCLUSION: Rates of informed choice about DSS were low, but there was no evidence to support that hypothesis that conducting testing at that same time as other tests increased rates of informed choice. This may reflect the limitations of conducting the trial in one centre.

Low uptake of prenatal screening for Down syndrome in minority ethnic groups and socially deprived groups: a reflection of women's attitudes or a failure to facilitate informed choices?

BACKGROUND: It is not known if lower uptake of prenatal screening for Down syndrome in women from minority ethnic groups and socioeconomically disadvantaged women reflects more negative attitudes towards undergoing the test or women not acting in line with their attitudes i.e. not making an informed choice. METHODS: Uptake of prenatal screening, attitudes towards undergoing the test, uptake-attitude consistency, and informed choice were assessed in a prospective study of 1499 pregnant women attending two UK hospitals. RESULTS: Uptake was higher in white and socioeconomically advantaged women than in other women. There were no differences in attitudes towards undergoing the test; all women expressed relatively positive attitudes. Uptake-attitude consistency was higher in white and socioeconomically advantaged women than others, particularly in those with positive attitudes towards undergoing the test (76% white women with positive attitudes had the test compared with 45% South Asian women [difference 31%, 95% confidence interval (95% CI) 18-43] and 78% socioeconomically advantaged women compared with 63% more disadvantaged women (difference 15%, 95% CI 7-24)). Controlling for demographic variables, South Asian and socioeconomically disadvantaged women with positive attitudes were less likely to make an informed choice than other women [odds ratio (OR) 0.22, 95% CI 0.10-0.45 and OR 0.62, 95% CI 0.41-0.93, respectively]. CONCLUSION: Lower uptake of screening for Down syndrome in women from minority ethnic groups and socioeconomically disadvantaged women does not reflect more negative attitudes towards screening but rather lower rates of informed choice, as assessed in this study. Healthcare systems appear to facilitate informed choices in the context of prenatal screening for Down syndrome screening less well for women from minority ethnic groups and those who are socioeconomically disadvantaged than for other women.

Increasing screening uptake amongst those intending to be screened: the use of action plans.

This experimental study investigates an intervention designed to increase rates of antenatal screening uptake in those intending to undergo antenatal screening. Eighty-eight pregnant women intending to undergo prenatal screening were alternately allocated to standard care or asked to write a simple plan for attending or making an appointment. Twenty-five (63%) in the intervention group made an action plan. There was no difference in uptake of screening between the intervention group and the control group, nor between those making an action plan and the control group. Within the intervention group, those making an action plan had higher screening uptake (21/25, 84%) than those not making one (7/15, 47%; CI(95) difference = 8-66%, P = 0.017). Asking women who intend to undergo screening to make an action plan does not increase screening uptake. This result raises doubts about introducing simple action plans in a clinical situation as an effective means of changing behaviour.

Informed choice: understanding knowledge in the context of screening uptake.

This study evaluates a scale measuring knowledge about a screening test and investigates the association between knowledge, uptake and attitudes towards screening. One thousand four hundred ninety-nine pregnant women completed the knowledge scale of the multidimensional measure of informed choice (MMIC). Three hundred forty-five of these women and 152 professionals providing antenatal care also rated the importance of the knowledge items. Item characteristic curves show that, with one exception, the knowledge items reflect a spread of difficulty and are able to discriminate between people. All items were seen as essential or helpful by both women and health professionals, with two items seen as particularly important and one as unimportant. There were some differences between health professionals, women with low risk results and women with high risk results. Knowledge was not associated with uptake, attitude, or the extent to which uptake was consistent with women's attitudes towards undergoing the test.

The multi-dimensional measure of informed choice: a validation study.

The aim of this prospective study is to assess the reliability and validity of a multi-dimensional measure of informed choice (MMIC). Participants were 225 pregnant women in two general hospitals in the UK, women receiving low-risk results following serum screening for Down syndrome. The MMIC was administered before testing and the Ottawa Decisional Conflict Scale was administered 6 weeks later. The component scales of the MMIC, knowledge and attitude, were internally consistent (alpha values of 0.68 and 0.78, respectively). Those who made a choice categorised as informed using the MMIC rated their decision 6 weeks later as being more informed, better supported and of higher quality than women whose choice was categorised as uninformed. This provides evidence of predictive validity, whilst the lack of association between the MMIC and anxiety shows construct (discriminant) validity. Thus, the MMIC has been shown to be psychometrically robust in pregnant women offered the choice to undergo prenatal screening for Down syndrome and receiving a low-risk result. Replication of this finding in other groups, facing other decisions, with other outcomes, should be assessed in future research.

Newborn bloodspot results: predictive value of screen positive test for thalassaemia major.

AIM: There are limited published data on the performance of the percentage of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. This paper aims to analyse data derived from a national newborn bloodspot screening programme for sickle cell disease on the performance of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. METHODS: Newborn bloodspot sickle cell screening data from 2,288,008 babies were analysed. Data reported to the NHS Sickle Cell and Thalassaemia Screening Programme in England for the period 2005 to 2012 were also reviewed to identify any missed cases (4,599,849 babies). RESULTS: Within the cohort of 2,288,008 births, 170 babies were identified as screen positive for beta thalassaemia major using a cut-point of 1.5% HbA. There were 51 identified through look-back methods and 119 prospectively identified from 4 screening laboratories. Among 119 babies with prospective data, 7 were lost to follow up and 15 were false positive results. Using a cut-off value of 1.5% Hb A as a percentage of the total haemoglobin as a screening test for beta thalassaemia major in the newborn provides an estimated sensitivity of 99% (from the look back arm of the study) with a positive predictive value of 87% (from the prospective arm of the study). Excluding infants born before 32 weeks gestation, the positive predictive value rose to 95%. CONCLUSION: A haemoglobin A value of less than 1.5% is a reliable screening test for beta thalassaemia major in the newborn period.

Offering antenatal sickle cell and thalassaemia screening in primary care: a pre-post evaluation of a brief type of communication skills training.

OBJECTIVE: To evaluate brief communication skills training for healthcare professionals (HCPs) in offering antenatal sickle cell and thalassaemia (SCT) screening in primary care. DESIGN: Descriptive study within a cluster randomised controlled trial in 17 inner city practices. METHODS: 126 HCPs were invited to attend a training session. Outcome measures were: attendance; perceived usefulness of training; comfort and confidence in offering screening; offering screening at pregnancy confirmation consultations; gestational age at test uptake. RESULTS: 62% (78/126) HCPs attended training and 61 completed both pre- and post-training questionnaires. There were 49 new joiners and locums not in post at the start of the trial. After training, HCPs reported greater comfort [4.8 vs 5.4, p = 0.05] and confidence [4.6 vs 5.6, p<0.001] in offering screening. Pregnant women consulting trained HCPs were offered screening more frequently and at an earlier gestational age than those consulting untrained HCPs (75% vs 44%, χ(2) = 122, p<0.001; 91.5 days (attending training) vs 98.5 days (did not attend training) vs 101.8 days (new joiners and locums), F = 8.49, df 1069,2 p = 0.001). CONCLUSION: Brief communication skills training for HCPs in offering antenatal SCT screening in primary care is feasible and can be effective. PRACTICE IMPLICATIONS: Ways of maximising HCP attendance in training sessions requires consideration.

Impact on informed choice of offering antenatal sickle cell and thalassaemia screening in primary care: a randomized trial.

OBJECTIVES: Offering antenatal sickle cell and thalassaemia (SCT) screening early in pregnancy can maximize the range of post-screening choices available, however these benefits should not be obtained at the expense of informed choice.  This study examined whether offering this screening in primary care at the time of pregnancy confirmation compromises women making informed choices. Design Partial factorial, cluster randomized controlled trial. SETTING: 25 general practices in two socially deprived UK areas. Participants 464 pregnant women offered antenatal SCT screening. Intervention Practices were randomly allocated to offer pregnant women screening:  i) in primary care at time of pregnancy confirmation, with parallel partner testing (n = 191), ii) in primary care at time of pregnancy confirmation, with sequential partner testing (n = 158), or iii) in secondary care by midwives, with sequential partner testing (standard care, n = 115). Main outcome Informed choice - a classification based on attitudes, knowledge and test uptake. RESULTS: 91% of woman underwent screening. About a third (30.6%) made an informed choice to accept or decline screening: 34% in primary care parallel group; 23.4% in primary care sequential and 34.8% in secondary care sequential. Allowing for adjustments, rates of informed choice did not vary by intervention group: secondary care versus primary care with parallel partner testing OR 1.07 (95% CI 0.56 to 2.02); secondary care versus primary care with sequential partner testing OR 0.67 (95% CI 0.36 to 1.25).  Uninformed choices were generally attributable to poor knowledge (65%). CONCLUSION: Offering antenatal SCT screening in primary care did not reduce the likelihood that women made informed choices. Rates of informed choice were low and could be increased by improving knowledge.

Screening for sickle cell and thalassaemia in primary care: a cost-effectiveness study.

BACKGROUND: Haemoglobinopathies, including sickle cell disease and thalassaemia (SCT), are inherited disorders of haemoglobin. Antenatal screening for SCT rarely occurs before 10 weeks of pregnancy. AIM: To explore the cost-effectiveness of offering SCT screening in a primary care setting, during the pregnancy confirmation visit. DESIGN AND SETTING: A model-based cost-effectiveness analysis of inner-city areas with a high proportion of residents from ethnic minority groups. METHOD: Comparison was made of three SCT screening approaches: 'primary care parallel' (primary care screening with test offered to mother and father together); 'primary care sequential (primary care screening with test offered to the mother and then the father only if the mother is a carrier); and 'midwife care' (sequential screening at the first midwife consultation). The model was populated with data from the SHIFT (Screening for Haemoglobinopathies In First Trimester) trial and other sources. RESULTS: Compared to midwife care, primary care sequential had a higher NHS cost of £34,000 per 10,000 pregnancies (95% confidence interval [CI] = £15,000 to £51,000) and an increase of 2623 women screened (95% CI: 1359 to 4495), giving a cost per additional woman screened by 10 weeks of £13. Primary care parallel was dominated by primary care sequential, with both higher costs and fewer women screened. CONCLUSION: The policy judgement is whether an earlier opportunity for informed reproductive choice has a value of at least £13. Further work is required to understand the value attached to earlier informed reproductive choices.

Offering antenatal sickle cell and thalassaemia screening to pregnant women in primary care: a qualitative study of GPs' experiences.

BACKGROUND: Timely antenatal sickle cell and thalassaemia (SC&T) screening for all women in primary care facilitates informed decision making, but little is known about its implementation. AIM: To assess the feasibility of offering antenatal SC&T screening in primary care at the time of pregnancy confirmation. DESIGN OF STUDY: Cross-sectional investigation of GPs' beliefs and perceived practices. METHOD: Informal face-to-face interviews with 34 GPs. SETTING: Seventeen inner-city general practices that offered antenatal SC&T screening as part of a trial. RESULTS: GPs identified both barriers and facilitators. Organisational barriers included inflexible appointment systems and lack of interpreters for women whose first language was not English. Professional barriers included concerns about raising possible adverse outcomes in the first antenatal visit. Perceived patient barriers included women's lack of awareness of SC&T. Hence, GPs presented the test to women as routine, rather than as a choice. Organisational facilitators included simple and flexible systems for offering screening in primary care, practice cohesion, and training. Professional facilitators included positive attitudes to screening for SC&T. Perceived patient facilitators included women's desire for healthy children. CONCLUSION: GPs reported barriers, as well as facilitators, to successful implementation but the extent to which screening could be regarded as offering 'informed choice' remained fundamental when making sense of these barriers and facilitators.