Antenatal screening for haemoglobinopathies in primary care: a cohort study and cluster randomised trial to inform a simulation model. The Screening for Haemoglobinopathies in First Trimester (SHIFT) trial.

OBJECTIVES: To assess the effectiveness, cost-effectiveness, acceptability and feasibility of offering universal antenatal sickle cell and thalassaemia (SCT) screening in primary care when pregnancy is first confirmed and to model the cost-effectiveness of early screening in primary care versus standard care. DESIGN: A population-based cohort study, cluster randomised trial and refinement of a published decision model. SETTING: Twenty-five general practices from two UK primary care trusts (PCTs) in two inner city boroughs with a high proportion of residents from minority ethnic groups. PARTICIPANTS: Practices were considered eligible if they agreed to be randomised and they were able to provide anonymous data on all eligible pregnant women. Participants were at least 18 years old and consented to take part in the evaluation. INTERVENTIONS: Practices were allocated to intervention, using minimisation and stratifying for PCT and number of partners at the practice, as follows: screening in primary care with parallel father testing (test offered to mother and father simultaneously; n = 8 clusters, 1010 participants); screening in primary care with sequential father testing (test offered to father only if mother identified as carrier; n = 9 clusters, 792 participants); and screening in secondary care with sequential father testing (standard care; n = 8 clusters, 619 participants). MAIN OUTCOME MEASURES: Data on gestational age at pregnancy confirmation and screening date were collected from trial practices for 6 months before randomisation in the cohort phase. The primary outcome measure was timing of SCT screening, measured as the proportion of women screened before 70 days' (10 weeks') gestation. Other outcomes included: offer of screening, rates of informed choice and proportion of women who knew the carrier status of their baby's father by 77 days (11 weeks). RESULTS: For 1441 eligible women in the cohort phase, the median [interquartile range (IQR)] gestational age at pregnancy confirmation was 7.6 weeks (6.0 to 10.7 weeks) and 74% presented in primary care before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR 12.6 to 18.0 weeks). Only 4.4% were screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7 to 9.3 weeks). In the intervention phase, 1708 pregnancies from 25 practices were assessed for the primary outcome measure. Completed questionnaires were obtained from 464 women who met eligibility criteria for the main analysis. The proportion of women screened by 10 weeks (70 days) was 9/441 (2%) in standard care, compared with 161/677 (24%) in primary care with parallel testing, and 167/590 (28%) in primary care with sequential testing. The proportion of women offered screening by 10 weeks (70 days) was 3/90 (3%) in standard care (note offer of test ascertained for questionnaire respondents only), compared with 321/677 (47%) in primary care with parallel testing, and 281/590 (48%) in primary care with sequential testing. The proportion of women screened by 26 weeks (182 days) was similar across the three groups: 324/441 (73%) in standard care, 571/677 (84%, 0.09) in primary care with parallel testing, and 481/590 (82%, 0.148) in primary care with sequential testing. The screening uptake of fathers was 51/677 (8%) in primary care with parallel testing, and 16/590 (3%) in primary care with sequential testing, and 13/441 (3%) in standard care. The predicted average total cost per pregnancy of offering antenatal SCT screening was estimated to be 13 pounds in standard care, 18.50 pounds in primary care with parallel testing, and 16.40 pounds in primary care with sequential testing. The incremental cost-effectiveness ratio (ICER) was 23 pounds in primary care with parallel testing and 12 pounds in primary care with sequential testing when compared with standard care. Women offered testing in primary care were as likely to make an informed choice as those offered screening by midwives later in pregnancy, but less than one-third of women overall made an informed choice about screening. CONCLUSIONS: Offering antenatal SCT screening as part of pregnancy-confirmation consultations significantly increased the proportion of women screened before 10 weeks (70 days), from 2% in standard care to between 16% and 27% in primary care, but additional resources may be required to implement this. There was no evidence to support offering fathers screening at the same time as women. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00677850.

A multidisciplinary approach for improving services in primary care: randomised controlled trial of screening for haemoglobin disorders.

OBJECTIVE: To investigate the feasibility of improving screening for carriers of haemoglobin disorders in general practice by using a nurse facilitator to work with primary care teams and the relevant haematology laboratories; to identify problems in communication between all those involved in delivering the service, and to implement solutions. DESIGN: Two year, practice based randomised controlled trial. SETTING: North London area where 29% of residents and 43% of births are in ethnic groups at risk for haemoglobin disorders. SUBJECTS: 26 of the 93 practices using the services of the area's haematology laboratory agreed to take part and were randomly divided into control and intervention practices. MAIN OUTCOME MEASURE: Change in number of requests for screening tests for haemoglobin disorders made by control and intervention practices in baseline and intervention years. RESULTS: The number of screening tests requested varied from 0-150 in the 93 practices in the baseline year. Study practices tended to have made a moderate number of requests (10-50) during this period. During the intervention year intervention practices made 292 more requests (99% increase) and control practices made 74 fewer requests (23% decrease; P=0.001 for difference in median change). Four practices, three of which were singlehanded, accounted for 75% of the increase. The number of requests from intervention practices, adjusted for baseline requests, was 3.2 times higher than control practices (P<0.0001). CONCLUSION: General practitioners and practice nurses are willing to undertake a new genetic screening service (or expand an existing one) if they are persuaded that it benefits the health of a significant proportion of their practice population. They need appropriate tools (for example, information materials for carriers and groups at risk), and the laboratory must be sensitive to their needs. Preconceptional carrier screening and counselling need to be coupled with antenatal screening.

Screening and counselling for sickle cell disorders and thalassaemia: the experience of parents and health professionals.

Shortfalls in haemoglobinopathy provision result in patients and their carers receiving inadequate support. This paper, by drawing on material from a project evaluating service provision to families caring for a child with a sickle cell disorder or thalassaemia, discusses screening and counselling services. It explores the perspectives of parents, front-line practitioners, managers and health commissioners. Poor quality care, inadequate information and professionals' insensitivity were salient themes in parental accounts. The parents' experience also confirms the problems faced by minority ethnic people in having their welfare needs recognised, more generally. Although our focus in on genetic conditions affecting minority communities in the UK, the issues we address are at the heart of the 'new genetics'.

Patterns of mortality in sickle cell disease in the United Kingdom.

Eighteen of 384 patients entered on the Brent sickle cell disease register died between 1974 and 1989, a mortality of one per 128 years of follow up. Two children died from acute splenic sequestration and a third died from fulminant pneumococcal septicaemia: none was taking prophylactic penicillin. Acute chest syndrome was the cause of death in eight young adults and one child. Three deaths occurred after surgery. Cerebrovascular accidents contributed to the cause of death in three cases and there were two sudden unexplained deaths. Ten of the deaths occurred at home or within 24 hours of admission to hospital. Post mortem examinations were made in 14 cases, but the histological appearances of acute chest syndrome were often not recognised. In most cases for whom information was available, the cause of death (chest syndrome, pneumococcal sepsis, postoperative complications) could have been prevented.

Training of counsellors on sickle-cell disorders in Africa.

Falling infant and childhood mortality rates, especially in urban centres, have allowed greater survival of individuals with sickle-cell disorders (SCD), and the need to provide appropriate services has become pressing. The training and employment of counsellors on SCD, shown here to be popular and feasible, seems an essential first step towards the development of a community-based and appropriate policy for coping with SCD in Africa.

Counselling for prenatal diagnosis of sickle cell disease and beta thalassaemia major: a four year experience.

A non-directive programme of prenatal counselling was used during a four year period. Forty-three couples at risk for having a baby with a haemoglobinopathy were identified. Prenatal diagnosis was offered in 19 pregnancies to 14 couples at risk of having a baby with sickle cell anaemia and in two pregnancies in two couples at risk of a baby with beta thalassaemia major, who presented before the 18th week of pregnancy. Six couples at risk for sickle cell anaemia accepted prenatal diagnosis in 10 pregnancies, as did both couples at risk for thalassaemia. Couples who were eligible for prenatal diagnosis but refused it tended not to have been informed about sickle cell disease before counselling, one partner was more frequently absent at the time of the initial counselling session, or they either had no children with sickle cell disease or the children were not severely affected. Other factors influencing their decision included a poor obstetric history and rejection of abortion, mainly on moral grounds. The approximately 50% uptake of prenatal diagnosis in this initial study highlights the complex issues involved. Our experience indicates that with systematic screening and counselling in the antenatal clinic, and with increased awareness of the haemoglobinopathies, couples at risk will be in a better position to make informed decisions.

Sickle cell disease in Britain.

Sickel cell disease is common in urban areas of Britain and it is estimated that in London alone there are nearly 2000 patients. One hundred and eighty four patients with sickle cell disease are known to the Central Middlesex Hospital, and 155 of those attend the sickle cell clinic regularly. The commonest cause for admission to hospital is acute painful or vaso-occlusive crisis, which accounts for 80% of all acute admissions; 12% of admissions are for acute chest syndrome. Comparison of clinical features in Brent and in Jamaica shows that the Brent patients with homozygous sickle cell anaemia are admitted with painful crises more frequently than Jamaican patients. However, the frequency of admissions for chest syndrome and priapism, and the incidence of splenomegaly are similar. Leg ulcers are uncommon in Brent. Patients with sickle cell haemoglobin C disease appeared more severely affected in Jamaica than in Brent. During the past two years 3165 newborn babies have been screened for sickle cell disease at the Central Middlesex Hospital: five babies with homozygous sickle cell anaemia and three babies with sickle cell haemoglobin C disease were detected. The overall incidence of sickle cell trait was 3.2% and of haemoglobin C trait 0.8%. A significant number of babies with sickle cell disease are born in London every year. It is essential that such babies are detected at birth and offered prophylaxis against pneumococcal infection, which is one of the major causes of infant mortality. Sickle cell disease is becoming an important blood disease in Britain and firm guidelines for the management of acute and chronic complications are required.

Screening cord blood for sickle haemoglobinopathies in Brent.

Between 1981 and 1983, 3165 consecutive specimens of cord blood were tested at the Central Middlesex Hospital for the presence of an abnormal haemoglobin: the incidence of sickle cell trait was 2.8%, of HbC trait 0.9%, and the overall incidence of an abnormal haemoglobin at birth was 6.9%. Five babies with homozygous sickle cell disease, three with HbSC, and three with either HbCC or HbC beta thalassaemia were detected. Twenty two per cent of the mothers were of Afro-Caribbean origin. The cost of the test was 30p. An H6000 blood count was carried out on 1000 consecutive cord blood samples. The mean red cell volume was 97.95 (SD 3.67) fl. Thirteen cord blood samples had a mean cell volume below 85 fl, and all contained Hb Barts. In addition, six samples with a mean cell volume between 86 and 92 fl also showed Hb Barts on electrophoresis. The overall incidence of Hb Barts was 2.1%. These results indicate that the incidence of HbSS and HbSC on neonatal screening in Brent is similar to that found in the urban areas of North America and that the number may be predicted from the number of births to mothers of Afro-Caribbean origin.