Allison Streetly

Significant haemoglobinopathies: guidelines for screening and diagnosis

Antenatal screening/testing of pregnant women should be carried out according to the guidelines of the NHS Sickle Cell and Thalassaemia Screening programme. Newborn screening and, when necessary, follow up testing and referral, should be carried out according to the guidelines of the NHS Sickle Cell and Thalassaemia Screening programme. All babies under 1 year of age arriving in the UK should be offered screening for sickle cell disease. Preoperative screening for sickle cell disease should be carried out in patients from ethnic groups in which there is a significant prevalence of the condition. Emergency screening with sickle solubility tests must always be followed by definitive analysis. Laboratories performing antenatal screening should utilize methods capable of detecting significant variants and be capable of quantitating haemoglobins A 2 and F at the cut-off points required by the national antenatal screening programme. The laboratory must ensure a provisional report is available within three working days from sample receipt.

Implementation of universal newborn bloodspot screening for sickle cell disease and other clinically significant haemoglobinopathies in England : screening results for 2005-7

Early results from the National Health Service Sickle Cell and Thalassaemia Screening programme covering the whole of England are reported following the implementation of the national newborn blood-spot screening programme. Of the 13 laboratories performing screening, 10 chose high-performance liquid chromatography as the first screen, with isoelectric focusing as the second confirmatory test. Screening results for April 2005 to March 2007 are presented and include data from all the laboratories screening newborns in England, and almost 1.2 million infants. The screen-positive results show a national birth prevalence of almost 1 in 2000. The birth prevalence in London is five times that of most of the rest of the country. Over 17 000 carriers have been identified. Approximately seven per 1000 samples are reported as post-transfusion with wide ethnic category variation. Given the prevalence of the conditions, and coverage by ethnicity, 3–4 screen-positive cases could be missed each year. National implementation of newborn screening in England has increased the number of children identified with sickle cell disease, in many areas almost doubling the workload. Underascertainment of the condition has allowed a downplaying of the scale of need. It may also have contributed to infant mortality rates in urban areas as babies died without a diagnosis or treatment. The value of a co-ordinated national approach to policy development and implementation is emphasised by the English experience. The programme provides a model for Europe as well as other countries with significant minority populations, such as Canada. Potentially it also offers important lessons for Africa where the World Health Organization is supporting the introduction of newborn screening.

Positive screening and carrier results for the England-wide universal newborn sickle cell screening programme by ethnicity and area for 2005–07

Aims The overall aim of the new national newborn programme is to identify infants at risk of sickle cell disease to allow early detection and to minimise deaths and complications. Methods Universal screening for sickle cell disease was introduced in England between September 2003 and July 2006. The 13 newborn laboratories each screen between 25 000 and 110 000 babies a year using the existing dried bloodspot cards. The specified conditions to be screened for include sickle cell anaemia (Hb SS), Hb SC disease, Hb S/β thalassaemia, Hb S/DPunjab and Hb S/OArab. Data are reported on screening results by ethnic group and geographical area. Results The prevalence of screen positive results across England is 1:2000. There is a 25-fold variation by geographical area. African babies make up 61% of all screen positive results despite representing only 4% of total births. Combined carrier rates vary widely by ethnicity, from 1.85 per 1000 (1:540) in ‘White British’ to 145 per 1000 (1:7) in ‘African’ babies. Refusal rates for screening show variation by ethnicity. Conclusions These results provide useful information both about the frequency of these conditions and the carrier state and their geographic and ethnic distribution across England. This can be used to refine counselling information and are also useful to target and plan services and public information.

Implementation of the newborn screening programme for sickle cell disease in England: results for 2003-2005.

Objectives This paper reports early screening results from the newborn sickle cell disease screening programme recently implemented in England. Setting England. Screening is offered at 5-8 days of age as part of the existing bloodspot test and offered to all babies irrespective of ethnicity. Methods The laboratory methods recommended are high performance liquid chromatography (HPLC) and iso-electric focusing (IEF). 15 Two methods of analysis must be applied to all screen positive results. The conditions screened for are:- Sickle cell anaemia (Hb SS), Hb SC disease, Hb S/β-thalassaemia, Hb S/DPunjab, Hb S/OArab, Hb S/HPFH. Carriers identified for the common haemoglobin variants are reported to parents and follow-up counselling is offered. A bespoke laboratory quality assurance programme has been established which has defined standards of satifactory performance. Results Provisional figures from the first seven months of screening (up to March 2004) 108,255 infants were screened gave a screen positive rate of 1:900 for these high prevalence areas and a carrier rate of 2.7%. Figures for 2004-2005 show about 250 significant screen positive results for sickle cell disorders and about 6,500 carriers were identified. The birth prevalence for screen positive results from 2004-05 is 1:1500. We estimate that when there is countrywide data, the national birth prevalence will be about 1:2000-1:2,500. Conclusion The results from the national newborn sickle cell screening programme in England - show that the sickle cell disorders are as common as cystic fibrosis (CF) in England, although the distribution of cases is concentrated in London and other urban areas. The findings and approach to implementation adopted in England may be of interest to other Western European countries with increasing rates of sickle cell disease who are considering such programmes and also to other developed countries.

Lessons from thalassaemia screening in Iran

Screening programmes must consider societal values

Variation in coverage by ethnic group of neonatal (Guthrie) screening programme in south London

Abstract Objectives : To determine whether coverage of the neonatal (Guthrie) screening programme in Britain is different for groups at highest risk of sickle cell disease and to identify possible reasons for incomplete coverage. Design : Descriptive study of coverage of screening programme and its variation by mobility, district of residence, and ethnic group. Subjects - 1727 infants born between 1 October and 31 December 1991. Setting-Former West Lambeth and Camberwell District Health Authorities, London. Main outcome measure : Proportion of infants with an identifiable screening test result. Results : Screening covered 1663/1727 (96.3%) infants overall (745/786 (94.8%) in West Lambeth; 918/941 (97.6%) in Camberwell). The relative odds ratio of an African infant not having been tested compared with a white infant was 3.05 (95% confidence interval 1.30 to 7.14) (2.08 (0.86 to 5.01) after adjustment for mobility and district of residence). For infants whose families moved into the districts after the birth compared with those born and resident in the districts the relative odds ratio of having been tested was 10.16 (4.85 to 21.29). The odds ratio of locally delivered infants in West Lambeth not having been tested compared with those in Camberwell was 2.12 (1.08 to 4.16) after adjustment for ethnic group. Conclusion : Coverage of the screening programme is incomplete and poorer in infants of African ethnic group than in white infants. Poorer coverage is also associated with mobility of the family around the time of birth. The findings have implications for using the neonatal programme for testing for sickle cell disease and other disorders. Arrangements for monitoring the existing screening programme are inadequate and an improved system should be established, similar to the scheme that monitors the immunisation programme.

A national screening policy for sickle cell disease and thalassaemia major for the United Kingdom. Questions are left after two evidence based reports.

Sickle cell disease and thalassaemia major are serious health problems for inner city populations in Britain, but services are inconsistent and policy guidance is unclear1–4 The NHS Health Technology Assessment Programme commissioned two systematic reviews to identify the objectives of the screening programmes and to determine whether, and in which populations, screening using haematological tests should be either selective or universal. The decision on who to screen in areas where not everyone is tested is based on questions to identify ethnic origin. The two reports provide similar estimates for the burden of disease. One estimated that each year 28–60 fetuses are conceived and 17 infants are born with thalassaemia and that 133–238 fetuses are conceived and 160 infants are born with sickle cell disease in England.5 The other report gave estimates for the United Kingdom of 44 and 171 respectively for conceptions.6 Both reports show that the population at risk has an uneven geographical distribution. For this reason, selective rather than …

Coordinated neonatal screening programme for haemoglobin disorders is needed.

EDITOR—Modell et als audit of prenatal diagnosis for haemoglobin disorders shows the lack of a public health approach to the issue in the United Kingdom.1 Firstly, numbers of affected births for sickle cell disease in the United Kingdom are not reported and, in fact, are not known. This reflects the lack of a coordinated neonatal screening programme (despite good evidence of the effectiveness of neonatal screening in reducing mortality) and of adequate data …

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.

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.