Screening For Sickle Cell Disorders Research Articles

Newborn screening for sickle cell disorders using tandem mass spectrometry: three years' experience of using a protocol to detect only the disease states.

Background Tandem mass spectrometry (MS/MS) has recently become an alternative method for the newborn screening of sickle cell disorders (SCD), as it is able to detect haemoglobin (Hb) peptides following digestion of bloodspots with trypsin. Using the SpOtOn Diagnostics Reagent Kit, we previously developed a screening protocol to detect only the disease states of SCD, using action values based on the ratio between the variant Hb peptide to wild-type peptide abundances for the HbS, C, DPunjab, OArab, E and Lepore peptides. Methods Action values using the ratios between the wild type HbA (ßT1-3) peptides and the foetal Hb (γT2) peptide were developed to identify bloodspot samples from premature and transfused infants. An evaluation was undertaken to assess the transferability of the action values onto an additional MS/MS instrument. We report here our experience using this MS/MS protocol. Results During a three-year period, we screened 100,456 babies and identified 10 SCD cases (1 HbS/HPFH, 5 HbS/S and 4 HbS/C) and a case of HbE/ß-thalassaemia that was identified as a by-product. The Hb variant to wild-type peptide ratio action values were transferable to a second MS/MS instrument. Our protocol prevented the identification of an estimated 810 carrier infants. Gestational age-related action values for HbA to HbF peptide ratios were required to minimize the number of samples referred for second-line testing to exclude ß-thalassaemia. Conclusion MS/MS is a robust alternative screening technology for SCD; in addition, it also optimizes the use of equipment and expertise that currently exist in newborn screening laboratories.

‘Who's the guy in the room?’ Involving fathers in antenatal care screening for sickle cell disorders

Fathers are increasingly invited to take part in antenatal care of which screening for sickle cell trait is a part. Expectations about involvement reflect changing perceptions of fatherhood and negotiation of gendered identities. Current policy supports male involvement, but is less clear on what basis and with what consequences. In exploring this, our qualitative study, using semi-structured interviews, presents the experiences of fathers who have recently undergone antenatal screening for sickle cell. The sample was generated in discussion with eight non-governmental organisations. We recruited 24 fathers from nine UK cities. Our analysis outlines the importance of ‘presence’, in which fathers rely on nurturing definitions of fatherhood to display their sense of responsibility. Fathers, however, struggled to find a meaningful role as traditional masculinities became juxtaposed with new and complex forms of gender organisation, creating the potential for estrangement. To conclude, screening policy makes an appeal to emergent masculinities. It also generates risks and compromises choice, due to the normative values implicit in the screening process, reinforced by the more controlling aspects of health surveillance. This creates confusion among fathers, who are not sure why they have been invited into the antenatal space.

Parents' responses to receiving sickle cell or cystic fibrosis carrier results for their child following newborn screening.

Universal newborn screening for sickle cell disorders and cystic fibrosis aims to enable the early identification and treatment of affected babies. Screening can also identify infants who are healthy carriers, with carrier results being the commonest outcome for parents and professionals to discuss in practice. However it is unclear what the effect will be on parents on being informed of their baby's carrier result. Semi-structured face-to-face interviews were conducted with a purposeful sample of 67 family members (49 mothers, 16 fathers, 2 grandparents) of 51 infants identified by universal newborn screening as carriers of cystic fibrosis (n=27) and sickle cell (n=24), across all health regions in England. Data were analysed by thematic analysis with subsequent respondent validation. Untoward anxiety or distress among parents appeared influenced by how results were conveyed, rather than the carrier result per se. Parents who had more prior awareness of carrier status or the possibility of a carrier result assimilated the information more readily. Being left in an information vacuum while awaiting results, or before seeing a professional, led some parents to fear that their child had a serious health condition. Parental distress and anxiety appeared mostly transient, subsiding with understanding of carrier status and communication with a professional. Parents regarded carrier results as valuable information and sought to share this with their families and to inform their children in the future. However parents needed greater support after communication of results in considering and accessing cascade testing, and negotiating further communication within their families.

Guidelines for screening, diagnosis and management of hemoglobinopathies.

The β-thalassemias and sickle cell disorders are a major health burden in India. Diagnosis and management of these disorders both in adults and in newborns using appropriate approaches and uniform technology are important in different regions of a vast and diverse country as India. In view of a National Thalassemia Control Program to be launched soon, a need was felt for guidelines on whom to screen, cost-effective technologies that are to be used as well as for establishing prenatal diagnosis programs in regional centers. Newborn screening for sickle cell disorders is in its infancy in India and uniform approaches need to be followed. Also, included are guidelines for monitoring and managing patients who are now growing older and need comprehensive care as well as management of complications of the disease.

Newborn screening for haemoglobinopathies by high performance liquid chromatography (HPLC): diagnostic utility of different approaches in resource-poor settings.

Sickle cell disease is a major health burden in India. The aim of the study was to compare the diagnostic utility of two different approaches on automated high performance liquid chromatography (HPLC) for newborn screening for sickle cell disorders and other haemoglobinopathies in India. Newborn babies of sickle heterozygous mothers were tested by HPLC using two different kits, the β-thal short kit, which is routinely used for screening for haemoglobinopathies in most laboratories, and the sickle cell short kit which is specific only for neonatal samples. Confirmation of the sickle and α genotypes was done by molecular analysis. Of the 601 babies tested, 276 were normal, 284 were sickle heterozygous and 41 were sickle homozygous using the β-thal short kit. Using the sickle cell short kit, a discrepancy was seen in one newborn sample where a normal baby was identified as a sickle heterozygous baby. α-Genotyping was done in 42 babies and 16 of them had α gene deletions. The presence of α thalassaemia could be suspected in 15 of these 16 babies based on a spike at the start of the chromatogram using the β-thal short kit. In comparison, using the sickle cell short kit the diagnosis of α thalassaemia was difficult based on the percentage of the FAST peak. Further, other rare α chain Hb variants were also missed. The β-thal short kit was more versatile than the sickle cell short kit for screening for haemoglobinopathies in newborns in our population.

First case of Hb Fontainebleau with sickle haemoglobin and other non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders

ObjectiveTo evaluate the significance of non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders.Methods1534 newborn babies were screened in the last 2 years for sickle...

Communication of carrier status information following universal newborn screening for sickle cell disorders and cystic fibrosis: qualitative study of experience and practice

To describe and explore current practice, methods and experience of communicating carrier status information following newborn screening for cystic fibrosis (CF) and sickle cell (SC) disorders, to inform practice and further research. Three linked qualitative studies. All nine health regions in England. Child health screening coordinators in all English health regions, health professionals communicating results to parents and parents of newborn carriers. A preliminary phase of semi-structured telephone interviews with child health screening coordinators in all nine English health regions, and thematic analysis of data; semi-structured face-to-face interviews with purposeful samples of 67 family members of 51 infants identified by universal newborn screening as carriers of CF or SC with data analysis by constant comparison; and semi-structured telephone interviews, and focus groups, with a key informant sample of 16 differing health professionals currently tasked with communicating results to parents in a range of ways, with thematic analysis of data. Methods for and respondents' experiences of communication of carrier results varied considerably within and between regions, and within and between SC and CF contexts. Approaches ranged from letter or telephone call alone, to in-person communication in the clinic or at home, with health professionals from haemoglobinopathy, CF, screening and genetics backgrounds, or from community and primary care, such as health visitors with SC carrier results. Health professionals identified pros and cons of different methods, preferring opportunity for face-to-face communication with parents where possible, particularly for CF carrier results. They were concerned by regional variations in protocols, the lack of availability of translated information on SC carrier results, and the feasibility of sustaining more 'specialist' involvement at current levels, particularly for SC carriers. Parents were often poorly prepared for the possibility of a newborn carrier result. Some had felt overloaded by screening information received during pregnancy or prior to newborn screening, or found this information failed to meet their needs. Opportunity for face-to-face communication of results was valued by parents of SC carriers and appeared particularly necessary for those without prior knowledge of SC carrier status or where English was not their first language. Indirect communication of results by letter appeared effective and feasible for parents more aware of SC carrier status from antenatal or earlier experience, and where this communication contained an unambiguous opening statement emphasising 'your child is not ill'. Face-to-face communication of CF carrier results by professionals with screening, CF or genetics backgrounds worked well for parents, but communication and information was crucially lacking at the earlier stage of repeat blood spot testing, creating considerable distress among half of respondents. Respondents had no particular preference for the type of health professional who communicated results to them, as long as they were well informed and could answer their queries. Parents regarded carrier results as valuable information gained fortuitously. Methods of communication of newborn carrier results vary considerably across England. Parents' needs for timely and appropriate information may not be met consistently or adequately. Respondents' experiences suggest a need for greater recognition of communication with individuals occurring across a screening pathway, rather than as a discrete event.

CARRIER DETECTION AND CLINICAL UNCERTAINTY: THE CASE FOR PUBLIC HEALTH ETHICS

In their response to our commentary, Ross and Clayton provide a clinical rationale for the disclosure of carrier status results generated incidentally through newborn screening for sickle cell disorders, suggesting that carriers are at increased risk for heat stroke in extreme conditions.1 A better case for nondisclosure, they argue, might be made for carrier status for cystic fibrosis, as there are no data to suggest that cystic fibrosis carriers bear health risks.1 We welcome the opportunity to respond. Our commentary was written in response to existing debates that assume the benign nature of carrier status. Guiding documents2–4 have not suggested a clinical rationale for disclosure. Instead, there is an apparent consensus that it is unethical to withhold carrier information. We argued that withholding data is not the only moral harm to consider. In fact, in the context of a public health intervention, without informed consent, routine disclosure actually involves a requirement that parents learn their infant's carrier status—an imperative that is itself morally troubling.5 While it is reasonable to consider the clinical implications of carrier status in this debate, in contrast to Ross and Clayton, we believe that the nature of the health risks from sickle cell carrier status strengthen the case for nondisclosure. This is because newborn screening is a public health intervention, where the burden of proof rests with those who sanction screening to demonstrate the value of early disease identification and to ensure that its benefits outweigh its harms. To disclose carrier status because of the clinical risks it identifies rather than as an incidental finding of no clinical significance evokes a clinical calculus. Yet carrier status cannot possibly meet the clinical standard for screening and disclosure. Moreover, guidance regarding the clinical significance of sickle cell carrier status is contradictory. In the United Kingdom, parents of sickle cell carrier infants are warned of the risks of general anesthesia and surgery6; in the United States, while other risks are identified, these specific harms are not.7 In the current era of genetic risk information, as we learn more and more about genetic variants that create disease susceptibilities in partial and complex ways, such uncertainty is to be expected. Cystic fibrosis carrier status may not prove to be an exception.8 In the context of clinical uncertainty, we hold firm to our conclusion that public health ethics, and not a clinical calculus, must guide population-wide newborn screening policy.

Current Practice for Imparting Carrier Status Detected by Newborn Screening for Sickle Cell Disorders and Cystic Fibrosis in England

Current Practice for Imparting Carrier Status Detected by Newborn Screening for Sickle Cell Disorders and Cystic Fibrosis in England

Red blood cell disorders in Rwandese neonates: screening for sickle cell disease and glucose-6-phosphate dehydrogenase deficiency

To determine the prevalence of haemoglobin (Hb) variants and glucose-6-phosphate dehydrogenase (G6PD) deficiency in Rwanda. During a two-month period in 2005, 987 cord blood samples were obtained in two hospitals in Kigali and Butare, Rwanda. Screening for sickle cell disorders, other Hb disorders, G6PD deficiency and other rare erythroenzymopathy deficiencies was done using isoelectric focusing techniques and quantitative kinetic assays, respectively. The prevalence of Hb S trait was 2.7% and that of G6PD deficiency was 3.8%. No neonate suffered from a sickle cell disease (homozygous for Hb S or compound heterozygous for Hb S), from another clinically significant haemoglobinopathy, or from pyruvate kinase or glucose phosphate isomerase deficiency. Sickle cell disorders should be considered a public health problem in Kigali and Butare. A systematic neonatal screening programme for those disorders, and to diagnose G6PD deficiency, seems reasonable, but local health priorities must be considered. Adapted management of hereditary sickle cell and G6PD disorders should be available.

Neonatal screening for sickle cell disorders in Ouagadougou, Burkina Faso: a pilot study

To determine the incidence of sickle cell disorders (SCDs) and the feasibility of a neonatal screening programme in Ouagadougou. During 2000, 2003 and 2004, 2341 cord blood samples obtained in five maternity hospitals in Ouagadougou were screened for SCDs using an isoelectric focusing technique. The feasibility of a neonatal screening programme was evaluated. The incidence of SCD was 1:57; 14 neonates were homozygous for haemoglobin (Hb)S and 27 were compound heterozygotes for HbSC. Thirty-two neonates were homozygous for HbC. The incidence of the HbC trait was 1:6; incidence of the HbS trait was 1:14. A centralized laboratory for neonatal screening of SCDs was established. SCDs should be considered a major public health problem in Ouagadougou. A neonatal screening programme should be implemented, but to be effective it requires strategies adapted to the local situation.

Disclosing to parents newborn carrier status identified by routine blood spot screening

Newborn blood spot screening programmes are designed to detect serious conditions affecting individuals, where early treatment can improve health. It is suggested that screening can improve the experience of diagnosis for parents. For example, without newborn screening, when a child with cystic fibrosis becomes symptomatic a period of uncertainty can arise prior to diagnosis. These potential advantages of screening need to be weighed against potential disadvantages of screening at individual and population levels. Some newborn screening programmes inadvertently identify newborn infants who, although not affected by the condition, carry a gene for it and can pass on that gene to their children; these are 'genetic carriers'. Knowledge of newborn carrier status can lead to: testing of parents and family members, and concern about possible affected future siblings should both parents be identified as carriers; the possibility of such testing revealing the putative father is not the biological father; concern about the child's future reproductive choices; and unjustified anxiety about the health of the carrier newborn. There is an urgent need to develop clear guidance as to how to respond, with advances in technology fuelling the expansion of newborn blood spot screening and raised expectations of informed consent and disclosing test results. Depending on the condition for which screening is offered, options include: employing tests that do not identify carrier status, if available; identifying acceptable ways of disclosing carrier status; or identifying acceptable ways of not disclosing carrier status. These options are illustrated by screening programmes for sickle cell disorders and cystic fibrosis. Currently, there are no screening tests available for sickle cell disorders that do not identify carrier status. For cystic fibrosis, the policy choice is between an extended period of testing, and a screening result that is available sooner for most newborns, but inadvertently identifies carrier babies. The aim of this review was to assess the impact of disclosing to parents newborn carrier status inadvertently identified by routine newborn blood spot screening. We searched for reports addressing disclosing newborn carrier status to parents following newborn screening for sickle cell disorders and cystic fibrosis in: commercially available electronic databases (October 2002), specialist registers, online journals, online abstracts and conference abstracts. We also scanned the reference lists of included papers. Studies addressing the impact of disclosing carrier status using a soundly controlled trial or randomised controlled trial. Two researchers independently scanned titles and abstracts for relevance using the pre-specified inclusion criteria. Full reports of selected citations were then located and screened again for relevance by two researchers independently. At each stage, results were compared and discrepancies resolved by discussion. We found no controlled trials about disclosing carrier status. There is a need to develop and evaluate the effects of interventions to support the disclosure of carrier status to parents following newborn screening.

Neonatal screening for sickle cell disorders.

Neonatal screening for sickle cell disorders.

Screening for sickle cell disorders: part 2

This second article in the series on screening for sickle cell disorders (SCDs) looks at midwife educational needs, and whether they are equipped to deal with clients with SCDs. Their awareness and understanding of SCD may be influenced by misconception and ignorance surrounding ethnic minority needs. The need for equity of care, including the importance of trained genetic counsellors is also addressed. The lack of such specialised services outside of larger inner cities is proof of inequality of service for the population in need outside these areas. The summary of findings concludes that midwives’ overall knowledge of SCD is poor and this ultimately affects their understanding of screening protocols, and the issues surrounding ethnicity.

Screening for sickle cell disorders: part 1

The purpose of this article is to explore the issues surrounding sickle cell disorders (SCDs) and how they affect antenatal and neonatal screening. The literature reviewed examined several aspects which influenced care including, whether current midwifery services are meeting client need, and if the screening policies in place are adequate in today’s multicultural climate. In part one, the findings of the author suggest that SCDs are generally very poorly understood by midwives working outside large city areas. Inexposure to a multicultural setting, and misconceptions on race and ethnicity, are some of the areas identified that result in lack of awareness and possible racial bias within the maternity arena.

The feasibility of using ethnicity as a primary tool for antenatal selective screening for sickle cell disorders: pointers from the research evidence

The Department of Health has announced a linked antenatal and neonatal screening programme for haemoglobinopathies by 2004 in a comprehensive national plan for the National Health Service in Britain. In response the National Screening Committee has commenced development work on how such a programme can best be implemented, including investigation of the effectiveness of a question about ethnic origin as a basis for selection. In addition, two recent health technology assessment reports have assessed alternative options for antenatal and neonatal haemoglobinopathy screening programmes in the United Kingdom. Both reports and commentators have emphasised the importance of developing a standardised instrument for collecting ethnicity data and recommended early development of such work. An examination of the evidence base on the use of ethnicity as a primary screening tool reveals substantial variability in practice and in the quality of data collected, with risk group misclassification as high as 20% against a recommended target of under 5.5%. The literature on the conceptual basis and structure of ethnicity questions, method of assignment in data collection, and level of resolution on categorisation is reviewed to identify the most appropriate content and format of a screening question for the haemoglobinopathies. Question options are evaluated, including the use of an extended 2001 Census classification and a ‘non-North European’ identifier and a candidate question based on ‘family origins’ is offered for debate. Finally, issues relating to the testing of the efficiency of an ethnicity question and the operationalising of its use for antenatal sickle cell screening are discussed.

The effects of neonatal screening for sickle cell disorders on lifetime treatment costs and early deaths avoided: a modelling approach.

The aim of the study was to calculate the cost to the UK National Health Service of providing treatment services for patients with sickle cell disorders. The rates of differential morbidity and mortality, in the first 10 years of life, between screen-detected early diagnosed and clinically presenting late diagnosed cohorts of sickle cell disorder patients are also estimated. A cost model was developed, based on predictions of survival and the incidence of sickle cell disorder-related events. Direct data from the NHS are lacking, so data were incorporated from disparate sources. Patients with sickle cell disorders were divided into two categories: those with sickle cell anaemia and those with sickle HbC disease. Differentiating between sickle cell anaemia and sickle HbC disorder patients, the results show that the undiscounted (discounted at 6 per cent) lifetime treatment costs range from pound sterling 92323 (pound sterling 24917) to pound sterling 185614 (pound sterling 53861). The number of early deaths avoided per 100 births, as a result of early diagnosis through screening, ranges from 0.57 to 1.25. The resulting estimates may act as a guide to those involved in the planning of health care provision with regard to the resources required to treat sickle cell disorder patients. Such information may also be incorporated into the evaluation of both antenatal and neonatal screening programmes for sickle cell disorders.

Audit of process of antenatal screening for sickle cell disorders at a north London hospital

Antenatal screening for haemoglobin disorders (sickle cell disorders and thalassaemias) is now routine.1 Couples who are at risk have a strong preference for prenatal diagnosis during the first trimester,2 but...

Neonatal screening for sickle cell disorders: what about the carrier infants?

<h3>Summary points</h3> Neonatal screening for sickle cell disorders detects between 17 and 100 carrier infants for each child detected as having sickle cell disorder Information on neonatal carrier status is an unavoidable outcome of the neonatal screening process Withholding information from parents is not justified Further research is needed to evaluate the benefits and risks of this information and the effectiveness of different policies for follow up This is relevant to future developments in molecular genetics, which may place health