Screening Program For Hemoglobinopathies Research Articles

Premarital hemoglobinopathy screening program results of a province in the Black Sea region of Turkey: three years’ experience

ABSTRACT Objectives Hemoglobinopathies are a global public health problem with high mortality and morbidity and very expensive treatment. Disease can be reduced and prevented with hemoglobinopathy screening tests. It is possible to identify carriers with the hemoglobinopathy screening program applied in many countries of the world and in Turkey. This study aims to evaluate the results of the national premarital hemoglobinopathy screening program carried out in primary healthcare institutions. Methods The research is of epidemiological and cross-sectional type. Electrophoresis results examined within the scope of the premarital hemoglobinopathy screening program in Samsun between 1 January 2019 and 31 December 2021 were evaluated retrospectively. Age, gender, year of screening, and hemoglobinopathy screening results were obtained from the records. In the statistical analysis of the data, p < 0.05 was accepted. Results The median age of 52,338 people screened under the hemoglobinopathy screening program was 29.0 (16.0–86.0) years. About 54.1% (n = 28,309) of those who were screened were female, and it was found that the least screening was done in 2020 (n = 15,765 (30.1%)). As a result of the screening, the frequency of the β-thalassemia (β-thal) trait was 1.37% (n = 676), the frequency of the abnormal HbS was 0.04% (n = 20). The frequency of β-thal trait was statistically significantly higher in 2020 (1.5%) compared to other years (p = 0.029). When the results were analyzed by gender, the rate of women with abnormal HbS (3.7%) was significantly higher than the others (p = 0.017). Conclusions This study presents the results of the national hemoglobinopathy screening program in Northern Turkey and the β-thal and the abnormal HbS rates were found to be low. The data obtained will be useful in monitoring hemoglobinopathy disorders and evaluating the current program’s effectiveness in the future. It will allow decision-makers to implement policy changes and prioritize new programs.

A Novel System for Newborn Screening of Thalassemia and Hemoglobinopathies Using Capillary Electrophoresis Is Superior Than Isoelectric Focusing

Introduction:Thalassemia (thal) and hemoglobinopathies (Hb variants) is highly prevalent in Thailand and nearly all Southeast Asian countries. In developed countries such as US and European countries, a newborn screening program for thal and hemoglobinopathies (NBS-Hb) has been incorporated in a routine healthcare to detect those with abnormal Hb in particular Hb S (Sickle cell disease) to provide early intervention for affected patients. Application of detecting patients and carriers could be useful for many developing countries such as Thailand as a part of our prevention and control program at a national level. At presence, isoelectric focusing (IEF) is a widely used platform for NBS-Hb, however a new capillary electrophoresis (CE) has recently been developed. It is of interest to evaluate whether which system provides a better efficiency under a circumstance with various types of thal and Hb variants.Objectives:To evaluate whether IEF or CE, is more effective for Hb screening at neonatal period and to develop new diagnostic criterion for different types of Hb variants in ThailandMethods:After informed consent by parent, the dried blood spot (DBS) samples were collected by heel prick puncture from 2-day old babies and processed in two Hb screening methods; IEF & ISOSCAN RESOLVE® SYSTEM Neonatal Hemoglobin Kits (Perkin Elmer, Turku, Finland) and Capillarys 2 NEONAT FAST® (SEBIA, Évry, France). These DBS were also extracted gDNA used for gold standard molecular method covering >98% of common globin mutations found in Thailand; 7-deletional α-thal GAP-PCR, 6-non-deletional α-thal ARMS-PCR, 16 mutations of β-thal ARMS-PCR, PCR-RFLP by Mnl I restriction cleavage for Hb E disorder and/or DNA sequencing. The statistics analysis was performed by PASW 18 Software (SPSS Inc, 2015) to analyze the detection efficiency of IEF vs. CE. Cut-off levels of Hb variants were also determined by using receiver operating characteristic (ROC) curve to set up diagnostic criterion.Results: The study recruited 1,213 healthy newborns (48.4% male and 51.6% female) with average 38 weeks of gestational age (GA). The profiles of IEF pattern and CE histogram were analyzed. Hb E was the most common Hb variants of β-globin gene found and Hb Bart's (γ4) was indicative of α-thal, both were confirmed by molecular methods. Comparison between the efficiency of IEF vs. CE on detecting Hb variants showed a higher efficiency of CE on Hb Bart's detection for most α-thal carriers and on Hb E detection in Hb E trait than those of IEF for sensitivity, specificity, and accuracy as shown in Table 1. There was no difference between two platforms on Hb H disease, homozygous Hb E and β-thal/Hb E. In order to set up cut-off levels of Hb Bart's, Hb E and Hb A for each globin genotypes by ROC curve analysis, the cut-off levels provided from CE seemed to be more clear and discriminative than those of IEF as shown in Table 2. The cut-off levels of Hb Bart's of ≥7.40%, ≥0.75%, ≥0.45%, and ≥0.10% were suggested different α-globin abnormalities; Hb H, αº-, non-deletional and deletional α+-thal carrier, respectively. Detection of Hb E of ≥0.25%, ≥4.85%, and ≥0.95% were suggestive of Hb E carrier, Hb E homozygote, and β-thal/Hb E, respectively. Interestingly, we can screen for β-thal carriers using a lower Hb A level (≤10.35%) and Hb A/Hb F ratio (≤0.115). This data was analyzed from 11 β-thal carrier newborns confirmed by DNA testing compared to 148 GA-sex matched newborn controls with normal β-globin genotype. These cut-off levels based on CE were powerful on detecting thal diseases (Hb H and β-thal/Hb E) and carriers of Hb E, αº- and non-deletional α+-thal. However, our screening criterions still have a limitation on fully detecting deletional α+-thal and β-thal traits.Conclusions:Our data suggested that neonatal CE platform is more effective system for Hb screening with excellent efficiency and precision to detect Hb variants compared to conventional IEF. Using NBS-Hb by CE could successfully screen for all important thal carriers in one simple test. Implementing our NBS-Hb to the national level would be simplest way to generate a national registry that can be linked to our national health database of severe diseases and carriers. By applying this approach into a national scale might be the only measure to effectively control the health burden of thal and hemoglobinopathies in Thailand where provides high prevalence of defective globin genes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Immigration and screening programs for hemoglobinopathies in Italy, Spain and Turkey.

Sickle cell disease (SCD) and thalassemias are the most common monogenic diseases in the world. The number of migrants and refugees in Europe and Turkey, in the past decade, has increased dramatically due to war, violence or prosecutions in their homeland. Prevention and management of haemoglobin disorders is well established and managed in countries where these conditions were traditionally endemic or in countries that have a longstanding tradition of receiving migrants. Therefore, preventive and diagnostic programmes regarding hemoglobinopathies in immigrant populations have been implemented. The purpose of this paper it to report a summary of the experience gained in Italy, Spain and Turkey in migrants, asylum seekers and refugees. (www.actabiomedica.it)

Two years of premarital screening program for hemoglobinopathies in Karbala, Iraq; Outcome and options for improving the program.

Background: Thalassemia and sickle cell disease are common autosomal recessive disorders and are the most widespread single gene disorder that considered important public health problems. Premarital screening is important step in prevention of hemoglobinopathies. Aim: to evaluate the outcome of 2 years of the premarital screening program in Karbala and options to improve that program. Methods: A descriptive cross-sectional study by assessment of 2 years of premarital screening in Karbala Blood Disease Center started from January 2019 till December 2020. Total number of individuals screened for hemoglobinopathies in that period was 1306 (653 couples) referred from five marital clinics, Complete blood count was done for all screened couples. Results: The bulk number of tested individuals was in 2019 because of the corona pandemic, nearly half of those couples were relatives, the majority was referred from Al-Husseini hospital, about 5% of these marriages were contraindicated to be accomplished and 3 % were cautious. β-Thalassemia minor was the main type of abnormal hemoglobinopathies discovered. Conclusion: Some risky marriages were prevented by doing the premarital screening but still we need other concerted efforts to improve the outcome of the program.

Clinical Utility of Confirmatory Genetic Testing to Differentiate Sickle Cell Trait from Sickle-β+-Thalassemia by Newborn Screening.

Hemoglobin separation techniques are the most commonly used laboratory methods in newborn screening and confirmatory testing programs for hemoglobinopathies. However, such protein-based testing cannot accurately detect several hemoglobinopathies in newborns, especially when β-thalassemia mutations are involved. Here, we describe a consecutive cohort of newborns who were identified by newborn screening to have a likely diagnosis of sickle-β+-thalassemia (having an “FSA” pattern) who were determined to have sickle cell traits by confirmatory and genetic testing. We illustrate the clinical utility of genetic testing to make a correct and timely diagnosis in the setting of newborn screening for hemoglobinopathies.

HBB: c.316-125A>G and HBB: c.316-42delC: Phenotypic Evaluations of Two Rare Changes in the Second Intron of the HBB Gene

We report two very rare changes in the second intron of the HBB gene, a substitution at nucleotide (nt) 726 [IVS-II-726 (A>G) (β+), NM_000518, HBB: c.316-125A>G] and a deletion of a cytosine at nt 809 [IVS-II-809 (–C) (β), NM_000518, HBB: c.316-42delC] identified during the screening program for hemoglobinopathies in the resident Sicilian population. The purpose of this study was to evaluate the clinical implication of these rare changes, particularly in coinheritance with known mutations in the globin clusters, in order to conduct an appropriate genetic counseling for at-risk couples. Molecular analysis detected the first rare nt substitution in two cases in simple heterozygosity and in two cases in association with other known mutations on globin genes, while the deletion was identified in a pregnant woman, carrier of β-thal, and in her fetus at prenatal diagnosis (PND) for hemoglobinopathies. The present study emphasizes the importance of sharing the observed changes in the globin gene cluster, especially in the case of new or rare undefined mutations, in order to facilitate the determination of their phenotypic expression and possible interactions with known molecular defects.

Utility of screening golf ball inclusions in hemoglobin H disease and its clinico-hematological profile

BACKGROUND: In India, hemoglobinopathy screening programs focus on reducing the burden of beta-thalassemia by screening the antenatal females and young adolescents. Although alpha (α)-thalassemia is common in the Mediterranean countries, alpha (α)-thalassemia screening and diagnosis are performed in a few centers in India. HbH disease is an uncommon clinical phenotype of α-thalassemia with variable clinical presentation. The hallmark feature of HbH is the presence of golf ball inclusions in the red cells demonstrated with supravital staining. PATIENTS AND METHODS: Here, we discuss an algorithmic approach to screen hemograms for thalassemic indices, followed by evaluation of reticulocyte preparation after 40 minutes (supravital stain preparation for golf ball inclusions). If golf ball inclusions were positive, Hb analysis on Hb-capillary zone electrophoresis (Hb-CZE)was done. RESULTS: We received 28,000 samples for complete hemogram and blood film examination, over a period of 8 months. Reticulocyte count was required in 11,600 samples out of which 13 cases were positive for golf ball inclusions. Of these, nine were identified as HbH disease on Hb-CZE. These patients presented with pallor and generalized weakness. On examination, jaundice (3/9 patients) and hepatosplenomegaly (4/9 patients) were relatively uncommon. The majority of them (6/9) required infrequent blood transfusions. All patients had microcytic hypochromic red cell indices with median HbA of 89% (range: 68.1%–96.9%), HbA2 of 1.4% (range: 0.8%–1.7%), and fast-moving band in zone 15 (HbH) of 5.6% (range: 1.4%–30.3%) on Hb-CZE. CONCLUSION: We emphasize a systematic screening of hemograms and peripheral smears along with a simple and cost-effective screening test for golf ball inclusions to diagnose HbH disease that often poses a clinical dilemma due to its variable clinical presentation.

Hemoglobin variants identified in the Uganda Sickle Surveillance Study

AbstractThe Uganda Sickle Surveillance Study analyzed dried blood spots that were collected from almost 100 000 infants and young children from all 10 regions and 112 districts in the Republic of Uganda, with the primary objective of determining the prevalence of sickle cell trait and disease. An overall prevalence of 13.3% sickle cell trait and 0.7% sickle cell disease was recently reported. The isoelectric focusing electrophoresis technique coincidentally revealed numerous hemoglobin (Hb) variants (defined as an electrophoresis band that was not Hb A, Hb F, Hb S, or Hb C) with an overall country-wide prevalence of 0.5%, but with considerable geographic variability, being highest in the northwest regions and districts. To elucidate these Hb variants, the original isoelectric focusing (IEF) gels were reviewed to identify and locate the variant samples; corresponding dried blood spots were retrieved for further testing. Subsequent DNA-based investigation of 5 predominant isoelectric focusing patterns identified 2 α-globin variants (Hb Stanleyville II, Asn78Lys; Hb G-Pest, Asp74Asn), 1 β-globin variant (Hb O-Arab, Glu121Lys), and 2 fusion globin variants (Hb P-Nilotic, β31-δ50; Hb Kenya, Aγ81Leu-β86Ala). Compound heterozygotes containing an Hb variant plus Hb S were also identified, including both Hb S/O-Arab and HbS/Kenya. Regional differences in the types and prevalence of these hemoglobin variants likely reflect tribal ancestries and migration patterns. Algorithms are proposed to characterize these Hb variants, which will be helpful for emerging neonatal hemoglobinopathy screening programs that are under way in sub-Saharan Africa.

A comprehensive screening program for β-thalassemia and other hemoglobinopathies in the Hooghly District of West Bengal, India, dealing with 21 137 cases

We here present a report of population screening programs (January 2012–December 2015) conducted by the Thalassemia Control Unit, Imambara Sadar Hospital, Chinsurah, Hooghly in the Hooghly District of West Bengal, India for prevention of thalassemia. We screened β-thalassemia (β-thal) heterozygotes and homozygotes, and Hb E (HBB: c.79G > A)-β-thal compound heterozygotes. Among 21 137 cases, we found 1968 heterozygotes and 192 homozygotes or compound heterozygotes. Results were evaluated with standard hematological analyses including red cell indices, hemoglobin (Hb) typing and quantification. The participants of the screening program were divided into six groups (children, pre-marriage cases, post-marital cases, family members of affected individuals, family members of carriers and pregnant women). While considering the average frequency of carriers, many reports recorded both related individuals (family members of trait and affected individuals) as well as unrelated individuals such as school children and pregnant women. These would have to be considered separately and only the unrelated individuals taken to estimate carrier frequencies in this article that would give more realistic data on carrier frequency of unrelated individuals.

Report on Ten Years’ Experience of Premarital Hemoglobinopathy Screening at a Center in Antalya, Southern Turkey

Thalassemia and hemoglobinopathies are a major public health problem in Turkey. Hemoglobinopathy prevention programs (HPPs) were started in 33 provinces situated in Thrace, Marmara, Aegean, Mediterranean and South Eastern regions of Turkey in 2003. A premarital hemoglobinopathy test is mandatory and free of charge in this program. According to the Ministry of Health reports, 46 first level hemoglobinopathy diagnostic centers were established for premarital tests. Within the last 10 years, approximately 79.0% of married individuals per year were screened by the centers. While the percentage of premarital screening tests was 30.0% of all couples in 2003, it reached 86.0% in 2013. The number of newborn with thalassemia and hemoglobinopathies were 272 in 2002 and dropped to 25 in 2013. There has been a 90.0% reduction in affected births. Our hemoglobinopathy diagnostic center was established in 2003 and licensed by the Ministry of Health in 2004. We studied a total of 89,981 blood samples from premarital tests for 10 years and the incidence of β- and α-thalassemia (β- and α-thal) trait was found to be 6.57 and 3.56%, respectively. The distribution of the most common abnormal hemoglobins (Hbs) was: Hb S (HBB: c.20A > T) (0.31%), Hb D-Los Angeles (HBB: c.364G > C) (0.15%), Hb G-Coushatta (HBB: c.68A > C) (0.06%) and Hb E (HBB: c.79G > A) (0.02%). A total of 60 couples, both carrying β-thal trait, were directed to the prenatal diagnosis (PND) center in 10 years. The premarital hemoglobinopathy screening program is running successfully at our center and other centers in Turkey.

The Problem of Borderline Hemoglobin A2 Levels in the Screening for β-Thalassemia Carriers in Sardinia

Background: The increase in HbA2 is the most important parameter for the identification of thalassemia carriers. However, in routine screening for hemoglobinopathies, some cases are difficult to classify because the level of HbA2 is not typically elevated. In this work, we report the results of a molecular investigation on a cohort of subjects with borderline HbA2. Methods: All subjects with a β-thalassemia carrier partner and a borderline percentage level of HbA2 were investigated for the presence of a pathological mutation in the β-globin gene. All negative subjects were screened for both the KLF1 mutation and the presence of ααα/ or αααα/ alleles. The subjects with reduced MCV and/or MCH were also screened for deletional and nondeletional α-globin gene defects. Results: Various β-globin mutations and KLF1 gene defects are the most common genetic determinants responsible for this phenotype in our population. Conclusion: KLF1 mutations are important in a screening program for hemoglobinopathies. An increase in HbF in association with borderline HbA2 levels is a useful but not exclusive marker that suggests the investigation of this gene. On the basis of our findings, we are able to suggest the molecular procedure to use in a population characterized by a high prevalence of thalassemia carriers.

The Prevalence of Hemoglobinopathies in Young Adolescents in the Province of Muğla in Turkey: Results of a Screening Program

Thalassemia is an autosomal recessive inherited blood disorder. It is prevalent in Mediterranean countries such as Sardinia, Greece, Cyprus, Turkey, Lebanon and also Southeast Asia. Our aim was to investigate the carrier prevalence of thalassemia and other hemoglobinopathies in adolescents who live in Muğla Province, Turkey. We analyzed retrospectively the surveys conducted at primary schools between 1997 and 2013. Complete blood count (CBC) and high performance liquid chromatography (HPLC) were used to screen for thalassemia and hemoglobinopathies. Patients were diagnosed as having thalassemia trait if the mean corpuscular volume (MCV) was ≤80.0 fL, mean corpuscular hemoglobin (Hb) was ≤27.0 pg and Hb A2 levels were ≥3.5%. A total of 164 814 students were analyzed. The median age of the students was 13.5 years (minimum 13.0, maximum 14.0). The total number of students with abnormal HPLC results was 5861 (3.8%). There was a significant decrease in the newborn of new thalassemia patients found with screening programs for hemoglobinopathies in Muğla Province from 1997 to 2013. The number of students with abnormal HPLC results for thalassemia, sickle cell disease and other Hb traits were 3.2, 0.15 and 0.4%, respectively. It is important to recognize that including Hb, MCV, red blood cell (RBC) count and HPLC tests for carrier screening are necessary to find hemoglobinopathies. Our study supported that the number of new patients significantly decreased using these screening programs from 1997 to 2013.

Neonatal screening program for hemoglobinopathies in the city of São Carlos, state of São Paulo, Brazil: analysis of a series of cases

ObjectiveTo analyze the neonatal screening program for hemoglobinopathies in São Carlos, Southeast Brazil, by investigating a series of cases in which the screening test was abnormal. More specifically, it was aimed to know the information regarding the neonatal screening received by mothers at the hospital and at primary health care, in addition to information related to genetic counseling. MethodsA descriptive study that enrolled 119 mothers, accounting for 73% of all children born between 2010 and 2011 with abnormal results of neonatal screening for hemoglobinopathies. The mothers completed a questionnaire that assessed the information received at hospital and primary health care, and issues related to genetic counseling. Descriptive statistics was performed. ResultsOf the 119 participating mothers, 69 (58%) had children with sickle cell trait, 22 (18.5%) with hemoglobin C trait, 18 (15.1%) with alpha thalassemia trait and, in 10 cases (8.4%), the result was inconclusive. At the hospital, 118 mothers (99.2%) received information about where to go to collect the test and 115 (96.6%) were informed about the correct time to collect the test. Only 4 mothers (3.4%) were informed about which diseases are investigated and the risks of not performing the screening. Seventeen mothers (14.3%) recognized the difference between trait and disease, and 42 (35.3%) considered that a positive screening test could have implications for future pregnancies. In 70 cases (58.8%), the child's physician was not informed about the screening test results. ConclusionsThe neonatal screening program needs further improvement. In both scenarios investigated, health professionals demonstrated a lack of training in providing information to mothers and families.

Triagem neonatal de hemoglobinopatias no município de São Carlos, São Paulo, Brasil: análise de uma série de casos

ObjectiveTo analyze the neonatal screening program for hemoglobinopathies in Sao Carlos, Sotheast Brazil, by investigating a series of cases which the screening test was abnormal. More specifically, it was aimed to know the information regarding the neonatal screening received by mothers at hospital and at primary health care, in addition to information related to genetic counseling. MethodsA descriptive study that enrolled 119 mothers, accounting for 73% of all children born between 2010 and 2011 with abnormal results of neonatal screening for hemoglobinopathies. The mothers completed a questionnaire that assessed the information received at hospital and primary health care, and issues related to genetic counseling. Descriptive statistics was performed. ResultsAmong the 119 participating mothers, 69 (58%) had children with sickle cell trait, 22 (18.5%) with hemoglobin C trait, 18 (15.1%) with alpha thalassemia trait and, in 10 cases (8.4%), the result was inconclusive. At hospital, 118 mothers (99.2%) received information about where to go to collect the test and 115 (96.6%) were oriented about the correct time to collect the test. Only 4 mothers (3.4%) were informed about which diseases are investigated and the risks of not performing the screening. Seventeen mothers (14.3%) recognized the difference between trait and disease, and 42 (35.3%) considered that a positive screening test could have implications for future pregnancies. In 70 cases (58.8%), the child physician was not informed about the screening test results. ConclusionsThe neonatal screening program need further improvement. In both scenarios investigated, health professionals demonstrated a lack of training in guiding mothers and families.

National neonatal screening program for hemoglobinopathies: how far have we advanced?

Thanks to the efforts of Dr. Robert Guthrie at the beginning of the sixties, neonatal screening has become a true diagnostic tool for diseases that, if not detected early, can result in important complications to the health of the child.1 Today, neonatal screening represents one of the main advances in the prevention of pediatric diseases, and is based on diagnosing pathologies that are relatively frequent and severe, that can be detected by methods that are simple, efficient and adaptable to large-scale application, and that can be treated to substantially modify the course of the disease.2 In Brazil, neonatal screening was first initiated by professor Benjamin Schmidt in 1976, but for a long time, there was no investment in or commitment to the treatment and followup of screened children.3,4 After 2001, the Ministry of Health, through the Bill #822/GM, instituted the National Neonatal Screening Program (NNSP)5 in the public healthcare system, incorporating the principles of neonatal screening: universal access to early diagnosis, and intervention in the disease with the use of therapies and interdisciplinary care, mandating a hierarchy of responsibilities and competencies at the federal, state and municipal levels. Sickle cell disease and other hemoglobinopathies were included in the NNSP,5 allowing the adoption of prophylactic measures and complete treatment of children with these diseases before the development of clinical complications, thereby having an impact on morbidity and mortality.6–12 Screening should be considered a public health service with universal access and monitoring of screened individuals.

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BackgroundIn 2001, the Brazilian Ministry of Health added hemoglobinopathies to the National Neonatal Screening Program to be implemented in three steps. In order to meet the proposed goals, it is crucial to establish periodic assessments of this program with the aim of monitoring its implementation.ObjectiveTo assess the scope and the efficiency of the stages of the National Newborn Screening Program in identifying hemoglobin S.MethodsA cross-sectional study was developed with the results of the heel prick test using the high performance liquid chromatography method for babies born in Mato Grosso do Sul from 2006 to 2010. The following variables were investigated: year, number of live births, total screening, coverage ratio, prevalence, time between the child birth and the blood collection; age at diagnosis; age at the time of the first consultation; and time between the diagnosis and the first appointment.ResultsOver the five years of the study, the mean coverage rate was 91.77%. The prevalences of hemoglobin FAS and hemoglobin FS were 1.65% and 0.011%, respectively. Blood samples from 43.48% of children were collected from the second to the seventh day. The age at diagnosis was within the first 28 days in 87.80% of the screened children. The lowest mean indices for the first consultation and the time between the diagnosis and the first appointment (58.8 and 46.4 days, respectively) occurred in 2010.ConclusionsThe scope of the National Neonatal Screening Program for hemoglobinopathies is good, with a large number of individuals being tested. Efficiency is a suitable indicator to assess the program steps. Three points are recommended: the training of the individuals involved, studies to assess the assistance provided to the affected child, and genetic counseling to the mothers.© 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. All rights reserved.

Newborn screening program for hemoglobinopathies in Rio de Janeiro, Brazil

Newborn screening for hemoglobinopathy in Brazil has been decentralized until 2001 when the Health Ministry of Brazil established the National Newborn Hemoglobinopathy Screening Program. The State of Rio de Janeiro started a program in collaboration with the State Health Department and the Institute of Hematology in Rio (HEMORIO). The goal of this study was to evaluate the effectiveness of the first 10 years of the Newborn Hemoglobinopathy Screening Program in identifying and managing infants with Sickle cell disease (SCD) in the State of Rio de Janeiro. Blood samples from 1,217,833 neonates were analyzed by High Performance Liquid Chromatography. Infants with SCD were enrolled in comprehensive treatment programs. Data showed that 4.87% of the newborns were heterozygous for a hemoglobin variant, 0.08% were homozygous or doubly heterozygous for abnormal hemoglobins and 95.02% had normal hemoglobin. All the 912 newborns with SCD were referred for treatment at HEMORIO, 34 (3.7%) of these died due to acute chest syndrome, sepsis or splenic sequestration. Four more children died of unknown causes. The implementation of the Rio de Janeiro Newborn Screening Program gradually increased the area of the State covered by the program. Data collected during the 10 years of the program showed reduction in mortality of patients with SCD in comparison to available historical statistical data before the implementation of the national screening program. This 10-year study showed that early diagnosis and treatment of newborns was associated with improved survival and quality of life of Brazilian children with SCD.

Prenatal and newborn screening for hemoglobinopathies

The hemoglobinopathies encompass a heterogeneous group of disorders associated with mutations in both the alpha-globin and beta-globin genes. Increased immigration of high-risk populations has prompted the implementation of prenatal and newborn screening programs for hemoglobinopathies across Europe and North America. In Canada, the UK, and other European countries, prenatal screening to identify hemoglobinopathy carriers and offer prenatal diagnostic testing to couples at risk is linked to newborn screening, while in the United States, it is still not universally performed. The structure of screening programs, whether prenatal or postnatal, universal or selective, varies greatly among these countries and within the United States. The laboratory methods used to identify hemoglobinopathies are based on the prevalence of hemoglobinopathies within the population and the type of screening performed. Advances in molecular testing have facilitated the diagnosis of complex thalassemias and sickling disorders observed in ethnically diverse populations. This review summarizes the current approaches and methods used for carrier detection, prenatal diagnosis, and newborn screening.

Hemoglobin Fontainebleau [a21(B2)Ala&gt;Pro]: The second report from India

Structural hemoglobin (Hb) variants are mainly due to point mutations in the globin genes resulting in single amino acid substitutions. Until date, about 200 alpha chain variants have been identified and they are usually detected during the hemoglobinopathy screening programs. Under a community control program for hemoglobinopathies, which involved screening of antenatal cases followed by prenatal diagnosis if indicated. Here, we report a rare alpha globin gene variant Hb Fontainebleau [a21(B2)Ala>Pro] detected in the heterozygous condition in a 35-year-old pregnant lady screened during this program. This is the second report of this alpha globin variant from India. Unlike the earlier case from India where Hb Fontainebleau was reported in a neonate who was also a carrier of Hb Sickle and had no clinical problems, this case presented with a bad obstetric history associated with the secondary infertility. However, the presence of the variant and the obstetric complications may be unrelated.

Effectiveness of preoperative screening for sickle cell disease in a population with a newborn screening program: a cohort study

Published clinical practice guidelines recommend that all patients from ethnic groups with a high prevalence of sickle cell disease (SCD) undergo preoperative screening for this hemoglobinopathy. Newborn Screening Ontario initiated a universal sickle hemoglobinopathy screening program in 2006 as part of its regional newborn screening program. The primary objective of this study was to determine the effectiveness of selective preoperative screening for SCD based on at-risk ethnicity in Ontario, a region that has a universal newborn sickle hemoglobinopathy screening program. The hematology laboratory database at our hospital was searched to identify all children who underwent preoperative sickle cell screening in the 42-month period starting in November 2006 (when the newborn sickle hemoglobinopathy screening program was introduced) and ending in April 2010. Medical records of all children testing positive on hemoglobin analysis were reviewed to determine perioperative outcomes. Our search strategy identified 710 children who were born after the introduction of newborn screening and who underwent preoperative screening. Thirty-five of these children had abnormal sickle solubility tests - one (0.14%) was a new diagnosis (not identified by newborn screening), one had been diagnosed previously, and 33 (4.65%) were identified as having sickle cell trait. Sixty children had more than one preoperative screening test performed (range, 2-4). Six of the 35 children with abnormal sickle solubility results underwent repeated testing. Preoperative screening based on at-risk ethnicity alone is an ineffective method of identifying additional children with SCD in Ontario, a population with universal newborn sickle hemoglobinopathy screening. In an effort to avoid unnecessary repeat testing, we propose an algorithm to help physicians decide whether to initiate preoperative sickle cell screening for children.