Newborn screening for sickle cell disease: Effect on mortality

Department of Hematology/Oncology, Children's Hospital, Oakland, CA 94609.
Pediatrics (Impact Factor: 5.47). 07/1988; 81(6):749-55.
Source: PubMed


Newborn screening for sickle cell disease has been recommended as a method of decreasing patient mortality. However, its effectiveness in accomplishing this has not been reliably measured. To help determine the effectiveness, 10 years of experience in newborn screening have been summarized. The effects of early patient enrollment in a comprehensive treatment program on long-term morbidity and mortality are reported. From 1975 to 1985, 84,663 newborns were screened regardless of race or ethnic background. Bart's hemoglobin was present in 5%, hemoglobin AS in 2.6%, and hemoglobin AC in 0.75%. Excluding Bart's, approximately 3.6% of all newborns were carriers for hemoglobinopathy. Sickle cell disease occurred in 1:951 births (58 hemoglobin SS, 25 hemoglobin FSC, three hemoglobin S-beta +-thalassemia, and three hemoglobin S-beta O-thalassemia). In addition, one in every 4,233 newborns had a clinically significant thalassemia syndrome (eight hemoglobin FE, ten hemoglobin F only, two hemoglobin H). Compared with other newborn screening programs in California, (congenital hypothyroidism, 1:3,849; phenylketonuria 1:22,474, galactosemia 1:74,103), hemoglobinopathies are the most prevalent congenital disease. Eighty-one newborns with sickle cell disease were followed for 7.2 years. Patients experienced 513 hospitalizations, including 13 episodes of sepsis with or without meningitis and ten acute sequestration crises. The overall mortality rate for patients with sickle cell anemia diagnosed in the newborn period was 1.8%. In comparison, the clinical course of 64 patients with sickle cell anemia diagnosed after 3 months of age and followed for an average of 9.4 years was analyzed. Five of these patients died. In two of these, sickle cell anemia was diagnosed at the time of the death.(ABSTRACT TRUNCATED AT 250 WORDS)

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    • "Newborn screening (NBS) coupled with early prophylactic penicillin, immunizations, comprehensive care, and parental education has been shown to significantly reduce SCD morbidity and mortality [5], [6]. The main objectives of NBS for haemoglobinopathies are 1.Detection and treatment of neonates affected with SCD and 2. Detection of carriers and provision of genetic counseling to their families. "
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    ABSTRACT: Hemoglobinopathies are highly prevalent diseases and impose a public health burden. Early diagnosis and treatment can ameliorate the course of these diseases and improve survival. Despite purported high incidence of hemoglobinopathies in Lebanon, there are no nationwide screening programs. In this study, newborn screening utilizing high pressure liquid chromatography was executed in all public hospitals across Lebanon between 2010 and 2013. All newborns with an abnormal hemoglobin (Hb) were offered genetic counseling and all those with disease were enrolled in comprehensive hemoglobinopathy clinics. Among newborns, 2.1% were found to have an abnormal Hb variant with sickle Hb being the most common while 0.1% were found to have sickle cell disease (SCD). The majority of those with SCD had non-Lebanese origins. The most common causes of hospitalizations in infants with SCD were acute splenic sequestration and pain crises. No bacteremia or other life threatening infections were noted. At a median follow up 14 months (follow up range 7 to 34 months), all children with disease are alive and compliant with treatment. Systematic screening for SCD and other Hb variants was shown to be feasible, cost effective, and of accurate predictive value. This program was also clinically effective because it led to the identification of babies with disease and to providing them with free early multidisciplinary care. Conclusively, a newborn screening program should be implemented across Lebanon to detect hemoglobinopathies and initiate early therapeutic and preventive strategies and genetic counseling.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "The Recommended Uniform Screening Panel (RUSP) promulgated by the US Department of Health and Human Services includes S,S disease (sickle-cell disease), S,Beta-thalassemia, and S,C disease. Because early detection can lead to effective medical treatment [3] [4], screening for hemoglobinopathies is a routine component of newborn screening laboratories [5] including North America, the United Kingdom [6], Europe [7], India, Brazil, and parts of the Caribbean. Commonly used methodologies for hemoglobin (Hb) analysis in dried-blood spots (DBS) include isoelectric focusing gels (IEF) [8] [9] [10] and high-performance liquid chromatography with detection by UV (HPLC–UV) [6] [8] [11]. "
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    ABSTRACT: Hemoglobinopathies are mutations resulting in abnormal globin chain structure; some have clinically significant outcomes such as anemia or reduced lifespan. Five β-globinmutations are (c.20A>T, p.E6V), (c.19G>A, p. E6K),(c.79G>A, p.E26K),(c.364G>C, p.E121Q), and(c.364G>A, p.E121K), resulting in HbS (sickle-cell hemoglobin), HbC, HbE,HbD-Los Angeles, and HbO-Arab, respectively. One α-globin mutation is (c.[207C>G or 207C>A], p.N68K), resulting in HbG-Philadelphia. HPLC-ESI-MS/MS analysis of dried-blood spot (DBS) punches from newborns extracted with a trypsin-containing solution provides greater than 90% coverage of α-, β-, and γ-globinamino acid sequences. Because the(c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), (c.364G>A, p.E121K), and (c.[207C>G or 207C>A], p.N68K)mutations generate globinpeptides with novel amino acid sequences, detecting one of these peptides in DBS extracts is indicative of the presence of ahemoglobinopathy in the newborn. The method described here can distinguish normal β-globin peptides from the mutant HbS,HbC, HbE,HbD-Los AngelesandHbO-Arab peptides, as well as normal α-globin peptide from the mutant HbG-Philadelphia peptide, allowing the identification of unaffected heterozygotes such as HbAS, and of compound heterozygotes such as HbASG-Philadelphia. This HPLC-ESI-MS/MS analytical approach provides informationthat is not available from traditional hemoglobin analyses such as isoelectric focusing and HPLC-UV. It is also capable of determining the amino acid sequence of hemoglobinpeptides, potentially allowing the detection of numerous hemoglobinopathiesresulting from point mutations.
    Full-text · Article · Jun 2013 · Clinica chimica acta; international journal of clinical chemistry
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    • "It is estimated that at least 1.6 million immigrants from different populations at risk for sickle cell disease (SCD) are living in the Netherlands and that *10% are carriers of hemoglobinopathy (Heijboer et al., 2001; Giordano et al., 2004). It is known that early identification and treatment of children with SCD result in a decrease in morbidity and mortality (Gaston et al., 1986; Vichinsky et al., 1988). Therefore, in 2007 SCD was included in the NBS program for all newborns, regardless of ethnicity. "
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    ABSTRACT: In 2007, the neonatal screening program in the Netherlands was expanded to include hemoglobinopathies. Newborns with sickle cell disease (SCD), as well as SCD carriers are identified. The benefit of reporting SCD carriers includes detection of more couples at risk (both parents are carriers) who can be informed about future reproductive choices, a responsibility of their general practitioner (GP). We evaluated knowledge, ideas, and actions of GPs after reporting SCD carriers and explored and analyzed potential barriers. A questionnaire study. A total of 139 GPs responded to our questionnaire (49%). Ninety GPs (90%) stated they informed parents of the test result. In only 23 cases (23%) both parents had themselves tested for hemoglobinopathies. Eighty-one GPs (64%) stated that they did not have enough clinical experience with SCD. Almost half of the GPs indicated that they did not experience any barriers in counseling patients (n=60, 48%). At the moment, the goal of the neonatal screening for SCD carriers has not been achieved as the majority of parents were not tested for hemoglobinopathies after disclosure of carrier status in their newborn. With GPs reporting few barriers in counseling parents and only indicating a lack of knowledge and clinical experience, more effort is required to provide better information to GPs to help facilitate their work.
    Full-text · Article · May 2011 · Genetic Testing and Molecular Biomarkers
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