Newborn Screening For Sickle Cell Disease Research Articles

MALDI-MS in first-line screening of newborns for sickle cell disease: results from a prospective study in comparison to HPLC.

Newborn screening (NBS) for sickle cell disease (SCD) requires a robust, high-throughput method to detect hemoglobin S (HbS). Screening for SCD is performed by qualitative methods, such as isoelectric focusing (IEF), and both qualitative and quantitative methods such as high performance liquid chromatography (HPLC), capillary electrophoresis (CE), and tandem mass spectrometry (MS/MS). All these methods detect HbS, as well as low-level or absent HbA, and also other variants of hemoglobin. HPLC is considered as a reference method for NBS, because of its high sensitivity and specificity in detecting HbS. NeoSickle®, a fully automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platform, combined with automated sample processing, a laboratory information management system and NeoSickle® software for automatic data interpretation, has increased the throughput of SCD testing. The purpose of this study was to compare the performances of NeoSickle® and HPLC. A prospective study was conducted including 9,571 samples from the NBS program to compare MALDI-MS using NeoSickle® with an HPLC method. Correlation between the two methods was studied. For the MALDI-MS method, sensitivity, specificity, NPV, and PPV were calculated. We found over 99.4 % correlation between the HPLC and MALDI-MS results. NeoSickle® showed 100 % of sensitivity and specificity in detecting SCD syndrome, leading to positive and negative predictive values of 100 %. NeoSickle® is adapted to NBS for SCD, and can be used in first-line high-throughput screening to detect HbS, and beta-thalassemia major warning. When HbS is detected, second-line use of another specific method as HPLC is necessary.

National Long-Term Follow-up of Children with Sickle Cell Disease Diagnosed By Newborn Screening in the Netherlands: Overview of the Morbidity and Mortality

Background: Sickle cell disease (SCD) is a genetic red blood cell disorder associated with increased morbidity and mortality. Newborn screening for SCD was introduced in January 2007 in the Netherlands to enable early diagnosis and initiation of preventive measures. The objective of this study was to assess the effect of newborn screening on the morbidity and mortality of children living with SCD in the Netherlands, 16 years after its implementation. Methods: In this national cohort study all children with SCD diagnosed by newborn screening were included. Patients were followed between 1 January 2007 and 31 March 2023 until end of follow-up, death or successful stem cell transplantation. Following informed consent, data were collected from medical files on SCD genotype, treatment, mortality and development of SCD-related complications. The incidence rate of SCD-complications was presented as lifetime-event per 100 person-years for the total duration of follow-up and for the age categories: 0-4, 5-11, and 12-16 years. Results: In total, 391 out of 540 eligible patients (72%) with SCD were included in all hospitals with patients with SCD under treatment, accounting for 3047 person-years. The mean age at the end of follow-up was 7.8 years (SD±4.5). The majority of patients had SCD genotype HbSS (58%), followed by HbSC (28%). As for the mortality, five patients died during follow-up, primarily at or below the age of 2 years (4/5, 80%). In three patients, the cause of death was related to SCD, including infection (n=2; aged 1.2 and 2.0 years) and acute splenic sequestration (n=1; 2.0 years). The SCD-related complications are presented in Table 1. The most common SCD complication in this cohort was vaso-occlusive crisis (including dactylitis) with hospitalization. SCD-related complications that mainly developed within the first 4 years of life, were vaso-occlusive crisis, acute hemolytic crisis, aplastic crisis, severe infections, splenic sequestration and ischemic cerebral infarction. Acute chest syndrome occurred equally in all age categories. Other SCD-related complications developed to a lesser extent in our cohort, and at a later age in adolescence or adulthood. Conclusion: In this cohort of neonatally screened children with SCD, a substantial number of SCD-complications occurred in the first 4 years of life. This study underlines the importance of parental education and 24/7 availably, high level acute specialized clinical care for these children from birth on. Further analysis to identify risk factors at young age for a severe phenotype will be conducted, to enable more targeted interventions in a timely manner. Hopefully, this will lead to reduction of disease burden, improving the quality of life in children living with SCD in the Netherlands.

High Throughput Newborn Screening for Sickle Cell Disease - Application of Two-Tiered Testing with a qPCR-Based Primary screen.

Sickle cell disease (SCD) is a group of hemoglobinopathies with a common point mutation causing the production of sickle cell hemoglobin (HbS). In high-throughput newborn screening (NBS) for SCD, a two-step procedure is suitable, in which qPCR first pre-selects relevant samples that are differentiated by a second method. Three NBS centers using qPCR-based primary screening for SCD performed a laboratory comparison. Methods using tandem MS or HPLC were used for differentiation. In a benchmarking test, 450 dried blood samples were analyzed. Samples containing HbS were detected as reliably by qPCR as by methods established for hemoglobinopathy testing. In a two-step screening approach, the 2nd-tier-analyses have to distinguish the carrier status from pathological variants. In nine months of regular screening, a total of 353,219 samples were analyzed using two-stage NBS procedures. The 1st-tier screening by qPCR reduced the number of samples for subsequent differentiation by>99.5%. Cases with carrier status or other variants were identified as inconspicuous while 78 cases with SCD were revealed. The derived incidence of 1:4,773, is in good agreement with previously published incidences. In high-throughput NBS for SCD, qPCR is suitable to focus 2nd-tier analyses on samples containing HbS, while being unaffected by factors such as prematurity or transfusions. The substantial reduction of samples numbers positively impacts resource conservation, sustainability, and cost-effectiveness. No false negative cases came to attention.

Potential for a large-scale newborn screening strategy for sickle cell disease in Mali: A comparative diagnostic performance study of two rapid diagnostic tests (SickleScan® and HemotypeSC®) on cord blood.

Sickle cell disease (SCD) is a life-threatening disease requiring reliable early diagnosis. We assessed the acceptability and diagnostic performances of two rapid diagnostic tests (RDTs) to identify SCD (HbSS, HbSC, HbS/β-thalassaemia) or SCD carrier (HbS/HbC) in a pilot SCD newborn screening (NBS) strategy in Mali. All consenting delivering women were offered SCD NBS using cord blood sampling on two RDTs (SickleScan® and HemotypeSC®) compared to the high-performance liquid chromatography (HPLC) gold standard to detect SCD states. From April 2021 to August 2021, 4333 delivering women were eligible of whom 96.1% were offered NBS: 1.6% refused, 13.8% delivered before consenting and 84.6% consented; 3648 newborns were diagnosed by HPLC; 1.64% had SCD (0.63% HbSS, 0.85% HbSC, 0.16 HbS/β-plus-thalassaemia); 21.79% were SCD carrier. To detect accurately SCD, SickleScan® had a sensitivity of 81.67% (95% confidence interval [CI]: 71.88-91.46) and a negative predictive value (NPV) of 99.69% (95% CI: 99.51-99.87); HemotypeSC® had a sensitivity of 78.33% (95% CI: 67.91-88.76) and a NPV of 99.64% (95% CI: 99.44-99.83). To detect SCD carrier: SickleScan® sensitivity was 96.10% (95% CI: 94.75-97.45) and NPV, 98.90% (95% CI: 98.51-99.29); HemotypeSC® sensitivity was 95.22% (95% CI: 93.74-96.70) and NPV, 98.66% (95% CI: 98.24-99.03). Routine SCD NBS was acceptable. Compared with HPLC, both RDTs had reliable diagnostic performances to exclude SCD-free newborns and to identify SCD carriers to be further confirmed. This strategy could be implemented in large-scale NBS programmes.

Sickle Cell Disease Newborn Screening—An Audit of a Twin Island State Pilot Program

The prevalence of Sickle Cell Disease (SCD) within the Caribbean region remains second only to that of West Africa. The Newborn Screening (NBS) Program in Antigua and Barbuda remains heavily dependent on grants, therefore ultimately facing sustainability challenges. Early intervention and implementation of preventative measures post-NBS result in significant improvements in morbidity, quality of life, and survival. This audit reviewed the pilot SCD NBS Program in Antigua and Barbuda from September 2020 to December 2021. A conclusive result was received by 99% of babies eligible for screening, 84.3% of which were HbFA, whilst 9.6% and 4.6% were HbFAS and HbFAC, respectively. This was comparable to other Caribbean countries. Sickle Cell Disease was noted in 0.5% of babies screened, which translates to 1 in 222 live births. Eighty-two percent of mothers were aware of their sickle cell status, compared to 3% of fathers. The importance of instituting a quality improvement team post the initiation of a screening program and the need for a robust public education program have been demonstrated by this audit.

Long-Term Follow-up of Dutch Patients with Sickle Cell Disease Diagnosed By Newborn Screening - Effect on the Morbidity and Mortality in the Netherlands

Background: Sickle cell disease (SCD) is associated with increased morbidity and mortality compared to the general population. To enable early preventive measures to improve clinical outcome, newborn screening for SCD was introduced in January 2007 in the Netherlands. The objective of this study is to assess the residual risk of death and the incidence of major disease-related complications during the first fifteen years of life in children diagnosed with SCD by newborn screening. Methods: In this prospective, national multicenter cohort study, all children born after 1 January 2007 and diagnosed with SCD by newborn screening were included. Following informed consent, data were collected from medical files on SCD genotype, treatment, mortality and occurrence of major disease-related complications including hospitalization for vaso-occlusive crises (VOC), severe infections (sepsis, meningitis, osteomyelitis) and neurological complications. Overall survival and survival without specific SCD-related complications were analyzed by Kaplan-Meier curves. Results: Preliminary data of 197 (38%) of the 520 eligible subjects from 8 centers in the Netherlands, with a total follow-up of 1,585 patient-years are presented. The median age on July 1st 2022 was 8.0 years (IQR range: 4.0 - 11.0 years). The majority of children (55%) had severe SCD (genotypes HbSS or HbSβ0 thalassemia), the remainder had another genotype including HbSC or HbSβ+ thalassemia. Survival at the age of 15 years was 99.5%. One patient died at the age of 1 year due to pneumococcal sepsis. Eight patients (4%) had a severe infection (meningitis, sepsis, osteomyelitis) caused by Streptococcus Pneumoniae in 3/8 cases with 1 fatal outcome as described above. Two patients experienced a symptomatic cerebral infarction at the age of 11 months and 1.5 years, respectively. Both patients had comorbidities, increasing the risk of a cerebral infarction. The mean survival time without admission for VOC was 7.3 years (95% CI: 6.2-8.5) for HbSS/HbSβ0 thalassemia and 11.5 years (95% CI: 10.1-12.8) for HbSC/HbSβ+ thalassemia, respectively (p < 0.001) (Figure 1). Conclusion: In this Dutch cohort of neonatally screened patients with SCD, infectious complications were the main cause of severe comorbidity and mortality. Further analysis to identify risk factors for infectious complications will be performed in the final analyses to target additional preventive measures that may lower the risk of infection in this specific group of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P-062: MATRIX COMPARISON OF HEMOTYPESC AND SICKLESCAN POINT-OF-CARE DIAGNOSTICS FOR EARLY DIAGNOSIS OF SICKLE CELL DISEASE IN RURAL SUB-SAHARAN AFRICA

Purpose: In sub-Saharan Africa, universal sickle cell disease-newborn screening (SCD-NBS) programs are nonexistent due to high costs associated with conventional laboratory technologies, competing for national healthcare priorities, and budgetary constraints. However, the recent emergence of lateral-flow immunoassay microtechnology point-of-care tests (POCT) such the SickleSCAN™ and HemoTypeSC™ present exciting opportunities to change the status quo and potentially revolutionize healthcare for children as best practice for early diagnosis of SCD. Materials and methods: We perform a matrix comparison of diagnostic accuracy in field conditions for the SickleSCAN™ and HemoTypeSC™ tests. We assessed the performance characteristics of SickleSCAN™ and HemoTypeSC™ by evaluating children with positive Emmel test for HbSS, HbSC, and HbAS; and children, including newborns, without known coagulopathy in a rural district in Sierra Leone. Results: A total of seventy-four (33 females/41 males) children from three participating community health centers were analyzed by both methods. The ages ranged from twenty-four hours old to seventeen years old. HemoTypeSC™ and SickleSCAN™ correctly identified hemoglobinopathy phenotypes in 26 children with positive Emmel test as follows: twenty HbSS and four HbAS. Two positive Emmel test results (HbAS) were identified as HbAC and HbAA by the two tests indicating that the two tests have excellent sensitivity and specificity for the identification of the HbS pattern, consistent with SCD. Of the 74 samples that had two SCD POCT scores, there was no discordant result between the HemoTypeSC™ and the SickleSCAN™. Results for both tests were as follows: HbAA 36 (46.8%), HbAS 17 (22.1%), HbSC 1 (1.3%), and HbSS (26.0%). No newborns were identified with sickle cell disease (HbSS). The two tests identified seven newborns with sickle cell trait (HbAS). Twenty-one newborns had the normal HbAA genotype. Overall, HemoTypeSC™ and SickleSCAN™ exhibited sensitivity and specificity of 100% and 100% respectively for all possible phenotypes (HbAA, HbAS, and HbSS) detected. Conclusion: The HemoTypeSC and SickleSCAN tests demonstrated 100% concordance for identifying homozygote healthy people, sickle cell trait, and disease patients in this study. Our matrix comparison study highlighted the potential use of POCTs as both first?tier and second-tier screening and confirmation tests when presumptive SCD or trait is indicated. This is an acceptable practice for SCD screening as the current consensus is to use the same method on the same sample if no second?tier screening method is available and to confirm the screening result with a second method on a second sample to make a diagnosis. We, therefore, conclude that POCTs are suitable for population and newborn screening for the HbS phenotype in limited-resource settings where the disease burden is greatest and conventional laboratory methods are nonexistent. The authors do not declare any conflict of interest

Clinical features at diagnosis of sickle cell disease prior to universal newborn screening in Alberta.

Sickle cell disease (SCD) is an inherited multisystem disorder with complications starting in the first year of life. Newborn screening (NBS) can identify infants with SCD and is associated with decreased morbidity and mortality. Variation in availability of NBS in Canada, and lack of standardized screening for immigrant children, may lead to delayed diagnosis. This was a retrospective cohort study of 126 children aged 0-18 years with SCD registered with the SCD clinic at the Alberta Children's Hospital between January 2003 and January 2018, prior to province-wide universal NBS for SCD. Patient demographic information, circumstances of diagnosis, and other contextual information were collected from patient health records. Descriptive statistics were used to summarize data, with Mood's median test used to compare medians between groups. Forty-three (35%) patients were born in Alberta. Patients were mostly (95.3%) of African descent. Of patients born in Alberta, 63% (26/43) were diagnosed at >12 months of age, with a median age at diagnosis of 18 months (IQR = 4-39). This was significantly older (P < 0.001) than children born in the USA or in Canadian provinces with SCD NBS programs, where the median age at diagnosis was zero months (N = 36). Of the 42% of patients born outside North America, 64% were diagnosed following an acute complication. This study highlights the importance of NBS for early detection and management of SCD, and the importance of screening at-risk immigrants who may not have received NBS for SCD.

P1502: LONG-TERM FOLLOW-UP OF DUTCH PATIENTS WITH SICKLE CELL DISEASE DIAGNOSED BY NEONATAL SCREENING – EFFECT ON THE MORBIDITY AND MORTALITY IN THE NETHERLANDS.

Background: Sickle cell disease (SCD) is associated with increased morbidity and mortality compared to the general population. To initiate early preventive measures, newborn screening for SCD has been introduced in January 2007 in the Netherlands. Aims: The objective of this study is to assess the effectiveness of this neonatal screening for SCD by describing the residual risks of death and major disease-related events during the first fourteen years of life in children diagnosed with SCD at birth in the Netherlands. Methods: Here we report the first data of the largest center (Amsterdam UMC) of this prospective, national multicenter cohort study. Following informed consent, data were collected from medical files of all children diagnosed by neonatal screening. Descriptive data on SCD genotype and occurrence of major disease-related events are presented, including hospitalization for vaso-occlusive crisis (VOC), acute chest syndrome, severe infections and neurological complications. Overall survival and survival without specific SCD-related complications were analyzed by Kaplan-Meier curves. Results: Up until now, 98 (56%) out of 174 eligible subjects from this institution were included, with a total follow-up of 805 patient-years. The majority (55%) had the severe genotype (HbSS/ beta0-thalassemia), the remainder had genotypes HbSC or HbS/beta+-thalassemia. Survival by the age of 14 was 98.9%, with 1 death at the age of 1 years due to sepsis, most likely related to SCD. Seven patients (7.1%) had a severe infection (meningitis, sepsis, osteomyelitis) caused by Streptococcus Pneumoniae in 3/7 cases. Antibiotic prophylaxis was prescribed for all 7 patients before they reached the age of 1 year, and 6/7 patients had been fully vaccinated with the 23 valent pneumococcal vaccine. Two patients experienced a symptomatic cerebral infarction at the age of 11 months and 1.5 years, respectively. At the age of 10 years the survival without hospitalization for vaso-occlusive crisis was 27% (95% CI: 12.7 – 43.14%) and 51% (25.3 – 72.0%) for the SS/Sβ0 and SC/Sβ+ genotype, respectively. Image:Summary/Conclusion: In this cohort of neonatally screened patients with SCD, the SCD-related mortality and morbidity is still impressive with 1% mortality, 7 severe infections, and 2 patients with a CVA. A final analysis of the effect of neonatal screening for SCD will follow after completion of data collection in all participating centers in the Netherlands.

Factors Associated with Acceptability of Newborn Screening for Sickle Cell Disease in Lubumbashi City, Democratic Republic of the Congo

Objective: Sickle cell disease (SCD) is a major genetic disease that occurs early in childhood and can cause considerable morbidity and even death. Newborn screening (NBS) is one of the effective health services that have lowered the burden of SCD in wealthy countries. Surprisingly, NBS programs are essentially non-existent in subSaharan Africa, where the majority of babies are born with this condition. The objective of this study was to determine the level of acceptability of NBS and the factors influencing it in the population of Lubumbashi city in the Democratic Republic of the Congo. Material and Methods: From December 1, 2020, to December 31, 2020, data on sociodemographic characteristics, knowledge, and attitudes related to NBS for SCD were collected from 2032 adults in Lubumbashi city using a semi-structured and pre-tested questionnaire. Results: There was a good knowledge of SCD as a hereditary blood disorder (77.7%). NBS’s acceptability rate was 84.5%. Age (P = 0.002), sex (P = 0.025), and religion (p&lt;0.001) were found to be significantly associated with the NBS acceptability. Conclusion: According to the findings of this study, NBS is widely accepted in Lubumbashi. The primary challenges to its adoption are likely to be financial and practical rather than social or cultural.

Clinical Utility of the Addition of Molecular Genetic Testing to Newborn Screening for Sickle Cell Anemia.

Sickle cell disease (SCD) is a group of related yet genetically complex hemoglobinopathies. Universal newborn screening (NBS) for SCD is performed in the United States and many other nations. Classical, protein-based laboratory methods are often adequate for the diagnosis of SCD but have specific limitations in the context of NBS. A particular challenge is the differentiation of sickle cell anemia (SCA) from the benign condition, compound heterozygosity for HbS and gene-deletion hereditary persistence of fetal hemoglobin (HbS/HPFH). We describe a sequential cohort of 44 newborns identified over 4.5 years who had molecular genetic testing incorporated into NBS for presumed SCA (an “FS” pattern). The final diagnosis was something other than SCA in six newborns (12%). Three (7%) had HbS/HPFH. All had a final, correct diagnosis at the time of their first scheduled clinic visit in our center (median 8 weeks of age). None received initial counseling for an incorrect diagnosis. In summary, genetic testing as a component of NBS for SCD is necessary to provide correct genetic counseling and education for all newborns' families at their first visit to a sickle cell center. Genetic testing also permits the use of early, pre-symptomatic hydroxyurea therapy by preventing infants with HbS/HPFH from receiving unnecessary therapy. We argue that genetic testing should be incorporated into contemporary NBS for SCD.

Community based screening for sickle haemoglobin among pregnant women in Benue State, Nigeria: I-Care-to-Know, a Healthy Beginning Initiative

BackgroundHaemoglobin genotype screening at prenatal care offers women an opportunity to be aware of their genotype, receive education on sickle cell disease (SCD) and may increase maternal demand for SCD newborn screening. In developed countries, most pregnant women who access prenatal care and deliver at the hospital receive haemoglobin genotype screening. In settings with low prenatal care attendance and low hospital deliveries, community-based screening may provide similar opportunity for pregnant women. We assessed the feasibility and acceptability of integrating haemoglobin genotype screening into an existing community-based HIV program.MethodsOnsite community-based integrated testing for HIV, hepatitis B virus and haemoglobin electrophoresis, were conducted for pregnant women and their male partners. Community Health Advisors implementing the NIH and PEPFAR-supported Healthy Beginning Initiative (HBI) program provided education on SCD, collected blood sample for haemoglobin electrophoresis and provided test results to participants enrolled into the HBI program. We concurrently conducted a cross-sectional study using a pretested, semi-structured, interviewer administered questionnaire to collect demographic data and assess awareness of individual haemoglobin “genotype” among HBI pregnant women participants.ResultsIn this study, 99.9% (10,167/10,168) of pregnant women who received education on SCD accepted and completed the survey, had blood drawn for haemoglobin electrophoresis and received their results. A majority of participating pregnant women (97.0%) were not aware of their haemoglobin “genotype”. Among the participants who were incorrect about their haemoglobin “genotype”, 41.1% (23/56) of women who reported their haemoglobin “genotype” as AA were actually AS. The odds of haemoglobin “genotype” awareness was higher among participants who were in younger age group, completed tertiary education, had less number of pregnancies, and attended antenatal care. Overall prevalence of sickle cell trait (AS) was 18.7%.ConclusionsIt is feasible to integrate haemoglobin “genotype” testing into an existing community-based maternal-child program. Most pregnant women who were unaware of their haemoglobin “genotype” accepted and had haemoglobin genotype testing, and received their test results. Increasing parental awareness of their own haemoglobin “genotype” could increase their likelihood of accepting newborn screening for SCD.

Knowledge, Attitude, And Practice of Genotype Screening among Junior and Senior Secondary School Students in Gwagwalada Area Council, FCT Abuja

Background: The knowledge, attitude and practice of genotype screening is very important in the control and prevention of sickle cell disease (SCD). Methods of preventing this disease include preschool and premarital screening, genetic counseling, prenatal diagnosis, preconception diagnosis and implantation of normal embryos after in vitro fertilization and in vitro therapy using stem cell transplantation. The objective of this study is to determine the knowledge, attitude and the practice of genotype screening among junior and senior secondary school students in Gwagwalada Area Council, FCT, Abuja. Methodology: This was a cross-sectional descriptive study conducted among students aged 11-23 years in junior and senior secondary schools in Gwagwalada. A sample size of 264 was studied. A multi-stage sampling technique was used to select the schools, classes and participants. Data was collected by means of self-administered and semi-structured questionnaire. Demographic variables and associations were tested using Chi-square test with the level of statistical significance set at p <0.05, at 95% confidence interval. Results: This study showed that the students had good knowledge of SCD as 81.5% and 88.0% of the Junior Secondary School (JSS) and Senior Secondary School (SSS) students respectively knew the causes of SCD, 89.5% and 92.7% of the JSS and SSS students knew it could be transmitted from parents to offspring, and 83.3% and 88.0% of the JSS and SSS students knew that marriage of two AS partners could result in a sickle cell child. Also. this study revealed that the students had positive attitudes to SCD as 68.5% and 72.6% of the JSS and SSS students agreed that pre-school practice could prevent SCD while 79.8% and 80.7% of the JSS and SSS students also agreed pre-marital screening could prevent SCD. In addition, 50.9% and 48% of the JSS and SSS students agreed that newborn screening for SCD should be encouraged. The practice of genotype screening was however found to be poor as much as 45.7% and 24.6% of the JSS and SSS students respectively do not know their genotypes, p = 0.001. Conclusion: The students generally have good knowledge and positive attitudes towards genotype screening; however, the practice of genotype screening was poor. The school authorities should therefore ensure pre-school genotype screening and teaching on SCD should be incorporated early into the school curriculum to reduce the burden of the disease.

Newborn screening for sickle cell disease in France

Newborn screening (NBS) for sickle cell disease (SCD) in France has allowed the identification of 9,260 children with SCD since 1989, including 583 in 2019. In mainland France, however, SCD screening is targeted to newborns identified at risk of SCD, i.e born from parents originating from countries with a high SCD prevalence. This screening program, combined to prophylactic measures and a well-organized social and health network in France, has demonstrated considerable efficacy in reducing childhood mortality as well as severe infectious, anemic and neurovascular complications in childhood. SCD NBS has additionally allowed the identification of 180,687 heterozygous (AS) children since 1989. The increasing incidence of SCD (1/1,303 new-borns identified in 2019 versus 1/2,089 in 2009) now pleads for universal NBS and strong advocacy regarding SCD, the most frequent disease identified by NBS in France, and a major public health issue.

Implementing newborn screening for sickle cell disease in Korle Bu Teaching Hospital, Accra: Results and lessons learned.

Early diagnosis of sickle cell disease (SCD) through newborn screening (NBS) is a cost-effective intervention, which reduces morbidity and mortality. In sub-Saharan Africa (SSA) where disease burden is greatest, there are no universal NBS programs and few institutions have the capacity to conduct NBS. We determined the feasibility and challenges of implementing NBS for SCD in Ghana's largest public hospital. The SCD NBS program at Korle Bu Teaching Hospital (KBTH) is a multiyear partnership between the hospital and the SickKids Center for Global Child Health, Toronto, being implemented in phases. The 13-month demonstration phase (June 2017-July 2018) and phase one (November 2018-December 2019) focused on staff training and the feasibility of universal screening of babies born in KBTH. During the demonstration phase, 115 public health nurses and midwives acquired competency in heel stick for dried blood spot sampling. Out of 9990 newborns, 4427 babies (44.3%) were screened, of which 79 (1.8%) were identified with presumptive SCD (P-SCD). Major challenges identified included inadequate nursing staff to perform screening, shortage of screening supplies, and delays in receiving screening results. Strategies to overcome some of the challenges were incorporated into phase one, resulting in increased screening coverage to 83.7%. Implementing NBS for SCD in KBTH presented challenges with implications on achieving and sustaining universal NBS in KBTH and other settings in SSA. Specific steps addressing these challenges comprehensively will help build on the modest initial gains, moving closer toward a sustainable national NBS program.

Feasibility and acceptability of early infant screening for sickle cell disease in Lagos, Nigeria-A pilot study.

In Nigeria, about 150000 babies are born annually with sickle cell disease (SCD), and this figure has been estimated to increase by 100% by the year 2050 without effective and sustainable control strategies. Despite the high prevalence, newborn screening for SCD which allows for early prophylactic treatment, education of parents/guardians and comprehensive management is not yet available. This study explored a strategy for screening in early infancy during the first and second immunization visits, determined the prevalence, feasibility and acceptability of early infant screening for SCD and the evaluation of the HemoTypeSC diagnostic test as compared to the high-performance liquid chromatography (HPLC) gold standard. A cross-sectional study was conducted in two selected primary health care centres in Somolu local government area (LGA) in Lagos, Nigeria. Two hundred and ninety-one mother-infant pairs who presented for the first or second immunization visit were consecutively enrolled in the study following written informed consent. The haemoglobin genotype of mother-infant pairs was determined using the HemoTypeSC rapid test kit. Confirmation of the infants' Hb genotype was done with HPLC. Data were analysed with SPSS version 22. Validity and Predictive value of HemotypeSC rapid screening test were also calculated. Infant screening for SCD was acceptable to 86% of mothers presenting to the immunization clinics. The prevalence of SCD among the infant cohort was 0.8%. The infants diagnosed with SCD were immediately enrolled in the paediatric SCD clinic for disease-specific care. The HemoTypeSC test had 100% sensitivity and specificity for sickle cell disease in early infancy compared to HPLC. This study affirms that it is feasible and acceptable for mothers to implement a SCD screening intervention program in early infancy in Lagos State. The study also demonstrates the utility of the HemotypeSC rapid testing for ease and reduced cost of screening infants for SCD.

Influence of gender norms in relation to child's quality of care: follow-up of families of children with SCD identified through NBS in Tanzania.

Introducing newborn screening (NBS) services for sickle cell disease (SCD) in Africa has been proven to be one of the most cost-effective approach to reducing morbidity and mortality associated with this condition. In view of this evidence, efforts have been made by countries in Africa where SCD prevalence is high to pilot NBS programmes and to strengthen comprehensive care services for SCD. While it is important to reap the benefits of NBS for SCD in Africa in terms of overall quantitative measures, it is also important to understand how certain social and cultural conditions may disproportionately influence the outcomes of screening for some groups. The aim of this study was to analyse the role of gender norms before and after NBS for SCD in Tanzania, and to assess how they influence the quality of care of diagnosed children. Using qualitative methods, we did in-depth interviews with families of children with SCD identified through the NBS services and focus group sessions with nurses working in neonatal and postnatal sections of regional referral hospitals in Dar es Salaam. By analysing the experiences of both the families and nurses, we were able to provide evidence on, firstly, the gendered relations that undergird childcare and, secondly, how those relations influence the quality of care the child may potentially receive. The results emphasize the importance of studying the social implications of SCD in Africa, especially with regard to improving the quality of care for patients with SCD in the region. We propose simple interventions, including gender-conscious health education and genetic counselling, which can help to improve the community understanding of genetic diseases while also reducing gender-related inequalities related to SCD care in Africa.

Newborn Screening for Sickle Cell Disease in Tanzania: The Past, Present and Future

Sickle Cell Disease (SCD) is an inherited disorder of the Haemoglobin molecule of the red blood cells that is associated with serious complications and reduced life expectancy. Over 75% of people with SCD live in Sub-Saharan Africa (SSA), and this proportion are projected to increase to 85% by the year 2050. In Tanzania, approximately 11,000 babies are born with SCD each year, ranking 5th in the world. The high prevalence of SCD in SSA is compounded by the disproportionately higher mortality compared to that observed in the high-income countries. In Tanzania, SCD is a major contributor to under-five mortality and is estimated to account for 7% of all-cause mortality in this age group. Newborn screening (NBS) is the practice of testing babies right after delivery to ascertain whether they have diseases that are potentially lethal if not treated early. Where routinely practiced, NBS has significantly reduced morbidity and mortality associated with such diseases. The Sickle Cell Programme at Muhimbili University of Health and Allied Sciences (MUHAS) in Dar-es-salaam and Bugando Medical Center in Mwanza have both conducted pilot NBS for SCD, showing that the intervention is generally feasible and acceptable in Tanzania. The successful introduction and expansion of NBS in Tanzania will require careful planning and advocacy at community to national level.

Fifteen years of newborn sickle cell disease screening in Madrid, Spain: an emerging disease in a European country.

Sickle cell disease (SCD) describes a set of chronic inherited anemias characterized by hemolysis, episodes of vaso-occlusion, and high infectious risk, with high morbidity and mortality. Newborn screening (NBS) for SCD allows family health education and early start of infectious prophylaxis. In the Community of Madrid, a pilot universal NBS study found that the SCA birth prevalence was 1/5851 in newborns, higher than expected, confirming the need to include early detection in the NBS program. The aim of the present prospective single-center study is to analyze the results of newborn SCD screening in Madrid in terms of epidemiological data and its inclusion in a comprehensive care program during the last 15years, between 1st of May 2003 and 1st of May 2018. During the study period, 1,048,222 dried bloodspots were analyzed. One hundred ninety-seven patients were diagnosed with possible SCD (HPLC phenotype of FS, FSA, FSC, FSE, FSDPunjab, FSOArab), with 187 patients finally confirmed (birth prevalence 1/5552 newborns, 0.18 per 1000 live births), and 1 out of 213 infants carried Hb S. All of them were seen by a specialist clinician; median age at the first visit consultation was 35days and median age at the beginning of penicillin treatment was 66days. The Madrid SCD NBS program achieved high rates of sensitivity and specificity and good quality of care assistance. Establishing a good relationship with the family, a strong education program, and a multidisciplinary team that includes social workers and a psychologist are needed to ensure the success of early intervention.

Parental Notification Via Text Messaging for Infant Sickle Screening Programs: Exploration of Feasibility and Acceptability in Uganda.

Sickle cell disease (SCD) in Africa has high prevalence, morbidity, and early mortality. Difficulties in reaching parents following infant SCD screening dampen program effectiveness. Text messaging may support initial postscreening parental notification. We explored SCD awareness, and feasibility and acceptability of text messaging about screening follow-up among convenience samples of caretakers with children under 5 years (n=115) at 3 sites: a SCD family conference or 2 general pediatric clinics in urban or rural Uganda. Two thirds of the conference-based participants and 8% at clinic sites had affected children. At the clinics, 64% of caretakers were aware of SCD. In all, 87% claimed current possession of mobile phones; 89% previously had received messages. A sample text on the availability of screening results and need to bring their child to SCD clinic was at least partially understood by 82%. Overall, 52% preferred communication for initial follow-up by telephone over text message. Concerns about texting included phone access, privacy or cost, and readability of messages. Caretakers identified concerns about distance, cost, or preference for another clinic as additional barriers to SCD follow-up. Findings suggest that text messaging to caretakers may be feasible, but less acceptable compared with a telephone call about initial follow-up from newborn SCD screening.