Simultaneous newborn screening for sickle cell disease, biotinidase deficiency and hereditary tyrosinemia type 1 with an optimized tandem mass spectrometry protocol

Sickle cell disease is a genetically inherited blood disorder that manifests early in life with resultant significant health complications. Globally, nearly three quarters of all affected babies are in sub-Saharan Africa. Early identification of babies with sickle cell disease through newborn screening followed by early linkage to care is recommended. However, the program has not been widely adopted in the sub-Saharan Africa. The Kenyan ministry of health, in 2020, published a policy on newborn screening for sickle cell disease from levels 2-6 healthcare facilities. However, evidence on acceptability of newborn screening to scale up newborn screening program is scarce. Few studies have been conducted across the sub-Saharan Africa to assess the acceptability of newborn screening for sickle cell disease with conflicting results. This study assessed factors associated with acceptability of newborn screening among mothers of newborns delivered at Homa bay county teaching and referral hospital, western Kenya. This study employed a cross-sectional design among postnatal mothers at Homa bay county teaching and referral hospital with 399 postnatal mothers enrolled into the study. After obtaining informed consent from the postnatal mothers, a semi-structured questionnaire was used for data collection. Maternal sociodemographic characteristics, knowledge, and perception were assessed. Babies were also screened for sickle cell disease using Sickle SCAN point-of-care test. The acceptability was calculated as percentage of mothers accepting to have their babies screened. Data were analyzed using logistic regression to explore factors associated with acceptability of newborn screening for sickle cell disease. Ninety-four percent of mothers accepted newborn screening for sickle cell disease. Only maternal age and occupation were significantly associated with acceptability of newborn screening for sickle cell disease. Mothers aged 25-34 years were 3 times less likely to accept newborn screening for sickle cell disease than those younger mothers than 25 years (OR=0.33;95%CI = 0.13-0.86; p = 0.024).Similarly, mothers in the formal employment were 6 times less likely to accept newborn screening for sickle cell disease than those who were students (OR= 0.16; 95%CI = 0.03-0.84; p = 0.031).Mothers who were in formal employment were 25 times less likely to accept newborn screening for sickle cell disease than those who were students in the multivariate logistic analysis model (aOR= 0.04; 95% CI = 0.00-0.78; p = 0.034). The acceptability of newborn screening for sickle cell disease is high in the county. The Homabay county ministry of health should implement routine newborn screening for sickle cell disease in all healthcare facilities conducting deliveries of newborns.

Successful Simultaneous Screening of Sickle Cell Disease, HIV and Tuberculosis in Rural Guinea Bissau, West Africa through Rapid Tests and a Standardized Clinical Questionnaire: An Outreach Program Due to a Public-Private Partnership

Illinois introduced mandatory newborn screening (NBS) for sickle cell disease (SCD) in 1989 and for cystic fibrosis (CF) in 2008. We examined maternal understanding of NBS for SCD and CF, and their knowledge of the genetics, symptoms, and treatments of both conditions. Our methods consisted of conducting interviews of inpatient post-partum women (>18 years and English speaking). Our results showed that of the 388 eligible participants, 34 self-identified as sickle cell carriers, 1 with SCD and 1 as a CF carrier. Almost 3/4 were African American (282/387). Although all but 5 women had prenatal care, only 35% (133/378) recalled their prenatal care provider mentioning NBS, and only 56% (217/388) of participants recalled nursery staff mentioning NBS. There was more self-reported familiarity with SCD (3.32/5) than CF (1.97/5, P < 0.001). Over 2/3 (260/388) of participants could not answer CF knowledge questions because they had never heard of CF. Among those who had heard of the conditions, mean knowledge scores were 66% for SCD (n = 372) and 63% for CF (n = 128). Bivariate analysis identified education, age, race, marital status, and insurance status as statistically significant. After linear regression education remained significant for both conditions. We conclude that in a sample of predominantly African American post-partum women, we found poor understanding of NBS, greater familiarity with SCD, and significant knowledge gaps for both SCD and CF. There are many missed educational opportunities for educating parents about NBS and specific conditions included in NBS panels in both the obstetric clinics and the nursery.

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life.

SummaryBackgroundSickle cell disease is highly prevalent in sub-Saharan Africa, where it accounts for substantial morbidity and mortality. Newborn screening is paramount for early diagnosis and enrolment of affected children into a comprehensive care programme. Up to now, this strategy has been greatly impaired in resource-poor countries, because screening methods are technologically and financially intensive; affordable, reliable, and accurate methods are needed. We aimed to test the feasibility of implementing a sickle cell disease screening programme using innovative point-of-care test devices into existing immunisation programmes in primary health-care settings.MethodsBuilding on a routine immunisation programme and using existing facilities and staff, we did a prospective feasibility study at five primary health-care centres within Gwagwalada Area Council, Abuja, Nigeria. We systematically screened for sickle cell disease consecutive newborn babies and infants younger than 9 months who presented to immunisation clinics at these five centres, using an ELISA-based point-of care test (HemoTypeSC). A subgroup of consecutive babies who presented to immunisation clinics at the primary health-care centres, whose mothers gave consent, were tested by the HemoTypeSC point-of-care test alongside a different immunoassay-based point-of-care test (SickleSCAN) and the gold standard test, high-performance liquid chromatography (HPLC).FindingsBetween July 14, 2017, and Sept 3, 2019, 3603 newborn babies and infants who presented for immunisation were screened for sickle cell disease at five primary health-care centres using the ELISA-based point-of-care test. We identified 51 (1%) children with sickle cell anaemia (HbSS), four (<1%) heterozygous for HbS and HbC (HbSC), 740 (21%) with sickle cell trait (HbAS), 34 (1%) heterozygous for HbA and HbC (HbAC), and 2774 (77%) with normal haemoglobin (HbAA). Of the 55 babies and infants with confirmed sickle cell disease, 41 (75%) were enrolled into a programme for free folic acid and penicillin, of whom 36 (88%) completed three visits over 9 months (median follow-up 226 days [IQR 198–357]). The head-to-head comparison between the two point-of-care tests and HPLC showed concordance between the three testing methods in screening 313 newborn babies, with a specificity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC, and a sensitivity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC.InterpretationOur pilot study shows that the integration of newborn screening into existing primary health-care immunisation programmes is feasible and can rapidly be implemented with limited resources. Point-of-care tests are reliable and accurate in newborn screening for sickle cell disease. This feasibility study bodes well for the care of patients with sickle cell disease in resource-poor countries.FundingDoris Duke Charitable Foundation, Imperial College London Wellcome Trust Centre for Global Health Research, and Richard and Susan Kiphart Family Foundation.

HemoTypeSC Demonstrates >99% Field Accuracy in a Sickle Cell Disease Screening Initiative in Children of Southeastern Uganda.

# Background Nigeria bears the highest burden of sickle cell disease (SCD) in the world. Neonatal screening programmes for SCD in other countries have been associated with remarkable reductions in mortality and morbidity. In Nigeria, there is an ongoing effort to implement a large scale SCD neonatal screening program with long-term follow-up. This study was conducted to assess the adequacy of knowledge and perspectives of the target population with regard to newborn screening for sickle cell disease and also to identify likely barriers and challenges to the successful implementation of the programme. # Methods Two hundred and five mothers of young infants (≤ 2 months old) and 181 mothers of SCD affected children were recruited from primary, secondary and tertiary health facilities in Ibadan, south-western Nigeria over a period of six weeks. Questionnaires were administered to the mothers assisted by a translator where necessary, in order to determine some of the factors influencing the mothers' knowledge and perspectives towards SCD and their decision to accept neonatal screening. T-test was used to compare means of scores. Chi-square test was used to test associations between differences in proportions. Univariate and multivariate analyses were used to determine which factors could influence baseline knowledge about SCD. Multiple logistic regression using stepwise selection was used to determine which factors were important in predicting the acceptance of neonatal screening by the mothers. # Results Higher level of education of the mothers (*P*=0.013) and having an affected child (*P*\<0.001) were the major factors associated with increased knowledge base and healthy perspectives towards SCD. Fewer than 50% of the mothers had moderate knowledge of SCD and its genetic inheritance, and had also heard of neonatal screening for SCD diagnosis before the survey. Two-thirds of mothers of the young infants were willing to have their babies or future children screened and most would prefer the babies be screened at an immunization center rather than at birth centers (*P*\<0.001). Awareness of, and perspectives towards SCD and neonatal screening influenced the mothers' acceptance of screening for their babies (*P*\<0.05). In addition, many of the mothers would need permission from their husbands or a relative to have their babies screened. # Conclusion Large scale awareness on the part of the community about SCD and the benefits of neonatal screening is necessary for successful implementation of the planned neonatal screening programme. Government funding and support for community education along with facilities for programme implementation are needed to kick off the program in Ibadan, Nigeria.

Evaluation of a Novel Newborn Screening Follow-up Program for Infants with Sickle Cell Disease

Sickle Cell Disease Births and Social Vulnerability (2016-2020): A Report from the Sickle Cell Data Collection Program

The Portuguese Newborn Screening Program currently includes 28 pathologies: congenital hypothyroidism, cystic fibrosis, 24 inborn errors of metabolism, sickle cell disease and spinal muscular atrophy. This pilot study for sickle cell disease newborn screening, including 188,217 samples, was performed between May 2021 and December 2023, with phase I, including 24,130 newborns, in the Lisbon and Setubal districts and phase II, including 164,087 newborns, in the whole country. DBS samples were analyzed through capillary electrophoresis. In phase I, a high birth incidence of sickle cell disease was found (1:928 NBs), resulting from the identification of 24 HbSS and 2 HbSC patients. This birth incidence decreased but remained significant when the pilot study for sickle cell disease newborn screening was expanded to a national level, with the identification of 67 sickle cell disease patients (59 HbSS and 8 HbSC), revealing a birth incidence of 1:2449 NBs. These data suggest that this condition is becoming increasingly relevant in Portugal, thus reflecting a general European trend, where sickle cell disease is already recognized as a public health problem. Therefore, it highlights the importance of its integration into the Portuguese National Newborn Screening Program panel in January 2024, thus allowing the early identification and clinical follow-up of these patients.

Objective: To pilot a newborn screening program for sickle cell disease (SCD) in St. Vincent and the Grenadines using a novel partnership method to determine the feasibility of a universal newborn screening program in this country. Methods: A prospective study of mothers and their newborns was conducted between January 1, 2015, and November 1, 2015, at the country’s main hospital. Mothers of infants born at this hospital were offered screening for SCD for their infants. If accepted, the newborn’s heel-stick blood specimen was obtained and mailed to the South Carolina Department of Health and Environmental Control Newborn Screening Laboratory for testing. Samples were analyzed for variant hemoglobins using standard laboratory techniques and results were communicated to local physicians. Feasibility was determined by a benchmark of having >50% of SCD patients receive the diagnosis and initiate disease-specific care by 3 months of age. Descriptive statistics were completed using SAS 9.4. Results: There were 1147 newborn infants screened for SCD. Of these, 123 (10.7%) had results indicative of sickle trait and 3 patients (0.3%) were diagnosed with SCD: 1 with HbSS and 2 with HbSC. All 3 patients with SCD received treatment before 3 months of age. Conclusions: A newborn screening program is feasible in this population when partnered with an established newborn screening laboratory.

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.

BackgroundInternational health research in malaria-endemic settings may include screening for sickle cell disease, given the relationship between this important genetic condition and resistance to malaria, generating questions about whether and how findings should be disclosed. The literature on disclosing genetic findings in the context of research highlights the role of community consultation in understanding and balancing ethically important issues from participants’ perspectives, including social forms of benefit and harm, and the influence of access to care. To inform research practice locally, and contribute to policy more widely, this study aimed to explore the views of local residents in Kilifi County in coastal Kenya on how researchers should manage study-generated information on sickle cell disease and carrier status.MethodsBetween June 2010 and July 2011, we consulted 62 purposively selected Kilifi residents on how researchers should manage study-generated sickle cell disease findings. Methods drew on a series of deliberative informed small group discussions. Data were analysed thematically, using charts, to describe participants’ perceptions of the importance of disclosing findings, including reasoning, difference and underlying values. Themes were derived from the underlying research questions and from issues emerging from discussions. Data interpretation drew on relevant areas of social science and bioethics literature.ResultsPerceived health and social benefits generated strong support for disclosing findings on sickle cell disease, but the balance of social benefits and harms was less clear for sickle cell trait. Many forms of health and social benefits and harms of information-sharing were identified, with important underlying values related to family interests and the importance of openness. The influence of micro and macro level contextual features and prioritization of values led to marked diversity of opinion.ConclusionsThe approach demonstrates a high ethical importance in many malaria endemic low-to-middle income country settings of disclosing sickle cell disease findings generated during research, alongside provision of effective care and locally-informed counselling. Since these services are central to the benefits of disclosure, health researchers whose studies include screening for sickle cell disease should actively promote the development of health policy and services for this condition in situations of unmet need, including through the prior development of collaborative partnerships with government health managers and providers. Community consultation can importantly enrich ethical debate on research practice where in-depth exploration of informed views and the potential for difference are taken into account.

Sickle Cell Disease (SCD) is an autosomal recessive disorder with a substantial global burden. Despite its particularly high incidence in sub-Saharan Africa, early diagnosis remains limited in many countries. The objective of this study was to implement a newborn screening programme for SCD in one of the largest maternity hospitals in Angola and to support the subsequent pediatric follow-up of the affected children. Between June 2023 and December 2024, all children born in or attending the main hospital for vaccination were screened after parental or guardian consent. Blood was collected by heel-prick onto filter paper, and haemoglobin electrophoresis was performed by isoelectric focusing. Samples identified as HbSS were confirmed by PCR-RFLP, and atypical electrophoretic patterns were further analysed by DNA sequencing. In a total of 13,256 samples analysed the prevalence of HbSS was 1.38% (n=183), and 20.31% (n=2692) were HbAS. Other variants identified (n=44) included HbE, HbC, and α-globin gene alterations. Of the infants diagnosed with SCD, 106 (58%) families were successfully contacted, but only 76 (42%) children initiated regular medical follow-up and prophylactic treatment (penicillin, multivitamins, and vaccinations. 30 families (28%) declined treatment and just one declined follow-up. These findings confirm the high prevalence of SCD in Angola and demonstrate the capacity of newborn screening programmes in reducing early morbidity and mortality. However, the substantial proportion of families refusing follow-up highlights the need for strengthened community health education to improve understanding of SCD.

Sickle cell disease (SCD) is a common and potentially life-threatening haematological disorder. In high-income countries, universal newborn screening and timely interventions have markedly reduced infant mortality. In contrast, in low-resource settings, diagnosis often occurs only in late childhood, once clinical manifestations have developed. The high cost, technical complexity, and limited availability of conventional diagnostic methods remain major barriers to implementing neonatal screening programmes in sub-Saharan Africa and other resource-constrained regions. We assessed the diagnostic performance of Sickle SCAN®, a prototype rapid immunoassay designed to qualitatively detect HbA, HbS, and HbC. The test is based on a lateral flow immunoassay format and provides results at the point of care. Cord blood samples from 365 newborns were analysed with Sickle SCAN® and results were compared against the reference standard of capillary electrophoresis. Sickle SCAN® accurately identified haemoglobin phenotypes in 97.3% of cases (95% CI: 95.0%-98.7%). For HbAA, sensitivity was 97.8% (95% CI: 94.9%-99.3%) and specificity was 96.5% (95% CI: 92.0%-98.9%). For HbAS, sensitivity was 95.8% (95% CI: 90.5%-98.6%) and specificity 98.0% (95% CI: 95.3%-99.3%). Importantly, no false-positive or false-negative results were observed for HbSS and HbAC, yielding 100% sensitivity and specificity for these phenotypes. Our findings demonstrate that Sickle SCAN® is a highly accurate, rapid, and low-cost tool for neonatal SCD screening. Its use could substantially reduce diagnostic delays, lower programme costs, and improve accessibility to early detection in resource-limited settings, thereby contributing to improved child survival.