Newborn Screening for Sickle Cell Disease in the United States: Gaps in Medical Care for the Pediatric Clinicians.

Is integrating sickle cell disease and HIV screening logical?

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.

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.

After completing this article, readers should be able to: 1. List examples of disorders for which tandem mass spectrometry (MS/MS) can screen. 2. Delineate potential difficulties with MS/MS newborn screening. Tandem mass spectrometry (MS/MS) technology has shown tremendous promise in newborn screening pilot programs worldwide with its capacity to measure numerous metabolites from a dried blood spot virtually simultaneously with an extremely rapid throughput per sample (approximately 2 min). The expansion of newborn screening programs by inclusion of an additional 15 to 30 metabolic disorders has the potential to decrease significantly the morbidity and mortality associated with inborn errors of metabolism and could offer the clinician critical diagnostic information when caring for an acutely ill neonate. Newborn screening for metabolic disorders began in 1962 in the United States, with the introduction of the Guthrie bacterial inhibition assay for phenylketonuria (PKU) in a Massachusetts voluntary program. Child health advocates, including the National Association for Retarded Citizens and the March of Dimes Birth Defects Foundation, developed model legislation and lobbied for passage of newborn screening laws at the state level. As a result of these efforts, newborn screening for PKU was legally mandated in most states in the early 1960s. The success of newborn screening for PKU led to development of tests for other conditions, including metabolic disorders (eg, galactosemia, maple syrup urine disease [MSUD], homocystinuria, and biotinidase deficiency), endocrinopathies (eg, congenital hypothyroidism and congenital adrenal hyperplasia), hemoglobinopathies (eg, sickle cell disease and thalassemias), and cystic fibrosis. Different states screen for a variable number of these disorders, with most screening for three to six conditions (Figure⇓ ). Such differences reflect state political and economic environments, technologic capabilities of public health departments, regional ethnic composition, and community expectations. All states screen for PKU and congenital hypothyroidism, and 48 states screen for galactosemia. Other inborn …

Newborn screening for sickle cell disease, other hemoglobinopathies and G6PD deficiency is one of the most important means of decreasing mortality and morbidity in high prevalence areas. Nine years experience in newborn screening in Qatif Central Hospital are summarized. All newborns in Qatif Central Hospital had cord blood screening for sickle cell disease, other hemoglobinopathies and G6PD deficiency using alkaline and electrophoresis, agar gel electrophoresis for sickle cell disease and fluorescent screening technique for G6PD deficiency. Families of infants with minor hemoglobinopathies and G6PD deficiency were informed about the results in the well baby clinic. From December 1992 to December 2001, 24 012 newborn were screened. 21 858 (91.03%) were Saudi and 2154 (8.97%) were non-Saudi. In the Saudi hemoglobin electrophoresis patterns, AF (normal) was found in 49.52%, hemoglobin FS (sickle cell disease) + FS Bart s (sickle cell disease with alpha thalassemia) in 2.57%, hemoglobin AFS (sickle cell trait) + AFS Bart s (sickle cell trait with alpha thalassemia) in 21.14%, and alpha thalassemia (based on elevated Bart s hemoglobin > or = 2%) in 35.68%. G6PD deficiency was found in 37.02% and 21.27% in males and females, respectively. Of 563 Saudi newborn with a presumptive diagnosis of sickle cell disease, 48 (8.5%) did not come to the hematology clinic or were not contactable. The diagnosis of sickle cell anemia or sickle thalassemia was confirmed in 513 patients, and 2 cases were found to have sickle cell trait on repeat testing. Many parents found it hard to accept the initial diagnosis and the resulting impact on their relationship with one another. Prevention and early identification of sickle cell disease, other major hemoglobinopathies and G6PD deficiency remains the cornerstone of management of these diseases. The main barriers to successful neonatal screening for hemoglobinopathies are the level of the education and deficiency in manpower. We recommend including newborn screening for hemoglobinopathies and G6PD deficiency in the national hypothyroidism screening program in the eastern province and the establishment of a special center for hemoglobinopathies with a high standard of medical care in Qatif.

Newborn Screening for Sickle Cell Disease in Italy : Report of 7 Years of a Low Cost and Reproducible Program in an Area of Immigration of High Risk Population

Understanding Gaps in Current Practices of Newborn Screening Follow-up for Sickle Cell Disease in the United States

The burden of sickle cell disease in Western Kenya is substantial; however, there is limited research on the effectiveness of rapid diagnostic tests for the condition. This study evaluated the feasibility of using the SICKLECHECK™ rapid test kit for detecting sickle cell disease at Bungoma County Referral Hospital, Kenya. A cross-sectional study was carried out between October 2023 and February 2024 and included both healthy children and children with a known haemoglobin phenotype. The SICKLECHECK™ rapid screening test was compared to Bio-Rad™ high-performance liquid chromatography, which served as the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated using MedCalc™ statistical software. The study involved 194 children (98 girls and 96 boys), aged between 10 weeks and 15 years, with haemoglobin profiles sickle cell negative (n = 78), sickle cell trait (n = 21), and sickle cell disease (n = 95). The SICKLECHECK™ test demonstrated sensitivity, specificity, negative predictive value, and accuracy exceeding 97%, with a positive predictive value of 94.18% for haemoglobin A. It also effectively distinguished between normal (sensitivity 97.44%, specificity 99.14%), carrier (sensitivity 90.48%, specificity 98.27%), and disease (sensitivity 98.95%, specificity 98.99%) phenotypes. Based on the findings in this study, SICKLECHECK™ could be a reliable point-of-care diagnostic tool for sickle cell disease. The encouragement of healthcare facilities, especially in resource-limited settings, to adopt the SICKLECHECK™ rapid test for routine screening and diagnosis of sickle cell disease is recommended. This study highlights the diagnostic reliability of the SICKLECHECK™ rapid test in accurately identifying and differentiating sickle cell disease, trait, and normal haemoglobin phenotypes, reinforcing its potential role in strengthening early diagnosis efforts in clinical settings.

In Illinois, newborn screening (NBS) for sickle cell disease (SCD) began in 1989 and for cystic fibrosis (CF) in 2008. We measured pediatricians' knowledge and attitudes regarding CF and SCD, the significance of carrier status, and NBS methodologies. Of 730 eligible Illinois pediatricians randomly selected from the American Academy of Pediatrics Web-based directory, 391 (54%) fully or partially completed the survey. Approximately three-fifths were women, two-thirds were Caucasians, and one-quarter had specialty training. Ninety-seven percent (377/390) and 93% (364/391) of respondents have at one point cared for a patient with SCD and CF, respectively, and virtually all support NBS for SCD (389/391, 99.5%) and CF (382/389, 98%). Overall mean knowledge of SCD (81.2%) and CF (84.5%) was high but did not correlate with self-reported familiarity. Questions regarding the interpretation of NBS results were less well understood, with 37% of our respondents unaware that Illinois NBS identifies all infants with sickle cell trait, and 28% unaware that Illinois NBS does NOT identify all infants who are CF carriers. Pediatricians support NBS but need additional education about the meaning of a positive and negative screen with respect to carrier detection to effectively counsel or appropriately refer.

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.

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

Introduction: Sickle cell disease (SCD) is a serious genetic disorder, often diagnosed early, which can lead to significant complications. Although newborn screening (NBS) for SCD is an effective intervention for reducing the impact of SCD in developed countries, it remains poorly accessible in sub-Saharan Africa, where the disease is particularly prevalent. This study assessed the acceptability of NBS and the factors influencing it among pregnant women in Bukavu, in the Democratic Republic of the Congo. Methods: A survey of pregnant women in Bukavu was conducted between December 1, 2023, and January 31, 2024. Data were collected using a semi-structured questionnaire covering sociodemographic characteristics, knowledge, and attitudes toward NBS. Multiple logistic regression was used to identify factors associated with NBS acceptability. Results: Out of a total of 350 respondents approached, 300 voluntarily agreed to answer our questionnaire, resulting in a response rate of 85.7%. Among them, the acceptability rate of NBS was 80.0%. Logistic regression analysis indicated that recognizing SCD as a blood disorder was strongly linked to the acceptability of NBS (adjusted OR = 2.6; 95% CI [1.4-4.9], p=0.002). In addition, individuals who were aware that SCD could be diagnosed at any point in life were more inclined to accept NBS (adjusted OR = 2.0; 95% CI [1.1-3.8], p=0.024). There were no significant associations observed with age, marital status, educational level, professional occupation, religion, knowledge of electrophoretic status, and awareness that SCD can be diagnosed in the neonatal period, or awareness that SCD can be diagnosed at any other time in life. Conclusion: This study demonstrates a significant level of acceptability of NBS among pregnant women in Bukavu, which is influenced by their understanding of SCD and knowledge about diagnostic possibilities. Implementing awareness-raising initiatives focused on key topics, such as the benefits of NBS, the implications of early diagnosis, the availability of follow-up care, increasing knowledge about SCD as a blood disorder, and its potential for diagnosis at any stage of life, could further enhance acceptability.

# 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.

Newborn screening for sickle cell disease: whose reproductive benefit?

Systematic, Point-of-Care Newborn Screening and Treatment for Sickle Cell Disease in Rural Mali, West Africa: Results from an Ongoing Implementation Project