National Neonatal Screening Program Research Articles

Neuropsychological and quality of life outcomes in PKU patients: expert recommendations of assessment tools in Brazil.

Phenylketonuria (PKU) is an inborn error of metabolism caused by deficient activity of phenylalanine hydroxylase. In Brazil, the National Neonatal Screening Program enables early treatment of patients with PKU, which prevents them from developing severe neurological damage and mental disabilities. However, between 20 and 30% of early-treated patients with PKU present focal cognitive deficits, including deficits in working memory, processing speed, and psychiatric symptoms such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD). Therefore, age-specific neuropsychiatric and cognitive tests are important components of PKU patient care. To date, there are no officially approved guidelines or recommendations of tools in Portuguese validated for use in Brazil that could be applied to assess these parameters in patients with PKU. To recommend tools validated for use in Brazil that can be used in daily clinical practice to assess quality of life and neuropsychological outcomes in patients with PKU. Six Brazilian experts discussed about eligible tools based on their clinical experience, the feasibility of their use in clinical routines, and their availability in public health services. Before the meeting, an independent review of the literature was conducted to identify the currently validated tools in Brazil, using the MEDLINE and SciELO databases. The experts recommended nine tools to assess quality of life (Peds-QL, SF-36 or WHOQOL-bref), executive function (BRIEF or Bayley-III), IQ (SONR 2½-7[a] or WASI) and ADHD (MTA-SNAP-IV and ASRS). These instruments may be easily incorporated into clinical practice and improve the quality of multidisciplinary care of patients with PKU.

Neonatal hearing screening in Soba University Hospital, Khartoum, Sudan: a cross-sectional study

BackgroundHearing loss in children constitutes a serious obstacle to their optimal development; early detection of hearing disability is vital to improve the outcome of management; currently, in Sudan, there is no national neonatal hearing screening program. The aim of this study is to discuss the results of neonatal hearing screening among newborns admitted to neonatal intensive care unit (NICU) and well-baby nursery, at Soba University Hospital, Khartoum (Sudan), and to reflect the magnitude of risk factors for hearing impairment present in these two different groups of newborns.MethodsIn this hospital-based cross-sectional study, newborns who were admitted to the NICU or being observed in the well-baby nursery in the period from February 2014 to February 2019 were screened for hearing loss using automated otoacoustic emission (OAE) device after recording the risk factors for hearing loss according to the Joint Committee on Infant Hearing (JCIH) year 2007 position statement and after conducting a detailed ear and general physical examination. Newborns who failed this screening test were rescreened using the same device after 48 h, and if they failed again, they underwent confirmatory auditory brainstem response test when they are 6 months old.ResultsOne thousand one hundred twenty newborns were tested; 736 were NICU and 384 were well-baby nursery newborns. The prevalence of hearing impairment after confirmatory test was found to be 10.8 per 1000 in the NICU group and 5.2 per 1000 in the well-baby nursery group considering that the drop rate for the confirmatory test was 50% and 66% respectively which is very high and reflect the poor compliance to the program. The risk factors for hearing loss were more encountered in the NICU group compared to well-baby nursery group. Unmonitored ototoxic drug use was found to be very prevalent and need urgent reconsideration.ConclusionIn this study, the estimated prevalence of neonatal hearing impairment is alarming; risk factors are very evident especially in the NICU group; this reflect the urgent need for establishing an efficient national program for neonatal hearing screening and working to eliminate the preventable risk factors for neonatal hearing impairment in this developing country.

Neonatal screening for spinal muscular atrophy: A pilot study in Brazil.

Spinal muscular atrophy (SMA) is considered one of the most common autosomal recessive disorders, with an estimated incidence of 1 in 10,000 live births. Testing for SMA has been recommended for inclusion in neonatal screening (NBS) panels since there are several therapies available and there is evidence of greater efficacy when introduced in the pre/early symptomatic phases. In Brazil, the National Neonatal Screening Program tests for six diseases, with a new law issued in 2021 stating that it should incorporate more diseases, including SMA. In the present study, dried blood spot (DBS) samples collected by the Reference Services of Neonatal Screening of RS and SP, to perform the conventional test were also screened for SMA, using real-time PCR, with SALSA MC002 technique. A total of 40,000 samples were analyzed, enabling the identification of four positive cases of SMA, that were confirmed by MLPA. Considering our sampling, Brazil seems to have an incidence comparable to the described in other regions. This work demonstrated that the use of the MC002 technique in samples routinely collected for the conventional NBS program is suitable to screen for SMA in our conditions and can be included in the expansion of the neonatal screening programs.

Evaluation of permanent and transient congenital hypothyroidism in cases referred from National Neonatal Screening Program.

The incidence of congenital hypothyroidism (CH) has increased world-wide. Lowering cut-off in screening programs has led to an increase in the rate of transient CH. We aimed to evaluate the rates of permanent and transient CH in cases referred from the screening program and to investigate the clinical and laboratory factors which predict transient CH. In 109 cases referred from the neonatal screening program to our hospital, from September 2015 to April 2018, 52 primarily diagnosed CH cases were prospectively evaluated. Regularly followed up, 44 CH cases were included in the study at the end of 3 years. 38.2 ± 1.31 weeks (w) and mean birthweight 3021.3 ± 389.6gram (g) in the transient CH group; both were significantly lower compared to permanent CH cases with 39.06 ± 1.33 w and 3375.3 ± 425.3g (P=0.025, P=0.007) respectively. Transient CH rate was found to be 50% (all hypoplastic) in the dysgenesis group and 73.3% in groups with normal and hyperplasic thyroid gland. While fT4 , thyroid-stimulating hormone, and thyroglobulin levels at diagnosis do not predict transient/permanent CH, levothyroxine (LT-4) dosage was significantly lower in the transient CH group in all years. The optimal cut-off value with highest sensitivity and specificity for LT-4 dosage as a predictive marker to differentiate transient CH from permanent CH was 2.27μg/kg/day (P=0.004; sensitivity: 71%, specificity: 83%) at 1st year, 1.85μg /kg/day (P=0.013; sensitivity: 66%, specificity: 72%) at 2nd year and 1.69μg /kg/day at 3rd year (P < 0.0001; sensitivity: 90%, specificity: 83%). Transient CH is more frequent than expected. Our results suggest that LT-4 requirement may be a good marker for predicting transient CH, while thyroid hormone levels at the time of diagnosis do not significantly predict permanent and transient CH. Therefore, infants with CH requiring LT-4 doses <2.27 μg/kg/day at 1st year, <1.85 μg /kg/day at 2nd year may be re-evaluated earlier to discriminate transient CH rather than at 3 years of age.

Etiological, clinical, and laboratory evaluation of congenital hypothyroidism and determination of levothyroxine (LT4) dose at treatment interruption in differentiating permanent vs. transient patients.

Congenital hypothyroidism (CH) is the most common cause of preventable but irreversible mental retardation in children, although the risk has been widely abolished by national neonatal screening programs. The aim of this study was to determine, (a) the cause of CH, (b) the etiological cause of persistent CH and (c) to investigate the role of laboratory and clinical data in predicting persistent and transient CH. Patients diagnosed with CH, who started L-thyroxine treatment and were followed up for at least three years were included. Patient data were reviewed retrospectively. Serum thyroid hormones were measured four weeks after discontinuation of therapy at age three or earlier. Cases with a thyroid-stimulating hormone (TSH) value of >10 mIU/mL were accepted as permanent hypothyroidism, while cases with normal TSH values for six months after cessation were accepted as transient hypothyroidism. There were 232 treated cases, of whom 108 (46.6%) were female, and 169 (72.8%) were eventually diagnosed with transient CH. The best cut-off point for predicting permanent status was determined as LT4 cut-off dose ≥1.45 mcg/kg/day. The median (range) duration of L-thyroxine treatment in transient hypothyroid cases was 24 (range: 6-36) months, and treatment was discontinued before the age of three years in 64%. There were 232 treated cases, of whom 108 (46.6%) were female, and 169 (72.8%) were eventually diagnosed with transient CH. The best cut-off point for predicting permanent status was determined as LT4 cut-off dose ≥1.45 mcg/kg/day. The median (range) duration of L-thyroxine treatment in transient hypothyroid cases was 24 (range: 6-36) months, and treatment was discontinued before the age of three years in 64%.

Endoplasmic reticulum stress in leukocytes from phenylketonuric patients

Abstract Objectives Phenylketonuria (PKU) is a proteinopathy due to the deficiency of phenylalanine hydroxylase (PAH) enzyme. The pathological elevation of phenylalanine (Phe) and its metabolites in PKU is linked to neurological hallmarks and mental disabilities. The aim of this study was to examine the hypothesis that high levels of Phe caused endoplasmic reticulum (ER) stress in PKU patients. Methods We primarily evaluated ER stress markers glucose-regulated protein78 (GRP78) and C/-EBP homologous protein (CHOP), and thiobarbituric acid-reactive substances (TBARS) as a biomarker of oxidative stress in leukocytes and correlated it with blood Phe values from patients with PKU. Patients in this study were selected from individuals who were diagnosed with PKU as a result of the national neonatal screening program and undergone treatment at our university hospital. The subjects were divided into four groups: healthy controls, patients with hyperphenylalaninemia (HPA), BH4-responsive patients with PKU and patients with classic PKU. GRP78, CHOP and TBARS levels were estimated in leukocytes isolated from whole blood of subjects, Phe and tyrosine levels were determined in plasma. Results The levels of Phe in BH4-responsive PKU and classic PKU groups were statistically higher as compared to healthy controls, and Phe levels were higher in classic PKU compared to HPA group. CHOP levels were elevated by 35.3% in BH4-responsive group compared to control. GRP78, CHOP and TBARS showed no statistical differences between control and patient groups. GRP78 was also negatively correlated with Phe levels. Conclusions These results suggested that blood Phe concentrations might not be associated to ER stress in white blood cells obtained from the PKU patient groups under treatment.

Actualities in neonatal endocrine and metabolic screening.

Neonatal metabolic screening has proven to be an important tool for the early detection of innate metabolic errors. Despite the fact that simple and effective methods of testing for metabolic diseases have been identified since the middle of the twentieth century, no consensus has been reached so far on the content of neonatal metabolic screening panels. There are large differences between countries in the number of metabolic diseases identified through national metabolic screening programs, ranging from zero to several tens, the most common testing being for phenylketonuria and congenital hypothyroidism (including in Romania). Given the fact that rare but treatable diseases have been identified in recent decades, reducing the financial burden on the health system, it would be useful to include them in the national neonatal metabolic screening program.

Analysis of national coverage of neonatal cystic fibrosis screening in Brazil from 2008 to 2017

Introduction The Brazilian neonatal screening program established in 2001 included the investigation of cystic fibrosis (CF) in the phase III of the program. For this purpose, the immunoreactive trypsin (IRT) measurement was added to the newborn screening test. The purpose of National Neonatal Screening Program is to reach 100% of live births in Brazil. The aim of this study was to analyze the coverage of neonatal Screening for Cystic Fibrosis (CF) in Brazil from 2008 to 2017. Materials and methods This is an ecological study design based on data collected from the Brazilian Outpatient Information System regarding the detection of IRT as a component of the heel stick test from 2008 to 2017. Moreover, we gathered data from the Brazilian Live Birth Information System referring to live births from 2008 to 2017. We calculated the coverage of IRT measurement for every 100 live births, using the number of IRT measurement procedures as the numerator and the number of live births stratified by federative units (states), as well as by the Brazilian regions as the denominator. These regions correspond to the divisions of the national territory based on criteria such as natural, social, cultural and economic aspects. Results From 2008 to 2017, the regions presented the following coverage medians: South (84.1%), Southeast (71.4%), Midwest (47.3%) Northeast (12.3%) and North (10.9%). In the analysis of federative units, in the years 2013 to 2017, Paraná and Distrito Federal presented the highest median of coverage (100%), while the states with the lowest median were Rio Grande do Norte (12.1%), Amazonas (16.8%) and Paraíba (27.5%). Highest coverage was found in the South region, where are located most of the states with high socioeconomic development and high supply of health services, while the lowest coverage was found in the North region, where are located manly the states with low socioeconomic development and low supply of health services. According to data from the Brazilian Ministry of Health, the universalization of neonatal screening for cystic fibrosis occurred in 2013, however, at the end of this year, most states in the North and Northeast regions had not registered IRT measurements in the Outpatient Information System. Conclusion Although the coverage of neonatal screening for CF has improved nationwide over the years of the study, the disparity in the coverage of IRT measurements at the interregional and interstate levels is notable. Systematic implementation of neonatal screening for cystic fibrosis with equity and access to the entire population is suggested, leading to a greater number of children benefiting from treatment and a better quality of life.

Incidence of hemoglobinopathies and diagnostic algorithm in newborns in the state of Mato Grosso do Sul

Introduction: Hemoglobinopathies are inherited disorders that affect the normal aspect of human hemoglobin (Hb). The disorders can be structural defect in one of globin subunits (variant hemoglobin) or reduction in the rate of globin chain synthesis (thalassemia). In this scenario, Hb S stands out as the most frequent hemoglobinopathy in the world and it’s responsible for sickle cell disease (SCD). HbS can be found in different combinations, resulting in extreme clinical conditions; it can range since a severe presentation - sickle cell anemia (HbSS) to asymptomatic - sickle cell trait (HbAS). Since 2013, screening for hemoglobinopathies has been covered by the National Neonatal Screening Program (NNSP) and aims to diagnose and intervene in cases of hemoglobinopathies in all Brazilian newborns. In view of the large amount of abnormal Hb described and the different combinations of hemoglobinopathy, the diagnosis is complex and involves a trained professional team.Objective: To evaluate the incidence of abnormal Hb in newborns (NBs) in the state of Mato Grosso do Sul (MS) and propose a hemoglobinopathies diagnostic algorithm for health services in order to outline the appropriate conduct, such as treatment or genetic orientation. Methodology. Cross-sectional, observational, descriptive and quantitative study, carried out between January 2019 and February 2020, involving 42,032 RNs from MS through the PNTN. Abnormal Hb samples were analyzed using electrophoretic, chromatographic techniques (HPLC-Ultra2 and Genesys, Trinity Biotech) and molecular techniques (PCE-RE and GAP- PCR) by Neonatal Screening Laboratory of MS and university laboratory. Results: It was found that 1070 newborns (mean age: 12.4 days) had abnormal Hb, with hemoglobin profiles: 792 (74%) HbFAS, 238 (22.2%) HbFAC, 12 (1.1%) HbFSA, 10 (0.9%) HbFCA, 7 (0.7%) HbFAD, 4 (0.4%) HbFS, 4 (0.4%) HbFSC, 1 (0.1%) FC and 2 (0.2%) other Hb profiles not detected.Discussion and Conclusion: The creation of a hemoglobinopathies diagnostic algorithm becomes a great ally of health services for early interventions, when it’s necessary. The initial evaluation by HPLC quick scan is important to differentiate, according to the profile presented at birth, normal phenotypes (HbFA) from abnormal ones. The distinct phenotypes of HbFA must be analyzed by HPLC high definition. In case of doubts regarding about the type of hemoglobinopathy, confirmatory tests should be performed using molecular biology, such as RFLP-PCR, PCR-AE, GAP-PCR and DNA sequencing. The data collected show us that the Hb S trait is the most incident, followed by the HbC trait; none of both have significant clinical repercussions. On the other hand, for symptomatologic cases, there is SCD patients of different genotypes (Hb SS, Hb SC and Hb S/Beta + thalassemia). Thus, the importance of a diagnostic algorithm capable of optimizing the diagnosis and reducing errors in the identification of hemoglobinopathies is endorsed, as well as serving as support for the implementation of prophylactic practices, referral to specialized treatment and genetic orientation to the family in these cases.

Carriers of sickle cell disease: reflections of the Black people history on access to the health

A Revista Eletrônica de Comunicação, Informação &amp; Inovação em Saúde – Reciis comunica a publicação formal de retratação para extração do artigo: RAMOS, Edith Maria Barbosa; RAMOS, Paulo Roberto Barbosa; CARVALHO, Márcia Haydee Porto de; SILVA, Delmo Mattos da; DUTRA JÚNIOR, Paulo Henrique de Freitas. Portadores da doença falciforme: reflexos da história da população negra no acesso à saúde. Revista Eletrônica de Comunicação, Informação &amp; Inovação em Saúde, Rio de Janeiro, v. 14, n. 3, p. 681-691, 2020. DOI: https://doi.org/10.29397/reciis.v14i3.1182. desde que foram identificadas inconformidades com a política editorial da revista. Christovam Barcellos Igor Sacramento Kizi Mendonça de Araújo Editores científicos Retratação do artigo: https://www.reciis.icict.fiocruz.br/index.php/reciis/article/view/4118/version/2737

Update on the Swedish Newborn Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) was the fourth disorder added to the national Swedish neonatal screening program in 1986, and approximately 115,000 newborns are screened annually. Dried blood spot (DBS) screening with measurement of 17-hydroxyprogesterone (17OHP) is also offered to older children moving to Sweden from countries lacking a national DBS screening program. Here, we report an update on the CAH screening from January 2011 until December 2019. Results: During the study period, 1,030,409 newborns and 34,713 older children were screened. In total, 87 newborns were verified to have CAH, which gives an overall positive predictive value (PPV) of 11% and 21% for term infants. Including the five missed CAH cases identified during this period, this gives an incidence of 1:11,200 of CAH in Sweden. Among the older children, 12 of 14 recalled cases were found to be true positive for CAH. All patients were genotyped as part of the clinical follow-up and 70% of the newborns had salt wasting (SW) CAH and 92% had classic CAH (i.e., SW and simple virilizing (SV) CAH). In the group of 12 older children, none had SW CAH and two had SV CAH. Conclusion: The incidence of classic CAH is relatively high in Sweden. Early genetic confirmation with CYP21A2 genotyping has been a valuable complement to the analysis of 17OHP to predict disease severity, make treatment decisions and for the follow-up and evaluation of the screening program.

MON-101 Costa Rican National Primary Congenital Hypothyroidism Screening Program Evaluation. Retrospective Cohort Trial Between 2015 and 2017

Congenital hypothyroidism (CH) is one of the leading causes of intellectual impairment worldwide in infancy. The newborn screening has been able to prevent this mental disability, by a prompt initiation of therapy. Over the last years the incidence of HC has been increasing, mainly by lowering the screening cut-off level that leads to detection of milder cases. There is conflicting evidence if children with mild CH without treatment may develop neurological impairment in the future.Costa Rican newborn screening program in divided in three stages, measuring serum TSH concentrations from a heel prick aliquot of capillary blood dried onto a filter paper. Each test has different TSH cut-off values to determine if the newborn needs a clinical evaluation by an endocrinologist, needs another screening test or rules out hypothyroidism.We developed an observational, descriptive, retrospective study, based on medical records, to evaluate our newborn screening program performance. The study included the total national population of screened newborns from 2015 to 2017. Descriptive analysis and analytical analysis of variables were done, and test’s sensitivity and specificity were determined.The study analyzed 204.241 screened newborns, and 145 children referred to the Endocrinology Department of the National Children Hospital. This population represents 97% of births in these 3 years. The recall rate for a first positive test was 0.3%. Congenital hypothyroidism was confirmed in 73% of children referred to the Endocrinology Department because of a positive screening. Incidence was 1/1926 births. Detection rate was independent of birth weight nor gestational age. 45.3% of children diagnosed with CH were detected after the first screening test, 52.8% after the second screening test and 1.9% after the third screening test. Screening test analysis showed high sensitivity and specificity, with diagnostic accuracy above 90%, except for the third screening test. Free thyroxine measurements alone weren’t useful to predict CH diagnosis.The coverage of the national neonatal screening program extends almost to the entire population. Our test specificity is within international standards. Incidence of CH in Costa Rica is similar to that reported in medical literature. With current detection cut-off level, there is no need of performing a second mandatory evaluation to preterm and low weight newborns. The third screening test has a low performance rate, does not improve detection of children with CH significantly, and delays clinical evaluation by the endocrinologist. Prognosis of treated children with CH is excellent, with no evidence of severe cognitive deficit.

A Success Story: Review of the Implementation and Achievements of the National Newborn Screening Program for Congenital Hypothyroidism in Iran.

ContextToday, newborn screening for congenital hypothyroidism (CH) as one of the significant achievements in preventive medicine is integrated into the health systems of many countries worldwide. The national newborn screening for early identification of CH disorder in Iran was established in 2004. The purpose of this study was to review the national newborn screening for CH and its achievements in Iran.Evidence AcquisitionIn this study, we reviewed the structures, processes, main indicators, and achievements during the 15 years of implementing the national neonatal screening program for the diagnosis and treatment of CH in Iran.ResultsPrimary TSH measurement with backup thyroxine (T4) determination in infants with high TSH levels was used as the screening strategy in Iran. The coverage of this screening program was higher than 98%. By the end of 2017, 1,501,624 neonates were screened, among which 40,773 were diagnosed with CH and treated based on the national guidelines. The average incidence rate of CH during these years was approximately 2.6:1,000 live births.ConclusionsThe performance of the newborn screening program for congenital hypothyroidism in Iran is favorable, with over a 95% coverage rate. Due to the high recall rate and incidence rate of CH, it is essential to monitor the screening program in the country and also to conduct further studies to determine the main risk factors for the high recall rate and incidence of this congenital error.

Increase of breast-feeding in the past decade in Greece, but still low uptake: cross-sectional studies in 2007 and 2017.

To estimate breast-feeding prevalence in Greece in 2007 and 2017, compare breast-feeding indicators and maternity hospital practices between these years, and investigate breast-feeding determinants. Two national cross-sectional studies (2007 and 2017) using systematic cluster sampling of babies with the same sampling design, data collection and analysis methodology. Telephone interview with babies' mothers or fathers. Representative sample of infants who participated in the national neonatal screening programme (n549 in 2017, n586 in 2007). We found that breast-feeding indicators were higher in 2017 compared with 10 years before. In 2017, 94% of mothers initiated breast-feeding. Breast-feeding rates were 80, 56 and 45% by the end of the 1st, 4th and 6th completed month of age, respectively. At the same ages, 40, 25 and <1% of babies, respectively, were exclusively breast-feeding. We also found early introduction of solid foods (after the 4th month of age). Maternity hospital practices favouring breast-feeding were more prevalent in 2017, but still suboptimal (63% experienced rooming-in; 51% experienced skin-to-skin contact in the first hour after birth; 19% received free sample of infant formula on discharge). We observed an increasing trend in all breast-feeding indicators in the past decade in Greece, but breast-feeding rates - particularly rates of exclusive breast-feeding - remain low. Systematic public health initiatives targeted to health professionals and mothers are needed in order to change the prevailing baby feeding 'culture' and successfully implement the WHO recommendations for exclusive breast-feeding during the first 6 months of life.

Cognitive Function of Children and Adolescents With Congenital Adrenal Hyperplasia: Importance of Early Diagnosis.

ContextPatients with classic congenital adrenal hyperplasia (CAH) are treated postnatally with lifelong glucocorticoid (GC) replacement therapy. Previous results on general cognitive ability in individuals with CAH have been conflicting.ObjectiveTo evaluate long-term cognitive effects of GC replacement therapy and the impact of early diagnosis in children with CAH.Design and SettingObservational study with patients from a single research institute.Patients32 children with CAH (mean age 11.5 years) identified through the Swedish national neonatal screening program for CAH and 52 matched population controls (mean age 10.7 years). Eleven (6 female) children with CAH who were treated prenatally with dexamethasone (DEX), (CAH-DEX) (mean age 11.7 years).InterventionGC replacement therapy, neonatal screening for CAH.MeasuresCognitive abilities assessed with standardized neuropsychological tests (Wechsler scales, Span Board Test, Stroop Interference Test, NEPSY list learning).ResultsChildren with CAH (not prenatally treated) performed equally well as population controls on a series of tests assessing general intellectual ability and executive functions. No significant differences were observed in cognitive performance between patients with different genotypes (null, non-null). Patients with salt-wasting CAH performed poorer than patients with simple virilizing CAH in a test assessing visuo-spatial working memory (P = 0.039), although the performance was within the normal range for the population. Prenatally DEX-treated girls with CAH had lower verbal intellectual ability compared with CAH girls not exposed to prenatal treatment (P = 0.037).ConclusionChildren and adolescents with CAH who were diagnosed early via a neonatal screening program and treated with hydrocortisone had normal psychometric intelligence and executive functions.

How to perform and interpret the sweat test

Cystic fibrosis (CF) is the most common life-threatening autosomal-recessive disease affecting Caucasians in the western world. The sweat test is the main diagnostic test for CF. It is indicated as...

Country lack of preparation to face maternal immigrant and Roma problems related to neonatal screening

BackgroundNewborn screening is a public health tool for the early diagnoses and treatment of asymptomatic infants with inborn errors of metabolism. Biomarkers and enzyme activities are measured in dried blood spots (DBS) on Guthrie carts to diagnose diseases, which may later appear such as mental retardation and or other disorders could be presented. To evaluate the percentage and the educational status of mothers who do not respond to the requested for a second DBS of a suspected for a disease newborn. MethodsWe created a questioner about the educational status as well as the etiology of maternal lack of response for a second blood sample. ResultsMost of mothers who denied to respond were of low educational status and or immigrants, not knowing our native or English language. The rest were indifferent and or misunderstood the information letter they reserved. ConclusionsAmelioration of the educational status of mothers and or better cooperation with social workers and or midwives, nurses etc. Translation of the information booklet about National Neonatal Screening Program in to more foreign languages should be necessary.

Cases Referred from the Turkish National Screening Program: Frequency of Congenital Hypothyroidism and Etiological Distribution

Objective:The aim of this study was to evaluate cases referred from the congenital hypothyroidism (CH) newborn screening program.Methods:Infants referred to Pediatric Endocrinology between 30.09.2015 - 01.04.2018 because of suspected CH identified by National Neonatal Screening Program were prospectively evaluated.Results:Of the 109 newborns referred to our clinic, 60 (55%) were diagnosed with elevated neonatal thyroid stimulating hormone (TSH). The diagnosis of elevated neonatal TSH was made in 52 (47.7%) and eight (7.3%) infants at initial evaluation and after follow up, respectively of all referrals with 86.7% (52/60) diagnosed at initial visit. The median first and second heel prick times were 1.8 (0-7) and 8.72 (4-30) days. The median age at starting treatment of the infants diagnosed as a result of initial evaluation was 22.13 (7-53) days. Clinical findings associated with CH were present in 19 (36%) of patients. Etiology in patients diagnosed with elevated neonatal TSH on admission was: agenesis in one (2.08%); ectopia in one (2.08%); hypoplasia in 14 (29.16%); normal gland in situ 16 (33.3%); and hyperplasia in 16 (33.3%). The median time to normalization of TSH and free thyroxine concentrations after treatment initiation was 11.02 (4-30) and 9.03 (3-30) days, respectively.Conclusion:The rate of diagnosis in the first month was found to be 87%. The etiological incidence of both dysgenesis and dyshormonogenesis was equal at 33.3%. The majority of cases with normal thyroid gland will be diagnosed with transient hypothyroidism but some of them may be diagnosed with thyroid dyshormonogenesis so the rate of dyshormonogenesis will increase later after final diagnosis.

The Neonatal Screening Program in Brazil, Focus on Sickle Cell Disease (SCD).

Since 2001, the Brazilian Ministry of Health has been coordinating a National Neonatal Screening Program (NNSP) that now covers all the 26 states and the Federal District of the Brazilian Republic and targets six diseases including sickle cell disease (SCD) and other hemoglobinopathies. In 2005, the program coverage reached 80% of the total live births. Since then, it has oscillated between 80% and 84% globally with disparities from one state to another (>95% in São Paulo State). The Ministry of Health has also published several Guidelines for clinical follow-up and treatment for the diseases comprised by the neonatal screening program. The main challenge was, and still is, to organize the public health network (SUS), from diagnosis and basic care to reference centers in order to provide comprehensive care for patients diagnosed by neonatal screening, especially for SCD patients. Considerable gains have already been achieved, including the implementation of a network within SUS and the addition of scientific and technological progress to treatment protocols. The goals for the care of SCD patients are the intensification of information provided to health care professionals and patients, measures to prevent complications, and care and health promotion, considering these patients in a global and integrated way, to reduce mortality and enhance their quality of life.

The Use of HPLC as a Tool for Neonatal Cord Blood Screening of haemoglobinopathy: A Validation Study.

BackgroundNewborn cord blood screening identifies infants with underlying haemoglobinopathies before they develop the characteristic symptoms or sequelae.AimsThis study was performed to validate the interpretation high-performance chromatography (HPLC) along with complete blood count (CBC) results as a tool for universal neonatal screening of hemoglobin disorders in Oman.MethodsHPLC and CBC data on subjects who participated in the National Neonatal screening program at birth were obtained from archival records. The results recorded at birth were compared with a second study performed on the same subjects, after approval from the local medical research and ethics committee.ResultsOnly 290 subjects from amongst the original cohort of 3740 newborns could be recalled between April 2010 to March 2011, to repeat HPLC and CBC, as well as perform confirmatory DNA studies, wherever necessary. All these subjects had been documented to show an initial abnormal result. 31 cases who had no HbA at birth on HPLC were confirmed as either homozygous β-thalassaemia major (n=5 subjects) or homozygous sickle cell anemia (n=26 subjects) by appropriate DNA analysis. Additionally, amongst 151 subjects, 72 subjects were studied in the initial study by Hb Bart’s quantitation using the alpha thalassaemia short program at birth. In this cohort, 42 subjects with Hb Bart’s >1% at birth could be confirmed as having either deletional or non-deletional thalassaemia by GAP PCR studies. No case of HbH was detected in this cohort. Further, carrier status for structural hemoglobin variants (HbS, HbC, HbD, HbE) (n=67) and beta thalassaemia allele with low HbA at birth (n=29 out of 41) were confirmed by relevant molecular studies.ConclusionsThe study validated the earlier observation by 100% concordance with the results of CBC and HPLC. Presence of Hb Bart’s at birth does not always mean the presence of alpha thalassemia, as subjects with Hb Bart’s below 1% by quantitation, were shown to be normal by molecular studies.