Newborn Screening Results Research Articles

The follow-up results of newborn hearing screening of Gaziosmanpasa Taksim Research and Training Hospital.

This study aimed to present the results of newborns who were referred to advanced audiology centers after newborn hearing screening, and to determine concordance of our results with the American Academy of Pediatrics guidelines about the ages of hearing loss, aid fitting, and cochlear implantation. A total of 7502 newborns were screened in Gaziosmanpaşa Taksim Research and Training Hospital between March 2014 and June 2016 using the transient otoacustic emissions test as the first two steps and automated auditory brainstem response test for the third step. Newborns who had risk factors were screened using the automated auditory brainstem response only. Newborns who failed the screening tests were referred to advanced audiology centers. Of the 7502 newborns, 6736 (90%) completed the screening. The ratio of hearing loss was 0.08%. Six of 62 newborns who failed auditory brainstem response test and were referred to advanced audiology centers had severe bilateral hearing loss. One of the patients was not fitted with a hearing aid because the family refused it. The other one was not fitted an aid and did not undergo cochlear implantation because of severe and treatment-resistant acute otitis media. The age of diagnosis for the rest was before three months, and except for one patient, hearing aid fitting was before six months. The age of cochlear implantation was 12 months for two patients and 14 months for two patients. Ninety percent of patients completed the screening, the age of diagnosis for hearing loss was before three months and aid fitting was before six months, except for one patient. The results of the study were compatible with the diagnosis and treatment guidelines of the American Academy of Pediatrics.

Raising Awareness of False Positive Newborn Screening Results Arising from Pivalate-Containing Creams and Antibiotics in Europe When Screening for Isovaleric Acidaemia.

While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.

Planning, implementation, and initial results of newborn screening for Pompe disease and MPS I in Georgia

Planning, implementation, and initial results of newborn screening for Pompe disease and MPS I in Georgia

Psychosocial impact on mothers receiving expanded newborn screening results.

Expanded newborn screening (NBS) for genetic disorders has improved diagnosis of numerous treatable diseases, positively impacting children's health outcomes. However, research about the psychological impact of expanded NBS on families, especially mothers, has been mixed. Our study examined associations between maternal experiences of expanded NBS and subsequent psychosocial functioning and parenting stress in mothers whose infants received either true negative (TN), true positive (TP) or false positive (FP) results after a 4- to 6-month period. The Parenting Stress Index and the Depression, Anxiety and Stress Scale were used to assess symptoms of anxiety, stress and depression in 3 sets of mothers, whose infants received TN (n = 31), TP (n = 8) or FP (n = 18) results. Multivariate analyses of variance (MANOVA) results revealed no significant differences among these three groups of mothers regarding overall anxiety, stress and depression. However, FP mothers experienced lower levels of stress related to their own health compared to TN group. Two potential trends were also identified; results suggested TN mothers might experience higher levels of isolation than mothers in the TP group and that FP mothers might report higher stress levels in relation to spousal relationships compared to the TN group. FP mothers seemed to report similar or better levels of psychosocial functioning than TN mothers. Our findings are encouraging with respect to impacts of NBS on maternal well-being. We also identify key areas for improvement (parental education) and research (isolation and spousal relationships).

Next generation sequencing as a follow-up test in an expanded newborn screening programme

ObjectivesContrary to many western European countries, most south-eastern European countries do not have an expanded newborn screening (NBS) program using tandem mass spectrometry. This study would represent one of the first expanded NBS studies in south-eastern Europe and will enable the estimation of the incidences of IEM in Slovenia. We proposed an expanded NBS approach including next-generation sequencing (NGS) as a confirmational analysis. Design & methodsWe conducted a pilot study of expanded NBS for selected inborn errors of metabolism (IEM) in Slovenia including 10,048 NBS cards. We used an approach including tandem mass spectrometry followed by second tier tests including NGS. Based on the NBS results, 85 children were evaluated at a metabolic follow-up; 80 of them were analyzed using NGS. ResultsAltogether, glutaric acidemia type 1 was confirmed in one patient who was a compound heterozygote for two known causative GCDH variants. A patient with suspected very long-chain acyl-CoA dehydrogenase deficiency had negative metabolic follow-up tests, but had two heterozygous ACADVL variants; one known disease-causing variant and one indel, namely c.205-8_205-7delinsGC, that is predicted to be causative. Nine participants had elevated metabolites characteristic of 3-methylcrotonyl-CoA carboxylase deficiency, 2 of them had known causative homozygous variants in MCCC1. The other seven were heterozygous; two had a novel genetic variant c.149_151dupCCA (p.Thr50dup). Cumulative incidences of IEM in Slovenia were similar to other European countries. ConclusionsNGS proved to be valuable in explaining the abnormal metabolite concentrations in NBS as it enabled the differentiation between affected patients and mere heterozygotes, and it improved the turnaround time of genetic analysis. The results of this study will be instrumental in the routine implementation of expanded NBS in Slovenia.

AB113. Experiences from coordinating parents whose child with positive results of newborn screening of congenital adrenal hyperplasia

Background: Time frame for follow-up an infant with positive newborn screening (NBS) for congenital adrenal hyperplasia (CAH) is generally short. Since July 2006, CAH has been added into Taiwan NBS. Six centers located at different parts of Taiwan are responsible for confirmation of diagnosis and treatment. There have been 1,800,940 newborns screened, with 116 confirmed to have CAH. The coordinators at the confirmatory center are the first person who phone and discuss positive screening results to the parents. In Chinese tradition, infants are kept at home during the first month of life; thus, parents are reluctant to bring their child out for follow-up as instructed.

Contamination of dried blood spots - an underestimated risk in newborn screening.

Newborn screening (NBS) is an established screening procedure in many countries worldwide, aiming at the early detection of inborn errors of metabolism. For decades, dried blood spots have been the standard specimen for NBS. The procedure of blood collection is well described and standardized and includes many critical pre-analytical steps. We examined the impact of contamination of some anticipated common substances on NBS results obtained from dry spot samples. This possible pre-analytical source of uncertainty has been poorly examined in the past. Capillary blood was obtained from 15 adult volunteers and applied to 10 screening filter papers per volunteer. Nine filter papers were contaminated without visible trace. The contaminants were baby diaper rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The differences between control and contaminated samples were evaluated for 45 NBS quantities. We estimated if the contaminations might lead to false-positive NBS results. Eight of nine investigated contaminants significantly altered NBS analyte concentrations and potentially caused false-positive screening outcomes. A contamination with feces was most influential, affecting 24 of 45 tested analytes followed by liquid infant formula (HA) and urine, affecting 19 and 13 of 45 analytes, respectively. A contamination of filter paper samples can have a substantial effect on the NBS results. Our results underline the importance of good pre-analytical training to make the staff aware of the threat and ensure reliable screening results.

The Accuracy of Hospital ICD-9-CM Codes for Determining Sickle Cell Disease Genotype

Sickle cell disease affects more than 100,000 individuals in the United States, among whom disease severity varies considerably. One factor that influences disease severity is the sickle cell disease genotype. For this reason, clinical prevention and treatment guidelines tend to differentiate between genotypes. However, previous research suggests caution when using a claimsbased determination of sickle cell disease genotype in healthcare quality studies. The objective of this study was to describe the extent of miscoding for the major sickle cell disease genotypes in hospital discharge data. Individuals with sickle cell disease were identified through newborn screening results or hemoglobinopathy specialty care centers, along with their sickle cell disease genotypes. These genotypes were compared to the diagnosis codes listed in hospital discharge data to assess the accuracy of the hospital codes in determining sickle cell disease genotype. Eighty-three percent (sickle cell anemia), 23% (Hemoglobin SC), and 31% (Hemoglobin Sβ+ thalassemia) of hospitalizations contained a diagnosis code that correctly reflected the individual's true sickle cell disease genotype. The accuracy of the sickle cell disease genotype coding was indeterminate in 11% (sickle cell anemia), 12% (Hemoglobin SC), and 7% (Hemoglobin Sβ+ thalassemia) and incorrect in 3% (sickle cell anemia), 61% (Hemoglobin SC), and 52% (Hemoglobin Sβ+ thalassemia) of the hospitalizations. The use of ICD-9-CM codes from hospital discharge data for determining specific sickle cell disease genotypes is problematic. Research based solely on these or other types of administrative data could lead to incorrect understanding of the disease.

Evaluation and Importance of Our Newborn Hearing Screening Results

Evaluation and Importance of Our Newborn Hearing Screening Results

Indifferent or Uninformed? Reflections of Health Professionals on Parental Education and Consent for Expanded Newborn Screening in Israel, 2008–2016

Background: This study explored the views of health professionals regarding parental education and informed consent for newborn screening (NBS) following the expansion of the NBS program in Israel. Methods: 24 in-depth interviews with 22 practitioners involved in NBS in Israel, and internationally, were conducted and analyzed qualitatively. Results and discussion: 1. Program creators, who were involved in the development, design, implementation, and delivery of the expanded NBS program, were concerned about the “indifferent” attitude of parents of newborns to NBS as opposed to their high awareness and utilization of prenatal screening. 2. Program creators evaluated program success by different standards of parental education and informed consent than did practitioners, who were involved solely or mostly in the delivery of NBS results. The latter were skeptical about the possibility of obtaining informed consent and expressed diverse views about desired levels of education and consent. Eight years later, parental indifference to NBS is still a major concern for program creators, but not for practitioners. Conclusions: Program creators, due to their role and direct responsibility, assess NBS as an independent, stand-alone process about which parents should be informed and educated. Therefore, they focus on the indifference of parents to NBS as a non-optimal achievement of one programmatic aspect. Practitioners, on the other hand, perceive the medical care of the newborn holistically, focusing on the overall well-being of the baby. Therefore, they would be satisfied if the best possible medical care is provided to the newborn, by screening, confirmatory diagnosis, and follow up, even if parents are less informed about the process.

Congenital Galactosemia

Before the widespread use of newborn screening programs, galactosemia often presented with Escherichia coli sepsis late in the newborn period. Although newborn screening results are often available within 1 to 2 weeks, it is important to remember the subtle clinical features that may present themselves earlier in the clinical course. Recognition of the clinical presentation and knowledge of the tests necessary to diagnose the disease can lead to early detection and immediate interventions, thereby decreasing the severity of long-term outcomes. This review focuses on galactosemia, with an emphasis on classic galactosemia: the pathophysiology, genetics, clinical features both in the neonatal period as well as later in infancy and childhood, screening and diagnostic testing, and treatment and management strategies.

A Paper-Based Test for Screening Newborns for Sickle Cell Disease

The high cost, complexity and reliance on electricity, specialized equipment and supplies associated with conventional diagnostic methods limit the scope and sustainability of newborn screening for sickle cell disease (SCD) in sub-Saharan Africa and other resource-limited areas worldwide. Here we describe the development of a simple, low-cost, rapid, equipment- and electricity-free paper-based test capable of detecting sickle hemoglobin (HbS) in newborn blood samples with a limit of detection of 2% HbS. We validated this newborn paper-based test in a cohort of 159 newborns at an obstetric hospital in Cabinda, Angola. Newborn screening results using the paper-based test were compared to conventional isoelectric focusing (IEF). The test detected the presence of HbS with 81.8% sensitivity and 83.3% specificity, and identified SCD newborns with 100.0% sensitivity and 70.7% specificity. The use of the paper-based test in a two-stage newborn screening process could have excluded about 70% of all newborns from expensive confirmatory testing by IEF, without missing any of the SCD newborns in the studied cohort. This study demonstrates the potential utility of the newborn paper-based test for reducing the overall cost of screening newborns for SCD and thus increasing the practicality of universal newborn SCD screening programs in resource-limited settings.

Maternal Emotional Reactions towards Results of Newborn Hearing Screening: A Cross Sectional Survey

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Sigaranın Yenidoğan İşitme Fonksiyonu Üzerine Etkisi

Objectives: Maternal tobacco smoking has many negative effects on fetus. The aim of this study is to determine the effects of smoking during pregnancy on neonatal hearing screening. Smoking has been found positively associated with hearing loss in adults. Materials and Methods: A total of 919 women who were followed in Obstetrics and Gynecology Clinic of Ataturk Training and Research Hospital during pregnancy and who gave birth between 01 January 2011 - 30 December 2012 in the same clinic were included in the study with their newborn babies. Women with systemic diseases, pregnancy complications, familial hearing loss history and newborns in the neonatal unit were excluded. The included 919 pregnant women were divided into 2 groups; smokers (group 1) and non-smokers (group 2). Of these, age, gravidity, parity, gestational age, birth weight, mode of delivery, gender, newborn hearing screening results were statistically compared. Results: When smokers and non smokers were compared, no statistically significant differences were found in terms of age, parity, gestational age, birth weight, sex, and type of delivery, but the gravida difference was statistically significant. Smoker and non-smoker otoacoustic emission test results between groups had no significant difference. Conclusion: Smoking during pregnancy has harmful effects both on mother and fetus. In this study, the pregnancy was found to have no significant effect on newborn hearing screening. However, as the results are specific for this study, further studies are needed with the assessment of limitations.

Newborn screening for six lysosomal storage disorders in a cohort of Mexican patients: Three-year findings from a screening program in a closed Mexican health system.

To evaluate the results of a lysosomal newborn screening (NBS) program in a cohort of 20,018 Mexican patients over the course of 3years in a closed Mexican Health System (Petróleos Mexicanos [PEMEX] Health Services). Using dried blood spots (DBS), we performed a multiplex tandem mass spectrometry enzymatic assay for six lysosomal storage disorders (LSDs) including Pompe disease, Fabry disease, Gaucher disease, mucopolysaccharidosis type I (MPS-I), Niemann-Pick type A/B, and Krabbe disease. Screen-positive cases were confirmed using leukocyte enzymatic activity and DNA molecular analysis. From July 2012 to April 2016, 20,018 patients were screened; 20 patients were confirmed to have an LSD phenotype (99.9 in 100,000 newborns). Final distributions include 11 Pompe disease, five Fabry disease, two MPS-I, and two Niemann-Pick type A/B patients. We did not find any Gaucher or Krabbe patients. A final frequency of 1 in 1001 LSD newborn phenotypes was established. NBS is a major public health achievement that has decreased the morbidity and mortality of inborn errors of metabolism. The introduction of NBS for LSD presents new challenges. This is the first multiplex Latin-American study of six LSDs detected through NBS.

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis

To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P < .006) but no differences in anxiety or vulnerability (P > .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families.

The results of newborn hearing screening by means of transient otoacoustic emissions – has anything changed over 10 years?

ObjectivesUniversal newborn hearing screening (UNHS) has become the standard of care in many countries. The aim of this study was to evaluate the results of UNHS after ten years of the program in Poland and to compare them with the results of 2003. MethodsIn the study, we analyze the results of UNHS in the University Hospital in Poznan, Poland. Between 01.01.2013 and 31.12.2013, 6827 children were examined by means of otoacoustic emissions. ResultsRisk factors (RF) were identified in 772 (11.3%) newborns, which is significantly less than 10 years ago (p < 0.05). The most frequent RF were: ototoxic medications, treatment in neonatal intensive care unit (NICU) and prematurity < 33 weeks of gestation. In 2003, the most frequent were ototoxic medications and prematurity, less frequent was treatment in NICU and more common was low Apgar score.In 51 (6.6%) newborns with RF, the result of OAE was positive either unilaterally or bilaterally. In infants without RF the result was positive unilaterally in 22 (0.4%) and bilaterally in 14 (0.2%) patients. These results are significantly lower than in our former study.The relative risk of positive result was the highest in infants with complex congenital anomalies (RR = 44.99), craniofacial anomalies (RR = 17.46) and mechanical ventilation for > 5 days (RR = 10.69). In our previous study, the highest RR of positive test results was in infants with family history, congenital malformations and low Apgar score.We found that most predictive as to the final diagnosis was bilaterally positive OAE test. In most patients, the second check confirmed the diagnosis, independently of RF.The number of false positive tests at the 1st level of screening is significantly lower now than 10 years ago, probably due to better staff training. ConclusionsLong term monitoring and the appropriate management of hearing deficit in children is essential. UNHS seems to be the most efficient way of finding children who require treatment of hearing impairment. The prevalence of most risk factors of hearing deficit has significantly changed over the years. The number of false positive results has significantly decreased over the years thanks to better staff training.

Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience.

Despite implementation of newborn screening (NBS), outcomes in cobalamin C disease (cblC) remain poor. Therapy with hydroxycobalamin and betaine is widely used, but dietary recommendations vary among metabolic centers. We present a longitudinal analysis of the relationship between metabolic control, diet, and outcomes in a cohort of cblC patients. We completed a retrospective analysis of 12 patients with cblC referred for abnormal NBS results and followed in our center between 1999 and 2015. Of the patients, 87.5% had intellectual disability and 75% had retinopathy; 16.7% had one episode of mild acidosis. However, no patients manifested major metabolic decompensation. Developmental outcomes correlated more closely with initial metabolic abnormalities than with long-term metabolic control. Increased intake of medical foods resulted in better control but also perturbations in the ratios of essential amino acids and lower z-scores for head circumference. We found no relationship between diet and cognitive outcomes. Although dietary therapy for cblC patients improves metabolic control, few patients experience metabolic decompensation regardless of diet. Increased incomplete protein intake is not correlated with improvements in outcomes. Overall, outcomes are poor despite early initiation of therapy and regardless of the dietary strategy used.Genet Med advance online publication 02 February 2017.

Van Bölgesi Yenidoğan İşitme Tarama Sonuçları ve Literatür Taraması

Van Bölgesi Yenidoğan İşitme Tarama Sonuçları ve Literatür Taraması

Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers.

Identification of very long-chain acyl-CoA dehydrogenase deficiency is possible in the expanded newborn screening (NBS) due to the increase in tetradecenoylcarnitine (C14:1) and in the C14:1/C2, C14:1/C16, C14:1/C12:1 ratios detected in dried blood spots. Nevertheless, different confirmatory tests must be performed to confirm the final diagnosis. We have revised the NBS results and the results of the confirmatory tests (plasma acylcarnitine profiles, molecular findings, and lymphocytes VLCAD activity) for 36 cases detected in three Spanish NBS centers during 4 years, correlating these with the clinical outcome and treatment. Our aim was to distinguish unambiguously true cases from disease carriers in order to obtain useful diagnostic information for clinicians that can be applied in the follow-up of neonates identified by NBS.Increases in C14:1 and of the different ratios, the presence of two pathogenic mutations, and deficient enzyme activity in lymphocytes (<12% of the intra-assay control) identified 12 true-positive cases. These cases were given nutritional therapy and all of them are asymptomatic, except one. Seventeen individuals were considered disease carriers based on the mild increase in plasma C14:1, in conjunction with the presence of only one mutation and/or intermediate residual activity (18-57%). In addition, seven cases were classified as false positives, with normal biochemical parameters and no mutations in the exonic region of ACADVL. All these carriers and the false positive cases remained asymptomatic. The combined evaluation of the acylcarnitine profiles, genetic results, and residual enzyme activities have proven useful to definitively classify individuals with suspected VLCAD deficiency into true-positive cases and carriers, and to decide which cases need treatment.