Newborn Screening Results Research Articles

Analytical Evaluation of the Ideal Strategy for High-Throughput Flow Injection Analysis by Tandem Mass Spectrometry in Routine Newborn Screening

The introduction of tandem mass spectrometry (MS/MS) to clinical laboratories and the advent of expanded newborn screening (NBS) were crucial changes to public health programs worldwide. Speed, robustness, accuracy, selectivity, and specificity of analysis are all requirements of expanded NBS and are needed to minimize false positive results risks, to possibly eliminate false negatives, and to improve the positive predictive value of NBS. In this study, we firstly evaluated the analytical performances of the RenataDX Screening System, a fully integrated flow-injection MS/MS (FIA-MS/MS) IVD system for high-throughput dried blood spot (DBS) analysis in a routine NBS laboratory. Since a choice of several commercial NBS kits is available, we sought to compare NeoBaseTM 2 (PerkinElmer®) and MassChrom® (Chromsystems) non-derivatized kits on the RenataDX platform by evaluating their analytical performances. Moreover, we verified the degree of correlation between data obtained by the two different NBS MS/MS kits by FIA-MS/MS of over 500 samples. Our data suggest that both methods correlate well with clinically insignificant differences that do not impact the NBS result. Finally, while NeoBase™ 2 offers an easier and faster sample preparation, MassChrom® provides a cleaner sample extract which empirically should improve instrument reliability.

Provider Perspectives on the Impact of the COVID-19 Pandemic on Newborn Screening.

The onset of the COVID-19 pandemic caused significant changes in healthcare delivery. Telemedicine rapidly and unexpectedly became the primary vehicle for ambulatory management. As newborn screen (NBS) referrals require varying levels of acuity, whether telemedicine could be used as a safe and effective medium to return these results were unknown. We sent an online survey to metabolism providers internationally to investigate triage differences of abnormal NBS results during the COVID-19 pandemic. The survey compared personal practice for the periods of March–June 2019 and March–June 2020. Responses were received from 44 providers practicing in 8 countries. Nearly all (93%) practiced in areas of widespread SARS-COV-2 community transmission during spring 2020. There was a significant expansion of telemedicine use for NBS referrals at the onset of the COVID-19 pandemic (OR: 12, 95% CI: 3.66–39.3, p < 0.0001). Telehealth primarily replaced in-person ambulatory metabolism visits. The increased frequency of virtual care was similar across NBS analytes. Providers found telehealth for NBS referral equally efficacious to in-person care. Institutional patient surveys showed no difference in satisfaction with provider communication, provider empathy, or appointment logistics. Our survey was limited by unprecedented disruption in healthcare delivery, necessitating further validation of telegenetics for NBS in the post-pandemic era. Nevertheless, our findings demonstrate that telemedicine is potentially a viable and practical tool for triaging abnormal NBS results.

Primary care providers' role in newborn screening result notification for cystic fibrosis.

To explore primary care providers' (PCPs') role in result notification for newborn screening (NBS) for cystic fibrosis (CF), given that expanded NBS has increased the number of positive screening test results, drawing attention to the role of PCPs in supporting families. Cross-sectional survey and qualitative interviews. Ontario. Primary care providers (FPs, pediatricians, and midwives) who received a positive CF NBS result for an infant in their practice in the 6 months before the study. Whether the PCP notified the family of the initial positive CF screening result. Data from 321 PCP surveys (response rate of 51%) are reported, including 208 FPs, 68 pediatricians, and 45 midwives. Interviews were completed with 34 PCPs. Most (65%) surveyed PCPs reported notifying the infant's family of the initial positive screening result; 81% agreed that they have an important role to play in NBS; and 88% said it was important for PCPs, rather than the NBS centre, to notify families of initial positive results. With support and information from NBS centres, 68% would be extremely or very confident in doing so; this dropped to 54% when reflecting on their recent reporting experience. More than half (58%) of all PCPs said written point-of-care information from the NBS centre was the most helpful format. Adjusted for relevant factors, written educational information was associated with a lower rate of notifying families than written plus verbal information (risk ratio of 0.79; 95% CI 0.69 to 0.92). In the interviews, PCPs emphasized the challenge of balancing required content knowledge with the desire for the news to come from a familiar provider. Most PCPs notify families of NBS results and value this role. These data are relevant as NBS programs and other genomic services expand and consider ways of keeping PCPs confident and actively involved.

Newborn screening for cystic fibrosis: Role of primary care providers in caring for infants with positive screening results.

To explore primary care providers' (PCPs') preferred roles and confidence in caring for infants receiving a positive cystic fibrosis (CF) newborn screening (NBS) result, as well as management of CF family planning issues, given that expanded NBS has resulted in an increase in positive results. Mailed questionnaire. Ontario. Ontario FPs, pediatricians, and midwives identified by Newborn Screening Ontario as having had an infant with a positive CF NBS result in their practice in the previous 6 months. Primary care providers' preferred roles in providing well-baby care for infants with positive CF screening results. Overall, 321 of 628 (51%) completed surveys (208 FPs, 68 pediatricians, 45 midwives). For well-baby care for infants confirmed to have CF, 77% of PCPs indicated they would not provide total care (ie, 68% would share care with other specialists and 9% would refer to specialists completely); for infants with an inconclusive CF diagnosis, 50% of PCPs would provide total care, 45% would provide shared care, and 5% would refer to a specialist; for CF carriers, 89% of PCPs would provide total care, 9% would provide shared care, and 2% would refer. Half (54%) of PCPs were extremely or very confident in providing reassurance about CF carriers' health. Only 25% knew how to order parents' CF carrier testing; 67% knew how to refer for prenatal diagnosis. Confidence in reassuring parents about the health of CF carrier children was associated with providing total well-baby care for CF carriers (risk ratio of 1.50; 95% CI 1.14 to 1.97) and infants with an inconclusive diagnosis (risk ratio of 3.30; 95% CI 1.34 to 8.16). Most PCPs indicated willingness to treat infants with a range of CF NBS results in some capacity. It is concerning that some indicated CF carriers should have specialist involvement and only half were extremely or very confident about reassuring families about carrier status. This raises issues about possible medicalization of those with carrier status, prompting the need for PCP education about genetic disorders and the meaning of genetic test results.

A Clinical Study on Gestational Diabetes Mellitus and the Hearing of Newborns.

ObjectiveThis study aimed to explore the impact of gestational diabetes mellitus (GDM) on the results of newborn hearing screening.MethodsA total of 666 pregnant women who gave birth in the Obstetric Department of Sunshine Ronghe Hospital from August 2017 to May 2018 were randomly selected, and 69 of these pregnant women had GDM and were assigned into group 1 (excluding other diseases). The average age of these patients was 31.07 years. A further 597 pregnant women had no GDM and were assigned into group 2 (excluding other diseases). The average age of these patients was 30.02 years. The results of newborn hearing screening results in group 1 and group 2 were compared.ResultsComparisons of abnormal hearing screening between 2 groups are significant different (P < 0.05). In the GDM group, the results of hearing screening of newborns delivered by vaginal delivery and cesarean delivery were compared, yielding a P-value of > 0.05, and the difference was not statistically significant. In the non-GDM group, the results of hearing screening of newborns delivered by vaginal delivery and cesarean delivery were compared, yielding a P-value of >0.05, and the difference was not statistically significant.ConclusionGDM increases the incidence of abnormal hearing in newborns.

Newborn Hearing Screening Results of Duzce Province in the Western Black Sea Region

Aim: We aimed to evaluate the results of newborn hearing screening (NHS) conducted at Düzce Atatürk State Hospital, and review the results with the relevant literature. Material and Methods: The hearing screening results of 20071 newborns whose hearing screening was conducted at Düzce Atatürk State hospital between January 2011 and December 2018 were evaluated retrospectively in this study. Refugees were not included in the study. Newborns without risk factors who came to the first test were evaluated with transient evoked otoacoustic emissions (TEOAE). If they failed from the first screening test were evaluated again 15 days later with TEOAE. Newborns who failed the second screening test were evaluated a third time with ABR. Newborns with risk factors were first evaluated with auditory brainstem response (ABR).The risky newborns who failed the first screening test were evaluated second time with ABR. Results: Hearing loss was present in 62 (0.30%) of the 20071 newborns and was unilateral in 35 (0.17%) and bilateral in 27 (0.13%) subjects. Conclusion: For the rehabilitation of babies with hearing loss, their treatment should be started as early as possible. Newborn hearing screening tests are a screening program that has been successfully applied in our country for many years and enables the detection of babies with hearing loss. With this screening program, babies with hearing loss can be detected at an early stage and their treatment and rehabilitation can be provided. The results of our study are consistent with other hearing screening results from our country.

Opinions of adults affected with later-onset lysosomal storage diseases regarding newborn screening: A qualitative study.

Lysosomal storage diseases (LSDs) are a heterogeneous group of conditions causing substrate accumulation leading to progressive organ damage. Newborn screening (NBS) for several LSDs has become available in recent years due to advances in technology and treatment availability. While early initiation of treatment is lifesaving for those with infantile presentations, controversy continues regarding diagnosis of milder, later-onset diseases in infancy, including creation of pre-symptomatic populations of 'patients-in-waiting', the potential for medicalization, stigmatization, and/or discrimination. In-depth interviews were conducted with 36 adults [11 with Fabry disease (FD), 8 with Gaucher disease (GD), and 17 with late-onset Pompe disease (LOPD)], to determine their perspectives on NBS for their respective conditions. Thirty-four of 36 participants were in favor of NBS; both participants not in favor had GD1. Emergent themes influencing participants favorably toward NBS included earlier age of onset, a long diagnostic odyssey, less efficacious treatment, and the desire to have made different life decisions (e.g., relationships, career, or lifestyle) with the knowledge of their diagnosis. Concerns about insurance discrimination and psychological or physical burdens were associated with less favorable opinions of NBS. The ability for parents to make future reproductive decisions based their child's NBS result was considered favorably by some participants and unfavorably by others. Participants' specific condition (GD1, FD, or LOPD) contributed to these experiences differently. Participants with LOPD and FD favored NBS to initiate earlier treatment and prevent irreversible organ damage, whereas fewer patients with GD1 mentioned this benefit. Participants with LOPD had the longest diagnostic odyssey, while those with FD were more likely to report feeling misunderstood and experiencing accusations of malingering, both contributing to favorable views of NBS. Results expand prior quantitative findings by illuminating how participants' lived experiences can shape opinions about NBS. By understanding how currently affected individuals perceive the lifelong impact of a NBS result, genetic counselors can provide better anticipatory guidance to the parents of individuals diagnosed with a later-onset LSD by NBS.

Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up.

X-linked adrenoleukodystrophy (ALD) is a recent addition to the Recommended Uniform Screening Panel, prompting many states to begin screening newborns for the disorder. We provide California’s experience with ALD newborn screening, highlighting the clinical and epidemiological outcomes observed as well as program implementation challenges. In this retrospective cohort study, we examine ALD newborn screening results and clinical outcomes for 1,854,631 newborns whose specimens were received by the California Genetic Disease Screening Program from 16 February 2016 through 15 February 2020. In the first four years of ALD newborn screening in California, 355 newborns screened positive for ALD, including 147 (41%) with an ABCD1 variant of uncertain significance (VUS) and 95 males diagnosed with ALD. After modifying cutoffs, we observed an ALD birth prevalence of 1 in 14,397 males. Long-term follow-up identified 14 males with signs of adrenal involvement. This study adds to a growing body of literature reporting on outcomes of newborn screening for ALD and offering a glimpse of what other large newborn screening programs can expect when adding ALD to their screening panel.

Our Newborn Hearing Screening Results of Infants with Congenital Hypothyroidism

Objective: We aimed to reveal newborn hearing screening test results and risk factors of babies diagnosed with congenital hypothyroidism (CH) in our hospital. Material and Methods: The files of the newborns who were evaluated within the scope of the national newborn screening program between January and December 2019 were retrospectively reviewed. Risk factors were evaluated by comparing newborn hearing screening test results of babies with CH and euthyroid control groups. Results: There was no significant difference between the two groups in terms of demographic and pregnancy datas. There was no significant difference between the CH and control groups in terms of the rate of failed/passed patients from the hearing screening tests. Patients with thyroid hypoplasia at CH group failed at a higher rate from the first hearing screening test. Conclusion: In this study, there was no significant difference between CH and control groups in terms of hearing screening results.

The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses.

BackgroundGlutaric acidemia type I (GA1) is an organic acidemia that is often unrecognized in the newborn period until patients suffer an acute encephalopathic crisis, which can be mistaken for nonaccidental trauma. Presymptomatic identification of GA1 patients is possible by newborn screening (NBS). However, the biochemical “low‐excretor” (LE) phenotype with nearly normal levels of disease metabolites can be overlooked, which may result in untreated disease and irreversible neurological sequelae. The LE phenotype is also a potential source of false negative (FN) NBS results that merits further investigation.MethodsSamples from six LE GA1 patients were analyzed by biochemical and molecular methods and newborn screen outcomes were retrospectively investigated.ResultsFive LE GA1 patients were identified that had normal NBS results and three of these presented clinically with GA1 symptoms. One additional symptomatic patient was identified who did not undergo screening. Semiquantitative urine organic acid analysis was consistent with a GA1 diagnosis in two (33%) of the six patients, while plasma glutarylcarnitine was elevated in four (67%) of the six and urine glutarylcarnitine was elevated in four (80%) of five patients. Five GCDH variants were identified in these patients; three of which have not been previously linked to the biochemical LE phenotype.ConclusionsThe data presented here raise awareness of potential FN NBS results for LE GA1 patients. The LE phenotype is not protective against adverse clinical outcomes, and the possibility of FN NBS results calls for high vigilance amongst clinicians, even in the setting of a normal NBS result.

Results of Newborn Hearing Screening in Sakarya

Amaç: Kalıcı işitme kaybı en sık görülen konjenital hastalıklardan biridir. İnsidansının bin canlı doğumda 1-3 arasında olduğu düşünülmektedir. Tarama yapılmazsa işitme kaybının en erken 2 yaşında anlaşılabildiği ve bunun da çocuğun gelişimi için oldukça kötü sonuçlar doğurduğu bildirilmiştir. Bu çalışmada Sakarya ilindeki hastanelerde 2018 yılında yapılan tüm yenidoğan işitme taramalarının değerlendirilmesi amaçlanmıştır. Yöntem: Araştırma Sakarya İlindeki hastanelerde 2018 yılında yapılan yenidoğan işitme taramalarını kapsamaktadır. Toplam 15235 yenidoğana ilk tarama testi yapılmıştır. Bulgular:Sakarya ilinde 2018 yılında 15235 bebeğe işitme taraması yapılmıştır. İlk tarama testini bebeklerin %33,7’si geçememiştir. İkinci tarama testine alınan 5135 bebeğin 131’i ikinci tarama testini de geçemediği için ileri tetkik ve tedavilerinin yapılması için referans hastaneye sevki yapılmıştır. Sonuç:İlk taramanın tüm hastanelerde standart yapılamaması tarama programının başarısındaki en önemli engellerden biridir. Hastanelerin bu konuda sertifikalandırılması ve taramadan kalan bebek sıklıklarının düzenli takip edilmesinin programı daha başarılı kılacağını düşünmekteyiz.

Mode of delivery was associated with transient changes in the metabolomic profile of neonates.

To estimate potential differences in neonatal metabolomic profiles at birth and at the time of newborn screening by delivery mode. A prospective study at Women's Clinic at Landspitali-The National University Hospital of Iceland. Women having normal vaginal birth or elective caesarean section from November 2013 to April 2014 were offered participation. Blood samples from mothers before birth and umbilical cord at birth were collected and amino acids and acylcarnitines measured by tandem mass spectrometry. Results from the Newborn screening programme in Iceland were collected. Amino acids and acylcarnitines from different samples were compared by delivery mode. Eighty three normal vaginal births and 32 elective caesarean sections were included. Mean differences at birth were higher for numerous amino acids, and some acylcarnitines in neonates born vaginally compared to elective caesarean section. Maternal blood samples and newborn screening results showed small differences that lost significance after correction for multiple testing. Many amino acids and some acylcarnitines were numerically higher in cord blood compared to maternal. Many amino acids and most acylcarnitines were numerically higher in newborn screening results compared to cord blood. We observed transient yet distinct differences in metabolomic profiles between neonates by delivery mode.

An Unusual Case of Chest Pain in a 9-Year Old Immigrant

CASE PRESENTATION: A nine-year-old female with no past medical history presented to the emergency department with a two-week history of chest pain associated with tactile fevers and cough. One-year prior, she traveled by foot from Venezuela to the United States crossing through five countries and was detained in both Panama and the U.S. border prior to arriving in Atlanta four months ago. On physical exam, she appeared thin and emaciated, with decreased breath sounds on the right, but otherwise was in no respiratory distress with normal oxygen saturations. Initial work-up revealed leukocytosis, normocytic anemia, elevated inflammatory markers, and a normal blood smear. Chest X-Ray showed a dense opacity of the right upper lobe with mass effect of the right main stem bronchus (Image 1). Subsequent CT scan was notable for a large cavitary lesion of the right upper lobe concerning for abscess (Image 2) with hilar lymphadenopathy and a small spleen. She was empirically started on vancomycin and ceftriaxone but narrowed to clindamycin after sputum culture grew MRSA. One week into hospitalization, her anemia worsened, prompting a hemoglobin electrophoresis test, which revealed the delayed diagnosis of hemoglobin SS disease complicated by acute chest syndrome. She improved on antibiotics without blood transfusions and was discharged in stable condition to complete a four-week course of oral clindamycin. Chart review revealed multiple missed appointments, and she has been lost to follow-up. DISCUSSION: This case highlights many important takeaways healthcare providers must consider when providing care to immigrant patients. Although three-quarters of newborns with sickle cell disease (SCD) are born in sub-Saharan Africa, there is a generous and underappreciated population affected within Latin America, where many developing countries lack newborn screening programs. In the U.S., providers often rely on newborn screening results, which over time has likely decreased our index of suspicion in older children for conditions we typically diagnose prenatally or in the newborn period. Despite multiple subspecialties being involved in this patient’s care, providers failed to consider SCD as a possible etiology despite early findings of anemia and a small spleen on CT scan. Although advancements in newborn screening, genetic counseling, and prenatal ultrasound have changed the prevalence and presentations of genetic and congenital disorders, we as providers must maintain a high index of suspicion. Additionally, fear of deportation, language barriers, limited financial resources, and low health literacy are some of the many barriers immigrant patients face when seeking care in this country. In this case, the family spoke French Creole; access to a language line was crucial. Providers must ensure families have an appropriate understanding of the disease process and address socio-cultural and economic concerns to prevent at risk children from being lost to follow-up.

Analysis of parent perception of newborn screening for lysosomal disorders

Lysosomal storage disorders (LSD) are a family of rare metabolic disorders that include Pompe disease and Mucopolysaccharidosis Type 1 (MPS1). Pompe disease is caused by deficiencies in the lysosomal enzyme alpha-glucosidase (GAA). This diagnosis is generally divided into infantile and late onset, but can exist along a spectrum. The main feature of Pompe disease is progressive muscle weakness, and in the infantile onset form, cardiomyopathy is present as well. MPS1 results from a deficiency in the lysosomal enzyme alpha-L-iduronidase (IDUA). Features include progressive neurological disease, skeletal abnormalities, cardiac disease, corneal clouding, hearing loss and hepatomegaly. The diagnosis has been stratified into MPS1 or attenuated MPS1, and severity or development of symptoms is dependent on the type. Both Pompe disease and MPS1 were recently added to the newborn screening panel. With their addition, a number of challenges have occurred including negative psychosocial impact on parents of infants who have an abnormal newborn screening result. The purpose of this study was to examine the experience and perceptions of parents/caregivers of an infant who had a positive newborn screening result for Pompe disease or MPS1. A survey was distributed via email and mailer, to parents and caregivers followed by the UPMC Children’s Hospital of Pittsburgh and the Children’s Hospital of Philadelphia. The survey consisted of questions specific to newborn screening of LSDs. Parent responses, were consistent with the literature, indicating that this period was categorized by stress and uncertainty. Of the five respondents, 100% described initial disclosure of the newborn screening results as difficult. Responses suggest that negative emotions were fueled by lack of information provided about the results, and provider’s lack of knowledge. Similar to published literature, this study indicated the majority of infants are not diagnosed with the most severe forms of the disorders. Results of this study may have implications for how genetic counselors care for these families and how they communicate with other providers. Likewise, it demonstrates public health relevance given the large scale in which newborn screening is utilized. This information can be used by providers in their own practice and may even influence standard of care.

Differences in Newborn Screening Results Among Women with Gestational Diabetes Mellitus

Multiple studies undertaken on cord blood demonstrate analyte perturbations in infants exposed to gestational diabetes mellitus (GDM). Cord blood as a sample is influenced by maternal and placental metabolism. Newborn screening (NBS), performed after the first 24 hours of life reflects early neonatal metabolism. We compared NBS analytes between women with and without GDM with different management approaches in the Treatment of Booking of Gestational Diabetes (TOBOGM) pilot randomised controlled trial. Pregnant women with GDM risk factors were randomised to early or deferred GDM treatment following an oral glucose tolerance test (<20 weeks gestation). Women without GDM served as “decoys”. From the decoy group 11 developed GDM (screened at 26-28 weeks), were analysed separately; their results were compared with the other groups. De-identified controls were chosen from NBS results from the same analytic run matched for sex, birthweight and gestational age. Results were available for 73/78 women participating in the pilot and 358 de-identified controls. Tyrosine levels (μmol/l; whole blood)were higher in the late GDM group vs early, deferred treatment, and decoy groups (medians:106.28; IQR: 96.73-151.11) (76.33; 64.64-97.90) (75.68; 66.59-110.88)(73.74; 58.32-90.36) (p=0.009) and remained elevated when compared to normal, age-matched controls (106.28; 96.73-151.11) (87.26; 68.55-111.26) (p value=0.01) Immunoreactive trypsinogen (μgm/l; whole blood)was highest in the early treatment group when compared with group-specific controls (22.30; 13.90-29.90 vs 14.00, 10.60-21.10) (p=0.02). These results provide evidence of biochemical perturbations detectable on NBS of in-utero exposure to hyperglycemia and treatment and provide data for hypothesis building.

Results of Newborn Hearing Screening, Tepecik Education and Research Hospital

The Anatolian Journal of Family Medicine is an international periodical on family medicine and primary health care, published three times a year on independent, unbiased, double-blinded and peer-review principles.

Our newborn hearing screening results.

OBJECTIVE:The aim of the study was to evaluate the results of neonatal hearing screening in our hospital with the help of literature and to question and reveal the risk factors to gain healthy individuals and to raise awareness for all health workers and the public who are interested in this subject.METHODS:A total of 16,388 newborn infants were evaluated between October 2009 and January 2018. All newborns were screened with transient evoked otoacoustic emissions (TEOAEs) test. Risk factors were investigated. The test repetition and auditory brainstem response (ABR) measurements were performed on newborns who could not pass the TEOAE test and the newborns in the risky group after 15 days.RESULTS:A total of 116 newborns (0.7%) were suspected to have hearing loss. Twenty-seven newborns (0.16%) were found to be in intensive care unit. Twelve newborns (0.07%) had permanent hearing loss. Then, in order: 9 newborns (0.05%) had received phototherapy and 7 newborns (0.04%) were born to consanguineous marriages. In addition, 3 newborns (0.02%) had a low birth weight and 1 newborn (0.006%) had a history of fever.CONCLUSION:Screening tests should be performed in all newborns for early detection of hearing loss. Even though frequency of hearing loss is higher in newborns with risk factors, the treatment should be started within 6 months, the latest, and newborns should be referred for rehabilitation and training.

Newborn Screening using Dried Blood Spot for Seven Metabolic Disorders- A Retrospective Study from a Tertiary Care Hospital in Southern India

Introduction: Newborn Screening (NBS) is an important public health measure in many developed countries. In developing countries like India, the benefits of NBS have been acknowledged and that screening is slowly gaining attention. Aim: To estimate the proportion for seven conditions screened in a tertiary care hospital in Southern India namely Congenital Hypothyroidism (CH), Congenital Adrenal Hyperplasia (CAH), Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, Biotinidase Deficiency (BD), Galactosemia, Phenylketonuria (PKU) and Cystic Fibrosis (CF). Materials and Methods: The present descriptive study was conducted at a tertiary care teaching hospital in Southern India during a three year period between January 2018 to December 2020. A retrospective analysis of the results of NBS by dried blood spots was done. There were 3152 live births during this period out of which 1649 babies were screened (52% coverage). Heel prick samples after 48 hour of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for confirmatory tests. Results: The CH, BD and G6PD deficiency were the most common disorders with a proportion of 1:824, 1:1649 and 1:1649, respectively. Galactosemia, CF and PKU were not found in study population. Conclusion: These results need to be corroborated with larger studies from the same geographical area.

Evaluation of a Common Internal Standard Material to Reduce Inter-Laboratory Variation and Ensure the Quality, Safety and Efficacy of Expanded Newborn Screening Results When Using Flow Injection Analysis Tandem Mass Spectrometry with Internal Calibration.

In 2015, the newborn screening (NBS) programmes in England and Wales were expanded to include four additional disorders: Classical Homocystinuria, Isovaleric Acidemia, Glutaric Aciduria Type 1 and Maple Syrup Urine Disease, bringing the total number of analytes quantified to eight: phenylalanine, tyrosine, leucine, methionine, isovalerylcarnitine, glutarylcarnitine, octanoylcarnitine and decanoylcarnitine. Post-implementation, population data monitoring showed that inter-laboratory variation was greater than expected, with 90th centiles varying from 17% to 59%. We evaluated the effect of stable isotope internal standard (IS) used for quantitation on inter-laboratory variation. Four laboratories analysed routine screening samples (n > 101,820) using a common IS. Inter-laboratory variation was determined for the eight analytes and compared with results obtained using an in-house common IS (n > 102,194). A linear mixed-effects model was fitted to the data. Using a common IS mix reduced the inter-laboratory variation significantly (p < 0.05) for five analytes. For three analytes, the lack of significance was explained by use of individual laboratory “calibration factors”. For screening programmes where laboratories adhere to single analyte cut-off values (COVs), it is important that inter-laboratory variation is minimised, primarily to prevent false positive results. Whilst the use of a common IS helps achieve this, it is evident that instrument set-up also contributes to inter-laboratory variation.

Development of Strategies to Decrease False Positive Results in Newborn Screening.

The expansion of national newborn screening (NBS) programmes has provided significant benefits in the diagnosis and early treatment of several rare, heritable conditions, preventing adverse health outcomes for most affected infants. New technological developments have enabled the implementation of testing panel covering over 50 disorders. Consequently, the increment of false positive rate has led to a high number of healthy infants recalled for expensive and often invasive additional testing, opening a debate about the harm-benefit ratio of the expanded newborn screening. The false-positive rate represents a challenge for healthcare providers working in NBS systems. Here, we give an overview on the most commonly used strategies for decreasing the adverse effects due to inconclusive screening results. The focus is on NBS performance improvement through the implementation of analytical methods, the application of new and more informative biomarkers, and by using post-analytical interpretive tools. These strategies, used as part of the NBS process, can to enhance the positive predictive value of the test and reduce the parental anxiety and healthcare costs related to the unnecessary tests and procedures.