Exploration of clinical and ethical issues in an expanded newborn metabolic screening programme: a qualitative interview study of healthcare professionals in Hong Kong.

INTRODUCTION: The Newborn Screening Programme for Inborn Errors of Metabolism (NBSIEM) enables early intervention and prevents premature mortality. Residual dried bloodspots (rDBS) from the heel prick test are a valuable resource for research. However, there is minimal data regarding how stakeholders in Hong Kong view the retention and secondary use of rDBS. This study aimed to explore views of the NBSIEM and the factors associated with retention and secondary use of rDBS among healthcare professionals in Hong Kong. METHODS: Between August 2021 and January 2022, semi-structured interviews were conducted with 30 healthcare professionals in obstetrics, paediatrics, and chemical pathology. Key themes were identified through thematic analysis, including views towards the current NBSIEM and the retention and secondary use of rDBS. RESULTS: After implementation of the NBSIEM, participants observed fewer patients with acute decompensation due to undiagnosed inborn errors of metabolism. The most frequently cited clinical utilities were early detection and improved health outcomes. Barriers to rDBS storage and its secondary use included uncertain value and benefits, trust concerns, and consent issues. CONCLUSION: This study highlighted healthcare professionals' concerns about the NBSIEM and uncertainties regarding the handling or utilisation of rDBS. Policymakers should consider these concerns when establishing new guidelines.

Home monitoring of haemoglobin A1c in diabetes: A systematic review and narrative synthesis on accuracy, reliability and patient acceptability.

AIM: In the UK people with diabetes who do not attend annual review appointments often have higher haemoglobin A1c (HbA1c ) levels. We aim to determine the acceptability of self-collected posted capillary blood samples, and if they produce accurate and reliable HbA1c results. METHODS: We include adult studies comparing capillary blood to venous blood for measuring HbA1c . We exclude methods not suitable for postage. Electronic databases of MEDLINE, Embase, CINAHL, Web of Science, Google Scholar and OpenGrey were searched from inception to September 2021, as well as relevant conference abstracts. Two reviewers performed study selection, data extraction and risk of bias assessment independently. Narrative synthesis was performed. RESULTS: Our search retrieved 3747 records. Following de-duplication and screening 30 articles were included. The mean difference (MD) and limits of agreement (LoA) between capillary and venous HbA1c were smaller and narrower respectively when micro/capillary tubes (micro/cap) were used for capillary blood storage compared to dried blood spots (capDBS) (micro/cap MD range -0.4 to 1.4 mmol/mol vs. capDBS MD range -4.3 to 7.2 mmol/mol, micro/cap LoA width 2.4 to 6 mmol/mol vs. capDBS LoA width 11.7 to 16.8 mmol/mol). After using self-collection kits, 83%-96% of participants reported satisfaction, 87%-99% found it easy and 69%-94% reported they would use it again. CONCLUSION: Microtubes/capillary tubes look promising as a method of self-collecting and posting capillary blood samples for the measurement of HbA1c based on the accuracy and reliability findings presented. DBS samples demonstrated comparatively poorer accuracy. Data on acceptability were limited and further research is needed.

Dried blood spot-based host genome analysis technique targeting pathological associations with hepatitis B: Development and clinical application in the Cambodian population.

AIM: Reports of patients with hepatitis B have highlighted associations between polymorphisms in the human leukocyte antigen (HLA)-DPB1, CXCL13, and CXCR5 genes and disease pathology. Owing to its potential to contribute to the development of new diagnostic and therapeutic methods, we aimed to establish a reliable host genome analysis technique that can be used in countries with inadequate infrastructure. METHOD: We compared multiple commercially available kits for dried blood spot (DBS)-based sample collection to develop a basic DBS-based host genome analysis technique. We then collected blood samples from Cambodian patients with hepatitis  B and performed single-nucleotide polymorphism genotyping and HLA allele typing by the DBS system. RESULT: We were able to perform single-nucleotide polymorphism genotyping and HLA allele typing with host DNA samples obtained using a combination of a HemaSpot™ filter paper-based device and a SMITEST® EX-R&D DNA extraction kit. The accuracy of genotyping using samples obtained by this method was not inferior to one using samples obtained by venipuncture. In the Cambodian population, significant associations of HLA-DPB1*04:01 with protection against chronic hepatitis B virus (HBV) infection, and HLA-DPB1*05:01 and HLA-DPB1*13:01 with susceptibility to chronic HBV infection were identified. CONCLUSION: Based on the DBS system, we clarified the associations of HLA-DPB1 alleles with chronic HBV infection in the Cambodian population for the first time. Because the DBS is a low-cost, durable, transportable, and easy-to-handle modality, genetic analysis based on the DBS system is a feasible strategy for obtaining a deeper understanding of HBV epidemiology, especially in middle- or low-income countries.

High-risk screening for Fabry disease in hemodialysis patients in Chiba Prefecture, Japan.

BACKGROUND: High-risk screening for Fabry disease in dialysis patients is an effective means for reducing the number of undiagnosed cases. However, such screening has not been conducted in Chiba Prefecture, Japan. Herein, we aimed to estimate the prevalence of Fabry disease among patients undergoing hemodialysis in Chiba Prefecture by high-risk screening using α-galactosidase A (αGal A) activity measurement, and examine the hemodialysis effect on αGal A activity. METHODS: Patients who underwent maintenance hemodialysis at 25 facilities in Chiba Prefecture were recruited. The αGal A activity was measured using the dried blood spot (DBS) test as the first screening. If the enzyme activity was lower than the cut-off, the second screening was performed with the same method before and after dialysis. RESULTS: Overall, 2924 patients (2036 men and 888 women) were included from which 94 cases (45 men and 48 women) showed decreased αGAL activity in the first screening and 3 (two men and one women) in the second screening. Genetic testing was performed in 3 patients, and the c.1078G > A mutation in GLA gene was detected in one male patient (0.03%). There has been a statistically significant decrease in αGal A activity of DBS at post-dialysis compared to that at pre-dialysis (20.5 ± 10.4 pmol/h/disk and 22.7 ± 11.5 pmol/h/disk, p < 0.0001). CONCLUSION: The prevalence of Fabry disease among patients undergoing hemodialysis in Chiba Prefecture was estimated as 0.03%. This is the first time that dialysis has been shown to affect the αGal A activity.

Pilot hepatitis C micro-elimination strategy in Pakistani migrants in Catalonia through a community intervention.

BACKGROUND AND AIMS: Pakistani migrants in Catalonia, Spain, could have high hepatitis C virus (HCV) prevalence. The aims of the HepClink study were (i) to implement and assess the quality of a micro-elimination strategy based on a community intervention and (ii) to obtain data from primary care (PC) registries as a baseline comparator. METHODS: The community intervention targeted Pakistani adults and consisted of education, screening and simplified access to treatment. Quality indicators were calculated (effectiveness, impact and acceptability). The testing rate, the prevalence of HCV antibodies and HCV-RNA were compared with those observed in the Pakistani population accessing PC in the previous year. RESULTS: A total of 505 participants were recruited through the community intervention (64.6% men, median 37 years) vs those accessing PC (N = 25 455, 70.9% men, median 38 years). Among study participants, 35.1% did not know about HCV and 9.7% had been previously tested. The testing rate in the community intervention was 99.4% vs 50.7% in PC. Prevalence was 4.6% vs 7.1% (p = .008) for HCV antibodies and 1.4% (3/6 new diagnoses) vs 2.4% (p = .183) for HCV-RNA. Among the six viremic patients, three began treatment within the intervention and two through the usual circuit and all completed the full course. CONCLUSIONS: This novel community intervention was well accepted and effective at reaching a Pakistani migrant population with a low-level knowledge of HCV and largely not tested before. The observed prevalence and the high unawareness of their HCV status justify a targeted screening in this group both in the community and in PC.

An improved functional assay in blood spot to diagnose Barth syndrome using the monolysocardiolipin/cardiolipin ratio.

Barth syndrome is an X-linked disorder characterized by cardiomyopathy, skeletal myopathy, and neutropenia, caused by deleterious variants in TAFAZZIN. This gene encodes a phospholipid-lysophospholipid transacylase that is required for the remodeling of the mitochondrial phospholipid cardiolipin (CL). Biochemically, individuals with Barth syndrome have a deficiency of mature CL and accumulation of the remodeling intermediate monolysocardiolipin (MLCL). Diagnosis typically relies on mass spectrometric measurement of CL and MLCL in cells or tissues, and we previously described a method in blood spot that uses a specific MLCL/CL ratio as diagnostic biomarker. Here, we describe the evolution of our blood spot assay that is based on the implementation of reversed phase-UHPLC separation followed by full scan high resolution mass spectrometry. In addition to the MLCL/CL ratio, our improved method also generates a complete CL spectrum allowing the interrogation of the CL fatty acid composition, which considerably enhances the diagnostic reliability. This addition negates the need for a confirmatory test in lymphocytes thereby providing a shorter turn-around-time while achieving a more certain test result. As one of the few laboratories that offer this assay, we also evaluated the diagnostic yield and performance from 2006 to 2021 encompassing the use of both the original and improved assay. In this period, we performed 796 diagnostic analyses of which 117 (15%) were characteristic of Barth syndrome. In total, we diagnosed 93 unique individuals with Barth syndrome, including three females, which together amounts to about 40% of all reported individuals with Barth syndrome in the world.

Assessing the acceptability of dried blood spot testing for HIV and STBBI among Métis people in a community driven pilot project in Alberta, Canada.

BACKGROUND: Little literature exists on culturally grounded approaches for addressing human immunodeficiency virus (HIV) and sexually transmitted and blood-borne infections (STBBI) among Métis people. The goal of this mixed-methods research was to explore the experiences of Métis community members participating in a dried blood spot testing (DBST) for HIV/STBBI pilot for Métis communities in Alberta, Canada, with the aim of assessing the acceptability of this testing method. METHODS: Grounded in community-based and Indigenous research approaches and working in partnership with a Métis community-based organization, data collection included a survey and four gathering circles with Métis DBST recipients at one of two community events, and semi-structured interviews with three DBST providers. RESULTS: Twenty-six of the 30 DBST recipients completed surveys, and 19 DBST recipients participated in gathering circles. Survey results suggest DBST is a highly acceptable STBBI testing method to Métis community members. Thematic analysis of gathering circle and interview transcripts revealed four broad themes related to the participants' experiences with DBST related to its acceptability (i. ease of DBST process, ii. overcoming logistical challenges associated with existing STBBI testing, iii. Reducing stigma through health role models and event-based, and iv. Métis-specific services). CONCLUSIONS: These findings illustrate the potential for DBST to be part of a culturally grounded, Métis-specific response to HIV and STBBI.

Development and Validation of a Multiplex Microsphere Immunoassay Using Dried Blood Spots for SARS-CoV-2 Seroprevalence: Application in First Responders in Colorado, USA.

Serological testing of large representative populations for antibodies to SARS-CoV-2 is needed to estimate seroprevalence, transmission dynamics, and the duration of antibody responses from natural infection and vaccination. In this study, a high-throughput SARS-CoV-2 multiplex microsphere immunoassay (MMIA) was developed for the receptor binding domain (RBD) and nucleocapsid (N) that was more sensitive than enzyme-linked immunosorbent assay (ELISA) (98% versus 87%). The MMIA was then applied and validated in 264 first responders in Colorado using serum and dried blood spot (DBS) eluates, compared to ELISA, and evaluated for neutralizing antibodies. Four percent (11/264) of first responders were seropositive in July to August 2020. Serum and DBS were highly correlated for anti-RBD and anti-N antibodies (R = 0.83, P < 0.0001 and R = 0.87, P < 0.0001, respectively) by MMIA. The MMIA accurately predicted SARS-CoV-2 neutralizing antibodies using DBS (R = 0.76, P = 0.037). On repeat antibody testing 3 months later, anti-RBD IgG decreased less rapidly than anti-N IgG measured by MMIA, with a median change in geometric median fluorescence intensity of 62% versus 79% (P < 0.01) for anti-RBD and anti-N IgG, respectively. This novel MMIA using DBS could be scalable for rapid and affordable SARS-CoV-2 serosurveillance in the United States and globally.

The testing of people with any risk factor for hepatitis C in community pharmacies is cost-effective.

New antiviral drugs with high efficacy mean the hepatitis C virus (HCV) can now be eliminated. To achieve this, it is necessary to identify undiagnosed cases of HCV. However, the costs of testing should be considered when judging the overall cost-effectiveness of treatment. This study describes the cost-effectiveness of a community pharmacy testing service in a population of people at risk of HCV living on the Isle of Wight (United Kingdom). Dry blood spot testing was conducted in anyone with a known risk factor for HCV in 20 community pharmacies. The outcomes and costs were entered into a Markov model. Cost and health utilities from the model were used to calculate an incremental cost-effectiveness ratio (ICER). In 24 months, 186 tests were conducted, 13 were positive for HCV RNA and six of these (46%) received treatment during the follow-up period. All achieved a sustained virological response at 3 months. The overall cost of the testing and treatment intervention was £242 183, and the ICER for the service was £3689 per quality-adjusted life year (QALY) gained. If screening had been restricted to just people with a history of injecting drug use (PWID) the ICER would have been £4865 per QALY gained. The service was effective at identifying people with HCV infection, and despite the additional cost of targeted testing, its cost-effectiveness was below the commonly accepted thresholds. In this setting, restricting targeted testing to PWID would not improve the cost-effectiveness.

Stimulant Use and Study Protocol Completion: Assessing the Ability of Men Who Have Sex with Men to Collect Dried Blood Spots for Laboratory Measurement of HIV Viral Load.

Stimulant use is associated with higher HIV viral load (VL) and sexual HIV transmission risk among men who have sex with men (MSM) living with HIV. There is little research on willingness of drug users living with HIV to fully participate in studies, especially those involving self-collection of biomarker data. This study presents findings from an at-home dried blood spot collection study measuring laboratory-quantified VL among U.S. HIV-positive MSM who reported high-risk sexual behavior and/or suboptimal antiretroviral therapy (ART) adherence to assess the association between drug-use behavior and (1) ability to complete a study protocol and (2) VL outcomes. Among recruited participants (n = 766), 35% reported stimulant drug use (amphetamines, cocaine, crack, crystal meth, ecstasy, or a combination of stimulant drugs), 39% reported using other drugs (heroin, marijuana, prescription opioids, and others), and 27% reported no drug use in the past 3 months. In all, 61% of enrolled participants completed the study protocol. Stimulant drug users were less likely (ARR 0.84; 95% CI 0.72-0.98) to complete the protocol than other drug users. Furthermore, other drug users were significantly less likely than non-drug users (ARR 0.52; 95% CI 0.28-0.97) to have an HIV VL result ≥ 1500 copies/mL. This study provides important estimates regarding the likelihood of participation in biomedical research activities among HIV-positive MSM with varying drug-use behaviors, showing that it is feasible to conduct such biomedical studies with drug-using MSM who report high-risk sexual behavior and struggle with their ART adherence.

Parents' perspectives on dried blood spot self-sampling from children with epilepsy: A mixed-method study.

AIM: Children with epilepsy often have concomitant diagnoses. Dried blood spot samples for drug monitoring can be collected by parents at home as an alternative to traditional sampling. This mixed-method study aimed to understand the parents' perspectives on blood self-sampling from their children and to identify factors contributing to successful sampling. METHOD: Parents who had collected a sample from their child during a visit to the neuropediatric clinic were asked to fill in a questionnaire. To get in-depth information and individual perspectives, parents and nurses participated in semi-structured interviews and analysed with thematic analysis. RESULTS: The results from questionnaires (n = 64) and interviews (n = 9) were interpreted together. Watching an instruction video and practical training contributed to successful sampling. 97% of the parents managed to collect a sample, 72% thought it was easy to perform, and 80% found self-sampling at home desirable. Factors for success were as follows: high motivation, prepared parents with pre-understanding, a pragmatic attitude, flexible education, effective communication and willingness to take on the role as a performer. Risk factors were as follows: conflict, fear, unprepared parents, confused or worried children. CONCLUSION: Voluntary self-sampling at home for parents of children with epilepsy is feasible and can reduce stress factors in everyday life.

[Effects of delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots].

OBJECTIVE: To explore effects of different delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots (DBS), so as to provide evidence for improving accurate and reliable detection by tandem mass spectrometry. METHODS: A total of 1 254 616 newborn DBS samples in Newborn Screening Center of Zhejiang Province were delivered and stored at room temperature (group A, n=338 467), delivered by cold-chain logistics system and stored at low temperature (group B, n=480 021), or delivered by cold-chain logistics system and stored at low temperature and low humidity (group C, n= 436 128), respectively. The concentrations of amino acids and carnitines in DBS were detected by tandem mass spectrometry. Data analysis was performed by SPSS 24.0 to explore the influence of temperature and humidity on the concentrations of amino acids and carnitines. RESULTS: The concentrations of amino acids and carnitines in the three groups were skewed, and the differences in amino acid and carnitine concentrations among groups were statistically significant (all P<0.01). The median concentration of tyrosine was lower in group A than those in group B and group C by 18%and 16%respectively, while there was no significant difference between the last two groups. The median concentrations of methionine were lower in group A and group B than that in group C by 15%and 11%, respectively. The median concentrations of arginine were lower in group A and group B than that in group C by 12%and 25%, respectively. The median concentration of free carnitine (C0) was higher in group A than that in group C by 12%, while there was no significant difference between group A and group B. The median concentrations of acetylcarnitine (C2), propionyl carnitine (C3), C3DC+C4OH, C5DC+C6OH and hexadecanoyl carnitine (C16) were lower in group A than those in group B and group C by 21%-64%. The concentrations of other amino acids and acylcarnitines differed little among three groups. The monthly median coefficients of variation of other amino acids and carnitines in group A were higher than those in group B and group C except for citrulline, C4DC+C5OH and isovalerylcarnitine (C5). CONCLUSIONS: Cold-chain logistics system and storage in low temperature and low humidity can effectively reduce degradation of some amino acids and carnitines in DBS, improve the accuracy and reliability of detection, and thus ensures the quality of screening for neonatal metabolic diseases.

Newborn screening for severe combined immunodeficiency: Evaluation of a commercial T-cell receptor excision circle-based method in Victorian dried blood spots.

AIM: Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency and is fatal in infancy if untreated. As early diagnosis is associated with improved outcomes, SCID is an ideal condition to consider for inclusion in a newborn screening (NBS) programme in Australia. In this feasibility study, we evaluated the EnLite Neonatal TREC kit for detection of T-cell receptor excision circles (TRECs) from NBS dried blood spots for the identification of known SCID patients in Victoria. METHODS: TREC copies/µL were measured retrospectively in 14 children diagnosed with SCID or complete DiGeorge syndrome (CDGS) from 2005 to 2015 at the Royal Children's Hospital, Melbourne. In addition, TREC copies/µL were measured for 501 prospective de-identified NBS cards. RESULTS: Of 14 known SCID or CDGS samples, 11 were correctly identified as presumptive positive samples with low or undetectable TREC on duplicate testing. The remaining three samples also had low or undetectable TREC on duplicate testing but were considered invalid due to insufficient ß-actin DNA amplification. Of the 501 prospective NBS samples, none were identified as presumptive positive samples on duplicate testing. CONCLUSIONS: The EnLite Neonatal TREC kit correctly identified known SCID or CDGS patients as presumptive positive samples, and initial cut-offs for TREC and ß-actin in the Victorian NBS population were determined. A larger pilot study is required to confirm these proposed cut-offs and to evaluate the cost and implementation of this screening programme in Victoria, Australia. Overall, this study provides preliminary data to support the introduction of this assay to the NBS programme in Victoria.

Detection of Plasmodium using filter paper and nested PCR for patients with malaria in Sanliurfa, in Turkey.

BACKGROUND: The objective of this study to detect Plasmodium and a subspecies of Plasmodium using filter paper in malaria endemic province, Sanliurfa, in Turkey, compare the results of nested PCR (nPCR) with microscopy for the diagnosis of malaria and present the epidemiological data of malaria. METHODS: This study was carried out in malaria-endemic Sanliurfa between 2008 and 2011. Finger prick blood samples, thick and thin Giemsa-stained blood smears, were collected from 153 malaria-suspected farmworkers. The Giemsa-stained blood smears were examined microscopically. The obtained DNA products, extracted from blood-spotted filter papers or from the thick blood smears, were analysed by nPCR to amplify the 18S ssrRNA Plasmodium gene with genus and specific primers. The results of the microscopy were compared to the nPCR results. RESULTS: Of the specimens, 7.2 % were determined as Plasmodium-positive by microscopy, whereas 9.8 % were determined as Plasmodium-positive by nPCR. Of the positive Plasmodium specimens, 93.33 % were identified as P. vivax. Four out of the 15 specimens that were microscopically diagnosed as negative were Plasmodium-positive with nPCR. When compared to the microscopy, the sensitivity, specificity, and positive predictive values of the nPCR were determined as 100, 97.2 and 73.3 %, respectively. nPCR was determined to be more sensitive and specific than microscopy. CONCLUSIONS: This study revealed that the accurate diagnosis of malaria by nPCR was compulsory in malaria-endemic Sanliurfa and nPCR should be applied routinely in laboratory studies.

Glomerular filtration rate measured by iohexol clearance: A comparison of venous samples and capillary blood spots.

BACKGROUND: Glomerular filtration rate (GFR) measured by iohexol clearance using venous samples is widely used. Capillary sampling on filter paper is easier to perform, may be less painful and spares the blood volume. The purpose of the study was to validate a blood spot method for measuring GFR in children aged 6 years or younger suffering from chronic kidney disease (CKD). METHODS: We examined 32 children with CKD, median age (range) 3.0 (0.3-6.2) years. Seven venous samples (10, 30/60, 120, 180, 210, 240, 300 min) were collected and GFR based on all samples was calculated for reference. Following injection of iohexol, blood spots were collected at 120, 180, 210 and 240 min and compared to the reference iohexol clearance. RESULTS: Median (range) reference GFR was 65 (6-122) mL/min/1.73 m(2). The 2, 3 and 4-point blood spot GFR were highly correlated to the reference GFR (r = 0.947, 0.945, 0.937). The mean relative bias between 2-point blood spot and reference GFR was 7.2%, and only 2.3% in the patients with reference GFR < 60 mL/min/1.73 m(2). The diagnostic accuracy for 2-point blood spot was: 87.5% and 96.9% within ± 15% (P15) and ± 30% (P30) of the reference GFR respectively. In patients with GFR < 60 mL/min/1.73 m(2), both P15 and P30 were 100%. CONCLUSIONS: GFR calculation based on blood spot iohexol measurement is an alternative method to traditional venous iohexol measurement in children. Our study demonstrates strong agreement between the blood spot and the venous GFR with acceptable bias, precision and diagnostic accuracy, especially in patients with GFR < 60 mL/min/1.73 m(2).

The use of dried blood spot sampling for the measurement of HbA1c: a cross-sectional study.

BACKGROUND: The use of dried blood spot (DBS) sampling is an alternative to traditional venous blood collection, and particularly useful for people living in rural and remote areas, and for those who are infirm, house-bound or time-poor. The objective of this study was to assess whether the measurement of glycated haemoglobin A1c (HbA1c) in DBS samples provided comparative and acceptably precise results. METHODS: Venous and capillary blood samples were collected from 115 adult participants. After proper instruction, each participant punctured his/her own finger and collected capillary blood samples on pieces of a proprietary cellulose filter paper. Each filter paper was subsequently placed inside a breathable envelope, stored at room temperature, and processed on the same day (D0), four (D4), seven (D7) and fourteen (D14) days after collection. HbA1c was measured in duplicates/triplicates in whole venous blood (WB), capillary blood (capDBS) and venous blood placed on the matrix paper (venDBS), by turbidimetric inhibition immunoassay. Intra-assay coefficients of variation (CV) were calculated. DBS values were compared to WB results using linear regression, Bland-Altman plots and cross-validation models. RESULTS: Eleven and 56 patients had type 1 and type 2 diabetes mellitus, respectively. Mean HbA1c levels were 6.22 ± 1.11 % for WB samples (n = 115). The median intra-assay CV was lower than 3 % for WB and capDBS on all days. Results from capDBS and venDBS showed high correlation and agreement to WB results, with narrow 95 % limits of agreement (except for results from D14 samples), as observed in Bland-Altman plots. When capDBS values were applied to equations derived from regression analyses, results approached those of WB values. A cross-validation model showed that capDBS results on D0, D4 and D7 were close to the WB results, with prediction intervals that were narrow enough to be clinically acceptable. CONCLUSIONS: The measurement of HbA1c from DBS samples provided results that were comparable to results from WB samples, if measured up to seven days after collection. Intra-assay coefficients of variation were low, results were in agreement with the gold-standard, and prediction intervals were clinically acceptable. The measurement of HbA1c through DBS sampling may be considered in situations where traditional venipuncture is not available. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ID ACTRN12613000769785.

[Can we rule out a congenital cytomegalovirus infection when the result of polymerase chain reaction in dried blood spots is negative?]. / ¿Podemos descartar infección congénita por citomegalovirus cuando la reacción en cadena de la polimerasa viral es negativa en la prueba del talón?

INTRODUCTION: The detection of cytomegalovirus (CMV) DNA by real time polymerase chain reaction (rt-PCR) in dried blood spots collected routinely for metabolic screening has been assessed for the retrospective diagnosis of congenital CMV (cCMV) infection in many studies, but not in Spain. The aim of this study is to analyze the diagnostic accuracy of this technique in our hospital. METHODS: A cross-sectional retrospective observational study was conducted including all patients born between January, 2007 and September, 2012 with confirmed cCMV infection. The assessment of CMV DNA was made by using rt-PCR in dried blood spots of these patients. RESULTS: Fourteen patients were included: 4/14 were symptomatic and 4/14 had sequelae. The detection of CMV DNA by rt-PCR was positive in only 7 patients. A statistically significant relationship between low viral load at birth and negative rt-PCR in dried blood spots was demonstrated. CONCLUSIONS: Despite the low number of patients included, our data highlight an important amount of false negative results in the DNA CMV detection by rt-PCR in these samples for the retrospective diagnosis of cCMV infection, especially in cases with low viral load at birth.