Screen-positive Infants Research Articles

339 Diagnostic dilemmas in cystic fibrosis screen–positive infants with F191V and low sweat chloride

339 Diagnostic dilemmas in cystic fibrosis screen–positive infants with F191V and low sweat chloride

Management of newborn screening for severe combined immunodeficiency at a quaternary referral centre—an updated algorithm

Severe combined immunodeficiency (SCID) is caused by critical genetic defects affecting the immune system. Early diagnosis and intervention are essential for preventing life-threatening infections, end-organ damage, and complications. Newborn screening for SCID is currently performed in many provinces and territories across Canada. The SickKids Newborn Screening Centre in Toronto, Ontario, is a quaternary referral centre that has evaluated SCID newborn screen-positive infants since the program’s introduction in 2013. Here, we provide updated algorithms for clinical investigation and follow-up of infants with an initial positive screen. Statement of novelty: We provide algorithms for the clinical follow-up of SCID newborn screen-positive infants at a quaternary referral centre.

Factors Affecting Age of Initial Specialty Clinic Evaluation Among Infants with Sickle Cell Disease in Kingston, Jamaica

To evaluate the effectiveness of newborn screening for sickle cell disease in eastern Jamaica by determining what proportion of screen-positive infants were registered with the Sickle Cell Unit (SCU) by two months (60 days) of age and identifying parents' perceptions of facilitators and barriers impacting age at registration. This cross-sectional study used a mixed method approach. Ages at diagnosis confirmation and first clinic visit were recorded for screen-positive infants born between February 1, 2015, and November 15, 2017. All parents were invited to complete the survey and early and late attendees were invited to participate in the qualitative aspect of the study. A researcher-designed questionnaire and an interview guide based on the Capability, Opportunity, Motivation, Behavior (COM-B), and Health Belief Models examined factors that may affect time to registration. Quantitative data were analyzed to yield descriptive statistics using Stata®v14. All interview data were coded. Similar codes were grouped together into themes. Most (97.7%) of the 133 screen-positive infants had their diagnosis confirmed. Only 40% had their first clinic visit by age 60 days. Denial of the diagnosis, poor communication, and the costs of treatment and transportation were perceived barriers to registration, whereas family support was a facilitator. Diagnosis confirmation was almost universal, but most infants did not attend clinic by two months of age. In-depth interviews have identified several facilitators and barriers that can be targeted to improve early registration.

#22 Does Cranial Ultrasound Differentiate Asymptomatic Congenital CMV (cCMV) Infection from cCMV with Central Nervous System Disease in Infants? Results from a Universal Screening Study in Minnesota, USA

Abstract Background Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits, including sensorineural hearing loss (SNHL). With the passage of a universal cCMV screening bill by the Minnesota legislature in 2021, it is imperative to define the optimal diagnostic approach for identified cases, particularly for asymptomatic infants. Cerebral ultrasound (US) is a safe, non-invasive technique to examine neonatal brains, and has been advocated by an international consensus panel as a modality for cCMV disease classification. This analysis described clinical manifestations of cCMV in infants identified by universal screening and characterized cranial US findings obtained during diagnostic evaluation. We correlated viral load in the newborn CMV screening saliva samples with clinical and US findings. Method Newborns were screened for cCMV at six Twin Cities nurseries by PCR of dried blood spots (DBS) obtained for routine newborn screening, and saliva collected 1-2 days after birth. Screen-positive infants had a confirmatory urine PCR test within 3 weeks of birth, and clinical evaluation that included cranial US. Results Through September 1, 2021, 19,017 newborns were screened for cCMV. 76 cases were identified (prevalence of 0.4%) by saliva or DBS, confirmed by urine CMV PCR testing. 76% (58/76) had asymptomatic cCMV; the remaining 24% were infants with cCMV disease. Nine had congenital or delayed-onset SNHL, of which 7 had abnormal US; 1 had normal US, and 1 did not have US performed. Median saliva viral load differed between infants with cCMV disease (3.3×104 IU/ml) and asymptomatic infants (8.6×106 IU/ml; p< 0.05, Fig. 1). Cranial US exams were available for 68 infants (51 asymptomatic, 17 with cCMV disease). 50 (74%) infants had normal US; 18 infants had abnormal US (Table 1). Of the 17 infants with cCMV disease, 12 had abnormal US, of which 4 showed cCMV disease-defining lesions. Of 51 asymptomatic infants, 6 had abnormal, and 45 normal, cranial US. Saliva viral loads did not vary between infants with normal vs. abnormal US (p=0.7). Conclusion PCR of newborn DBS and/or saliva revealed a prevalence of 4.0 per 1000 in a universal cCMV screening study. Surprisingly, an inverse relationship was observed between saliva viral load at birth and cCMV disease classification. Among babies with cCMV, the majority had normal cranial US, and most abnormalities were not pathognomonic for cCMV disease. Clarification is needed regarding which cranial US findings require detailed follow-up, including MRI, as universal cCMV screening programs move forward in clinical practice.

Outcomes of Cystic Fibrosis Screening-Positive Infants With Inconclusive Diagnosis at School Age.

Cystic fibrosis (CF) screen-positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children. Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive-screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes. The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls. Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.

Outcomes of repeat sweat testing in cystic fibrosis newborn screen positive infants.

Infants with a positive cystic fibrosis (CF) newborn screen, only one identified CFTR mutation (NBS+/1 mut), and an initial intermediate sweat chloride (30-59 mmol/L) should have repeat sweat chloride testing (SCT). However, the outcome of repeat SCT and the relationship between initial sweat Cl and subsequent CF diagnosis have not been reported. The objective of this study was to analyze the outcomes of repeat SCT and subsequent CF diagnosis in NBS+/1 mut infants based on their initial sweat chloride concentration. We retrospectively identified all infants born in Indiana from 2007 to 2017 with NBS+/1 mut and initial SCT in the intermediate range. For each infant, we recorded the initial and repeat SCT results and/or a final CF diagnosis. From 2007 through 2017 there were 2822 NBS+/1 mut infants of which 2613 (82%) had at least one SCT result. No infants with an initial SCT of 30-39 mmol/L were subsequently diagnosed with CF. Of the 31 infants with an initial SCT of 40-49 mmol/L, only 1 was subsequently diagnosed with CF. In contrast, 61% of those with SCTs of 50-59 mmol/L were later diagnosed with CF. These results suggest that infants with a positive NBS for CF and one CFTR mutationwhose initial sweat chloride concentration is 50-59 mmol/L need to be monitored more closely forCF with strong consideration for earlier repeat SCTs and immediate genotyping.

WS06.2 Nutritional and pulmonary outcomes of cystic fibrosis screen-positive infants with an inconclusive diagnosis

WS06.2 Nutritional and pulmonary outcomes of cystic fibrosis screen-positive infants with an inconclusive diagnosis

Newborn Screening for Cystic Fibrosis in Mersin Province: Yearly Assessment of the National Program.

A national newborn screening program for cystic fibrosis (CF) was started using immunoreactive trypsinogen (IRT) test on January 1, 2015, in Turkey. We aimed to analyze the characteristics of newborn screen-positive (NBSP) infants in Mersin province. The data on NBSP infants were retrospectively analyzed between 2015 and 2017 from records of Mersin Women & Children's Hospital and Mersin City Training and Research Hospital. A total of 82,273 newborns were screened for CF by IRT test between January 2015 and December 2017 in Mersin. Among those, 512 infants were defined as NBSP after two repeated IRT tests (IRT/IRT) (138 infants in 2015, 217 in 2016, and 157 in 2017). Sweat test was normal in the majority of infants (115 infants [83.3%] in 2015, 189 [87.1%] in 2016, and 129 [82.2%] in 2017). Overall, between 2015 and 2017, after two repeated sweat tests, 4 infants had sweat test results in the intermediate range and 9 infants had positive sweat tests. The incidence of CF for a 3-year period was approximately 1/9300 in our region. The positive predictive value of IRT test for defining CF was 1.8%, with a sensitivity of 90.0% and specificity of 99.4%. IRT/IRT test as a newborn screening strategy provides the opportunity for earlier diagnosis and treatment of CF patients. More data are needed to understand the frequency of CF on a national level.

The North Carolina Experience with Mucopolysaccharidosis Type I Newborn Screening

To evaluate the performance of a 2-tiered newborn screening method for mucopolysaccharidosis type I (MPS I) in North Carolina. The screening algorithm included a flow injection analysis-tandem mass spectrometry assay as a first-tier screening method to measure α-L-iduronidase (IDUA) enzyme activity and Sanger sequencing of the IDUA gene on dried blood spots as a second-tier assay. The screening algorithm was revised to incorporate the Collaborative Laboratory Integrated Reports, an analytical interpretive tool, to reduce the false-positive rate. A medical history, physical examination, IDUA activity, and urinary glycosaminoglycan (GAG) analysis were obtained on all screen-positive infants. A total of 62 734 specimens were screened with 54 screen-positive samples using a cut-off of 15% of daily mean IDUA activity. The implementation of Collaborative Laboratory Integrated Reports reduced the number of specimens that screened positive to 19 infants. Of the infants identified as screen-positive, 1 had elevated urinary GAGs and a homozygous pathogenic variant associated with the severe form of MPS I. All other screen-positive infants had normal urinary GAG analysis; 13 newborns had pseudodeficiency alleles, 3 newborns had variants of unknown significance, and 2 had heterozygous pathogenic variants. An infant with severe MPS I was identified and referred for a hematopoietic stem cell transplant. Newborn IDUA enzyme deficiency is common in North Carolina, but most are due to pseudodeficiency alleles in infants with normal urinary GAG analysis and no evidence of disease. The pilot study confirmed the need for second-tier testing to reduce the follow-up burden.

The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants

Purpose:We conducted a consented pilot newborn screening (NBS) for Pompe, Gaucher, Niemann Pick A/B, Fabry, and MPS 1 to assess the suitability of these lysosomal storage disorders (LSD) for public health mandated screening.Methods:At five participating high-birth-rate, ethnically diverse New York City hospitals, recruiters discussed the study with post-partum parents and documented verbal consent. Screening on consented samples was performed using multiplexed tandem mass spectrometry. Screen-positive infants underwent confirmatory enzymology, DNA testing, and biomarker quantitation when available. Affected infants are being followed for clinical management and long term outcome.Results:65,605 infants participated over four years, representing an overall consent rate of 74%. Sixty-nine infants were screen-positive. Twenty-three were confirmed true positives, all of whom were predicted to have late-onset phenotypes. Six of the 69 currently have undetermined disease status.Conclusion:Our results suggest that NBS for LSDs is much more likely to detect individuals at risk for late-onset disease, similar to results from other NBS programs. This work has demonstrated the feasibility of using a novel consented pilot NBS study design that can be modified to include other disorders under consideration for public health implementation as a means to gather critical evidence for evidence-based NBS practices.

Newborn blood spot screening for cystic fibrosis with a four-step screening strategy in the Netherlands

BackgroundNewborn screening for cystic fibrosis (NBSCF) was introduced in the Dutch NBS program in 2011 with a novel strategy. MethodsDutch NBSCF consisted of four steps: immuno-reactive trypsin (IRT), Pancreatitis-associated Protein (PAP), DNA analysis by Inno-LiPa (35 mutations), extended gene analysis (EGA) as fourth step and as safety net. Only samples with two CFTR-variants were considered screen-positive, but samples with one disease-causing variant were considered also screen-positive from April 2013. The first 5 years of NBSCF were evaluated during a follow-up ranging from 2 to 6.8 years for sensitivity, specificity, positive predictive value (PPV), ratio of CF/Cystic Fibrosis Screen Positive infants with an Inconclusive Diagnosis (CFSPID) and median age at diagnosis, and were compared to other novel strategies for NBSCF and European Cystic Fibrosis Society (ECFS) Best Practice Standards of Care. ResultsNBSCF achieved a sensitivity of 90% (95% CI 82%–94%), specificity of 99.991% (95% CI 99.989%–99.993%), PPV of 63% (95% CI 55%–69%), CF/CFSPID ratio of 4/1, and median age at diagnosis of 22 days, if samples with two variants as well as samples with one disease-causing variant were considered screen-positive. ConclusionThe program achieved the goal to minimize the number of false positives and showed a favourable performance but sensitivity and CF/CFSPID ratio did not meet criteria of EFCS Best Standards of Care. Changed cut-off values for PAP and IRT and classification of R117H-7T/9T to non-pathogenic may improve sensitivity to ≥95% and CF/CFSPID ratio to 10/1. PPV is estimated to be around 60%.

Coming to terms with the imperfectly normal child: attitudes of Israeli parents of screen-positive infants regarding subsequent prenatal diagnosis.

This study examines the interface between newborn screening and prenatal diagnosis from the point-of-view of parents of screen-positive children. Many conditions covered by newborn screening represent classic (autosomal recessive) Mendelian disorders. Parents of screen-positive infants therefore often come to learn that they are carriers of the disease, and face a decision whether to test for it in future pregnancies. Semi-structured interviews were conducted in 2015-2017 with 34 Israeli parents whose child was screen positive. Three major themes emanated from the parents' attitudes toward prenatal testing for the disease in prospective hypothetical pregnancies: rejection of prenatal testing for the disease associated with the screen positive, and relying instead on newborn screening to reveal if a future baby is also sick (18/34, 53%); support of prenatal testing to get more information (7/34, 21%) and support of prenatal testing in order to abort in case of a test positive (9/34, 26%). We discuss the importance of newborn screening for reproductive decision-making, highlighting the arguments associated with positive and negative parental views of the possibility of having another child with the same condition associated with the screen-positive of the child that had already been born. The conclusions challenge the common assertion that parents pursue the dream of the "perfect child" through prenatal diagnosis that "naturally" leads to selective abortion. The diversity of views expressed by Israeli parents of screen-positive children highlights the diversity of normative scripts of "genetic responsibility" in the context of parenthood.

The D313Y variant in the GLA gene - no evidence of a pathogenic role in Fabry disease in 2 Danish families

We conducted a consented pilot newborn screening (NBS) for Pompe, Gaucher, Niemann–Pick A/B, Fabry, and MPS 1 to assess the suitability of these lysosomal storage disorders (LSDs) for public health mandated screening.At five participating high–birth rate, ethnically diverse New York City hospitals, recruiters discussed the study with postpartum parents and documented verbal consent. Screening on consented samples was performed using multiplexed tandem mass spectrometry. Screen-positive infants underwent confirmatory enzymology, DNA testing, and biomarker quantitation when available. Affected infants are being followed for clinical management and long-term outcome.Over 4 years, 65,605 infants participated, representing an overall consent rate of 73%. Sixty-nine infants were screen-positive. Twenty-three were confirmed true positives, all of whom were predicted to have late-onset phenotypes. Six of the 69 currently have undetermined disease status.Our results suggest that NBS for LSDs is much more likely to detect individuals at risk for late-onset disease, similar to results from other NBS programs. This work has demonstrated the feasibility of using a novel consented pilot NBS study design that can be modified to include other disorders under consideration for public health implementation as a means to gather critical evidence for evidence-based NBS practices.

Value of heart murmurs and transcutaneous oxygen saturation in screening for neonatal congenital heart diseases

Objective To compare the importance of heart murmurs and transcutaneous oxygen saturation(SpO2)in screening neonatal congenital heart diseases(CHD), and to explore a reliable and easy-to-use method for the screening of CHD. Methods All infants (16 070 cases) born in Changzhou Maternal and Child Health Hospital from May 1st 2011 to April 30th 2013 were screened of CHD for heart murmurs and SpO2.The screen-positive infants were divided into 3 groups: heart murmurs group, abnormal SpO2 group and mixed group.All screen-positive infants received cardiac color ultrasound to make a definite diagnosis of CHD, so as to compare the values of heart murmurs and SpO2. Results Eight thousand seven hundred and ninety-nine boys and 7 271 girls were screened, in which the ratio was 1.21:1.00.One hundred and eighteen infants were screened positive, including 76 murmurs of which 45 were confirmed as CHD, 28 with abnormal SpO2 of which 18 were confirmed and 14 mixed of which 13 were confirmed, so the confirmation rates were 59.21%, 64.29% and 92.86%, respectively.The diagnostic rate of CHD in mixed group was higher than other 2 groups, which had statistical significance(P=0.045). The top three formation types of CHD were ventricular septal defect (VSD) (29/76 cases, 38.16%), patent ductus arteriosus (PDA) (13/76 cases, 17.11%) and atrial septal defect (ASD) (11/76 cases, 14.48%). Conclusions The combination of heart murmurs and SpO2 was useful in increasing detection and decreasing misdiagnosis of CHD. Key words: Infant, newborn; Congenital heart disease; Heart murmurs; Transcutaneous oxygen saturation; Screening

Maternal Consequences of the Detection of Fragile X Carriers in Newborn Screening.

The possibility of newborn screening for fragile X syndrome is complicated by the potential for identifying premutation carriers. Although knowing the child's carrier status has potential benefits, the possibility of late-onset disorders in carrier children and their parents raises concerns about whether such information would be distressing to parents and potentially more harmful than helpful. This study sought to answer this question by offering voluntary fragile X screening to new parents and returning results for both the full mutation and premutation FMR1 gene expansions. We tested the assumption that such information could lead to adverse mental health outcomes or decision regret. We also wanted to know if child age and spousal support were associated with the outcomes of interest. Eighteen mothers of screen-positive infants with the premutation and 15 comparison mothers completed a battery of assessments of maternal anxiety, postpartum depression, stress, family quality of life, decision regret, and spousal support. The study was longitudinal, with an average of 3 assessments per mother. The premutation group was not statistically different from the comparison group on measures of anxiety, depression, stress, or quality of life. A subset of mothers experienced clinically significant anxiety and decision regret, but factors associated with these outcomes could not be identified. Greater spousal support was generally associated with more positive outcomes. Although we did not find evidence of significant adverse events, disclosure of newborn carrier status remains an important consideration in newborn screening policy.

EPS01.7 Is confirmatory genetic testing of all CF screen positives in Ontario justified?

Objectives In April 2008, Newborn Screening Ontario (NSO) added cystic fibrosis (CF) to their screening panel. A two-tiered protocol is used which includes immunoreactive trypsinogen (IRT) and genetic testing with a panel of 39 +3 polymorphisms. The sweat chloride test is considered the gold standard to diagnose CF, and therefore is conducted on all screen positive infants. On these individuals, NSO recommends confirmatory genetic testing, which in our centre includes a larger panel of mutations (70+4 polymorphisms). Our objective is to elucidate the financial impact of conducting this extended panel for all positive screens. Methods A retrospective descriptive analysis of our internal database identified individuals who were referred from NSO with a single mutation, between April 2008 and December 2013, and were found to have a second mutation with our extended panel. The cost to our centre to run each extended panel is $300. Results 387 individuals were screen positive, of whom 22 (5.6%) had two mutations, 311 (80.1%) had one mutation, and 54 (13.9%) had no mutations. Our centre has expended $116,400 to identify 29 individuals with a second mutation. 19 of these infants had a negative sweat test, and 6 had a borderline sweat test. Conclusion Confirmatory testing has cost our centre an average of $20,000 per annum. A total of 29 individuals were identified with a second mutation through our extended panel, 19 of whom had normal sweats. Further follow up and research should be conducted to determine if identifying these individuals justifies the cost of confirmatory testing.

Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study.

Many regions have implemented newborn screening (NBS) for cystic fibrosis (CF) using a limited panel of cystic fibrosis transmembrane regulator (CFTR) mutations after immunoreactive trypsinogen (IRT) analysis. We sought to assess the feasibility of further improving the screening using next-generation sequencing (NGS) technology. An NGS assay was used to detect 162 CFTR mutations/variants characterized by the CFTR2 project. We used 67 dried blood spots (DBSs) containing 48 distinct CFTR mutations to validate the assay. NGS assay was retrospectively performed on 165 CF screen-positive samples with one CFTR mutation. The NGS assay was successfully performed using DNA isolated from DBSs, and it correctly detected all CFTR mutations in the validation. Among 165 screen-positive infants with one CFTR mutation, no additional disease-causing mutation was identified in 151 samples consistent with normal sweat tests. Five infants had a CF-causing mutation that was not included in this panel, and nine with two CF-causing mutations were identified. The NGS assay was 100% concordant with traditional methods. Retrospective analysis results indicate an IRT/NGS screening algorithm would enable high sensitivity, better specificity and positive predictive value (PPV). This study lays the foundation for prospective studies and for introducing NGS in NBS laboratories.

Indicators of newborn screening for congenital hypothyroidism in Sri Lanka: program challenges and way forward.

BackgroundMany of the countries in the Asia Pacific Region are just initiating newborn screening programs for selected metabolic and other congenital disorders. The present study is aimed at evaluating the congenital hypothyroidism screening program in the Southern region of Sri Lanka in terms of coverage, effectiveness of detecting and managing the cases.MethodsThe Newborn Screening System Database of Sri Lanka was reviewed from January 2011 to December 2012. The data of 47 babies who tested positive for hypothyroidism were analyzed.ResultsTotal of 78,167 babies (99.0% of live births) were screened. Of them, 5.8% (n = 4,472) were discharged within 12 hrs of delivery where as 58.1% (n = 44969) were discharged afterwards but within next 12 hrs (i.e., day 1). The positive predictive value for congenital hypothyroidism (CH) was 9.0%. The incidences of primary CH among screened infants were 1:1682. False positive rate among screened infants was maintained below 0.70%. Mean age of serum confirmation was 23.8 (±8) days.ConclusionsIn the light of the present findings, we would suggest direct communication systems, linking newborn screening program to the family unit. This would enhance timely follow-up for screen-positive infants and facilitate information sharing. Establishing a program with, public-private sector partnership should be considered. Costs could be contained if the specimen collection, its transportation and communication are carried out by this partnership and the laboratory tests are conducted by a non-profit organization such as a University in order to achieve the goal of universal coverage.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6963-14-385) contains supplementary material, which is available to authorized users.

Abnormal Newborn Screens and Acylcarnitines in HIV-exposed and ARV-exposed Infants

Antiretroviral drugs (ARV), specifically nucleoside analogs, are toxic to mitochondrial oxidative phosphorylation. Other metabolic pathways, such as fatty acid oxidation, organic acid metabolism and amino acid metabolism, are dependent on normal oxidative phosphorylation but remain unexamined as potential points of ARV toxicity. We analyzed newborn screening data from New York and compared proportions of abnormal newborn metabolic screens in HIV antibody screen-positive and HIV screen-negative neonates. Subsequently, we compared acylcarnitine levels in ARV-exposed (n = 16) and ARV-unexposed (n = 14) HIV-exposed infants to assess for dysfunctional fatty and organic acid metabolism. : The rate of abnormal newborn metabolic screens in HIV screen-positive infants was higher than that in the general population (2.2% versus 1.2%; P = 0.00025), most of which were for disorders of mitochondria-related metabolism. Abnormal acylcarnitine levels occurred more frequently in ARV-exposed compared with ARV-unexposed infants (43% versus 0%; P = 0.02). A higher proportion of positive metabolic screens in HIV screen-positive neonates suggests that HIV or ARV exposure is associated with dysfunctional intermediary metabolism in newborns. Abnormal acylcarnitine levels were more frequent in ARV-exposed infants, suggesting that ARV may perturb normal fatty acid oxidation in some infants. Studies designed to validate and determine the clinical significance of these findings are warranted.

Informatics of newborn screening for congenital hypothyroidism in Alberta 2005-08: flow of information from birth to treatment.

Alberta maintains a universal screening program for congenital hypothyroidism, a condition which, when treated promptly prevents neurological impairment. Because the program relies on multiple stakeholders working in different areas, it is not known how effective the overall process is in achieving timely treatment initiation. Our objective was to analyze and describe the informatics of this program. Data were collected from the Newborn Metabolic Screening Program and physician offices for hypothyroidism screen positive infants born between january 1, 2005 and May 31, 2008. Where data were available, times were determined for each interval: birth to sample collection, collection to receipt in central laboratory, receipt to report to the primary clinician, report to confirmatory test, and finally confirmation to thyroxin treatment. Complete information was found on the stages up until report generation. Although subsequent intervals had less complete data, all but 5 of the 57 newborns were followed to the endpoint of treatment initiation or diagnosis exclusion. The program was consistent and efficient in collecting, analyzing and reporting results to the primary physician by a median of 8 days (range 4-14 days). Subsequent steps resulted in a median time from birth to treatment of 11 days. There were 4 cases for which delays in clinician follow-up led to treatment initiation at 27, 34, 56 and 70 days. Newborn screening for congenital hypothyroidism in Alberta is efficient and consistent up until responsibility shifts to the community. Quality improvement work is needed to reduce potential delays.