Critical Congenital Heart Disease Newborn Screening Implementation: Lessons Learned.

Introduction The purpose of this article is to present the collective experiences of six federally-funded critical congenital heart disease (CCHD) newborn screening implementation projects to assist federal and state policy makers and public health to implement CCHD screening. Methods A qualitative assessment and summary from six demonstration project grantees and other state representatives involved in the implementation of CCHD screening programs are presented in the following areas: legislation, provider and family education, screening algorithms and interpretation, data collection and quality improvement, telemedicine, home and rural births, and neonatal intensive care unit populations. Results The most common challenges to implementation include: lack of uniform legislative and statutory mandates for screening programs, lack of funding/resources, difficulty in screening algorithm interpretation, limited availability of pediatric echocardiography, and integrating data collection and reporting with existing newborn screening systems. Identified solutions include: programs should consider integrating third party insurers and other partners early in the legislative/statutory process; development of visual tools and language modification to assist in the interpretation of algorithms, training programs for adult sonographers to perform neonatal echocardiography, building upon existing newborn screening systems, and using automated data transfer mechanisms. Discussion Continued and expanded surveillance, research, prevention and education efforts are needed to inform screening programs, with an aim to reduce morbidity, mortality and other adverse consequences for individuals and families affected by CCHD.

Evaluating cost and resource use associated with pulse oximetry screening for critical congenital heart disease: Empiric estimates and sources of variation.

BACKGROUND: Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is being implemented in the United States and internationally; however, few data are available on the associated in-hospital costs and use of resources. METHODS: Time and motion study in well-baby nurseries at two large urban hospitals in Utah using different approaches to pulse oximetry screening. Two observers recorded the time for each screening step together with provider and equipment characteristics. Structured questionnaire provided additional information on labor and equipment costs. RESULTS: Fifty-three CCHD screens were observed. At site A (n = 22), screening was mostly done by medical assistants (95%) using disposable probes (100%); at site B (n = 31), screening was mostly performed by certified nursing assistants (90%) using reusable probes (90%). Considering only first screens (n = 53), the median screen time was 8.6 min (range: 3.2-23.2), with no significant difference between sites. The overall cost ($ in 2014) of screening per baby was $24.52 at site A and $2.60 at site B. Nearly all the variation in cost (90%) was due to the cost of disposable probes; labor costs were similar between sites. CONCLUSION: CCHD screening by means of pulse oximetry is reasonably fast for most babies, leading to relative small labor costs with little variation by provider type. The main driver of costs is equipment: in a high throughput setting, reusable probes are currently associated with considerable cost saving compared with disposable probes. As programs expand to universal screening, improved and cheaper technologies could lead to considerable economies of scale.

Feasibility of newborn screening for guanidinoacetate methyltransferase (GAMT) deficiency.

Guanidinoacetate methyltransferase (GAMT) deficiency causes brain creatine deficiency characterized by developmental delays, speech delay, seizures and autism-like behavior. Identification and therapy at birth because of a positive family history has prevented intellectual disability and seizures in all cases reported. The objective of this study was to develop a method to identify patients with GAMT deficiency from newborn screening blood spots. Creatine and guanidinoacetate were extracted from 10,000 deidentified blood spots using the same protocol routinely used for newborn screening and quantified by stable isotope dilution using deuterated creatine and guanidinoacetate as internal standards. Residual dried blood spots from three infants with GAMT deficiency were used to evaluate the sensitivity of the method. A second tier test using UPLC-MS/MS was performed to analyze samples with a concentration of guanidinoacetate >2.44 µmol/L (99.5th centile of the normal population). Fifty four blood spots required second tier testing in addition to seven blood spots from three patients with GAMT deficiency retrospectively analyzed. With second tier testing, only the samples from GAMT deficiency patients had elevated concentration of guanidinoacetate. Our results show that GAMT deficiency can be identified in newborns using routine extraction methods. The cost of this additional screening is minimal, as it does not require additional instrumentation, procedure, or sample collection. The use of a second tier test can reduce the false positive rate to a minimum. Summary Brain creatine deficiency syndromes cause mental retardation that can be prevented if therapy is initiated early in life. This manuscript reports that infants with GAMT deficiency (one of the brain creatine deficiency syndromes) can be identified from elevated guanidinoacetate in newborn blood spots with virtually absent false-positive results using a second tier test.

Use of steroid profiling by UPLC-MS/MS as a second tier test in newborn screening for congenital adrenal hyperplasia: the Utah experience.

Newborn screening allows the diagnosis of congenital adrenal hyperplasia (CAH) before symptoms appear, preventing the severe and potentially life-threatening crisis associated with this disease in infancy. Traditional screening by enzyme immunoassay results in a large number of false positives. To reduce the number of unnecessary tests, anxiety to families and physicians, and the burden to the newborn screening follow-up program, we implemented a second-tier test for CAH using steroid profiling by an ultra-performance liquid chromatography-tandem mass spectrometry. We measured three steroids: 17-hydroxyprogesterone, androstenedione, and cortisol and correlated them with the age of infant at the time of sample collection and birth weight. Both age at collection and birth weight affected the levels of adrenal steroids, but the use of appropriate cut offs and analyte ratios allowed the identification of infants with CAH. This approach was effective in identifying infants with CAH, with both salt-wasting and simple virilizing forms, while reducing the false-positive rate from 2.6 to 0.09%.

Sociodemographic risk factors associated with autism spectrum disorders and intellectual disability.

This study examined the hypotheses that (1) sociodemographic risk factors in young children with autism spectrum disorders (ASD) and/or intellectual disability (ID) significantly vary by disability type, and (2) measures of income (mean adjusted gross income, mean federal taxes paid, and mean tax exemptions) significantly increase between 1994 and 2002, and are lower in families with a child with ASD and/or ID compared with the general population. A multiple source surveillance system utilizing a retrospective record review was used to identify ASD and ID cases from a population of 26,108 eight-year-old children born in 1994 and living in Utah in 2002. ASD without ID (ASD-only, n = 99) cases were significantly more likely to be male (P<0.01) and have mothers of White non-Hispanic ethnicity (P = 0.02). ASD with ID (ASD/ID, n = 33) cases were significantly more likely to be male (P<0.01) and have mothers older than 34 years (P = 0.03). ID without ASD (ID-only, n = 113) cases were significantly more likely to have fathers older than 34 years (P<0.01) and were significantly less likely to have mothers with >13 years education (P<0.01). Measures of income for cases at birth and at 8 years of age were not significantly lower than the general population and mean adjusted income of cases significantly increased from birth to 8 years of age. Investigations focused on defining early sociodemographic risk factors by different endophenotypes of ASD may assist in identifying risk factors for this complex group of neurodevelopmental disorders. Aggregate tax information may be a unique resource to utilize for population-based analysis.