Int. J. Neonatal Screen., Volume 3, Issue 4 (December 2017) – 9 articles

Screening newborns for critical congenital heart disease (CCHD) using pulse oximetry is recommended to allow for the prompt diagnosis and prevention of life-threatening crises. The present review summarizes and critiques six previously published estimates of the costs or cost-effectiveness of CCHD screening from the United Kingdom, United States, and China. Several elements that affect CCHD screening costs were assessed in varying numbers of studies, including screening staff time, instrumentation, and consumables, as well as costs of diagnosis and treatment. A previous US study that used conservative assumptions suggested that CCHD screening is likely to be considered cost-effective from the healthcare sector perspective. Newly available estimates of avoided infant CCHD deaths in several US states that implemented mandatory CCHD screening policies during 2011–2013 suggest a substantially larger reduction in deaths than was projected in the previous US cost-effectiveness analysis. Taking into account these new estimates, we estimate that cost per life-year gained could be as low as USD 12,000. However, that estimate does not take into account future costs of health care and education for surviving children with CCHD nor the costs incurred by health departments to support and monitor CCHD screening policies and programs. Full article

Establishing a newborn hearing screening programme in a low-income country with poor communication infrastructure has unique challenges. Data from 195 infants in three different patient populations in Malawi who underwent hearing screening using transient evoked otoacoustic emissions (TEOAE) testing were analysed to investigate the feasibility of a long-term screening programme. There were 65 infants in each group: infants from Group A were born in a private maternity unit, Group B attended a free community vaccination clinic, and Group C were receiving special care at a government hospital. 75% of infants requiring follow-up from the special-care baby unit were uncontactable following hospital discharge, and screening was discontinued there. Lost to follow-up rates after the first screen were lower from the private maternity unit (14%) and the community vaccination clinic (36%), and these screening programmes continue. A successful hearing screening programme requires extensive support services to manage infants requiring further testing and habilitation, this is not currently possible on a large scale in Malawi due to the small number of Audiology departments and trained staff. Full article

Homocystinuria (HCU) due to cystathionine-β-synthase deficiency is generally regarded as a rare disease, but within the Qatari population has an incidence of 1 in 1800 live births. Most newborn screening methods for HCU using dried blood spots (DBS) rely on the detection of an elevated methionine level or a rapid screen for total homocysteine (tHCY). However, screening based on methionine levels alone lacks specificity and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for tHCY exhibit variable results with high false positive rates. This report describes a LC-MS/MS method for detection of tHCY on DBS, with improved specificity. tHCY was extracted from DBS with a solution containing dithiothreitol and subsequently butylated with hydrochloric acid in n-butanol. The butyl esters were separated by liquid chromatography on a reverse-phase column and the homocysteine (HCY), detected by tandem mass spectrometry. The butyl ester of HCY eluted at 1.8 min. Total analysis time was 6.1 min per sample, including column flush and equilibration. This method allows for the quantification of tHCY over a linear range from 0.3 to 200 µM. Intraassay and interassay imprecision and recoveries were acceptable. Good concordance was observed with another LC-MS/MS method. Application of this method improves specificity and reduces false positive rates in screening for HCU. Full article

Tennessee initiated single-extremity staged screening by pulse oximetry for undetected CCHD in 2012. The algorithm begins with a saturation reading in the foot and allows an automatic pass if the foot pulse oximetry is 97% or greater. This was based on the principle that it is not possible to have a greater than 4% difference in the pulse oximetry between upper and lower extremities if the lower extremity is equal to or greater than 97%. This approach eliminates over 75,000 “unnecessary” pulse oximetry determinations in Tennessee each year without affecting the ability to detect CCHD before hospital discharge. Full article

Population-based newborn screening (NBS) using blood collected and dried on filter paper was developed in the 1960s and remains the international standard for NBS programs. Glue, used in the manufacture of dried blood collection cards, may present a source of contamination and is often considered as a possible cause of anomalous results in routine screening. Our study evaluates this potential contamination on NBS analyses. EBF#1003 glue was blotted onto dried blood collection cards made of Whatman grade 903 filter paper (Whatman#903) and adult whole blood was pipetted onto the dried glue blots. In addition, blank glue blots (i.e., no blood) and dried blood spots (DBSs) in the absence of glue were prepared. The DBSs and blank samples were run in duplicate as routine samples for NBS. DBS absorption time and diameter, the effect of glue on measurements (concentrations and variation) were assessed. DBS absorption time and shape were equivalent for DBSs prepared in the absence and presence of undiluted glue. DBS diameter increased when prepared in the presence of glue. When EBF#1003 was diluted prior to use, DBS absorption time increased, and DBSs were non-uniform. Glue, diluted or not, did not produce measurements above the established Limit of Detection (LOD) for all assays used in the current Dutch screening programme. For all analytes with concentrations in the quantifiable range, contamination with glue had no effect on measurement variation, as it appeared equivalent to variation in untreated DBSs. Our data show that, in the unlikely event of contamination of Whatman#903 with EBF#1003, there is no effect on the measured concentration of analytes. Full article

This review should be seen as a practical tool, one which we hope illustrates potential routes to follow when seeking to implement or lobby for severe combined immunodeficiency newborn screening (SCID NBS) at a national or regional level. Experience has shown that there are country- and region-wide variations in terms of awareness of the need for SCID NBS and the processes required to demonstrate and prove the importance of SCID NBS. This guide therefore aims to share experiences and equip readers with evidence while also directing them to key further reading and resources that provide support, data, and existing frameworks that are relevant to making the case for mandatory NBS for SCID. Full article

A national approach to screening for critical congenital heart disease (CCHD) using pulse oximetry was undertaken in the United States. Following the scientific studies that laid the groundwork for the addition of CCHD screening to the U.S. Recommended Uniform Screening Panel (RUSP) and endorsement by professional societies, advocates including physicians, nurses, parents, medical associations, and newborn screening interest groups were able to successfully pass laws requiring the screen on a state by state basis. Public health involvement and screening requirements vary by state. However, a common algorithm, education, and implementation strategies were shared nationally as well as CCHD toolkits to aid in the implementation in hospitals. Health Resources & Services Administration (HRSA) grants to pilot states encouraged the development of a public health infrastructure around screening, data collection, and quality measures. The formation of a CCHD NewSTEPs technical advisory work group provided a systematic way to tackle challenges and share best practices by hosting monthly meetings and webinars. CCHD screening is now required in 48 states, with over 98% of U.S. births being screened for CCHD using pulse oximetry. A standard protocol has been implemented in most states. While the challenges related to screening special populations and quantifying screening outcomes through the creation of a national data repository remain; universal implementation is nearly complete. Full article

Background: Quantification of T-cell-receptor-excision circles (TRECs) and kappa-deleting-recombination-excision circles (KRECs) from dried blood spots (DBS) allows detection of neonates with severe T-cell and/or B-cell lymphopenia that are potentially affected by severe combined immunodeficiency (SCID), as well as X-linked agammaglobulinemia (XLA). Methods: Determination of TRECs and KRECs using a triplex RT-PCR (TRECS-KRECS-β-actin) assay from prospectively collected DBS between February 2014 and December 2016 in three hospitals in Seville, Spain. Cut-off levels were TRECs < 6/punch, KRECs < 4/punch and b-actin > 700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (CDC) were included. Results: A total of 8943 DBS samples obtained from 8814 neonates were analysed. Re-punching was necessary in 124 samples (1.4%) due to insufficient β-actin values (<700 copies/punch). Preterm neonates (GA < 37 weeks) and neonates with a BW < 2500 g showed significantly lower TRECs and KRECs levels (p < 0.001). Due to repeated pathological results, ten neonates were re-sampled (0.11%), of which five neonates (0.055%) confirmed the pathological results: one case was a fatal chromosomopathy (TRECs 1/KRECs 4); two were extreme premature newborns (TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); and 2 neonates were born to mothers receiving azathioprine during pregnancy (TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All controls were correctly identified. Conclusions: Severe T- and B-cell lymphopenias were correctly identified by the TRECS-KRECS-β-actin assay. Prematurity and low BW are associated with lower TREC and KREC levels. Extreme prematurity and maternal immune suppressive therapy can cause false positive results of TRECs and KRECs values. Full article