Utility of routine urine CMV PCR and total serum IgM testing of small for gestational age infants: a single center review.

BACKGROUND: Due to the extremely low incidence of TORCH (toxoplasmosis, rubella, CMV, herpes simplex virus) infections, diagnostic testing of all small for gestational age (SGA) infants aimed at TORCH etiologies may incur unnecessary tests and cost. OBJECTIVE: To determine the frequency of urine CMV PCR and total IgM testing among infants with birth weight <10% and the rate of test positivity. To evaluate the frequency of alternative etiologies of SGA in tested infants. METHODS: Retrospective chart review of SGA infants admitted to the neonatal intensive care unit (NICU) at NYU Langone Medical Center between 2007 and 2012. Subjects were classified as being SGA with or without intrauterine growth restriction (IUGR). The IUGR subjects were then further categorized as having either symmetric or asymmetric IUGR utilizing the Fenton growth chart at birth. Initial testing for TORCH infections, which included serum total IgM, CMV PCR and head ultrasound, were reviewed and analyzed. RESULTS: Three hundred and eighty-six (13%) infants from a total of 2953 NICU admissions had a birth weight ≤10th percentile. Of these, 44% were IUGR; 34% being symmetric IUGR and 10% asymmetric. A total of 32% of SGA infants had urine CMV PCR and total IgM tested with no positive results. As expected, significantly higher percentage of symmetric IUGR infants were tested compared to asymmetric IUGR and non-IUGR SGA infants, (64% vs. 47% vs. 19%) P≤0.01. However, 63% of infants with a known cause for IUGR had same testing done aimed at TORCH infections. We calculated additional charges of $64,065 that were incurred by such testing. CONCLUSIONS: The majority of infants in our study who received testing for urine CMV PCR and total IgM aimed at TORCH infections had one or more other known non-infectious etiologies for IUGR. Because the overall yield of such testing is extremely low, we suggest tests for possible TORCH infections may be limited to symmetric IUGR infants without other known etiologies. Improved guidelines testing for TORCH infections can result in reducing hospital charges and unnecessary studies.

Utilization of ultrasonography to detect developmental dysplasia of the hip: when reality turns selective screening into universal use.

BACKGROUND: Developmental dysplasia of the hip (DDH) occurs in 3-5 of 1000 live births and is associated with known risk factors. In most countries, formal practice for early detection of DDH entails the combination of risk factor identification and physical examination of the hip, while the golden standard diagnostic instrument is hip ultrasonography (US). This practice is commonly referred to as selective screening. Infants with positive US findings are treated with a Pavlik harness, a dynamic abduction splint. The objective of our study was to evaluate hip US utilization patterns in Maccabi Healthcare Services (MHS), a large health plan. METHODS: Study population: All MHS members, born between June 2011 and October 2014, who underwent at least one US before the age of 15 months. STUDY VARIABLES: Practice specialty and number of enrolled infants. Positive US result was defined as referral to an abduction splint. Cost was based on Ministry of Health price list. Chi square and correlation coefficients were employed in the statistical analysis. RESULTS: Of the 115,918 infants born during the study period, 67,491 underwent at least one hip US. Of these, 60.6% were female, mean age at performance: 2.2 months. Of those who underwent US, 625 (0.93%) were treated with a Pavlik harness: 0.24% of the male infants and 1.60% of the female infants (p < 0.001). Analysis of physician practice characteristics revealed that referral to US was significantly higher among pediatricians as compared with general practitioners (60% and 35%, respectively). Practice volume had no influence on referral rate. Direct medical costs of the 107 hip US examinations performed that led to detection of one positive case (treated by Pavlik): US$10,000. CONCLUSIONS: Current pattern of hip US utilization for early detection of DDH resembles universal screening more closely than selective screening. This can inform policy decisions as to whether a stricter selective screening or a formal move to universal screening is appropriate in Israel.

An Exploration of Genetic Test Utilization, Genetic Counseling, and Consanguinity within the Inborn Errors of Metabolism Collaborative (IBEMC).

The Inborn Errors of Metabolism Collaborative (IBEMC) includes clinicians from 29 institutions collecting data to enhance understanding of metabolic conditions diagnosable by newborn screening. Data collected includes hospitalizations, test results, services, and long-term outcomes. Through evaluation of this data, we sought to determine how frequently genetic counseling had been provided, how often genetic testing was performed, and also determine the consanguinity rate in this population. A data query was performed with the following elements abstracted/analyzed: current age, metabolic condition, whether genetic counseling was provided (and by whom), whether genetic testing was performed, and consanguinity. Genetic counseling was provided to families 95.8% of the time and in 68.6% of cases by a genetic counselor. Genetic testing was performed on 68.0% of subjects, with usage highest for fatty-acid-oxidation disorders (85.1%). The rate of consanguinity was 2.38%. Within this large national collaborative there is a high frequency of genetic counseling, though in one-third of cases a genetic counselor has not been involved. Additionally, while metabolic conditions have historically been diagnosed biochemically, there is currently high utilization of molecular testing suggesting DNA testing is being incorporated into diagnostic assessments - especially for fatty-acid-oxidation disorders where the underlying genotype helps predict clinical presentation.

Expanded Newborn Screening: Information and Resources for the Family Physician.

Each year, 4 to 5 million newborns receive state-mandated screening. Although the Advisory Committee on Heritable Disorders in Newborns and Children has identified 34 core conditions that should be incorporated into screening programs, each state manages, funds, and maintains its own program. State programs encompass screening, as well as the diagnosis and coordination of care for newborns with positive findings. Testing for core disorders is fairly standardized, but more extensive screening varies widely by state, and the rigorous evaluation of new screening panels is ongoing. The core panel includes testing for three main categories of disorders: metabolic disorders (e.g., amino acid and urea cycle, fatty acid oxidation, and organic acid disorders); hemoglobinopathies; and a group of assorted conditions, including congenital hearing loss. Family physicians must be familiar with the expanded newborn screening tests to effectively communicate results to parents and formulate interventions. They must also recognize signs of metabolic disorders that may not be detected by screening tests or that may not be a part of standard newborn screening in their state. For infants with positive screening results leading to diagnosis, long-term follow-up involves ongoing parental education, regular medical examinations, management at a metabolic treatment center, and developmental and neuropsychological testing to detect associated disorders in time for early intervention.

Association of US State Implementation of Newborn Screening Policies for Critical Congenital Heart Disease With Early Infant Cardiac Deaths.

IMPORTANCE: In 2011, critical congenital heart disease was added to the US Recommended Uniform Screening Panel for newborns, but whether state implementation of screening policies has been associated with infant death rates is unknown. OBJECTIVE: To assess whether there was an association between implementation of state newborn screening policies for critical congenital heart disease and infant death rates. DESIGN, SETTING, AND PARTICIPANTS: Observational study with group-level analyses. A difference-in-differences analysis was conducted using the National Center for Health Statistics' period linked birth/infant death data set files for 2007-2013 for 26 546 503 US births through June 30, 2013, aggregated by month and state of birth. EXPOSURES: State policies were classified as mandatory or nonmandatory (including voluntary policies and mandates that were not yet implemented). As of June 1, 2013, 8 states had implemented mandatory screening policies, 5 states had voluntary screening policies, and 9 states had adopted but not yet implemented mandates. MAIN OUTCOMES AND MEASURES: Numbers of early infant deaths (between 24 hours and 6 months of age) coded for critical congenital heart disease or other/unspecified congenital cardiac causes for each state-month birth cohort. RESULTS: Between 2007 and 2013, there were 2734 deaths due to critical congenital heart disease and 3967 deaths due to other/unspecified causes. Critical congenital heart disease death rates in states with mandatory screening policies were 8.0 (95% CI, 5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100 000 births (n = 13) in 2013 (for births by the end of July); for other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per 100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n = 21) in 2013. Early infant deaths from critical congenital heart disease through December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after states implemented mandatory screening compared with prior periods and states without screening policies. Early infant deaths from other/unspecified cardiac causes declined by 21.4% (95% CI, 6.9%-33.7%), with an absolute decline of 3.5 (95% CI, 3.2-3.8) deaths per 100 000 births. No significant decrease was associated with nonmandatory screening policies. CONCLUSIONS AND RELEVANCE: Statewide implementation of mandatory policies for newborn screening for critical congenital heart disease was associated with a significant decrease in infant cardiac deaths between 2007 and 2013 compared with states without these policies.

[Newborn Hearing Screening - Results of a Parental Survey in Saxony-Anhalt]. / Neugeborenen-Hörscreening ­ Ergebnisse einer Elternbefragung in Sachsen-Anhalt.

Background: In recent years quality assurance has become an essential part of today's health-care system in the wake of the modern patient-oriented quality management. With the statutory introduction of newborn hearing screening (NHS) in 2009, a quality assurance of these early detection methods has become necessary. The aim of the study was to determine patient satisfaction in relation to the NHS in Saxony-Anhalt. Patients/Methods: During the period from November 2013 to April 2014, 394 parents were retrospectively interviewed about their experiences and expectations in relation to the NHS, using a standardised questionnaire. In total, 21 child care centres and 6 paediatric primary care centres from all over Saxony-Anhalt were involved. Results: It turns out that the majority of parents are satisfied with the NHS and 97.7% are in favour of the offer of an NHS. Of the surveyed parents, 69.3% felt the information as sufficient. However, only 66.2% of parents took a closer look at the leaflet issued by the G-BA. In addition, 17.7% of respondents are dissatisfied with the professional competence of the examining staff. Conclusion: The study shows that the general attitude among parents towards newborn hearing screening was very positive. They felt reassured by it although there are some aspects still open to criticism.

[Impact of the Overlap Region Between Acoustic and Electric Stimulation]. / Einfluss des Überlappungsbereichs zwischen akustischer und elektrischer Stimulation.

Patients with residual hearing in the low frequencies and ski-slope hearing loss with partial deafness at medium and high frequencies receive a cochlear implant treatment with electric-acoustic stimulation (EAS, "hybrid" stimulation). In the border region between electric and acoustic stimulation a superposition of the 2 types of stimulation is expected. The area of overlap is determined by the insertion depth of the stimulating electrode and the lower starting point of signal transmission provided by the CI speech processor. The study examined the influence of the variation of the electric-acoustic overlap area on speech perception in noise, whereby the width of the "transmission gap" between the 2 different stimulus modalities was varied by 2 different methods. The results derived from 9 experienced users of the MED-EL Duet 2 speech processor show that the electric-acoustic overlapping area and with it the crossover frequency between the acoustic part and the CI should be adjusted individually. Overall, speech reception thresholds (SRT) showed a wide variation of results in between subjects. Further studies shall investigate whether generalized procedures about the setting of the overlap between electric and acoustic stimulation are reasonable, whereby an increased number of subjects and a longer period of acclimatization prior to the conduction of hearing tests deemed necessary.

[Whole-genome sequencing in German clinical practice : Economic impacts of its use in selected areas of application]. / Ganzgenomsequenzierung in der deutschen Versorgung : Ökonomische Auswirkungen eines Einsatzes in ausgewählten Anwendungsgebieten.

BACKGROUND: The diagnostic use of whole-genome sequencing (WGS) is a growing issue in medical care. Due to limited resources in public health service, budget-impact analyses are necessary prior to implementation. OBJECTIVE: A budget-impact analysis for WGS of all newborns and diagnostic investigation of tumor patients in different oncologic indications were evaluated. METHODS: A cost analysis of WGS based on a quality-assured process chart for WGS at the German Cancer Research Center (DKFZ), Heidelberg, constitutes the basis for this evaluation. Data from the National Association of Statutory Health Insurance Funds and the Robert-Koch-Institute, Berlin, were used for calculations of specific clinical applications. RESULTS AND DISCUSSION: WGS in newborn screening leads to costs of € 2.85 bn and to an increase of total expenditure by 1.41%. Sequencing of all tumor patients would cost approximately € 0.84 bn, which corresponds to 0.42% of total expenditures. In all scenarios, the sole consideration of procedure costs results in increasing costs. However, in cost discussions potential savings (reduction of disease-related follow-up-costs, improved cost-effectiveness of medical measures etc.) should be considered. Such considerations are the subject of economic indication-specific evaluations. WGS has the potential to generate a large number of deterministic findings for which treatment options are limited. Hence, it is necessary to limit indications, in which WGS has proven medical evidence.

Newborn Hearing Screening: Making a Difference.

Newborn hearing screening has become the standard of care in the United States, with over 98% of infants born screened for hearing loss. Appropriate and timely follow-up is critical when an infant does not pass the screening. While there remains room for improvement, newborn hearing screening is making a difference.

Low vertebral ano-rectal cardiac tracheo-esophageal renal limb screening rates in children with anorectal malformations.

BACKGROUND: The aim of this study was to establish the rate of screening for associated cardiac, vertebral, spinal cord, urologic, and limb anomalies vertebral ano-rectal cardiac tracheo-esophageal renal limb (VACTERL) in children with anorectal malformation (ARM). METHODS: We performed a retrospective cohort study using the Medicaid Analytic eXtract database which contains enrollment and utilization claims and demographic information from all Medicaid enrollees. Patients born between January 2005 and December 2008 with International Classification of Diseases, Ninth Revision codes for a diagnosis of ARM within 30 days of life, an ARM procedure code during the first year of life, and a minimum of 12 months of continuous enrollment were included. VACTERL screening was determined using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes for diagnostic tests used to detect these anomalies. RESULTS: A total of 406 patients were identified (231 males). Evaluation of the spinal vertebrae was performed in 94% of patients (381 of 406). Spinal cord evaluation was performed in 57% (231 of 406): 52% (121 of 231) received spinal ultrasound (US), 24% (56 of 231) received spinal magnetic resonance imaging, and 23% (54 of 231) received both. Sacral radiographs were performed in 8% (32 of 406) and 77% (313 of 406) underwent an echocardiogram. Genitourinary evaluation was performed in 84% (341 of 406): 67% (229 of 341) received renal US, 8% (27 of 341) received abdominal US, and 25% (85 of 341) received both. Limb evaluation was recorded in 19% (76 of 406). Multiple screening including an echocardiogram, spinal radiograph, spinal cord evaluation, and renal evaluation was performed in 45% (181 of 406); 2% (7 of 406) did not receive any screening tests. CONCLUSIONS: Low VACTERL screening in children with ARM suggests that associated anomalies may be undiagnosed which may lead to increased long-term morbidity.

Progress in identifying infants with hearing loss­United States, 2006-2012.

Congenital hearing loss affects one to three of every 1,000 live born infants and negatively impacts children through delayed speech, language, social, and emotional development when undetected. To address this public health issue, jurisdiction-based Early Hearing Detection and Intervention (EHDI) programs are working to ensure all newborns are screened for hearing loss, receive follow-up diagnostic testing (DX) if they do not pass the screening, and are enrolled in early intervention (EI) services if diagnosed with a permanent hearing loss. Although substantial progress has been made in the provision and documentation of services, challenges remain because, unlike screening results, diagnostic test results and enrollment in EI are not consistently reported to the EHDI programs. Therefore, it is difficult for states and territories to know if infants received recommended follow-up services (diagnostic testing and/or EI services), often resulting in infants being classified at either stage as lost to follow-up (LFU)/lost to documentation (LTD). To assess progress toward identifying children with hearing loss and reducing LFU/LTD for DX (LFU/LTD-DX) and EI enrollment (LFU/LTD-EI), CDC analyzed EHDI surveillance data for 2006-2012. Results indicated that the number of jurisdictions reporting data increased from 49 to 57, rates of screening increased from 95.2% to 96.6%, rates of referral from screening decreased from 2.3% to 1.6%, rates of diagnosis among infants not passing their final screening increased from 4.8% to 10.3%, and enrollment in EI among children diagnosed with hearing loss increased from 55.4% to 61.7%, whereas rates for both LFU/LTD-DX and LFU/LTD-EI declined. These findings show sustained progress toward screening, identification, and enrollment in EI as well as highlighting the need for continued improvements in the provision and documentation of EHDI services.

A Systematic Review: The Utility of the Revised Version of the Score for Neonatal Acute Physiology Among Critically Ill Neonates.

The revised version of the Score for Neonatal Acute Physiology (SNAP-II) has been used across all birth weights and gestational ages to measure the concept of severity of illness in critically ill neonates. The SNAP-II has been operationalized in various ways across research studies. This systematic review seeks to synthesize the available research regarding the utility of this instrument, specifically on the utility of measuring severity of illness sequentially and at later time points. A systematic review was performed and identified 35 research articles that met inclusion and exclusion criteria. The majority of the studies used the SNAP-II instrument as a measure of initial severity of illness on the first day of life. Six studies utilized the SNAP-II instrument to measure severity of illness at later time points and only 2 studies utilized the instrument to prospectively measure severity of illness. Evidence to support the use of the SNAP-II at later time points and prospectively is lacking and more evidence is needed.

[Newborn screening : the point of view of the paediatrician]. / Dépistage néonatal : le point de vue du pédiatre.

Newborn screening is a public health effort that has changed the prognosis of some congenital diseases. Newborn screening programmes differ between countries in which it is organized. Demographic, epidemiological or economic factors play a role in the choice of the screening panel. In the French Community of Belgium, the programme focuses on 13 metabolic and endocrine diseases, hearing loss and hemoglobinopathies (Brussels and Liege). Newborn screening is a complex process that requires the involvement of all stakeholders : parent information, blood sampling or testing, lab analysis, follow-up of the results, initiate adequate care in case of positive test and genetic counselling. Newborn screening programmes will evolve in the next years. New therapeutic and diagnostic methods will make other genetic diseases candidates for screening. Whole genome sequencing may be the next expansion; it will create new opportunities but will pose new ethical dilemmas. We must all prepare now for future challenges.

The case for mandatory newborn screening for severe combined immunodeficiency (SCID).

Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency and is a paediatric emergency. Delay in recognising and detecting SCID can have fatal consequences and also reduces the chances of a successful haematopoietic stem cell transplant (HSCT). Screening for SCID at birth would prevent children from dying before HSCT can be attempted and would increase the success of HSCT. There is strong evidence to show that SCID fulfills the internationally-established criteria for a condition to be screened for at birth. There is also a test (the T-cell receptor excision circle (TREC) assay) that is now being successfully used in an increasing number of US states to screen for SCID in routine newborn Guthrie samples. Concerted lobbying efforts have highlighted the need for newborn screening (NBS) for SCID, and its implementation is being discussed in Europe both at EU and individual country level, but as yet there is no global mandate to screen for this rare and frequently lethal condition. This paper summarizes the current evidence for, and the success of SCID NBS, together with a review of the practical aspects of SCID testing and the arguments in favour of adding SCID to the conditions screened for at birth.

ICON: the early diagnosis of congenital immunodeficiencies.

Primary immunodeficiencies are intrinsic defects in the immune system that result in a predisposition to infection and are frequently accompanied by a propensity to autoimmunity and/or immunedysregulation. Primary immunodeficiencies can be divided into innate immunodeficiencies, phagocytic deficiencies, complement deficiencies, disorders of T cells and B cells (combined immunodeficiencies), antibody deficiencies and immunodeficiencies associated with syndromes. Diseases of immune dysregulation and autoinflammatory disorder are many times also included although the immunodeficiency in these disorders are often secondary to the autoimmunity or immune dysregulation and/or secondary immunosuppression used to control these disorders. Congenital primary immunodeficiencies typically manifest early in life although delayed onset are increasingly recognized. The early diagnosis of congenital immunodeficiencies is essential for optimal management and improved outcomes. In this International Consensus (ICON) document, we provide the salient features of the most common congenital immunodeficiencies.

Three cost-utility analyses of screening for intracranial hemorrhage in neonates with hemophilia.

BACKGROUND: Intracranial hemorrhage (ICH) in the newborn period is a potential cause of serious morbidity and mortality in individuals with hemophilia. The incidence of ICH is estimated to be 2% to 4%; however, depending on the mode of delivery, it may be considerably higher. Considering the varying sensitivities and costs of various imaging modalities, there remains controversy surrounding universal cranial imaging. Cost-utility analysis is the ideal tool to display the consequences of a decision made. METHODS: We constructed a decision tree to evaluate the direct and indirect costs, possible outcomes, and probabilities of ICH in neonates with hemophilia. We created 3 decision analysis models to evaluate the cost-utility of different screening modalities for ICH: ultrasound, computed tomography, and magnetic resonance imaging. Within each model, 3 different strategies were compared: screen all neonates; screen only neonates born by instrumented delivery; and not screen any neonates. A societal perspective was used for all models. The base case models were later reanalyzed in sensitivity analysis to account for uncertainties. RESULTS: Total costs for screening all neonates, screening only neonates born by instrumented delivery, and not screening any neonates were $9501, $9297, and $9347, respectively, for US, and $9761, $9351, and $9353, respectively, for CT. Screening instrumented deliveries using MRI had an incremental cost-effectiveness ratio of $12,440. CONCLUSIONS: Screening newborns born by an instrumented delivery appears to be the most cost-effective strategy irrespective of the imaging modality. Subsequent studies will require a longer time frame to factor in possible late effects of radiation, anesthesia, and the high cost of factor replacement and hospital admission.

Implementation of written consent for newborn screening in Victoria, Australia.

AIMS: There has been increasing evidence of a lack of public awareness of newborn screening and concern about inadequate consent being obtained from parents. Apprehension also exists in relation to storage and secondary use of screening samples. Our objective was to introduce a written consent process across Victoria as a means of strengthening programme transparency, quality and supporting parental choice. In addition, more comprehensive information covering all aspects of the programme was developed. METHODS: A 'two-stage' written consent protocol allowed parents to give separate consent for (i) their baby to be screened and (ii) secondary use of the sample in de-identified health research. At the time of sample collection, parents were asked to complete the consent form, included as part of the screening card. The protocol was piloted in four public hospitals and subsequently implemented statewide. RESULTS: Twelve months of laboratory data showed that although refusals for screening increased, overall participation remained above 99%. The percentage of parents opting out of research use was 6.5%. Provider compliance with the new protocol was high, with only 1.4% of cards received without a completed consent form. CONCLUSION: This quality improvement project has demonstrated that parents can participate more fully in newborn screening without jeopardising high uptake. As a secondary benefit, the public health resource of stored cards can be maintained with parental support. Future work needs to examine the quality of consent being given by parents and investigation of the reasons why some choose to decline.

[Results and lessons after 10 years of universal neonatal hearing screening in the Champagne-Ardenne region of France]. / Dépistage systématique de la surdité à la naissance : résultats et enseignements au terme de 10 ans de pratique en Champagne-Ardenne.

In France, universal newborn hearing screening has been mandatory since April23rd, 2012, but it began in the Champagne-Ardenne region on January 15th 2004. More than 99 % of 160 196 newborns have since been systematically screened in this region. Bilateral hearing impairment was thus identified in 116 infants when they were around 3.5 months old. Earlier diagnosis improves the outcome of deafness, which is only diagnosed around age 20 months without screening. The authors report their experience and the lessons learnt.

Limitations of routine neuroimaging in predicting outcomes of preterm infants.

INTRODUCTION: Preterm births are increasing in number and while the rates of cerebral palsy have declined, there are increasing numbers of infants who survive with handicaps. In some studies, up to 50 % of children will have morbidity when followed up to school age. METHODS: A review of current literature was conducted to determine the validity of routine cranial ultrasound scans (CUS) to predict neurodevelopmental outcomes, including motor and cognitive deficits. We also reviewed the additional benefit offered by including MRI scans in scanning protocols to enhance the reliability in predicting the neurodevelopmental sequelae of prematurity. RESULTS: CUS is valuable as a screening tool to determine significant brain injury when conducted regularly over the first weeks of life in preterm infants. Subtle changes on CUS are difficult to interpret and more precise information is offered by performing MRI scans. These are most often carried out at term equivalent age but earlier scans may be just as useful in predicting neurocognitive outcomes. When MRI scans are either normal or seriously abnormal, there is a very clear correlation with outcome to 2 years of age. Mild and moderate degrees of injury defined on MRI need more sophisticated scanning sequences to determine the likelihood of associated sequelae. Follow-up to school age is essential to diagnose more subtle cognitive delays. CONCLUSION: CUS provides a good screening tool to detect serious brain injury resulting in motor handicaps but MRI scans are complementary and necessary to accurately predict the outcomes of preterm infants, especially cognitive delays.