Newborn Screening Articles Spring 2012
- Clin Chim Acta. 2012 Jul 11;413(13-14):1141-4. Epub 2012 Mar 23.
Amino acid disorders detected by quantitative amino acid HPLC analysis in Thailand: An eight-year experience.
Vatanavicharn N, Ratanarak P, Liammongkolkul S, Sathienkijkanchai A, Wasant P.
Abstract
BACKGROUND:
Amino acid disorders are a major group of inborn errors of metabolism (IEM) with variable clinical presentations. This study was aimed to provide the data of amino acid disorders detected in high-risk Thai patients referred to our metabolic lab from all over the country.
METHODS:
From 2001 to 2009, we analyzed amino acids by HPLC in 1214 plasma and cerebrospinal fluid specimens. These specimens were obtained from patients with clinical suspicion of IEM or with positive newborn screening. The clinical data of the patients with confirmed diagnoses of amino acid disorders were also analyzed.
RESULTS:
Fifty-eight patients were diagnosed with amino acid disorders, including 20 cases (34.5%) with maple syrup urine disease, 13 (22.4%) with phenylketonuria and hyperphenylalaninemia, 13 (22.4%) with nonketotic hyperglycinemia, 9 (15.5%) with urea cycle defects, 2 (3.4%) with classical homocystinuria, and 1 (1.7%) with ornithine aminotransferase deficiency. There was considerable delay in diagnoses which led to poor outcomes in most patients.
CONCLUSION:
The prevalence of amino acid disorders in Thailand is distinct from other countries. This will guide the selection of the prevalent IEM for the future expansion of newborn screening program in this country.
- Endocrine. 2012 Jun;41(3):355-73. Epub 2012 Jan 7.
Clinical outcomes in the management of congenital adrenal hyperplasia.
Falhammar H, Thorén M.
Abstract
Congenital adrenal hyperplasia (CAH) is a group of disorders affecting adrenal steroid synthesis. The most common form, 21-hydroxylase deficiency, leads to decreased production of cortisol and aldosterone with increased androgen secretion. In classic CAH glucocorticoid treatment can be life-saving, and provides symptom control, but must be given in an unphysiological manner with the risk of negative long-term outcomes. A late diagnosis or a severe phenotype or genotype has also a negative impact. These factors can result in impaired quality of life (QoL), increased cardiometabolic risk, short stature, osteoporosis and fractures, benign tumors, decreased fertility, and vocal problems. The prognosis has improved during the last decades, thanks to better clinical management and nowadays the most affected patients seem to have a good QoL. Very few patients above the age of 60years have, however, been studied. Classifying patients according to genotype may give additional useful clinical information. The introduction of neonatal CAH screening may enhance long-term results. Monitoring of different risk factors and negative consequences should be done regularly in an attempt to improve clinical outcomes further.
- J Inherit Metab Dis. 2012 May 3. [Epub ahead of print]
Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1 - From blood spot to screening result.
Loeber JG, Burgard P, Cornel MC, Rigter T, Weinreich SS, Rupp K, Hoffmann GF, Vittozzi L.
Abstract
In many European countries neonatal screening has been introduced over the last 50years as an important public health programme. Depending on health care structure, available funds, local politics, input from professional groups, parent groups, and the general public this introduction has led to different approaches in the way the screening programmes have been set up, financed and governed. To get some insight about the current situation, in 2009 the European Union, via its EAHC agency, put out a call for a tender that was acquired by our project group. An online survey was compiled in which the whole screening programme was covered by a questionnaire. This survey covered the EU member states, (potential) candidate member states and EFTA countries, in total 40 countries. Results showed little consensus concerning 1. information of parents including informed consent; 2. which conditions are screened for, ranging from 1 to around 30 conditions; 3. sampling time post partum; 4. screening methodology including cut-offs values even between screening laboratories within countries.; 5. storage of residual specimens, varying from 3months to 1000 years. In addition, confirmatory diagnostics and follow-up also show large discrepancies (Burgard et al. 2011). In addition to the current practices report an expert opinion document has been produced with recommendations to the EU Commission for future improvements, e.g. in parallel to the way the USA has harmonized its practices based on recommendations by the American College of Medical Genetics (Watson et al., Pediatrics 117: S296-S307, 2006).
- Alcohol. 2012 May;46(3):269-76. Epub 2012 Mar 21.
Neonatal screening for prenatal alcohol exposure: Assessment of voluntary maternal participation in an open meconium screening program.
Zelner I, Shor S, Lynn H, Roukema H, Lum L, Eisinga K, Koren G.
Abstract
Meconium fatty acid ethyl esters (FAEEs) are validated biomarkers of fetal alcohol exposure. Meconium FAEE testing can potentially be used as a screen by health-care professionals to identify neonates at-risk for Fetal Alcohol Spectrum Disorder, thereby permitting diagnostic follow-up of these children and early intervention in those who develop disabilities. The purpose of this study was to assess whether women would willingly partake in a screening program of this nature. This was determined by launching a pilot screening program for prenatal alcohol exposure in a high-risk obstetric unit previously shown to have a high prevalence of FAEE-positive meconium via anonymous meconium testing. The program involved voluntary testing of meconium for FAEEs and long-term developmental follow-up of positive cases through an existing public health program. The participation rate in the screening program was significantly lower than when testing was conducted anonymously (78% vs. 95%, respectively; p0.05), and the positivity rate was 3% in contrast to 30% observed under anonymous conditions (p0.001). These low rates suggest that the majority of mothers who consumed alcohol in pregnancy refused to participate. We conclude that despite the potential benefits of such screening programs, maternal unwillingness to consent, likely due to fear, embarrassment, and guilt, may limit the effectiveness of meconium testing for population-based open screening, highlighting the need for public education and social marketing efforts for such programs to be of benefit.
- Am J Med Genet A. 2012 May;158A(5):1118-23. doi: 10.1002/ajmg.a.35312. Epub 2012 Apr 11.
Generation n + 1: Projected numbers of babies born to women with PKU compared to babies with PKU in the United States in 2009.
Resta R.
Abstract
Newborn PKU screening has been available since the mid-1960s, and the first group of screened babies is now a complete reproductive cohort (age 15-44). Untreated maternal PKU (MPKU) often results in significant developmental and physical disabilities in exposed fetuses, and could potentially offset some or all of the benefits produced by newborn PKU screening and dietary treatment. Based on the age distribution of the United States population in 2009, and using different estimates of PKU frequency (1/10,000; 1/15,000; 1/20,000), the projected number of babies born to women with PKU was compared to the projected number of babies born with PKU. In 2009, there were about 62,000,000 women age 15-44, with a fertility rate of 66.7 births/1,000 women. Of these women, depending on the incidence of PKU, 3,097-6,195 were estimated to have PKU, and they would have delivered 207-413 babies. In that same year, the number of births was 4,118,055, which would have resulted in 206-412 babies with PKU. Thus, in the United States, at all estimates of PKU frequency, the number of babies exposed to MPKU is equal to the number of babies born with PKU. This ratio varies with the fertility rate but is not dependent on the incidence of PKU. The benefits of newborn PKU screening and treatment could be significantly curtailed if adequate resources, education, and funding are not available to follow and monitor women with MPKU and their babies. © 2012 Wiley Periodicals, Inc.
- Amino Acids. 2012 May;42(5):1889-95. Epub 2011 Apr 21.
A simple method for the analysis by MS/MS of underivatized amino acids on dry blood spots from newborn screening.
Wang C, Zhang W, Song F, Liu Z, Liu S.
Abstract
The analysis by electrospray-ionization tandem mass spectrometry of amino acids with butyl esterification and isotopically labeled internal standard is routine in newborn screening laboratories worldwide. In the present study, we established a direct analysis method of higher accuracy that uses a non-deuterated internal standard. The automatic sampler and the pump of an LC apparatus were used to inject sample and mobile phase to MS, but no LC column was needed. The dry blood spot (DBS) material was prepared at levels of low, medium and high concentration; the running time was 1min. In parallel to the new procedure, we applied the established method to analyze nine amino acids on DBS of healthy newborns and phenylketonuria newborns. The newly proposed method of product ion confirmation scan along with multiple reaction monitoring resulted in a very accurate identification of each amino acid. Our innovative protocol had high sensitivity and specificity in the analysis of cases of suspected metabolic diseases.
- Arch Dis Child. 2012 May 1. [Epub ahead of print]
The impact of early identification of permanent childhood hearing impairment on speech and language outcomes.
Pimperton H, Kennedy CR.
Abstract
It is well established that permanent childhood hearing impairment (PCHI) has a detrimental impact on speech and language development. The past two decades have seen the gradual introduction of universal newborn hearing screening (UNHS) programmes coupled with early intervention programmes. We review studies that have capitalised on the advent of newborn hearing screening to assess the impact of early identification of PCHI on language outcomes in deaf children. The research supports the conclusion that, in children with PCHI, newborn hearing screening and early identification lead to beneficial effects on language development, with the most consistent evidence provided for links between early identification of PCHI and positive language outcomes. Future research needs to encompass a wider range of outcomes and to assess the impact of UNHS in adolescents and young adults.
- Clin Nurse Spec. 2012 May;26(3):164-8.
Outcome of clinical nurse specialist-led hyperbilirubinemia screening of late preterm newborns.
Nelson L, Doering JJ, Anderson M, Kelly L.
Abstract
PURPOSE/OBJECTIVE:
: The purpose of this project was to implement universal screening of all late preterm newborns for hyperbilirubinemia in a level I newborn nursery. RATIONALE/BACKGROUND:: Late preterm newborns have traditionally received the same level of care and monitoring as term newborns despite being at increased risk for morbidity and mortality.
DESCRIPTION OF THE PROJECT:
: An interdisciplinary clinical nurse specialist-led team guided by the Iowa Model of Evidence-Based Practice developed, piloted, and evaluated a standardized, coordinated approach to universal screening, assessment, and management of hyperbilirubinemia for late preterm newborns.
OUTCOMES:
: The readmission rate of late preterm newborns with hyperbilirubinemia in the 30 days after birth was reduced to zero, providing evidence of programmatic effectiveness.
INTERPRETATION/CONCLUSION:
: Universal screening of late preterm newborns for hyperbilirubinemia significantly improved outcomes in this vulnerable population.
IMPLICATIONS:
: Detection of hyperbilirubinemia through universal screening of late preterm newborns is recommended in newborn nurseries.
- Eur J Endocrinol. 2012 May;166(5):829-38. Epub 2012 Feb 2.
Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper.
Adachi M, Soneda A, Asakura Y, Muroya K, Yamagami Y, Hirahara F.
Abstract
OBJECTIVE:
To evaluate the effectiveness of mass screening of newborns for congenital hypothyroidism of central origin (CH-C) by measurement of free thyroxine (FT(4)) and thyroid-stimulating hormone (TSH).
DESIGN:
Questionnaire-based survey of CH-C patients born between 1999 and 2008 in Kanagawa prefecture, Japan.
METHODS:
TSH and FT(4) levels in dried blood spots on filter paper were measured using ELISA kits, and CH-C was diagnosed at FT(4) levels below a cutoff of 0.7 ng/dl (9.0 pmol/l). Survey results were collated with the database created by the screening organizer.
RESULTS:
Twenty-four CH-C patients (18 males) were identified, 14 of whom had multiple pituitary hormone deficiencies (group M), eight had isolated CH-C (group I), and two had undetermined pituitary involvement (group U). In groups M, I, and U, the number of patients with FT(4) levels below the cutoff value at screening was five (36%), seven (88%), and one (50%) respectively; other patients had been diagnosed clinically. Thus, 13 patients were true positives, while nine were false negatives, yielding screening sensitivity of 59.1% and positive predictive value of 11.5%. The calculated sensitivity was 81.8% at a higher cutoff value of 0.9 ng/dl (11.6 pmol/l). The overall incidence of CH-C was estimated at 1 in 30 833 live births, while that of CH of thyroidal origin (CH-T) is 1 in 3472 live births in Kanagawa prefecture (CH-T/CH-C, 8.9).
CONCLUSIONS:
Newborn screening with combined FT(4) and TSH measurements can identify a significant number of CH-C patients before manifestation of clinical symptoms, but a more appropriate FT(4) cutoff value should be considered.
- Eur J Hum Genet. 2012 May;20(5):484-5. doi: 10.1038/ejhg.2011.191. Epub 2011 Nov 9.
Newborn screening for sickle cell disease: whose reproductive benefit?
Ross LF.
- Eur J Hum Genet. 2012 May;20(5):486-7. doi: 10.1038/ejhg.2012.25. Epub 2012 Feb 29.
Reply to Ross' commentary: Reproductive benefit through newborn screening: preferences, policy and ethics.
Bombard Y, Miller FA.
- Eur J Hum Genet. 2012 May;20(5):498-504. doi: 10.1038/ejhg.2011.188. Epub 2011 Nov 9.
Health-care providers' views on pursuing reproductive benefit through newborn screening: the case of sickle cell disorders.
Bombard Y, Miller FA, Hayeems RZ, Wilson BJ, Carroll JC, Paynter M, Little J, Allanson J, Bytautas JP, Chakraborty P.
Abstract
Newborn screening (NBS) programs aim to identify affected infants before the onset of treatable disorders. Historically, benefits to the family and society were considered secondary to this clinical benefit; yet, recent discourse defending expanded NBS has argued that screening can in part be justified by secondary benefits, such as learning reproductive risk information to support family planning ('reproductive benefit'). Despite increased attention to these secondary benefits of NBS, stakeholders' values remain unknown. We report a mixed methods study that included an examination of providers' views toward the pursuit of reproductive risk information through NBS, using sickle cell disorder carrier status as an example. We surveyed a stratified random sample of 1615 providers in Ontario, and interviewed 42 providers across 7 disciplines. A majority endorsed the identification of reproductive risks as a goal of NBS (74-77%). Providers' dominant rationale was that knowledge of carrier status is an important and inherent benefit of NBS as it allows people to make reproductive choices, which is consistent with the goals of disease prevention. However, some challenged its appropriateness, questioning its logic, timing and impact on disease prevention. Others were sensitive to intruding on individuals' choices or children's independent rights. While the dominant view is consistent with discourse defending expanded NBS, it deviates from the traditional screening principles that underpin most public health interventions. Broader discussion of the balance between benefits to screened individuals and those to families and societies, in the context of public health programs, is needed
- J Med Ethics. 2012 May;38(5):299-303. Epub 2011 Dec 20.
Proceduralisation, choice and parental reflections on decisions to accept newborn bloodspot screening.
Nicholls SG.
Abstract
Newborn screening is the programme through which newborn babies are screened for a variety of conditions shortly after birth. Programmes such as this are individually oriented but resemble traditional public health programmes because they are targeted at large groups of the population and they are offered as preventive interventions to a population considered healthy. As such, an ethical tension exists between the goals of promoting the high uptake of supposedly 'effective' population-oriented programmes and the goal of promoting genuinely informed decision-making. There is, however, a lack of understanding with regard to how parents experience the tension between promoting uptake and facilitating informed choice. This paper addresses this issue, and data are presented to show how aspects of the timing, presentation of information and procedural routinisation of newborn screening serves to impact on the decisions made by parents.
- Lancet. 2012 May 1. [Epub ahead of print]
Screening of newborn babies: from blood spot to bedside.
Kemper AR, Martin GR.
- Lancet. 2012 May 1. [Epub ahead of print]
Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis.
Thangaratinam S, Brown K, Zamora J, Khan KS, Ewer AK.
Abstract
BACKGROUND:
Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. We assessed the performance of pulse oximetry as a screening method for the detection of critical congenital heart defects in asymptomatic newborn babies.
METHODS:
In this systematic review, we searched Medline (1951-2011), Embase (1974-2011), Cochrane Library (2011), and Scisearch (1974-2011) for relevant citations with no language restriction. We selected studies that assessed the accuracy of pulse oximetry for the detection of critical congenital heart defects in asymptomatic newborn babies. Two reviewers selected studies that met the predefined criteria for population, tests, and outcomes. We calculated sensitivity, specificity, and corresponding 95% CIs for individual studies. A hierarchical receiver operating characteristic curve was fitted to generate summary estimates of sensitivity and specificity with a random effects model.
FINDINGS:
We screened 552 studies and identified 13 eligible studies with data for 229 421 newborn babies. The overall sensitivity of pulse oximetry for detection of critical congenital heart defects was 76·5% (95% CI 67·7-83·5). The specificity was 99·9% (99·7-99·9), with a false-positive rate of 0·14% (0·06-0·33). The false-positive rate for detection of critical congenital heart defects was particularly low when newborn pulse oximetry was done after 24 h from birth than when it was done before 24 h (0·05% [0·02-0·12] vs 0·50 [0·29-0·86]; p=0·0017).
INTERPRETATION:
Pulse oximetry is highly specific for detection of critical congenital heart defects with moderate sensitivity, that meets criteria for universal screening.
- Mol Genet Metab. 2012 May;106(1):7-11. Epub 2012 Mar 21.
Galactosemia: When is it a newborn screening emergency?