Psychosocial Impact of a True-Positive, False-Positive, or Inconclusive Newborn Bloodspot Screening Result: A Questionnaire Study among Parents.

Expansion of newborn bloodspot screening (NBS) can increase health gain for more children but also increases the number of false-positive and uncertain results. The impact of abnormal and inconclusive NBS results on parental well-being and healthcare utilization was investigated. A questionnaire was sent to Dutch parents receiving an abnormal or inconclusive NBS result five weeks (T1) and four months (T2) post-NBS and compared to parents with a normal result (controls). In total, 35 true-positive (TP), 20 false-positive (FP), and 57 inconclusive (IC) participants and 268 controls filled out T1; 19 TP, 14 FP, 27 IC, and 116 controls filled out T2. Participants showed positive attitudes towards NBS. FP participants more often considered NBS less reliable. TP and FP participants experienced more negative emotions regarding the test result compared to controls at both T1 and T2, and IC only at T1. Parent-reported child vulnerability and perceptions of the newborn's health status and of parenthood showed no differences. TP and FP participants reported more healthcare utilization at T1, and mainly TP at T2. TP and IC participants showed more emergency department visits at T1. The findings can be used to improve NBS programs and optimize support for families with various NBS results.

Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model.

Objective: Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007-2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model. Methods: Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed. Results: The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model's performance. Conclusions: The PPV improved significantly (26-48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

Machine learning to improve false-positive results in the Dutch newborn screening for congenital hypothyroidism.

OBJECTIVE: The Dutch Congenital hypothyroidism (CH) Newborn Screening (NBS) algorithm for thyroidal and central congenital hypothyroidism (CH-T and CH-C, respectively) is primarily based on determination of thyroxine (T4) concentrations in dried blood spots, followed by thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) measurements enabling detection of both CH-T and CH-C, with a positive predictive value (PPV) of 21%. A calculated T4/TBG ratio serves as an indirect measure for free T4. The aim of this study is to investigate whether machine learning techniques can help to improve the PPV of the algorithm without missing the positive cases that should have been detected with the current algorithm. DESIGN & METHODS: NBS data and parameters of CH patients and false-positive referrals in the period 2007-2017 and of a healthy reference population were included in the study. A random forest model was trained and tested using a stratified split and improved using synthetic minority oversampling technique (SMOTE). NBS data of 4668 newborns were included, containing 458 CH-T and 82 CH-C patients, 2332 false-positive referrals and 1670 healthy newborns. RESULTS: Variables determining identification of CH were (in order of importance) TSH, T4/TBG ratio, gestational age, TBG, T4 and age at NBS sampling. In a Receiver-Operating Characteristic (ROC) analysis on the test set, current sensitivity could be maintained, while increasing the PPV to 26%. CONCLUSIONS: Machine learning techniques have the potential to improve the PPV of the Dutch CH NBS. However, improved detection of currently missed cases is only possible with new, better predictors of especially CH-C and a better registration and inclusion of these cases in future models.

Parents' views on accepting, declining, and expanding newborn bloodspot screening.

INTRODUCTION: The goal of newborn bloodspot screening (NBS) is the early detection of treatable disorders in newborns to offer early intervention. Worldwide, the number of conditions screened for is expanding, which might affect public acceptance. In the Netherlands, participation is high (>99%), but little is known about how parents perceive NBS. This study assessed parents' views on accepting, declining and expanding NBS. METHODS: A total of 804 of 6051 (13%) invited parents who participated in NBS in the Netherlands during the last two weeks of December 2019, and 48 of 1162 (4%) invited parents who declined participation in NBS in 2019 and 2020, completed a questionnaire. RESULTS: The most important reason for parents to participate in NBS was to prevent health complaints, whereas the most important reason to decline NBS was parents' viewpoint on life and the belief that the heel prick would be painful for the child. Compared to NBS participants, respondents who declined NBS were more actively religious, considered alternative medicine or lifestyle more important, were less inclined to vaccinate their child for infectious diseases, and reported more doubt about NBS participation (all differences p < .001). Informed choice was lower among respondents who declined NBS (44%) compared to participants in NBS (83%, p < .001), mostly due to insufficient knowledge. Of the NBS participants, 95% were positive about NBS expansion. Most NBS participants agreed to include conditions that could unintentionally reveal a diagnosis in the mother instead of the child (86%) or a condition that may not cause symptoms until later in the child's life (84%). CONCLUSION: Most participants made an informed decision to participate in NBS and are positive about screening for more conditions. Insights into parents' views on (non-)participation and expansion of NBS can help to ensure that NBS suits the population needs while safeguarding ethical principles for screening.

Economic Evaluation of Different Screening Strategies for Severe Combined Immunodeficiency Based on Real-Life Data.

Although several countries have adopted severe combined immunodeficiency (SCID) into their newborn screening (NBS) program, other countries are still in the decision process of adding this disorder in their program and finding the appropriate screening strategy. This decision may be influenced by the cost(-effectiveness) of these screening strategies. In this study, the cost(-effectiveness) of different NBS strategies for SCID was estimated based on real-life data from a prospective implementation study in the Netherlands. The cost of testing per child for SCID was estimated at EUR 6.36. The cost of diagnostics after screen-positive results was assessed to vary between EUR 985 and 8561 per child dependent on final diagnosis. Cost-effectiveness ratios varied from EUR 41,300 per QALY for the screening strategy with T-cell receptor excision circle (TREC) ≤ 6 copies/punch to EUR 44,100 for the screening strategy with a cut-off value of TREC ≤ 10 copies/punch. The analysis based on real-life data resulted in higher costs, and consequently in less favorable cost-effectiveness estimates than analyses based on hypothetical data, indicating the need for verifying model assumptions with real-life data. The comparison of different screening strategies suggest that strategies with a lower number of referrals, e.g., by distinguishing between urgent and less urgent referrals, are favorable from an economic perspective.

Improving the Dutch Newborn Screening for Central Congenital Hypothyroidism by Using 95% Reference Intervals for Thyroxine-Binding Globulin.

INTRODUCTION: Newborn screening (NBS) for congenital hypothyroidism (CH) in the Netherlands consists of thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG) measurements to detect thyroidal CH and central CH (CH-C). CH-C is detected by T4 or a calculated T4/TBG ratio, which serves as an indirect measure of free T4. TSH and TBG are only measured in the lowest 20 and 5% of daily T4 values, respectively. A recent evaluation of the Dutch NBS for CH showed that the T4 and T4/TBG ratio contribute to the detection of CH-C but also lead to a low positive predictive value (PPV). Dried blood spot (DBS) reference intervals (RIs) are currently unknown and may contribute to improvement of our NBS algorithm. MATERIALS AND METHODS: RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical & Laboratory Standards Institute guidelines in heel puncture cards from routine NBS in both sexes and at the common NBS sampling ages. Scatter plots were used to compare the healthy reference population to previously published data of CH-C patients and false positives. RESULTS: Analyses of 1,670 heel puncture cards showed small differences between subgroups and led to the formulation of total sample DBS RIs for T4 (56-118 nmol/L), TSH (<2.6 mIU/L), TBG (116-271 nmol/L), and the T4/TBG ratio (>20). 46% of false-positive referrals based on T4 alone had a TBG below the RI, indicating preventable referral due to partial TBG deficiency. One case of CH-C also had partial TBG deficiency (TBG 59 and T4 12 nmol/L blood). DISCUSSION/CONCLUSION: Established DBS RIs provided possibilities to improve the PPV of the Dutch CH NBS algorithm. We conclude that by taking partial TBG deficiency into account, approximately half of T4 false-positive referrals may be prevented while maintaining NBS sensitivity at the current level.

Costs and effects of conventional vision screening and photoscreening in the Dutch preventive child health care system.

BACKGROUND: Little is known about costs and effects of vision screening strategies to detect amblyopia. Aim of this study was to compare costs and effects of conventional (optotype) vision screening, photoscreening or a combination in children aged 3-6 years. METHODS: Population-based, cross-sectional study in preventive child health care in The Hague. Children aged 3 years (3y), 3 years and 9 months (3y9m) or 5-6 years (5/6y) received the conventional chart vision screening and a test with a photoscreener (Plusoptix S12C). Costs were based on test duration and additional costs for devices and diagnostic work-up. RESULTS: Two thousand, one hundred and forty-four children were included. The estimated costs per child screened were €17.44, €20.37 and €6.90 for conventional vision screening at 3y, 3y9m and 5/6y, respectively. For photoscreening, these estimates were €6.61, €7.52 and €9.40 and for photoscreening followed by vision screening if the result was unclear (combination) €9.32 (3y) and €9.33 (3y9m). The number of children detected with amblyopia by age were 9, 14 and 5 (conventional screening), 6, 13 and 3 (photoscreening) and 10 (3y) and 15 (3y9m) (combination), respectively. The estimated costs per child diagnosed with amblyopia were €1500, €1050 and €860 for conventional vision screening, €860, €420 and €1940 for photoscreening and €730 (3y) and €450 (3y9m) for the combination. CONCLUSIONS: Combining photoscreening with vision screening seems promising to detect amblyopia in children aged 3y/3y9m, whereas conventional screening seems preferable at 5/6y. As the number of study children with amblyopia is small, further research on the effects of these screening alternatives in detecting children with amblyopia is recommended.

The Methodological Quality and Challenges in Conducting Economic Evaluations of Newborn Screening: A Scoping Review.

INTRODUCTION: Cost-effectiveness (CEA) and cost-utility analyses (CUA) have become popular types of economic evaluations (EE) used for evidence-based decision-making in healthcare resource allocation. Newborn screening programs (NBS) can have significant clinical benefits for society, and cost-effectiveness analysis may help to select the optimal strategy among different screening programs, including the no-screening option, on different conditions. These economic analyses of NBS, however, are hindered by several methodological challenges. This study explored the methodological quality in recent NBS economic evaluations and analyzed the main challenges and strategies adopted by researchers to deal with them. METHODS: A scoping review was conducted according to PRISMA methodology to identify CEAs and CUAs of NBS. The methodological quality of the retrieved studies was assessed quantitatively using a specific guideline for the quality assessment of NBS economic evaluations, by calculating a general score for each EE. Challenges in the studies were then explored using thematic analysis as a qualitative synthesis approach. RESULTS: Thirty-five studies met the inclusion criteria. The quantitative analysis showed that the methodological quality of NBS economic evaluations was heterogeneous. Lack of clear description of items related to results, discussion, and discounting were the most frequent flaws. Methodological challenges in performing EEs of neonatal screenings include the adoption of a long time horizon, the use of quality-adjusted life years as health outcome measure, and the assessment of costs beyond the screening interventions. CONCLUSIONS: The results of this review can support future economic evaluation research, aiding researchers to develop a methodological guidance to perform EEs aimed at producing solid results to inform decisions for resource allocation in neonatal screening.

Critical evaluation of the newborn screening for congenital hypothyroidism in the Netherlands.

OBJECTIVE: Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency at birth due to disorders of the thyroid gland (thyroidal CH, CH-T), or the hypothalamus or pituitary (central CH, CH-C). The Dutch Newborn Screening (NBS) strategy is primarily based on determination of thyroxine (T4) concentrations in dried blood spots followed, if necessary, by thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) measurement enabling detection of both CH-T and CH-C. A calculated T4/TBG ratio serves as an indirect measure for free T4. A T4/TBG ratio ≤ 17 in a second heel puncture is suggestive of CH-C. DESIGN AND METHODS: In the present study, we evaluated 11 years of Dutch CH NBS using a database of referred cases by assessing the contribution of each criterion in the unique stepwise T4-TSH-TBG NBS algorithm. RESULTS: Between 2007 and the end of 2017, 1 963 465 newborns were screened in the Netherlands. Use of the stepwise algorithm led to 3044 referrals and the identification of 612 CH cases, consisting of 496 CH-T, 86 CH-C, and 30 CH of unknown origin diagnoses. We detected 62.8% of CH-C cases by the T4/TBG ratio in the second heel puncture. The positive predictive value (PPV) of the stepwise T4-TSH-TBG NBS algorithm was 21.0%. CONCLUSION: This evaluation shows that the Dutch stepwise T4-TSH-TBG NBS algorithm with a calculated T4/TBG ratio is of great value for the detection of both CH-T and CH-C in the Netherlands, at the cost of a lower PPV compared to TSH-based NBS strategies.

Evaluating progress towards triple elimination of mother-to-child transmission of HIV, syphilis and hepatitis B in the Netherlands.

BACKGROUND: In 2014 the World Health Organisation (WHO) established validation criteria for elimination of mother-to-child transmission (EMTCT) of HIV and syphilis. Additionally, the WHO set targets to eliminate hepatitis, including hepatitis B (HBV). We evaluated to what extent the Netherlands has achieved the combined WHO criteria for EMTCT of HIV, syphilis and HBV. METHODS: Data of HIV, syphilis and HBV infections among pregnant women and children (born in the Netherlands with congenital infection) for 2009-2015, and data required to validate the WHO criteria were collected from multiple sources: the antenatal screening registry, the HIV monitoring foundation database, the Perinatal Registry of the Netherlands, the national reference laboratory for congenital syphilis, and national HBV notification data. RESULTS: Screening coverage among pregnant women was > 99% for all years, and prevalence of HIV, syphilis and HBV was very low. In 2015, prevalence of HIV, syphilis and HBV was 0.06, 0.06 and 0.29%, respectively. No infections among children born in the Netherlands were reported in 2015 for all three diseases, and in previous years only sporadic cases were observed In 2015, treatment of HIV positive pregnant women was 100% and HBV vaccination of children from HBV positive mothers was > 99%. For syphilis, comprehensive data was lacking to validate WHO criteria. CONCLUSIONS: In the Netherlands, prevalence of maternal HIV, syphilis and HBV is low and congenital infections are extremely rare. All minimum WHO criteria for validation of EMTCT are met for HIV and HBV, but for syphilis more data are needed to prove elimination.

Cost-effectiveness of newborn screening for severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) is a condition that often results in severe infections and death at young age. Early detection shortly after birth, followed by treatment before infections occur, largely increases the chances of survival. As the incidence of SCID is low, assessing cost-effectiveness of adding screening for SCID to the newborn screening program is relevant for decision making. Lifetime costs and effects of newborn screening for SCID were compared to a situation without screening in the Netherlands in a decision analysis model. Model parameters were based on literature and expert opinions. Sensitivity analyses were performed. Due to earlier detection, the number of deaths due to SCID per 100,000 children was assessed to decrease from 0.57 to 0.23 and a number of 11.7 quality adjusted life-years (QALYs) gained was expected. Total yearly healthcare costs, including costs of screening, diagnostics, and treatment, were €390,800 higher in a situation with screening compared to a situation without screening, resulting in a cost-utility ratio of €33,400 per QALY gained.Conclusion: Newborn screening for SCID might be cost-effective. However, there is still a lot of uncertainty around the cost-effectiveness estimate. Pilot screening projects are warranted to obtain more accurate estimates for the European situation. What is Known: • Severe combined immunodeficiency (SCID) is a condition that often results in severe infections and death at a young age. • As the incidence of SCID is low, assessing cost-effectiveness of adding screening for SCID to the newborn screening program is needed. What is New: • Newborn screening for SCID is expected to reduce mortality from 0.57 to 0.23 per 100,000 children at additional healthcare costs of €390,800. The cost-utility ratio is €33,400 per QALY gained. • Due to large uncertainty around cost-effectiveness estimates, pilot screening projects are warranted for Europe.

Introducing Newborn Screening for Severe Combined Immunodeficiency (SCID) in the Dutch Neonatal Screening Program.

The implementation of newborn screening for severe combined immunodeficiency (SCID) in the Netherlands is a multifaceted process in which several parties are involved. The Dutch Ministry of Health adopted the advice of the Dutch Health Council to include SCID in the Dutch newborn screening program in 2015. As newborn screening for SCID is executed with a new, relatively expensive assay for the Dutch screening laboratory, an implementation pilot study is deemed instrumental for successful implementation. A feasibility study was performed in which the practicalities and preconditions of expanding the newborn screening program were defined. Cost-effectiveness analysis (CEA) indicated that SCID screening in the Netherlands might be cost-effective, recognizing that there are still many uncertainties in the variables underlying the CEA. Data and experience of the pilot study should provide better estimates of these parameters, thus enabling the actualization of CEA results. Prior to the implementation pilot study, a comparison study of two commercially available SCID screening assays was performed. A prospective implementation pilot study or so-called SONNET study (SCID screening research in the Netherlands with TRECs) started in April 2018 and allows the screening for SCID of all newborns in three provinces of the Netherlands for one year. Based on the results of the SONNET study, the Dutch Ministry of Health will make a final decision about national implementation of newborn screening for SCID in the Netherlands.

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.

OBJECTIVE:  To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined. SETTING:  Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting. PARTICIPANTS:  25 789 RhD negative pregnant women. MAIN OUTCOME MEASURES:  Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme. RESULTS:  A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme. CONCLUSIONS:  Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use.

Burden of Sickness Absence Due to Chronic Disease in the Dutch Workforce from 2007 to 2011.

INTRODUCTION: Chronic diseases are associated with productivity loss costs due to sickness absence. It is not always clear, however, which chronic diseases in particular are involved with how many sickness days and associated costs. OBJECTIVE: To determine the prevalence, additional days of sickness absence, and associated costs of chronic diseases among the Dutch working population from 2007 to 2011. METHODS: Prevalence of chronic diseases and additional days of sickness absence were derived from the Netherlands Working Conditions Survey (NWCS) from 2007 to 2011. The cost of each sickness absence day was based on linked personal income data. We used multiple regression analysis to derive the unconfounded additional days of sickness absence due to each chronic disease. RESULTS: Annually, approximately 37 % of the Dutch working population reported some type of chronic physical or psychological disease. No clinically relevant changes in prevalence of specific chronic diseases were observed in the studied period, nor in the number of additional sickness absence days or associated costs. The national financial burden due to sickness absence associated with chronic musculoskeletal disorders amounted to €1.3 billion annually. CONCLUSIONS: Chronic diseases result in substantial productivity loss due to sickness absence. Given the ageing population, the proposed increase in the state pension age and an increase in sedentary lifestyle and obesity, the prevalence of chronic diseases may be expected to rise. Coordinated efforts to maintain and improve the health of the working population are necessary to minimize socioeconomic consequences.

Helmet therapy in infants with positional skull deformation: randomised controlled trial.

OBJECTIVE: To determine the effectiveness of helmet therapy for positional skull deformation compared with the natural course of the condition in infants aged 5-6 months. DESIGN: Pragmatic, single blinded, randomised controlled trial (HEADS, HElmet therapy Assessment in Deformed Skulls) nested in a prospective cohort study. SETTING: 29 paediatric physiotherapy practices; helmet therapy was administered at four specialised centres. PARTICIPANTS: 84 infants aged 5 to 6 months with moderate to severe skull deformation, who were born after 36 weeks of gestation and had no muscular torticollis, craniosynostosis, or dysmorphic features. Participants were randomly assigned to helmet therapy (n=42) or to natural course of the condition (n=42) according to a randomisation plan with blocks of eight. INTERVENTIONS: Six months of helmet therapy compared with the natural course of skull deformation. In both trial arms parents were asked to avoid any (additional) treatment for the skull deformation. MAIN OUTCOME MEASURES: The primary outcome was change in skull shape from baseline to 24 months of age assessed using plagiocephalometry (anthropometric measurement instrument). Change scores for plagiocephaly (oblique diameter difference index) and brachycephaly (cranioproportional index) were each included in an analysis of covariance, using baseline values as the covariate. Secondary outcomes were ear deviation, facial asymmetry, occipital lift, and motor development in the infant, quality of life (infant and parent measures), and parental satisfaction and anxiety. Baseline measurements were performed in infants aged between 5 and 6 months, with follow-up measurements at 8, 12, and 24 months. Primary outcome assessment at 24 months was blinded. RESULTS: The change score for both plagiocephaly and brachycephaly was equal between the helmet therapy and natural course groups, with a mean difference of -0.2 (95% confidence interval -1.6 to 1.2, P=0.80) and 0.2 (-1.7 to 2.2, P=0.81), respectively. Full recovery was achieved in 10 of 39 (26%) participants in the helmet therapy group and 9 of 40 (23%) participants in the natural course group (odds ratio 1.2, 95% confidence interval 0.4 to 3.3, P=0.74). All parents reported one or more side effects. CONCLUSIONS: Based on the equal effectiveness of helmet therapy and skull deformation following its natural course, high prevalence of side effects, and high costs associated with helmet therapy, we discourage the use of a helmet as a standard treatment for healthy infants with moderate to severe skull deformation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18473161.

Novel strategies in newborn screening for cystic fibrosis: a prospective controlled study.

CONTEXT: Newborn screening for cystic fibrosis (CF) is included in many routine programmes but current strategies have considerable drawbacks, such as false-positive tests, equivocal diagnosis and detection of carriers. OBJECTIVE: To assess the test performance of two newborn screening strategies for CF. DESIGN, SETTING AND PARTICIPANTS: In 2008 and 2009, CF screening was added to the routine screening programme as a prospective study in part of The Netherlands. INTERVENTIONS: Two strategies were performed in all newborns. In the first strategy, concentrations of immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) were measured. In the second method, samples with IRT ≥60 µg/litre were analysed for 36 CFTR mutations, followed by sequencing when a single mutation was detected. Tests were positive only with two identified CFTR mutations. MAIN OUTCOME: Sensitivity, specificity and positive predictive value (PPV) of both screening strategies. RESULTS: 145,499 infants were screened. The IRT/PAP approach showed a sensitivity of 95.0%, a specificity of 99.897% and a PPV of 12.3%. Test properties for the IRT/DNA/sequencing strategy were respectively 100%, 100% and 64.9%. Combining both strategies (IRT/PAP/DNA/sequencing) led to a sensitivity of 95.0%, a specificity of 100% and a PPV of 87.5%. CONCLUSION: In conclusion, all strategies performed well. Although there was no statistically significant difference in test performance, the IRT/DNA/sequencing strategy detected one infant that was missed by IRT/PAP (/DNA/sequencing). IRT/PAP may be the optimal choice if the use of DNA technology must be avoided. If identification of carriers and equivocal diagnosis is considered an important disadvantage, IRT/PAP/DNA/sequencing may be the best choice.

Adolescents risky MP3-player listening and its psychosocial correlates.

Analogue to occupational noise-induced hearing loss, MP3-induced hearing loss may be evolving into a significant social and public health problem. To inform prevention strategies and interventions, this study investigated correlates of adolescents' risky MP3-player listening behavior primarily informed by protection motivation theory. We invited 1687 adolescents (12- to 19-year old) of Dutch secondary schools to complete questionnaires about their MP3-player listening, sociodemographic characteristics and presumed psychosocial determinants of MP3-player listening. Of all participants, 90% reported listening to music through earphones on MP3 players; 28.6% were categorized as listeners at risk for hearing loss due to estimated exposure of 89 dBA for ≥1 hour per day. Compared with listeners not at risk for hearing loss, listeners at risk were more likely not to live with both parents, to experience rewards of listening to high-volume levels, to report a high habit strength related to risky MP3 listening, and were less likely to be motivated to protect their hearing. Habit strength was the strongest correlate of risky listening behavior, suggesting that voluntary behavior change among adolescents might be difficult to achieve and that a multiple strategy approach may be needed to prevent MP3-induced hearing loss.

Young people: taking few precautions against hearing loss in discotheques.

This study evaluated adolescents' music-listening risk and protective behaviors in discotheques. While frequently standing close to the loudspeakers, taking few breaks, and hardly using hearing-protection devices, many are at risk of developing permanent hearing loss. Assessing visiting mode may be a first and quick screener to identify adolescents at risk.

Estimating adolescent risk for hearing loss based on data from a large school-based survey.

OBJECTIVES: We estimated whether and to what extent a group of adolescents were at risk of developing permanent hearing loss as a result of voluntary exposure to high-volume music, and we assessed whether such exposure was associated with hearing-related symptoms. METHODS: In 2007, 1512 adolescents (aged 12-19 years) in Dutch secondary schools completed questionnaires about their music-listening behavior and whether they experienced hearing-related symptoms after listening to high-volume music. We used their self-reported data in conjunction with published average sound levels of music players, discotheques, and pop concerts to estimate their noise exposure, and we compared that exposure to our own "loosened" (i.e., less strict) version of current European safety standards for occupational noise exposure. RESULTS: About half of the adolescents exceeded safety standards for occupational noise exposure. About one third of the respondents exceeded safety standards solely as a result of listening to MP3 players. Hearing symptoms that occurred after using an MP3 player or going to a discotheque were associated with exposure to high-volume music. CONCLUSIONS: Adolescents often exceeded current occupational safety standards for noise exposure, highlighting the need for specific safety standards for leisure-time noise exposure.

Discotheques and the risk of hearing loss among youth: risky listening behavior and its psychosocial correlates.

There is an increasing population at risk of hearing loss and tinnitus due to increasing high-volume music listening. To inform prevention strategies and interventions, this study aimed to identify important protection motivation theory-based constructs as well as the constructs 'consideration of future consequences' and 'habit strength' as correlates of adolescents' unsafe discotheque-visiting behavior. We invited 1687 adolescents (12-19 years old) at Dutch secondary schools to complete questionnaires about music-listening behaviors, sociodemographic characteristics and psychosocial determinants of behavior. Over 70% of participants reported to have visited discotheques; 24.6% of them were categorized as visitors at risk for hearing loss due to estimated exposure of 100 dBA for 1.25 hours per week or more without the use of hearing protection. Compared with visitors not at risk for hearing loss, those at risk were more likely not to live with both parents and less likely to consider future consequences and for them visiting high-volume music discotheques was more habitual. Risky exposure to high-volume music in discotheques is associated with several sociodemographic and psychosocial factors, with habit strength being the strongest correlate. Voluntary behavior change among adolescents might be difficult to achieve, because visiting discotheques seems to be strongly linked to current adolescent lifestyle.