Abstract Purpose Recent studies have shown an increased incidence of congenital hypothyroidism over the past 2 or 3 decades. The etiology of this change is unknown, but it has been related by several ...authors to lowering of cutoffs. We sought to determine whether the incidence of congenital hypothyroidism (CH) in France has changed. Methods We analyzed data from the nationwide neonatal screening program for CH during the period 1982–2012. We included all children having thyroid-stimulating hormone values above the threshold and for whom diagnosis of CH confirmed by the pediatrician. We estimated multicentric temporal trends in the annual incidence rates adjusted for screening methods for thyroid dysgenesis and eutopic gland. Results We found 6622 cases of CH (28.0 per 100,000 newborns); 1895 had a eutopic gland, and 4727 had thyroid dysgenesis. The incidence of eutopic glands showed a significant annual average increase of (5.1%; 95% confidence interval: 4.3–5.9) regardless of the screening method or screening center. This increase was confirmed in severe cases (thyroid-stimulating hormone ≥50: 2.1%; 95% confidence interval, 1.4–2.9). The incidence of dysgenesis remained constant. Conclusions The incidence of eutopic glands increased in France, not only in mild forms but also in severe cases.
Cystic fibrosis (CF) is an autosomal recessive disorder whose incidence has long been estimated as 1/2500 live births in Caucasians. Expanding implementation of newborn screening (NBS) programs now ...allows a better monitoring of the disease incidence, what is essential to make reliable predictions for disease management. This study assessed time trends in the birth incidence of CF over a long period (35 years: 1975-2009) in an area where CF is frequent (Brittany, France) and where NBS has been implemented for more than 20 years.
This study enrolled CF patients born in Brittany between January 1st 1975 and December 31st 2009 (n = 483). Time trends in incidence were examined using Poisson regression and mainly expressed using the average percent change (APC).
The average number of patients born each year declined from 18.6 in the late 1970's (period 1975-79) to 11.6 nowadays (period 2005-09). The corresponding incidence rates dropped from 1/1983 to 1/3268, which represented a decline close to 40% between these two periods (APC = -39.3%, 95% CI = -55.8% to -16.7%, p = 0.0020). A clear breakpoint in incidence rate was observed at the end of the 1980's (p < 0.0001). However, the incidence rate has remained quite stable since that time (annual APC = -1.0%, 95% CI = -3.0% to 1.1%, p = 0.3516).
This study provides an accurate picture of the evolution of the incidence of a genetic disease over a long period and highlights how it is influenced by the health policies implemented. We observed a 40% drop in incidence in our area which seems consecutive to the availability of prenatal diagnosis.
Objectives To describe optimization of a nationwide newborn screening program for cystic fibrosis (CF) that combines an immunoreactive trypsinogen (IRT) assay and DNA mutation analysis in dried blood ...samples at day 3. Study design Data from regional screening laboratories and CF care centers were centralized and periodically analyzed to allow adaptation, thus limiting the number of false-positive cases. Results A total of 2 717 905 infants were screened between 2002 and 2005. Flow chart protocol was modified twice. First, the IRT d3 cutoff value increased from 60 to 65 μg/L, thus decreasing the percentage of samples requiring mutation analysis from 0.82% to 0.64%. Second, for infants with no mutations using the screening panel, a recall for IRT was performed only if IRT d3 was > 100 μg/L; the percentage of recalls decreased from 0.51% to 0.12%, and the percentage of infants requiring a sweat test decreased from 0.14% to 0.01%. No significant change in the CF detection rate was observed after these 2 modifications. A total of 625 CF cases were detected, and 22 false-negative findings (3.4%) were observed, most of them inevitable, with a low initial IRT. Conclusions The centralized data analysis led to changes in the screening strategy to optimise the newborn screening program.
We report cystic fibrosis (CF) care center instructions for sweat testing in older siblings after implementation of the French nationwide newborn screening program, and we evaluate the incidence of ...unrecognized CF. Nearly 9% of families with an infant screened for CF were unaware of an affected older sibling. We strongly recommend sweat testing for all first-degree older children.
Objective To evaluate parental stress after a false-positive result at the time of the cystic fibrosis (CF) newborn screening (NBS), attributable to heterozygotism or persistent hypertrypsinemia. ...Study design A prospective study was conducted in 86 French families at 3, 12, and 24 months after NBS. A psychologist conducted interviews with a questionnaire, the Perceived Stress Scale, and the Vulnerable Child Scale. Results Overall, 96.5% of parents said they had been anxious at the time of the sweat test. However, 86% felt entirely reassured 3 months after the test. The mean Perceived Stress Scale score did not differ from that observed in the French population. Mean Vulnerable Child Scale scores were high, associated with a low Parental Perception of Child Vulnerability. These results did not differ significantly at 1 and 2 years. In total, 86% to 100% of families no longer worried about CF. All parents stated that they would have the test performed again for another child. Conclusions CF NBS can lead to false-positive results, causing parental anxiety, which quickly decreases after a sweat test performed soon after the phone call.
Severe combined immunodeficiency (SCID) refers to a group of genetic disorders characterized by greatly compromised cellular and humoral immunity. Children with SCID are asymptomatic at birth, but ...they die from infections within the first months of life if not treated. Quantification of T-cell receptor excision circles is an extremely sensitive screening method for detecting newborns who may have SCID.The goal of the DEPISTREC study was to evaluate the feasibility of nationwide newborn screening for severe T-cell lymphopenia in France as well as its economic and clinical utility.
The test universally used for neonatal screening for SCID was the quantification of TRECs on Guthrie cards. We compared a group of 190,517 babies from 48 maternities across the country who underwent newborn SCID screening with a control group of 1.4 million babies out of whom 28 were diagnosed with SCID without such screening during the course of the study.
Within the screening group, 62 babies were found to be lymphopenic, including three with SCID. The cost of screening ranged from 4.7€ to €8.15 per newborn. The average 18-month cost was €257,574 vs €204,697 in the control group.
In this large-scale study, we demonstrate that routine SCID screening is feasible and effective. This screening offers the additional benefit of aiding in the diagnosis of non-SCID lymphopenia. Economic evaluation allowed us to calculate the cost per test. Newborn screening may also prevent death by SCID before any curative treatment can be administered. The difference in cost between screened and control children could not be ascertained because of the very low numbers and death of one of the children tested.
To compare the cost effectiveness of adding a pancreatitis-associated protein (PAP) assay to common immunoreactive trypsinogen (IRT) and DNA cystic fibrosis (CF) newborn screening strategies.
Using ...data collected on 553,167 newborns, PAP cut-offs were calculated based on non-inferiority of the detection rates of classical forms of CF. Cost effectiveness was considered from the third-party payer's perspective using only direct medical costs, and the unit costs of PAP assays were assessed based on a micro-costing study. Robustness of the cost-effectiveness estimates was assessed, taking the secondary outcomes of screening (ie. detecting mild forms and CF carriers) into account.
IRT/DNA, IRT/PAP, and IRT/PAP/DNA strategies had similar detection rates for classical forms of CF, but the strategies involving PAP assays detected smaller numbers of mild forms of CF. The IRT/PAP strategy was cost-effective in comparison with either IRT/DNA or IRT/PAP/DNA. IRT/PAP/DNA screening was cost-effective in comparison with IRT/DNA if relatively low value was assumed to be attached to the identification of CF carriers.
IRT/PAP strategies could be strictly cost-effective, but dropping DNA would mean the test could not detect CF carriers. IRT/PAP/DNA strategies could be a viable option as they are significantly less costly than IRT/DNA, but still allow CF carrier detection.
Summary Objectives The focus of this report is hearing screening of newborns transferred from the regular nursery to a specialized area. The purpose of the study undertaken was: (1) to determine ...whether screening coverage in this population was achieved; (2) to establish whether the linkage between neonatal screening and the diagnostic follow-up was carried out correctly; (3) to better determine the incidence of permanent childhood hearing impairment (PCHI) in this at-risk population. Methods Six population centres averaging 12,000 births annually participated (Bordeaux, Lille, Paris, Marseille, Toulouse and Lyon). Automated auditory brainstem response (AABR) (Natus ALGO 3i® ) screening was performed in two stages: i.e. infants with initial “positive” results were screened a second time using the same technique. Of the 117,103 babies born during the study period, 4972 neonates were “transferred” and comprised the population for this report (4.2% of the total births). Results and discussion Screening results for 4972 “transferred” neonates were compared with those of non-transferred neonates ( N = 112,131). Screening coverage of eligible infants was significantly lower (75.4%) in “transferred” neonates (3750 infants screened) compared to 97.5% coverage of non-transferred neonates (109,349 infants screened). The rate of positive results after the first stage AABR was higher in the “transferred” population (11.1%) than in the non-transferred population (6.5%). Of the 415 “transferred” newborns with initial positive screens, 91.3% were rechecked as stipulated in the project protocol. The second pre-discharge AABR ascertained that in half of the cases auditory function had normalized in the day. Of the 183 “transferred” infants whose result remained suspect at the conclusion of both stages of the neonatal screen (4.9% of the tested population), only 70.5% returned to the audiology centre for diagnostic follow-up. The incidence of bilateral PCHI was markedly higher (4/1000) in “transferred” infants than in the non-transferred population (1.08/1000). Conclusions The difficulty of obtaining universal screening coverage in “transferred” infants was, unfortunately, verified in this prospective, multicentre study. Further, the diversity of our “transferred” population was not much greater than that revealed by careful analysis of published hearing screening studies in neonatal intensive care unit (NICU) infants. The influence of risk factors and their more or less complex combinations is apparent.
Objectives
To evaluate the French cystic fibrosis newborn screening algorithm, based on data tracked by a centralized monitoring process, from 2002 to 2014. The programme aimed to attain European ...Standards in terms of positive predictive value, sensitivity, the ratio of screen positive patients diagnosed with cystic fibrosis to infants who screen positive but with inconclusive diagnosis (CFSPID), and time to diagnosis.
Methods
Retrospective analysis of programme performance, compliance with the algorithm, and changes in screening strategy.
Results
Modifications in the flow chart protocol improved the positive predictive value to 0.31 while maintaining the sensitivity at 0.95. Among infants diagnosed with cystic fibrosis, or identified as CFSPID, sweat test results were obtained for 94%, and two mutations were identified after exhaustive screening for the gene, when applicable, in 99.6%. The rate of pending diagnosis was very low (0.5%). The ratio of infants with cystic fibrosis:CFSPID was 6.3:1. Age at initial visit at the CF centre was ≤ 35 days, respectively, in 53%/26%.
Conclusion
Performances were in agreement with European standards, but timeliness of initial visit needed improvement. Our data complement an accumulating body of evidence demonstrating that attention must be paid to such ethical considerations as limiting carrier detection and inconclusive diagnosis. Newborn screening programmes should have a rigorous centralized monitoring process to warrant adjustments for improving performance to attain consensus guidelines.
Newborn screening (NBS) for cystic fibrosis (CF) was implemented throughout France in 2002. It involves a four-tiered procedure: immunoreactive trypsin (IRT)/DNA/IRT/sweat test corrected was ...implemented throughout France in 2002. The aim of this study was to assess the performance of molecular CFTR gene analysis from the French NBS cohort, to evaluate CF incidence, mutation detection rate, and allelic heterogeneity.
During the 8-year period, 5,947,148 newborns were screened for cystic fibrosis. The data were collected by the Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant. The mutations identified were classified into four groups based on their potential for causing disease, and a diagnostic algorithm was proposed.
Combining the genetic and sweat test results, 1,160 neonates were diagnosed as having cystic fibrosis. The corresponding incidence, including both the meconium ileus (MI) and false-negative cases, was calculated at 1 in 4,726 live births. The CF30 kit, completed with a comprehensive CFTR gene analysis, provides an excellent detection rate of 99.77% for the mutated alleles, enabling the identification of a complete genotype in 99.55% of affected neonates. With more than 200 different mutations characterized, we confirmed the French allelic heterogeneity.
The very good sensitivity, specificity, and positive predictive value obtained suggest that the four-tiered IRT/DNA/IRT/sweat test procedure may provide an effective strategy for newborn screening for cystic fibrosis.
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