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Examples of implemented neonatal hearing screening programs in Austria.

In order to improve early detection of congenital permanent childhood hearing impairment the Austrian ENT society recommended in 1995 that universal neonatal hearing screening be introduced ("Millstätter Concept"). Coverage is presently about 67% for full-term healthy neonates and 86% for neonates from intensive care units. For maternity units, referral rates between 1% and 3.7% have been reported (2.7-15% for intensive care units). The results of the screening test and follow-up in cases of failure have been documented in 37,543 neonates. Of this population, 91 infants (2.4 per 1000) showed bilateral permanent hearing loss. In these children intervention and management of the family started within the first months of life. These results justify the effort involved in introducing universal neonatal hearing screening.

Austria↗

Universal hearing screening using transient otoacoustic emissions in a community health clinic.

Since 1993, targeted screening of high risk Camden and Islington babies has been carried out in hospital using the transient otoacoustic emission (TEOAE) technique and auditory brainstem responses (ABR). Because targeted screening is difficult to implement, a community pilot study using TEOAE was started in 1995, covering 7% of the resident population. Although uptake has not been above 80%, client satisfaction has been high and numbers requiring more detailed tertiary assessment have been modest (0.5% of the population screened). A comparison was made between the cost of a universal neonatal screen using TEOAE and distraction testing at 7 months of age. The neonatal screen would be no more expensive to implement universally, even when equipment costs are included. A combination of a universal neonatal screen with distraction testing at 7 months for those not screened is likely to give 96% coverage of hearing screening in the first year of life.

Community Health Services↗

Incidence of congenital hypothyroidism: retrospective study of neonatal laboratory screening versus clinical symptoms as indicators leading to diagnosis.

Filter paper blood samples taken routinely from 100 239 newborn infants were radioimmunoassayed five years later for plasma thyrotrophin concentrations. In 32 cases (0.03%) these were found to be raised. Thirty one of these children were traced and subjected to follow up examination by a paediatrician and a psychologist. Of the 31 children, 15 were found to have been receiving treatment for congenital hypothyroidism since a median of 5 months of age (diagnosed group). Of the 16 others, seven children were found to have raised serum thyrotrophin concentrations and were classified as hypothyroid (undiagnosed group). The remaining nine children were euthyroid. Children in the diagnosed group had a mean Griffiths developmental quotient of 87 (control value 103; p less than 0.01), and five out of 13 showed impaired neurological development. Of the remainder, those in the undiagnosed group had a mean developmental quotient of 100 and those in the euthyroid group a mean developmental quotient of 107. In this study achieving a detection rate of congenital hypothyroidism of one in 3000 in a neonatal screening programme resulted in overdiagnosis of about a quarter of patients considered to have true positive findings. This was outweighed, however, by the early identification of all infants with the disease.

Child, Preschool↗

Neonatal thyroid screening as a monitoring tool for the control of iodine deficiency.

In conditions of iodine deficiency, the frequency distribution of neonatal thyroid-stimulating hormone (TSH) is shifted towards elevated values. Elevated serum TSH in the neonate indicates insufficient supply of thyroid hormones to the developing brain, and therefore constitutes the only indicator that allows prediction of brain damage, which is the main complication of iodine deficiency. This paper reviews studies on neonatal thyroid function in iodine deficiency and confirms the former statement by WHO/UNICEF/ICCIDD that the frequency of neonatal TSH above 5 mU/L blood is below 3% in conditions of normal iodine supply, that a frequency of 3-19.9% indicates mild iodine deficiency and that frequencies of 20-39.9% and above 40% indicate moderate to severe iodine deficiency, respectively. Neonatal thyroid screening appears as a particularly sensitive index in the monitoring of iodine supply at a population level.

Congenital Hypothyroidism↗

[Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience].

The results and the significance of neonatal mass-screening programmes for inborn errors of metabolism, conducted by the National Research Institute of Mother and Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the Beutler and Baluda test was introduced for galactosaemia, as well as the Efron urine test in infant screening for different inborn errors of metabolism. In the middle of the 70., neonatal mass-screening for cystic fibrosis (CF, mucoviscidosis) was started. Meconium tests and the sweat test with ion selective chloride electrode were used. Apart from inborn errors of metabolism, we also introduced a screening programme for neuroblastoma in which vaniline mandelic acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH level was assessed. The results of screening are shown in the tables and in the figures. In our opinion the best clinical results are obtained with screening for congenital hypothyroidism and for PKU, since very early detection and treatment in these diseases prevents severe mental retardation. We therefore consider that both these screening programmes should be treated as obligatory examinations in all neonates. Taking into consideration the fact that there are different types of hyperhenylalaninemias, the principles of differential diagnosis are discussed. Molecular genetic investigations, carried out in the NRIMC Department of Genetics proved to be a very important procedure in the verification of diagnosis of different mutations. The authors also discuss the problem of dietary treatment duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls, should not be discontinued during adolescence, since there is the problem of maternal PKU and the possibility of foetal damage. The results of our own investigations of maternal PKU are discussed. The significance of mass-screening for galactosemia is still under discussion. In our opinion, mass-screening for galactosemia is not useful and we have discontinued it. Selective screening has been started combined with molecular genetic studies in high risk families. In the future, we plan to prepare guidelines on the principles of diagnosis and treatment of galactosemia in children and women in the reproductive age. Mass-screening for cystic fibrosis is also still under discussion. The results of the early screening programmes were not satisfactory and the tests were discontinued. In 1998, after reorganisation of the whole system, CF screening, using tripsin-radioimmune assays, was started again. The new screening programme is combined with molecular genetic investigation of different mutations. It is still too early to assess the importance and success of this CF mass-screening programme. We decided to discontinue the screening for homocystinuria, histidinemia, tyrosinemia, leucinosis and for neuroblastoma, since these programmes did not comply with criteria of mass-screening. In 1997, major reorganisation of screening programmes for inborn errors of metabolism, at NRIMC, was undertaken. The Guthrie test for PKU was changed to a quantitative colorimetric method. The immuno-luminometric method is used for TSH estimation. The whole system is based on complete computer control of all the steps of screening, from blood sampling on filter paper until the final diagnosis. The advantages of this modern system of organisation of the screening programme are discussed.

Decision Trees↗

Epidemiology of permanent childhood hearing impairment in Trent Region, 1985-1993.

This retrospective study of permanent childhood hearing impairment (PCHI) > or = 40 dB HL in children born between 1985 and 1993 and resident in Trent Health Region, achieved an ascertainment of 92.9% of that expected from previous studies and 100% for the subset of children born between 1985 and 1990. The prevalence rate of all permanent hearing impairment > or = 40 dB HL for the birth cohort 1985-90 is 133 (95% confidence interval, (ci) 122-145) per 100,000 live births (1 in 750). Sixteen per cent of PCHI were postnatally acquired, late-onset or progressive impairments. Excluding these, the prevalence rate for congenital impairments is 112 (ci 101-123) per 100,000 (1 in 900). The rate for profound impairments > or = 95 dB HL is 24 (ci 20-30) per 100,000 live births (1 in 4150). Prevalence was increased sixfold for children with a history of neonatal intensive care and 14-fold for children with a family history, compared with children with no risk factors. A more than two-fold increase in prevalence was seen in Asian children. For the congenitally-impaired children born between 1985 and 1990, 29% had a stay in neonatal intensive care > or = 48 hours, 30% had a family history of permanent childhood hearing impairment, and 12% had a cranio-facial abnormality (CFA). Over 59% were potentially detectable by a targeted neonatal screening programme using these three high-risk factors. For 1985-1993, the overall yield of the targeted neonatal screening programmes available in three of the 11 health districts was 15% but increased over time. The overall yield from the Health Visitor distraction test was 30% but lower in districts with neonatal screening programmes. Only 59% of children had a stated aetiology, classified by time of onset into genetic, including syndromes and CFA (41%), pre- or peri-natal (10%), post-natally acquired (6%), and uncertain onset (2%). Just under 40% of the children were said to have another clinical or developmental problem, about half of whom had at least two additional problems. The median age at referral, confirmation of the impairment, prescription of the hearing aid and fitting of the hearing aid were, respectively, 10.4 months, 18.1 months, 24.4 months and 26.3 months. A more severe impairment was associated with earlier age. Small improvements in the median age of hearing aid prescription and fitting were seen over time. Twenty-five per cent of children were referred for genetic counselling, the proportion increasing systematically with the severity of the impairment. Based on evidence of the yield from hearing screens we suggest a wider implementation of neonatal screening and further consideration of the role of the health visitor distraction test in the identification of children with PCHI. To facilitate further assessment of services for hearing-impaired children we suggest implementation of a co-ordinated shared list of children with permanent hearing impairment on a region-wide basis to provide adequate numbers for comparison over time, and the routine collection of a minimum set of data for each child.

Age Distribution↗

Effect of the number of averaged responses in transient evoked otoacoustic emissions on the results of neonatal hearing screening.

This study examined the effect of the number of accepted responses in transient evoked otoacoustic emissions on the results of neonatal hearing screening programmes. The ILO88 Otodynamics Analyzer Quickscreen programme was used for all testing, and a three-stage procedure was adopted by averaging 20, 30, and 260 low-noise samples in total. The results were recorded after each stage of the testing in those cases in which, after the first 20 accepted responses, the "pass" criteria were met. Under these circumstances, 117 ears were included in the study from a total number of 334 screened ears. It was concluded that 20 averaged quiet responses are adequate for screened newborn babies to pass the test if the conditions of the "pass" criteria are fulfilled at this stage. In the rest of the newborn babies, testing should be continued using a larger number of clicks. For diagnostic and clinical purposes, the full 260 quiet samples must be used since the results indicated statistically better scores in response and reproducibility measures after the 260 averaged responses.

Cochlea↗

The potential of electrospray ionization mass spectrometry for the diagnosis of hemoglobin variants found in newborn screening.

Analytical procedures have been developed for the detection and diagnosis of sickle cell disease in newborn babies by analyzing the hemoglobin extracted from dried blood spots on Guthrie cards using electrospray ionization mass spectrometry (ESI-MS). An essential requirement is the ability to reliably differentiate two globin chains whose molecular weights differ by only 1 Da such as adult hemoglobin (Hb A) and Hb C. This has been achieved by improving the accuracy and precision of the molecular weight determination to a fraction of a dalton. We report the potential of mass spectrometry for screening neonates for these debilitating diseases by presenting results from 147 blood spots that had been characterized by phenotypic methods and which include samples from 20 sickle cell disease, 1 beta-thalassemia major, 57 sickle cell trait, and 39 normal babies. In all cases, the mass spectrometric results agreed with the results obtained using conventional analytical practice with high-performance liquid chromatography (HPLC) and isoelectric focusing (IEF). We show that mass spectrometry is a viable technique for the diagnosis of newborns with sickle cell disease or homozygous beta0-thalassemia.

Anemia, Sickle Cell↗

Screening for galactosaemia in Greece.

Galactosaemia appears to be one of the most appropriate disorders for routine newborn screening as almost normal outcome can be achieved in most of the identified cases. Galactose and galactose-1-phosphate were determined using Guthrie cards in a commercial kit based on a colorimetric microassay. Among 199,642 newborns, nine cases with classic galactosaemia, three with epimerase deficiency, six with compound Duarte2/heterozygotes for galactosaemia and four with compound2 Duarte homozygosity were found. Even though the number found among the screened neonates is small because it is such a rare disease, our results indicate one of the highest frequencies of the disease ever reported.

Age Factors↗

Screening for fragile X syndrome.

BACKGROUND AND AIM OF REVIEW. In 1991, the gene responsible for fragile X syndrome, a common cause of learning disability, was discovered. As a result, diagnosis of the disorder has improved and its molecular genetics are now understood. This report seems to provide the information needed to decide whether to use DNA testing to screen for the disorder. HOW THE RESEARCH WAS CONDUCTED. A literature search of electronic reference databases of published and 'grey' literature was undertaken together with hand searching of the most recent publications. RESEARCH FINDINGS. NATURAL HISTORY. Physical characteristics of fragile X syndrome include facial atypia, joint laxity and, in boys, macro-orchidism. Most affected males have moderate-to-severe learning disabilities with IQs under 50 whereas most females have borderline IQs of 70-85. Behavioural problems are similar to those seen with autism and attention-deficit disorders. Although fragile X syndrome is not curable there are a number of medical, educational, psychological and social interventions that can improve the symptoms. About 6% of those with learning disabilities tested in institutions have fragile X syndrome. Population prevalence figures are 1 in 4000 in males and 1 in 8000 in females. GENETICS. The disorder is caused by a mutation in a gene on the X chromosome which includes a trinucleotide repeat sequence. The mutation is characterized by hyper-expansion of the repeat sequence leading to down-regulation of the gene. In males an allele with repeat size in excess of 200, termed a full mutation (FM), is always associated with the affected phenotype, whereas in females only half are affected. Individuals with alleles having repeat size in the range 55-199 are unaffected but in females the sequence is heritably unstable so that it is at high risk of expansion to an FM in her offspring. This allele is known as a pre-mutation (PM) to contrast it with the FM found in the affected individual. No spontaneous expansions directly from a normal allele to an FM have been observed. SCREENING STRATEGIES. The principal aims of screenng for fragile X syndrome is to reduce the birth prevalence of the disorder, by prenatal diagnosis and selective termination of pregnancy, or by reducing the number of pregnancies in women who have the FM or PM alleles. Possible screening strategies are: routine antenatal testing of apparently low risk pregnancies, preconceptual testing of young women, and systematic testing in affected families ('cascade' screening). A secondary aim is to bring forward the diagnosis of affected individuals so that they might benefit from early treatment. Active paediatric screening and neonatal screening could achieve this but there is no direct evidence of any great benefit from early diagnosis. SCREENING TESTS. Cytogenetic methods are unsuitable for screening purposes. Southern blotting of genomic DNA can be used but is inaccurate in measuring the size of small PMs, there is a long laboratory turnaround time, and it is relatively expensive. The best protocol is to amplify the DNA using polymerase chain reaction on all samples, and when there is a possible failure to amplify, a Southern blot.(ABSTRACT TRUNCATED)

Costs and Cost Analysis↗

Hearing screening of neonates at risk.

OBJECTIVE: The aim of this study is to screen infants admitted to the Neonatal Intensive Care Unit (NICU) for hearing loss METHODS: One hundred and thirty newborns admitted to NICU were screened for hearing loss using otocaustic emission (OAE). Tympanometry was performed using Grason Stadler Incorporation (GSI) 37 and auditory brain response (ABR). RESULTS: Ninety-six of the infants had known risk factors such as prematurely, low birth weight, hyperbilirubinemia, asphyxia and congenital abnormalities. Out of 130 infants 80 passed the OAE test, 50 had to be rescreened, and 19 had ABR. Only 13 were found with moderate to severe hearing loss, 13.5% of at the risk infants. CONCLUSION: Hearing aids were provided from the age of 6 months, for 7 of the hearing impaired children. Parents of other children refused hearing aids and thought the child would talk when older, although they were full informed regading their children's hearing loss. Early identification and early intervention gives chances for infants to acquire speech and language. Parent's awareness will be stressed upon.

Acoustic Impedance Tests↗

Evaluation of the hepatitis B antenatal screening and neonatal immunization program in Amsterdam, 1993-1998.

In the enhanced antenatal hepatitis B screening and neonatal immunization program in Amsterdam, 691 hepatitis B surface antigen (HBsAg) positive expectant mothers were reported in the period 1993-1998. The coverage of the screening was calculated at 97%. HBsAg-prevalence was high in women from Ghana and South-East Asia, and lowest in Dutch women. Hepatitis B immune globulin (HBIg) was administered within 24h to 95.9% of the neonates; 99.7% completed the vaccination series. About 6 weeks after the third vaccination the titer antiHBs was > or =100 IU/l in 85% of children; in 12% the titers were 10-100 IU/l; 3% had titers <10 IU/l, of whom 3/521 initially had HBsAg. Low birth weight (OR 3.77), being a boy (OR 1.64) and country of origin were predictors of low postvaccination titers. Coordinated by 0.5 full time equivalent (fte) additional staff, the program was relatively cheap and successful.

Adult↗

Newborn screening for cystic fibrosis.

BACKGROUND: This review was performed to test the hypothesis that presymptomatic diagnosis, for example by newborn screening, and early treatment may prevent or reduce irreversible organ damage and thereby improve outcome and quality of life in patients with cystic fibrosis. OBJECTIVES: To determine whether there is evidence that early diagnosis of cystic fibrosis by means of neonatal screening, followed by current treatment, improves survival and long term morbidity, without unacceptable adverse effects. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Trials Register. Additional studies were identified by one of the reviewers from handsearching conference proceedings not included in the Cochrane Register. Pharmaceutical companies manufacturing screening tests for cystic fibrosis were also contacted to identify any trials of neonatal screening for cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudorandomised controlled trials, published and unpublished, comparing screening followed by early treatment to clinical diagnosis and later treatment in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Four reviewers independently assessed trial eligibility and methodological quality and two of these reviewers independently extracted data. MAIN RESULTS: Two trials involving a total of 1,124,483 neonates met inclusion criteria. A total of 210 patients with cystic fibrosis aged from zero to 11 years with a maximum follow-up of eleven years are included. Concealment of allocation was unclear in both studies. Sequence generation was adequate in one study and unclear in the other. Method to ascertain cases was similar in one study and not similar in the other. An intention-to-screen-analysis was possible in one study, but could not be made due to lack of data and was not performed in the other. Differences in study design, variation in outcomes reported and their summary measures precluded calculation of pooled screening estimates. Only data from one study could be analysed in this review. This study reported a reduced risk of weight and height below the fifth percentile among screened patients (odds ratio control compared with screened group for: weight 6.16, 95% Confidence Interval (CI) 2.44, 15.57 and height 5.03, 95% CI 1. 63, 15.63). Adverse effects among parents in the screened and control populations were examined, but it is difficult to assess how meaningful these results are as the timing of the administration of the questionnaire to each group was not clear. Estimation of direct medical costs of screening suggested it was cheaper to diagnose cystic fibrosis by screening rather than other methods. The costing methods used however were not fully described and costs have not been related to effect. REVIEWER'S CONCLUSIONS: There are few randomised controlled trials assessing the effectiveness of neonatal screening in cystic fibrosis. From the data available at this time, there is little evidence suggesting benefit from screening for cystic fibrosis in the neonatal period, although there is similarly little evidence of harm. This systematic review has identified the need for individual patient data from both included studies. Although we have not been able to perform a meta-analysis, this review provides a summary of all the information currently available from randomised controlled trials on the effectiveness of neonatal screening for cystic fibrosis.

Cystic Fibrosis↗

Successful screening for neonatal hip instability in Australia.

OBJECTIVE: Australian screening programmes for congenital dislocation of the hip (CDH) are characterized by lower neonatal hip instability (NHI) detection rates than more successful international programmes. Through creating a quality, accountable clinical screening programme for NHI detection, the present study aimed to establish the true incidence of NHI in Australian babies and to eliminate 'late diagnosed' CDH. METHODS: Doctors responsible for routine neonatal care were made accountable for NHI detection and examined 5166 consecutive live births in the first days of life between 1989 and 2000. Techniques for clinical NHI detection were taught, and doctors practised with teaching-mannequins. Paediatricians clinically determined true positive NHI cases and managed them for a 12-month period. Peer review of NHI detection rates was introduced to encourage accountability. Surveillance for 'late diagnosed' CDH occurred regularly through a variety of methods. RESULTS: One hundred babies with NHI were detected (19.4 per 1000): 77% were female; 26% were breech presentation, 25% had a family history of hip instability; and all received some form of splinting. Follow up for 85% of these babies at 12 months revealed no significant complications. Extensive searching has revealed no baby with 'late diagnosed' CDH from the study population in 12 years. One baby commenced treatment late (at 4 months) because of a failure of process following early NHI detection. CONCLUSIONS: The true incidence of NHI in Australia is > or =19 per 1000 births. Successful clinical CDH screening programmes using primary care doctors can be created and might eliminate 'late diagnosed' CDH.

Australia↗

Application of molecular genetics in public health: improved follow-up in a neonatal hemoglobinopathy screening program.

Newborn screening for the hemoglobinopathies has been shown to reduce morbidity and mortality, particularly for sickle cell anemia, by facilitating initiation of penicillin prophylaxis by 4 months of age. The purpose of the current investigation was to determine whether molecular genetic follow-up testing could be introduced into a neonatal hemoglobinopathy screening program and, if successfully introduced, whether it would reduce time to diagnostic confirmation. Between July 1, 1991, and October 7, 1992, 518 original dried blood specimens were referred from the Texas Department of Health Neonatal Hemoglobinopathy Screening Program for molecular genetic follow-up testing. Allele-specific cleavage (ASC) after amplification with matched and mismatched polymerase chain reaction primers was compared to allele-specific oligonucleotide (ASO) hybridization. By November 2, 1992, molecular genetic analyses were definitive in 506, and agreement was observed between ASC and ASO hybridization in all specimens analyzed. Approximately 13% of those initially screened FS were considered probable S/beta-thal by DNA and RNA testing. Rapid molecular genetic analysis contributed to a substantial reduction of the mean age at confirmation by approximately 50%, to about 2 months of age. ASC is a reliable method for molecular genetic analysis of dried blood specimens, providing methodology which can be readily automated. An automated method is demonstrated that is based on microtiter plate technology and will significantly reduce labor intensity and costs, while increasing sample throughput. Even with current manual testing methods, DNA and RNA analysis of initial newborn screening specimens will reduce the age at confirmation well under 4 months, the age cut-off for effective initiation of penicillin prophylaxis.

Alleles↗

[Screening of newborns for inborn errors of metabolism by tandem mass spectrometry].

Tandem mass spectrometry is an analytical method which is being implemented for neonatal screening. The method can determine the content of amino acids and acylcarnitines in neonatal screening samples in one integrated analysis. This allows detection of more than 20 inherited disorders of amino acid, fatty acid and organic acid metabolism. The aggregate incidence of these disorders is in the order of 1:4000. The principal disease which is detectable is medium-chain acyl-CoA dehydrogenase deficiency, which has an incidence of 1:10,000-1:20,000 in Northern Europe. Medium-chain acyl-CoA dehydrogenase deficiency puts the affected at risk of life-threatening metabolic crises, which are preventable if the condition has been diagnosed. Hence, the prognosis is excellent. The central theme for therapeutic management of medium-chain acyl-CoA dehydrogenase deficiency is carbohydrate supplementation, especially in situations of intercurrent illness. Tandem mass spectrometry screening will also enhance the present screening for phenylketonuria which employs a bacterial assay: the screening sample can be obtained 48-72 hours post partum, the false-positive rate will be reduced, and there will be no interference with antibiotics. Tandem mass spectrometry is being used in state-mandated screening panels in a few places and is being tested in pilot studies in many other places. A national prospective pilot project was launched on February 1, 2002 in Denmark. The project includes tandem mass spectrometry screening for galactosemia. In addition to neonatal screening, tandem mass spectrometry can be used for investigation of metabolic diseases, sudden unexpected death of infancy and shaken baby syndrome. Critical appraisal of tandem mass spectrometry will lead to improved health for infants affected by rare inherited disorders of metabolism.

Acyl-CoA Dehydrogenases↗

Impact of public health strategies on the birth prevalence of cystic fibrosis in Brittany, France.

Taking into account the situation of Brittany, a region of western France where cystic fibrosis (CF) is common and where a neonatal screening program was set up 14 years ago, the aim of this study was to determine the way in which the birth prevalence of CF has been influenced by the various public health strategies implemented in the region (neonatal screening, prenatal diagnosis, ultrasound examination and family testing). This study used the results of the neonatal screening program, which enabled a precise measure of the prevalence of CF at birth to be obtained. Over the same period, we collected data from prenatal diagnoses carried out in the region, first in families related to a CF child and also those made following the detection of an echogenic bowel upon routine ultrasound examination performed during pregnancy. The prevalence of CF at birth was estimated to be 1/2838 in the region over a 10-year period (1992-2001). By including the 54 CF-affected pregnancies that were terminated during these 10 years, the corrected birth prevalence of CF was 1/1972. Prenatal diagnosis was therefore responsible for a global decrease in CF prevalence at birth of 30.5%. This work constitutes the first study able to provide a precise measure of CF birth prevalence and of its evolution through the combined effects of neonatal screening, prenatal diagnosis, ultrasound examination and family testing.

Cystic Fibrosis↗