Cystic Fibrosis Newborn Screening Program Research Articles

Severe lung disease in children with cystic fibrosis missed in newborn screening.

Cystic fibrosis (CF) is now routinely diagnosed through newborn screening (NBS), but the tests employed in the USA have been evolving for two decades as missed cases become recognized and lab methods improve in association with more knowledge about CF genetics. New Jersey was among the first states to implement CF NBS in 2001 when it introduced the original two-tiered method that combined measurements of immunoreactive trypsinogen (IRT) with detection of the principal pathogenic variant (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With continuation of the IRT/DNA (F508del) algorithm for two decades and identification of screening false negative children, we decided to examine the condition of some missed cases with special attention to their respiratory status. To strengthen the arguments for quality improvement in New Jersey's CF NBS program, we reviewed and evaluated false negative cases to determine the potential extent of preventable patient suffering as a consequence of delayed diagnoses. Five children with CF who had false negative screening results were studied in detail. In each case there was a different cause of the negative screening results. They all had clinically significant/severe lung disease, ranging from chronic cough with CF pathogens on respiratory culture at a young age to respiratory failure. This case series highlights the consequences of false negative screening results, which served as the impetus to upgrade New Jersey's CF NBS algorithm. Implemented changes include lowering the IRT cutoff to 70 ng/mL and expanding to a 139 variant CFTR panel. In 2023, a floating IRT cutoff is anticipated to be implemented.

336 Improved detection by California cystic fibrosis newborn screening program in all races and ethnicities

336 Improved detection by California cystic fibrosis newborn screening program in all races and ethnicities

Improvement in cystic fibrosis newborn screening program outcomes with genetic counseling via telemedicine.

The Cystic Fibrosis Foundation (CF Foundation) recommends the provision of genetic counseling (GC) to help educate families and decrease anxiety around the cystic fibrosis (CF) newborn screening process. Unfortunately, access to genetic counselors is limited, especially for CFtrained genetic counselors. We hypothesized that the GC process for families could be improved by utilizing telemedicine to leverage the availability of two dedicated, CF trained genetic counselors to provide access to GC for several CF centers. In addition, we hoped to demonstrate that use of trained CF genetic counselors, delivering GC via telemedicine at the time of sweat testing, would provide families with understanding of CF genetics as well as result in high satisfaction with the newborn screening process. GC was provided by CF trained genetic counselors via telemedicine at the time of sweat testing. Following the counseling session, families were administered an anonymous written survey to evaluate their impression of the services provided. A subset of 50 families was recruited for an assessment of gained knowledge regarding CF genetics using the Ciske knowledge inventory. Using χ2 analysis, Ciske knowledge inventory data from our telemedicine GC families was compared to counseled and uncounseled Ciske historical controls. Lastly, in-depth interviews about the newborn screening process for CF were performed with 10families and interviews were coded for emerging themes. During the 4years of the study, 250 patients received GC. Overall comfort with the counseling rated 4.77 out of 5 using a Likert scale. After counseling by telemedicine, parents demonstrated improved understanding of the genetic implications of an abnormal CF newborn screen for their family, with 100% of families understanding that their child was a carrier for CF as compared to 97.2% of counseled (p = .023) and 78.5% of uncounseled (p = .0007) from Ciske historical controls. The study group also showed improvement in understanding of both parents possibly being carriers, with an 87.7% correct response rate compared to a 37.0% correct response rate in the counseled group (p < .0001) and a 35.4% correct response rate in the non-counseled group (p < .0001) from Ciske historical controls. Subgroup analysis at one site showed a significant increase in the number of infants with completed sweat tests from previous years (49% in 2013 vs. 80% in 2017 during the study, p < .0001). GC by telemedicine was well received by families and demonstrated improved family knowledge acquisition and understanding of CF as it related to risks for their child as well as identification of risks for other family members. Furthermore, in addition to an increase is those receiving GC, a subgroup analysis demonstrated a significant increase in the number of infants receiving sweat tests. This study demonstrates that GC via telemedicine for CF is feasible and demonstrates improvement in parent understanding of CF genetics. Furthermore, this method can be implemented effectively across a wide geographical area with a limited number of CF trained genetic counselors to improve access to care for patients and families.

Why cystic fibrosis newborn screening programs have failed to meet original expectations… thus far

This Commentary summarizes what the author has learned in 46 years of research on newborn screening (NBS) for cystic fibrosis (CF) combined with healthcare and public health practice. The original expectation was that screening for this relatively common, life-threatening genetic disorder would lead to consistently timely diagnoses in the neonatal period and be equitable. Unfortunately, this ambitious goal has not been achieved in the USA despite the availability of an excellent, although imperfect, 2-tiered screening test employing immunoreactive trypsinogen (IRT) and DNA analysis for pathogenic variants in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR). In fact, variations in the quality of NBS programs, inconsistencies in their operations, and disparities in outcomes have been prominent features. The causes include leadership challenges and deficiencies among both CF centers and NBS labs; failures to form effective partnerships among CF centers and with NBS programs; relatively rapid implementation after 2005 with variable quality planning; misunderstandings and erroneous dogma about CF; data limitations regarding IRT, especially cutoff values, and CFTR genetics; tolerance of suboptimal protocols and false negative results; problems in dried blood spot collections plus a lack of transparency and national oversight; partial lack of readiness, qualifications, funding and/or willingness to innovate with floating IRT cutoffs and DNA/CFTR analyses; follow up challenges/deficiencies impairing timeliness, including sweat testing limitations; and published guidelines that are more descriptive than sufficiently critical and directive. But the lessons learned through uniquely intensive CF NBS research have been enlightening and guided the U.S. Cystic Fibrosis Foundation to nationwide quality improvement initiatives.

Diagnostic and Communication Challenges in Cystic Fibrosis Newborn Screening.

As of December 2009, cystic fibrosis (CF) newborn screening (NBS) is performed in all 50 US states and the District of Columbia. Widespread implementation of CF newborn screening (CFNBS) in the US and internationally has brought about new and varied challenges. Immunoreactive trypsinogen (IRT) remains the first, albeit imperfect, biomarker used universally in the screening process. Advances in genetic testing have provided an opportunity for newborn screening programs to add CFTR sequencing tiers to their algorithms. This in turn will enable earlier identification of babies with CF and improve longer-term outcomes through prompt treatment and intervention. CFTR sequencing has led to the ability to identify infants with CF from diverse ethnic and racial backgrounds more equitably while also identifying an increasing proportion of infants with inconclusive diagnoses. Using the evolution of the New York State CF newborn screening program as a guide, this review outlines the basic steps in a universal CF newborn screening program, considers how to reduce bias, highlights challenges, offers guidance to address these challenges and provides recommendations for future consideration.

Evaluation of specificity and sensitivity of IRT/IRT protocol in the cystic fibrosis newborn screening program: 6-year experience of three tertiary centers.

We aimed to evaluate cutoff values of immunoreactive trypsinogen (IRT)/IRT and determine relationship between IRT values and clinical characteristics of children with cystic fibrosis (CF). This study is cross-sectional study. Data of children with positive newborn screening (NBS) between 2015 and 2021 were evaluated in three pediatric pulmonology centers. Age at admission, sex, gestational age, presence of history of meconium ileus, parental consanguinity, sibling with CF, and doll-like face appearance, first and second IRT values, sweat chloride test, fecal elastase, fecal fat, biochemistry results, and age at CF diagnosis were recorded. Sensitivity and specificity of IRT cutoff values were evaluated. Of 815 children with positive NBS, 58 (7.1%) children were diagnosed with CF. Median values of first and second IRT were 157.2 (103.7-247.6) and 113.0 (84.0-201.5) μg/L. IRT values used in current protocol, sensitivity was determined as 96.6%, specificity as 17.2% for first IRT, and 96.6% sensitivity, 20.5% specificity for second IRT. Positive predictive value (PPV) was determined as 7.1%. When cutoff value for first IRT was estimated as 116.7μg/L, sensitivity was 69.0% and specificity was 69.6%, and when cutoff value was set to 88.7μg/L for second IRT, sensitivity was 69.0% and specificity was 69.0%. Area under curve was 0.757 for first and 0.763 for second IRT (p < 0.001, p < 0.001, respectively). PPV was calculated as 4.3%. Conclusion: Although sensitivity of CF NBS is high in our country, its PPV is significantly lower than expected from CF NBS programs. False-positive NBS results could have been overcome by revising NBS strategy. What is Known: • Although immunoreactive trypsinogen elevation is a sensitive test used in cystic fibrosis newborn screening, its specificity is low. • In countries although different algorithms are used, all strategies begin with the measurement of immunoreactive trypsinogen in dried blood spots. What is New: • In our study, it was shown that use of the IRT/IRT protocol for cystic fibrosis newborn screening is not sufficient for the cut-off values determined by the high number of patients. • Newborn screening strategy should be reviewed to reduce false positive newborn screening results.

Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes

Newborn screening (NBS) for cystic fibrosis (CF) has been universal in the US since 2010, but its association with clinical outcomes is unclear. To describe the real-world effectiveness of NBS programs for CF in the US on outcomes up to age 10 years. This was a retrospective cohort study using CF Foundation Patient Registry data from January 1, 2000, to December 31, 2018. The staggered implementation of NBS programs by state was used to compare longitudinal outcomes among children in the same birth cohort born before vs after the implementation of NBS for CF in their state of birth. Participants included children with an established diagnosis of CF born between January 1, 2000, to December 31, 2018, in any of the 44 states that implemented NBS for CF between 2003 and 2010. Data were analyzed from October 5, 2020, to April 22, 2022. Birth before vs after the implementation of NBS for CF in the state of birth. Longitudinal trajectory of height and weight percentiles from diagnosis, lung function (forced expiratory volume in 1 second, [FEV1] percent predicted) from age 6 years, and age at initial and chronic infection with Pseudomonas aeruginosa using linear mixed-effects and time-to-event models adjusting for birth cohort and potential confounders. A total of 9571 participants (4713 female participants [49.2%]) were eligible for inclusion, with 4510 (47.1%) in the pre-NBS cohort. NBS was associated with higher weight and height percentiles in the first year of life (weight, 6.0; 95% CI, 3.1-8.4; height, 6.6; 95% CI, 3.8-9.3), but these differences decreased with age. There was no association between NBS and FEV1 at age 6 years, but the percent-predicted FEV1 did increase more rapidly with age in the post-NBS cohort. NBS was associated with older age at chronic P aeruginosa infection (hazard ratio, 0.69; 95% CI, 0.54-0.89) but not initial P aeruginosa infection (hazard ratio, 0.88; 95% CI, 0.77-1.01). NBS for CF in the US was associated with improved nutritional status up to age 10 years, a more rapid increase in lung function, and delayed chronic P aeruginosa infection. In the future, as highly effective modulator therapies become available for infants with CF, NBS will allow for presymptomatic initiation of these disease-modifying therapies before irreversible organ damage.

Newborn Screening for Cystic Fibrosis: A Qualitative Study of Successes and Challenges from Universal Screening in the United States.

Cystic fibrosis (CF) newborn screening (NBS) was universally adopted in 2009 in the United States. Variations in NBS practices between states may impact the timing of diagnosis and intervention. Quantitative metrics can provide insight into NBS programs (NBSP), but the nuances cannot be elucidated without additional feedback from programs. This study was designed to determine facilitators and barriers to timely diagnosis and intervention following NBS for CF. The median age at the first CF event for infants with CF within each state was used to define early and late states (n = 15 per group); multiple CF centers were invited in states with more than two CF centers. Thirty states were eligible, and 61 NBSP and CF centers were invited to participate in structured interviews to determine facilitators and barriers. Once saturation of themes was reached, no other interviews were conducted. Forty-five interviews were conducted (n = 16 early CF center, n = 12 late CF center, n = 11 early NBSP, and n = 6 late NBSP). Most interviewees reported good communication between CF centers and NBSP. Communication between primary care providers (PCPs) and families was identified as a challenge, leading to delays in referral and subsequent diagnosis. The misperception of low clinical risk in infants from racial and ethnic minority groups was a barrier to early diagnostic evaluation for all groups. NBSP and CF centers have strong relationships. Early diagnosis may be facilitated through more engagement with PCPs. Quality improvement initiatives should focus on continuing strong partnerships between CF centers and NBS programs, improving education, communication strategies, and partnerships with PCPs, and improving CF NBS timeliness and accuracy.

Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil

ObjectiveTo analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. MethodA population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. ResultsThe public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3–7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th–75th) of 9.0 (7.0–13.0) days. ConclusionsThe coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

P005 Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil

P005 Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil

Outcomes of early repeat sweat testing in infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/CF screen-positive, inconclusive diagnosis.

Reaching early and definitive diagnosis in infants with cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID) is a priority of all CF newborn screening programs. Currently, sweat testing (ST) is the gold standard for CF diagnosis or exclusion. We assessed outcomes in a cohort of Italian CRMS/CFSPID infants who underwent repeat ST in the 1st year of life. This multicentre, prospective study analysed clinical data and outcomes in CRMS/CFSPID infants born between September 1, 2018, and December 31, 2019, and followed until June 30, 2020. All subjects underwent CF transmembrane conductance regulator (CFTR) gene sequencing and the search for CFTR macrodeletions/macroduplications, and repeat ST in the 1st year of life. Fifty subjects (median age at end of follow-up, 16 months [range, 7-21 months]) were enrolled. Forty-one (82%) had the first sweat chloride (SC) in the intermediate range. During follow up, 150 STs were performed (range, 1-7/infant). After a median follow-up of 8.5 months (range, 1-16.2 months), 11 (22%) subjects were definitively diagnosed as follows: CF (n = 2 [4%]) at 2 and 5 months, respectively; healthy carrier (n = 8 [16%]), at a median age of 4 months (range, 2-8 months); and healthy (n = 1 [2%]) at 2 months of age. Inconclusive diagnosis remained in 39 (78%) infants. Early repeat ST in the 1st year of life can shorten the time to definitive diagnosis in screening positive subjects with initial SC levels in the intermediate range.

P015 Evaluation of the specificity and sensitivity of the cut-off values of immunoreactive trypsinogen in the cystic fibrosis newborn screening program

P015 Evaluation of the specificity and sensitivity of the cut-off values of immunoreactive trypsinogen in the cystic fibrosis newborn screening program

Newborn screening for CF in France: An exemplary national experience

Newborn screening (NBS) for cystic fibrosis (CF) was implemented throughout France since 2002, with a 3-tiered strategy consisting in an immunoreactive trypsinogen (IRT) measurement at day-3, a search for the most common mutations responsible for CF when the IRT value is above the cut-off level, and, if necessary, a safetynet retesting of IRT at day-21. Coordination and follow-up are ensured at the national level and NBS is carried out through a regional organization involving NBS centers, biochemical and molecular genetics laboratories. Sweat testing and comprehensive mutation gene analysis are then performed according to a defined algorithm. Between 2002 and 2014, screening for the 30 most common mutations identified 87% of the alleles and comprehensive mutation gene analysis performed when applicable identified more than 300 additional mutations and resulted in a detection rate of 99.8% of the mutated alleles. Program surveillance ensured at a national level allowed to carry out adaptation of cut-off levels and removal of the p.Arg117His mutation. Thanks to these modifications, the performance of the French NBS program for CF meets the European guideline standards regarding positive predictive values, sensitivity and time to initial visit at the CF center, thus making the strategy effective. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Cystic Fibrosis Diagnosis in Newborns, Children, and Adults.

The diagnosis of cystic fibrosis (CF) has traditionally relied on the presence of clinical features of the disease. Today, diagnosis through newborn screening (NBS) is becoming the standard of modern CF care. CF NBS programs can identify CF prior to clinical presentation, but for the advantages of an early diagnosis to accrue a scrupulous system must be in place to ensure all steps in the program are performing. As we move rapidly into the era of CF transmembrane conductance regulator (CFTR) protein modulators, the opportunity to start a presymptomatic infant, identified through CF NBS, on these agents offers the prospect of true disease-modifying interventions which could result in a paradigm shift in CF care.Conversely, the introduction of NBS has resulted in many children being asymptomatic at the time of diagnosis. Some screened newborns are classified as "CF Screening Positive, Inconclusive Diagnosis", or "CFTR-related metabolic syndrome" when the diagnosis can neither be confirmed nor excluded. Appropriate assessment and follow-up should be arranged at specialist centers as a proportion of these infants and adults will eventually be diagnosed with CF.Symptoms and signs are particularly pertinent when considering a diagnosis of CF outside the context of NBS. In older patients with a late diagnosis, the spectrum of clinical presentation can be very variable with vigilant clinicians from multiple specialties suspecting the diagnosis in conditions such as recurrent pulmonary infections, male infertility, pancreatitis, nasal polyposis, and malabsorption.In addition to clinical symptoms or positive NBS results, sweat test and genetic analysis are cornerstones in the diagnosis of CF, but in some cases the diagnosis cannot be confirmed on genetic or sweat testing. Difficult diagnosis may be supported by in vivo or ex vivo electrophysiology measurements on respiratory or intestinal epithelia. This can be done by either measuring transepithelial nasal potential difference or intestinal current measurements.

Devil in the detail of newborn screening for cystic fibrosis

The recognition that the sweat chloride concentration was elevated in people with cystic fibrosis (CF) was fundamental to its diagnosis and treatment.1 A sweat chloride >60 mmol/L was diagnostic of...

Initial regional evaluation of the Cystic Fibrosis Newborn Screening Program: data from the Mediterranean coast of Turkey

Background/ aimSince January 2015, the Cystic Fibrosis Newborn Screening (CFNS) program has been implemented in Turkey. We aimed to evaluate the demographic, clinical, and laboratory data of cases referred from the CFNS program and to determine the most suitable cut-off value for immunoreactive trypsinogen (IRT)-1 and immunoreactive trypsinogen (IRT-2) that are used in the CFNS program in Turkey.Materials and methodsA total of 156 Turkish Caucasian subjects were determined as positive cases during 3 years, from January 2015 to January 2018, and were referred to the pediatric pulmonology clinics of Akdeniz University Hospital, Antalya, Turkey, for the national CFNS program. The evaluation was made considering the IRT-1 and IRT-2 values, demographic characteristics, sweat test results, CFTR genotypes, and diagnoses.ResultsNine patients were diagnosed with cystic fibrosis (CF). Eight were diagnosed with CF-related metabolic syndromes and three were determined to be CF carriers. The ratio of CF to CF-related metabolic syndrome was determined as 1.1:1. Considering the limits of the present CFNS program and the IRT method, the positive predictive value (PPV) for the referred cases was determined as 5.8%. When a cut-off value of 105.6 ng/mL was taken for IRT-1, sensitivity was 100%, specificity was 59%, and PPV was 12.8%. For a cut-off value of 88.75 ng/mL for IRT-2, sensitivity was determined as 90%, specificity as 65%, and PPV as 15.2%.ConclusionThis is the first detailed clinical study to evaluate the data from the CFNS program along the Mediterranean coast of Turkey. As false positive results are extremely high in Turkey, there is an urgent need for revision of the IRT-1 and IRT-2 limits by evaluating the data of the whole country.

Newborn cystic fibrosis screening in southeastern Mexico: Birth prevalence and novel CFTR gene variants.

To use the results of the first five years of a cystic fibrosis newborn screening program to estimate the cystic fibrosis birth prevalence and spectrum of cystic fibrosis transmembrane conductance regulator ( CFTR) gene variants in Yucatan, Mexico. Screening was performed from 2010 to 2015, using two-tier immunoreactive trypsinogen testing, followed by a sweat test. When sweat test values were >30 mmol/L, the CFTR gene was analyzed. Of 96,071 newborns screened, a second sample was requested in 119 cases. A sweat test was performed in 30 newborns, and 9 possible cases were detected (seven confirmed cystic fibrosis and two inconclusive). The most frequently detected CFTR pathogenic variant (5/14 cystic fibrosis alleles, 35.7%) was p.(Phe508del); novel p.(Ala559Pro) and p.(Thr1299Hisfs*29) pathogenic variants were found. Cystic fibrosis birth prevalence in southeastern Mexico is 1:13,724 newborns. Immunoreactive trypsinogen blood concentration is influenced by gestational age and by the time of sampling. The spectrum of CFTR gene variants in Yucatan is heterogeneous.

Cystic fibrosis newborn screening programs: implications of the CFTR variant spectrum in nonwhite patients.

Cystic fibrosis newborn screening (CFNBS) has been offered across the United States since 2010. However, as compared with white patients with CF, CFTR variant identification in nonwhite populations remains inequitable. Utilizing the recent characterization of the nonwhite CF variant spectrum, we examined the effectiveness of current CFNBS molecular panels in identifying affected nonwhite newborns. Based on a cross-sectional evaluation of genotyping data from the CF Foundation Patient Registry that compared 3,496 nonwhite with 22,206 white CF patients, the current CFNBS algorithms used in the 50 states and the District of Columbia were analyzed. We assessed the percentage of CF patients of Hispanic, African, Asian, and Native American heritage who would not be identified by the molecular panels most commonly used. Compared with whites, variant detection was significantly lower in Hispanic, black, and Asian newborns (P ≤ 0.0001 each), as well as in Native American newborns (P values ranged from 0.001 to 0.0003), for the most common CFNBS panels. This study provides a perspective on the applicability of current panels to a diverse population and enables CFNBS programs to consider more inclusive test approaches to facilitate diagnosis, timely clinical intervention, and enhanced prognosis for CF patients of nonwhite and mixed ethnicities.Genet Med 19 1, 36-44.

Improving the Sensitivity and Positive Predictive Value in a Cystic Fibrosis Newborn Screening Program Using a Repeat Immunoreactive Trypsinogen and Genetic Analysis

To evaluate the performance of a new cystic fibrosis (CF) newborn screening algorithm, comprised of immunoreactive trypsinogen (IRT) in first (24-48hours of life) and second (7-14days of life) dried blood spot plus DNA on second dried blood spot, over existing algorithms. A retrospective review of the IRT/IRT/DNA algorithm implemented in Colorado, Wyoming, and Texas. A total of 1 520 079 newborns were screened, 32 557 (2.1%) had abnormal first IRT; 8794 (0.54%) on second. Furthermore, 14 653 mutation analyses were performed; 1391 newborns were referred for diagnostic testing; 274 newborns were diagnosed; and 201/274 (73%) of newborns had 2 mutations on the newborn screening CFTR panel. Sensitivity was 96.2%, compared with sensitivity of 76.1% observed with IRT/IRT (105ng/mL cut-offs, P<.0001). The ratio of newborns with CF to heterozygote carriers was 1:2.5, and newborns with CF to newborns with CFTR-related metabolic syndrome was 10.8:1. The overall positive predictive value was 20%. The median age of diagnosis was 28, 30, and 39.5days in the 3 states. IRT/IRT/DNA is more sensitive than IRT/IRT because of lower cut-offs (∼97 percentile or 60ng/mL); higher cut-offs in IRT/IRT programs (>99 percentile, 105ng/mL) would not achieve sufficient sensitivity. Carrier identification and identification of newborns with CFTR-related metabolic syndrome is less common in IRT/IRT/DNA compared with IRT/DNA. The time to diagnosis is nominally longer, but diagnosis can be achieved in the neonatal period and opportunities to further improve timeliness have been enacted. IRT/IRT/DNA algorithm should be considered by programs with 2 routine screens.

46 Microbiological airway flora in children with cystic fibrosis in the first year of life (To treat or not to treat, that's the question!)

In children with cystic fibrosis (CF) pulmonary microbial colonization and infection are important prognostic factors. In Germany a national CF newborn screening does not exist by now and only little is known about the microbial respiratory flora of children with CF in the first years of life. In Dresden a regional newborn screening program for eastern Saxony exists since 1996. Thus, a microbiological monitoring for patients with CF was already performed from diagnosis in the first month of life throughout babyhood and we collected data from 1997 on. In the following, we want to demonstrate the microbial colonization of 55 patients in our center in their first year of life. In all patients we found bacteria other than normal flora of mouth and throat. Most commonly we detected Staphylococcus aureus, Haemophilus influenzae and Escherichia coli, but also a variety of many other such as Klebsiella, Serratia, Streptococcus, Enterobacter, Enterococcus and Acinetobacter species, Bacillus cereus, Branhamella catarrhalis, and more. We also detected Pseudomonas aeruginosa and other Pseudomonas species already in patients at this young age. In several patients we found fungi in the throat swab, such as Aspergillus , Candida and Saccharomyces species. Most of the patients needed antibiotic therapy in their first year of life due to pulmonary exacerbation, but the clinical symptoms in many cases did not correlate with the microbiological findings by throat swab. With the introduction of a national newborn screening program for CF hopefully end of this year, we will have to discuss the influence of these bacterial findings in the first year of life on the prognosis and the need for treatment.