Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.

Defects in motile cilia and sperm flagella cause primary ciliary dyskinesia (PCD), characterized by chronic airway disease, infertility, and left-right laterality disturbances, usually as a result of loss of the outer dynein arms (ODAs) that power cilia/flagella beating. Here, we identify loss-of-function mutations in CCDC114 causing PCD with laterality malformations involving complex heart defects. CCDC114 is homologous to DCC2, an ODA microtubule-docking complex component of the biflagellate alga Chlamydomonas. We show that CCDC114 localizes along the entire length of human cilia and that its deficiency causes a complete absence of ciliary ODAs, resulting in immotile cilia. Thus, CCDC114 is an essential ciliary protein required for microtubular attachment of ODAs in the axoneme. Fertility is apparently not greatly affected by CCDC114 deficiency, and qPCR shows that this may explained by low transcript expression in testis compared to ciliated respiratory epithelium. One CCDC114 mutation, c.742G>A, dating back to at least the 1400s, presents an important diagnostic and therapeutic target in the isolated Dutch Volendam population.

There has been a steady increase in national CF NBS programmes across Europe with variable strategies and outcomes that reflect the different approaches.

After an experimental neonatal screening program for cystic fibrosis (CF) from 1973–1979, a follow-up study took place from 1980–1997. Patients were treated at specialized centres (C) or at local hospitals (non-C). Aims of the study were: 1) to determine whether the previously reported benefits from screening persisted with time and after adjustment for confounding variables; and 2) to investigate whether centre treatment was associated with improved prognosis of CF patients.Prognosis of patients detected by screening (S; n=24) was compared with patients detected clinically, born during (non-S; n=29) and after the screening programme (post-S; n=39). In addition, prognosis was compared between 45 C and 47 non-C patients. Multivariable regression analysis was used to compare survival and mixed-effects model regression analysis was used to compare clinical outcome between patients. The analyses included the variables screening, centre treatment, sex, meconium ileus and genotype.S patients had a significantly smaller decline in forced expiratory volume in one second (FEV1) (difference +2.74% predicted) and significantly lower immunoglobulin-G (IgG) levels (difference −473.69 mg·dL−1) than non-S patients until 12 yrs of age. At 12 yrs of age, vital capacity was significantly higher in S patients than in non-S patients (difference +362.79 mL). Survival seemed to be best for S patients compared to both non-S and post-S patients. Post-S patients were significantly heavier (difference in sd weight +0.77), had a significantly smaller decline in FEV1(difference +2.80% pred) and lower IgG levels (difference −453.04 mg·dL−1) than non-S patients until 12 yrs of age. C patients had a significantly improved survival (relative risk (RR) 0.18, 95% confidence interval 0.05–0.57) than non-C patients.Early diagnosis through neonatal screening leads to better preservation of lung function in the long term in cystic fibrosis patients. Management of cystic fibrosis patients in specialized centres improves survival.

To investigate the epidemiology of nontypeable Haemophilus influenzae in the respiratory tract of cystic fibrosis (CF) patients, H. influenzae isolates from sputum specimens of 40 CF patients were analyzed longitudinally for 2 years. The isolates were characterized by analysis of the major outer membrane protein (MOMP) patterns. MOMP variant H. influenzae strains were discriminated from distinct strains by randomly amplified polymorphic DNA analysis of genomic DNA. Multiple H. influenzae strains and MOMP variant strains were isolated from single sputum specimens of 29 patients. In 22 patients, a distinct H. influenzae strain persisted over time (median persistence, 8 months; range 2-24). In general, the appearance of MOMP variant strains did not coincide with the occurrence of exacerbations.

Background

Context Newborn screening for cystic fibrosis (CF) is included in many routine programmes but current strategies have considerable drawbacks, such as falsepositive 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 pancreatitisassociated protein (PAP) were measured. In the second method, samples with IRT $60 mg/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%.

al. Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth.