Diagnosis of cystic fibrosis in London and South East England before and after the introduction of newborn screening.

INTRODUCTION: Newborn screening (NBS) for cystic fibrosis (CF) was introduced to London and South East England in 2007. We wished to assess the details of missed cases, and to compare the age at diagnosis and other clinical parameters, prescreening and postscreening. METHODS: Retrospective and prospective case notes and database review of all newly diagnosed CF patients in our 7 CF centres, for 18 months before and 4 years after NBS started. RESULTS: 347 patients were diagnosed with CF. 126 patients were not screened (born before or abroad), and had a median age at diagnosis of 2.4 years, excluding those with meconium ileus (MI). Their median time to diagnosis from initial symptoms was 1 year, and in 10% it was >6 years. After NBS started, 170 were diagnosed by NBS (48% were already symptomatic); 7 moved into the region after NBS elsewhere; 34 presented with MI (6 were negative on NBS); and 10 screened children were missed (false negative cases). Median age of diagnosis was 3 weeks. Prevalence was 1 in 3991 live births. By 2 years of age (with data on 104 patients), 49 children (47%) had their first isolation of Pseudomonas aeruginosa, while 37 (36%) had their first growth of Staphylococcus aureus from respiratory cultures. CONCLUSIONS: NBS has significantly reduced the age of diagnosis, although many were symptomatic even at 3 weeks of age. A small number of patients with CF can still be missed by the screening programme, and the diagnosis should be considered even with a negative screen result.

Serum vitamin D levels in children with cystic fibrosis.

Osteopenia is increasingly recognized in adults with cystic fibrosis (CF), and is potentially related to vitamin D deficiency in both adulthood and childhood. Vitamin D supplements are recommended and prescribed to all pancreatic-insufficient patients. We aimed to ascertain whether vitamin D deficiency in children with CF was prevalent. 25-hydroxyvitamin D (25-OHD) was measured in 290 children attending a specialist pediatric CF clinic for annual assessment. 25-OHD levels were compared with reference values and to other biochemical markers, lung function, and growth. Levels were also analyzed by pancreatic status and by the presence of CF-related liver disease. Median 25-OHD was 65 (range, 9-190) nmol/l. One percent had levels below 15 nmol/l, and 6% had levels less than 25 nmol/l. Levels were lower in adolescents (P < 0.001) and during the "winter" months (P < 0.001). No relationship was found with pancreatic status or liver disease. In conclusion, the majority of children had normal 25-OHD levels. Interpretation is difficult due to a lack of knowledge of optimal levels of 25-OHD required for healthy bone accretion. Lower levels in adolescents may be a precursor to low levels in adulthood, and did not seem to be simply related to poor compliance with supplementation. This may reflect normal physiology.

The neorule: a new instrument to measure linear growth in preterm infants.

OBJECTIVES: To compare measurements of crown-heel length (CHL) made with the neorule with CHL measurements made with a stadiometer in term infants. To examine safety and reproducibility of CHL measurements in infants < 32 weeks gestational age (GA) using the neorule. METHODS: Three measurements of CHL were made by three teams during the first 2 days of life in healthy term infants. One team used the stadiometer and two the neorule. Two different teams made three measurements of CHL on four occasions at two week intervals in infants less than 32 weeks GA. Infants were continuously monitored, and any adverse event was recorded. RESULTS: Fifty term infants were studied, median (range) birth weight 3440 (2020-5010) g. The mean (SD, 95% confidence interval) difference between values obtained with the stadiometer and neorule was 0.08 (6.22, -1.69 to +1.85) mm and between the two neorule teams was 0.8 (4.48, -0.47 to +2.08) mm. Twenty preterm infants were studied, GA median (range) 29 (25(+0)-31(+6)) weeks, median (range) CHL 397 (339-475) mm. There were no adverse events. The difference (SD, 95%CI) between teams in the mean CHL measurement was 0.18 (4.79, -1.02 to +1.38) mm, with interobserver limit of agreement -9.2 to +9.6 mm and coefficient of variation 1.2%. There were no significant differences between measurements made by single observers; the F ratio was 0.449 (df = 61, p = 0.6). CONCLUSION: The neorule is a safe and accurate way to measure CHL in newborn infants.

How do we treat wheezing infants? Evidence or anecdote.

Consultant paediatricians were questioned about their management of wheezing disorders in infants. Salbutamol was the preferred bronchodilator for recurrent wheeze, whereas ipratropium was preferred in viral bronchiolitis. Doses of both medications varied widely. Both inhaled and oral corticosteroids were considered by most respondents. Practice does not clearly follow guidelines or evidence and presumably continues to be based on anecdote.

Comparison of resistance measured by the interrupter technique and by passive mechanics in sedated infants.

Airways resistance measured by the interrupter technique (Rint) requires little patient cooperation and has been successfully used in young children, but little studied in infants. The authors aimed to evaluate the measurement of Rint in infants, using a commercially available device (the MicroRint), by comparing it with an established technique to measure respiratory resistance: the single breath occlusion technique (SBT); and a measure of airflow obstruction during forced expiration. Infants <18 months old with a history of wheeze, sedated with triclofos for pulmonary function testing, had measurements taken and compared to Rint (using the MicroRint), respiratory system resistance (Rrs) by SBT, and to maximal flow at functional residual capacity (V'maxFRC). Paired data from 25 of 37 infants studied was obtained. There was a significant difference between Rint (mean 2.94+/-0.68) and Rrs (4.02+/-0.87), but the two measures were strongly correlated (r=0.7). Rint was negatively correlated with V'maxFRC (r=-0.63). Smaller infants failed to trigger the MicroRint. Interrupter resistance values in infants are significantly lower than values of respiratory system resistance obtained by passive mechanics. However, there is a strong correlation between the two measurements, as well as between resistance measured using the interrupter technique and maximal flow at functional residual capacity, which indicates that resistance measured using the interrupter technique may be a useful marker of airway obstruction in infants. There remain a number of theoretical and technical problems which require further exploration.

Persistent wheezing in infants with an atopic tendency responds to inhaled fluticasone.

BACKGROUND: The role of inhaled corticosteroids for the treatment of wheeze in infancy remains unclear. AIM: To investigate the effect of inhaled fluticasone on symptoms in a group of wheezy infants who had a high risk of progressing to childhood asthma. METHODS: A total of 52 infants, under 1 year of age, with a history of wheeze or cough and a history (personal or first degree relative) of atopy were prescribed either 150 microg fluticasone twice daily (group F) or placebo (group P), via metered dose inhaler, for 12 weeks following a two week run in period. Symptoms were scored in a parent held diary and the mean daily symptom score (MDS) and symptom free days (SFD) calculated for each two week period. RESULTS: Thirty seven infants completed the study. Both MDS and SFD improved significantly between the run in and final two week period in group F, but not group P, with a mean difference in change (95% CI) between groups of 1.12 (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD. CONCLUSION: Improvement of clinical symptoms in response to fluticasone can be shown in this high risk group of infants. In the absence of effective alternatives inhaled corticosteroids should be considered in this patient group.

Inhaled salbutamol for wheezy infants: a randomised controlled trial.

BACKGROUND: Salbutamol is frequently used as a bronchodilator for infants who wheeze. Many single dose studies have questioned its effectiveness. AIMS: To investigate the response of wheezy infants to salbutamol over an extended time period in order to elucidate either symptomatic relief or a protective effect. METHODS: Eighty infants under 1 year, with persistent or recurrent wheeze and a personal or family history of atopy, were recruited to a randomised, double blind, cross over, placebo controlled trial. Salbutamol (200 microg three times daily) or placebo were administered regularly over two consecutive treatment periods of four weeks via a spacer and mask. Symptoms of wheeze and cough were recorded in a diary. At the end of the study pulmonary function tests were performed before and after salbutamol (400 microg). RESULTS: Forty eight infants completed the diary study; 40 infants underwent pulmonary function testing. No difference in mean daily symptom score was observed between the salbutamol and placebo periods. There was no difference in the number of symptom free days. Compliance and forced expiratory flows remained unchanged and resistance increased following salbutamol. There was no relation between the response measured by symptom score or pulmonary function in individual patients. CONCLUSION: In wheezy infants with an atopic background, there was no significant beneficial effect of salbutamol on either clinical symptoms or pulmonary function. Clinical effects could not be predicted from pulmonary function tests. Salbutamol cannot be recommended as the bronchodilator of choice in this age group.