Incidence of Cystic Fibrosis in Ethnic Italians and Greeks and in Australians of Predominantly British Origin

The incidence of cystic fibrosis among the Australian born children of parents born in Italy was 1: 3 625 live births and among Australian born children of parents born in Greece 1: 3726. These incidences were significantly lower than the incidence for cystic fibrosis of 1: 2021 in children born to Australian born parents, about 90% of whom have ancestors born in the British Isles. The figures suggest there are significant variations in the incidence of cystic fibrosis in different European populations.     

Influence of five years of antenatal screening on the paediatric cystic fibrosis population in one region

BACKGROUND: Antenatal screening for cystic fibrosis has been endorsed by the US National Institutes of Health. Edinburgh is the only city in the UK with an established routine antenatal screening programme for cystic fibrosis. AIMS: To report the change in numbers of infants diagnosed with cystic fibrosis born in Edinburgh after the introduction of antenatal screening for the disease. POPULATION: Infants diagnosed as having cystic fibrosis (by sweat test or genotyping, or both) in the seven years before antenatal testing (1984-90) and the first five years of antenatal testing (1991-95). Children born in this region who had moved before diagnosis were identified from the UK cystic fibrosis survey database. RESULTS: The incidence of cystic fibrosis decreased from an average of 4.6 to 1.6 children each year with antenatal screening. The reduction in the incidence (65%) was greater than that accounted for by prenatal diagnosis and termination (36%). Of the eight children born with cystic fibrosis during the period of antenatal screening, five had been subject to antenatal screening: three had only one mutation identified, one was missed due to a laboratory error, and one was identified as a one in four risk, but prenatal diagnosis was not performed. CONCLUSIONS: Antenatal testing for cystic fibrosis has successfully reduced the incidence of cystic fibrosis in this region. Although the numbers are small, it is possible that the reduction in numbers may have been greater than might be expected from antenatal screening alone.     

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

Background  

This paper reports the findings of a South Australian qualitative, exploratory study of children and young people living with a chronic disease, and their perceptions and experiences of physical activity. The perceptions and experiences of their parents were also explored. The chronic diseases were type 1 diabetes, asthma and cystic fibrosis.     

Influence of five years of antenatal screening on the paediatric cystic fibrosis population in one region

BACKGROUND—Antenatal screening for cystic fibrosis has been endorsed by the US National Institutes of Health. Edinburgh is the only city in the UK with an established routine antenatal screening programme for cystic fibrosis.
AIMS—To report the change in numbers of infants diagnosed with cystic fibrosis born in Edinburgh after the introduction of antenatal screening for the disease.
POPULATION—Infants diagnosed as having cystic fibrosis (by sweat test or genotyping, or both) in the seven years before antenatal testing (1984-90) and the first five years of antenatal testing (1991-95). Children born in this region who had moved before diagnosis were identified from the UK cystic fibrosis survey database.
RESULTS—The incidence of cystic fibrosis decreased from an average of 4.6 to 1.6 children each year with antenatal screening. The reduction in the incidence (65%) was greater than that accounted for by prenatal diagnosis and termination (36%). Of the eight children born with cystic fibrosis during the period of antenatal screening, five had been subject to antenatal screening: three had only one mutation identified, one was missed due to a laboratory error, and one was identified as a one in four risk, but prenatal diagnosis was not performed.
CONCLUSIONS—Antenatal testing for cystic fibrosis has successfully reduced the incidence of cystic fibrosis in this region. Although the numbers are small, it is possible that the reduction in numbers may have been greater than might be expected from antenatal screening alone.

     

Australian Paediatric Surveillance Unit study of haemoglobinopathies in Australian children

Aim: The aims of this study were to determine the incidence and types of haemoglobinopathies in Australian children and their distribution among ethnic groups, and to collect information on timing of diagnosis of haemoglobinopathies in Australia. Methods: Between January 2004 and March 2006, the Australian Paediatric Surveillance Unit asked paediatricians to report all children under 15 years of age with a newly diagnosed haemoglobinopathy. A questionnaire requesting further information was forwarded to those clinicians. Carrier states such as thalassaemia minor were excluded. Results: Eighty‐four notifications of haemoglobinopathy were received by the Australian Paediatric Surveillance Unit, with 59 confirmed cases giving a national incidence of 0.74 per 100 000 children < 15 years of age per annum. Of 59 cases, 42 (71%) were Australian born. Twenty‐nine (35.6%) children had sickle cell disease, 17 (28.8%) had Hb H disease, six (10.2%) had beta‐thalassaemia major and 15 (25.4%) had compound heterozygous conditions. One child died from sickle cell disease. Of Australian born children, at least 10 mothers (23.8%) and 11 fathers (26.2%) were unaware of their carrier status pre‐partum (information unavailable for 13 mothers and 17 fathers). Only 11 parents (18.6%) had risks of haemoglobinopathy discussed with them antenatally and only three cases (5.1%) were diagnosed antenatally. Conclusions: We found that a small but significant number of children with haemoglobinopathies are being born in Australia despite existing programmes of testing at‐risk groups and neonatal screening. Haemoglobinopathies were also diagnosed in recent immigrants. Greater awareness of these conditions and enhancements of screening and detection programmes may be needed as the genetic diversity of the Australian population continues to develop.     

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.     

Screening for cystic fibrosis: a four year regional experience.

A four year regional screening programme to detect cystic fibrosis using measurement of immunoreactive trypsinogen is described. During this period 60 infants were diagnosed; 34 by screening, 12 born with meconium ileus, and 14 not identified by the screening assay but who presented with clinical symptoms at a later age, giving an incidence of cyst fibrosis in the region during this time of 1/1807. Screening has resulted in earlier detection of cystic fibrosis in many infants, thus allowing treatment to be instituted at an early age, and genetic counseling offered to the parents. There were a number of false positives and false negatives with the immunoreactive trypsinogen screening assay. In addition, eight infants who were sweat tested at an early age had a sweat sodium concentration of less than 70 mmol/l, although they were subsequently shown to have cystic fibrosis. These results confirm other published data showing that sweat sodium results may be low in very young infants with cystic fibrosis. At the time of diagnosis seven (20%) of the infants identified by screening were totally asymptomatic and several additional children had symptoms of such a type that the diagnosis of cystic fibrosis had not been considered at the time of screening. Despite the problems experienced it has been decided to continue screening.     

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history.

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.     

Cystic fibrosis mutations in Romania

We have investigated the genotype in 32 children with cystic fibrosis from Romania. The diagnosis of cystic fibrosis was made on the basis of typical clinical findings and sweat electrolyte levels using the pilocarpine iontophoresis method. Conclusion Genetic analysis of 32 children with cystic fibrosis from Romania showed a 25% incidence of DeltaF508 mutation and a 64.5% incidence of unknown mutations, 5 other known mutations and 1 new mutation 1717–2(A > G). Received: 26 December 1995 and in revised form: 14 May 1996 / Accepted: 24 May 1996     

Quality-of-life in children and adolescents with cystic fibrosis managed in both regional outreach and cystic fibrosis center settings in Queensland

OBJECTIVES: To assess the health-related quality-of-life (HRQOL) of children/adolescents with cystic fibrosis (CF) and compare HRQOL in children managed by cystic fibrosis outreach service (CFOS) with those treated in a cystic fibrosis center (CFC). To compare HRQOL of children with CF in Queensland with previously published HRQOL data from the United States and examine the relationship between HRQOL scores and pulmonary function. STUDY DESIGN: Participants were children/adolescents with CF and their parents managed by the Royal Children's Hospital Queensland at a CFC or CFOS. Two HRQOL surveys were used: PedsQL and Cystic Fibrosis Questionnaire (CFQ). RESULTS: There were 91 CFC and 71 CFOS participants with similar demographics. PedsQL total summary score was statistically higher in CFOS, P=.05. There was no significant difference in CFQ scores between groups. Queensland parents reported lower HRQOL for their children compared with US parents (P<.01) despite similar pulmonary function. Declining pulmonary function correlated with worse CFQ scores in adolescents, P<.05. CONCLUSIONS: Children living in regional Queensland reported as good as or slightly better HRQOL compared with children attending a CFC. Parent proxy HRQOL scores were generally low suggesting a reduced perception of HRQOL by parents for their children.     

Cystic fibrosis and family stress: effects of age and severity of illness

Stress and adjustment in mothers of children with cystic fibrosis was compared with that in a control group of mothers of healthy children. Mothers of children in four age groups were included: preschool, middle childhood, early adolescence, and late adolescence. Mothers of children with cystic fibrosis did not report significantly higher levels of stress than did the control group mothers; nor did they report greater feelings of inadequacy as parents. However, mothers of children with cystic fibrosis in two age groups, preschool and early adolescence, scored higher on a measure of depression than did mothers of healthy children in the same age groups. The relationship of illness severity to maternal stress and adjustment was examined in the cystic fibrosis group. The mother's subjective rating of the child's illness severity was a better indicator of her reported stress than was the Schwachman clinical rating. It appears that many mothers are able to adapt to the presence of cystic fibrosis in the family, although certain periods in the child's life and perceived increases in illness severity are associated with increased maternal distress.     

Clinical outcomes of newborn screening for cystic fibrosis.

AIM: To determine how early diagnosis of cystic fibrosis, using neonatal screening, affects long term clinical outcome. METHODS: Fifty seven children with cystic fibrosis born before neonatal screening was introduced (1978 to mid 1981) and a further 60 children born during the first three years of the programme (mid 1981 to 1984), were followed up to the age of 10. The cohorts were compared on measures of clinical outcome, including height, weight, lung function tests, chest x-ray picture and Shwachman score. RESULTS: Age and sex adjusted standard deviation scores (SDS) for height and weight were consistently higher in children screened for cystic fibrosis than in those born before screening. At 10 years of age, average differences in SDS between groups were 0.4 (95% CI -0.1, 0.8) for weight and 0.3 (95% CI -0.1, 0.7) for height. This translates to an average difference of about 2.7 cm in height and 1.7 kg in weight. Mean FEV1 and FVC (as percentage predicted) were significantly higher in the screened cohort at 5 and 10 years of age, with an average difference of 9.4% FEV1 (95% CI 0.8, 17.9) and 8.4% FVC (95% CI 1.8, 15.0) at 10 years. Chest x-ray scores were not different between the groups at any age, but by 10 years screened patients scored an average 5.3 (95% CI 1.2, 9.4) points higher on the Shwachman score. CONCLUSION: Although not a randomised trial, this long term observational study indicates that early treatment made possible by neonatal screening may be important in determining subsequent clinical outcomes for children with cystic fibrosis. For countries contemplating the introduction of neonatal screening for cystic fibrosis, its introduction to some areas in a cluster randomised design will permit validation of studies performed to date.     

Malnutrition in cystic fibrosis: Psychosocial functioning of patients and their families

The relationship between nutritional status and psychosocial functioning was examined in 35 children with cystic fibrosis, aged 7-16 years. Twelve malnourished children and their families were compared with 23 well nourished children and their families. Established measures of adjustment and coping in the children, parents and families were used. Few statistically significant differences between the two groups emerged, and all comparisons of psychosocial functioning were not significant. The results of the study suggest that there is no relationship between the nutritional status of the child with cystic fibrosis and the current psychosocial adjustment and coping of child, parents and family.     

Quality of life in chronic illness: children, parents and paediatricians have different, but stable perceptions

AIM: Quality of life assessments can be helpful to estimate the well-being of chronically ill children. The aim of this study was to investigate the differences in perception of health-related quality of life (HRQoL) among children, parents and paediatricians at the time of diagnosis and after initial treatment in four chronic diseases. METHODS: HRQoL was assessed with the Health Utilities Index mark 3 (HUI3). The HUI3 consists of eight attributes (vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain). RESULTS: Nineteen paediatricians and 60 patients (aged 10-17 years) and their parents with newly diagnosed acute lymphoblastic leukaemia, juvenile idiopathic arthritis, asthma or with cystic fibrosis admitted for pneumonia participated in the study. Health and well-being perceptions were clearly different among paediatricians, parents and patients, both at diagnosis and after initial treatment. Perception differences were more prominent in the subjective attributes, emotion and pain. The agreement for these attributes was 23% and 5%, respectively. Paediatricians assessed the patients to have less pain than the patients and parents did. The reverse was true for the attribute emotion. At follow-up, the agreement was higher for the attributes ambulation and pain. CONCLUSION: At the onset of a chronic disease and after initial treatment, paediatricians, parents and children have different perceptions of the child's quality of life, particularly as to the subjective attributes pain and emotion. In view of these differences in perception among patients, their caregivers and paediatricians, this study suggests that whenever possible, multi-respondent assessment of HRQoL should be considered.     

Influenza vaccination among household contacts of children with cystic fibrosis and healthy children

BACKGROUND:

It is recommended that household contacts of children with cystic fibrosis and household contacts of children <2 years of age receive annual influenza vaccinations. There is little information documenting whether this recommendation is being followed.

METHODS:

A 20-question survey was distributed to caregivers of children with cystic fibrosis and to caregivers of healthy children <17 years of age seen in a Saskatoon (Saskatchewan) tertiary care centre. Survey questions addressed the influenza vaccination status of the child and household contacts. Respondents were also asked to rate the influence of various factors on the decision to vaccinate, using a 5-point Likert scale.

RESULTS:

Reported vaccination rates were 21%, 25% and 7% among household contacts of children with cystic fibrosis, children <2 years of age and children ≥2 years of age, respectively. Advice from their physician, belief that they were too healthy, and inconvenient times and locations of vaccination centres were significant influences when compared among the three groups. Other main deterrents to vaccination were belief that the vaccine does not prevent influenza and belief that its side effects are greater than its benefits.

CONCLUSION:

By understanding motivators and barriers to vaccination among household contacts of children with cystic fibrosis, effective strategies may be implemented to improve vaccination coverage against influenza. Strong recommendations by clinicians and improved access to vaccination centres are essential components in improving influenza vaccination coverage.     

Passive smoking and impaired lung function in cystic fibrosis

Passive smoking was measured in 57 children with cystic fibrosis and in 51 controls using a questionnaire and a measurement of urinary cotinine concentration. In the cystic fibrosis group, cotinine was significantly lower than in the controls. Also in this group, when the parents smoked the child's forced expiratory volume in one second decreased by 4% and the forced vital capacity by 3% for every 10 cigarettes smoked in the household each day.     

Passive smoking and impaired lung function in cystic fibrosis.

Passive smoking was measured in 57 children with cystic fibrosis and in 51 controls using a questionnaire and a measurement of urinary cotinine concentration. In the cystic fibrosis group, cotinine was significantly lower than in the controls. Also in this group, when the parents smoked the child's forced expiratory volume in one second decreased by 4% and the forced vital capacity by 3% for every 10 cigarettes smoked in the household each day.     

Newer therapies for cystic fibrosis

Cystic fibrosis is the most common lethal inherited disease in Caucasians in the UK, with an incidence of approximately one in 2500 live births. It is a heterogeneous disease which reflects different mutations in the cystic fibrosis transmembrane conductance regulator gene, modifier genes and environmental influences. The median life expectancy of children with cystic fibrosis born in the UK is approximately 30 years. Longer survival is the result of improvements in basic therapies including airway clearance, aggressive use of antibiotics and optimizing nutrition. Care given in a specialist centre has also been shown to improve survival. Despite this progress, pulmonary disease still accounts for most of the morbidity and is the cause of death in over 90% of patients with cystic fibrosis. This review will focus on newer therapies aimed at pulmonary disease which are now being used in the clinical setting, and other novel therapies which are still at the research stage.     

13C and H2 breath tests to study extent and site of starch digestion in children with cystic fibrosis.

BACKGROUND: Starch is an important source of energy for children with cystic fibrosis, but little is known about their capacity to digest it. METHODS: A 13C breath test was used to measure starch digestion and oxidation in 16 children with cystic fibrosis (median [range] age, 7.9 [4-15] years; 7 girls, 9 boys) and 5 normal healthy control subjects (median age, 8.3 [7-13] years; 3 girls, 2 boys). A test meal of 13C flour and lactulose was consumed and breath samples were obtained half-hourly thereafter for 6 hours to measure 13C enrichment by isotope ratio mass spectrometry and H2 by electrochemistry. The test was repeated on 10 children with cystic fibrosis when they were taking pancreatic supplements. RESULTS: The median (range) cumulative percentage 13C dose recovery (cPDR), was 35% (18-52%) in control subjects, 18% (9-33%) in children with cystic fibrosis without enzymes, and 29% (22-51%) in those with pancreatic supplements. cPDR differed significantly between healthy control subjects and children with cystic fibrosis without enzymes (p = 0.01) and between children with cystic fibrosis with and without enzymes (p < 0.0001), but there was no difference between control subjects and children with cystic fibrosis taking enzymes (p = 0.5). Eight children with cystic fibrosis had a cPDR within control range, and in six there was a second peak in 13CO2 enrichment coincident with an increase in H2. CONCLUSIONS: Starch digestion and oxidation are diminished in children with cystic fibrosis, but pancreatic enzymes restored them to near normal levels. A second peak in 13CO2 enrichment, suggestive of colonic starch fermentation was absent in healthy children, but present in some children with cystic fibrosis and abolished by pancreatic enzymes.