Community-wide screening for cystic fibrosis carriers could replace newborn screening for the diagnosis of cystic fibrosis

Most babies with cystic fibrosis (CF) are born to parents who did not know they were carriers until their baby was diagnosed with CF, usually by newborn screening. It is only after the birth of their first child with CF that couples are offered genetic counselling and reproductive choices. Most use this information for prenatal testing of subsequent pregnancies. With the high uptake of first trimester screening for Down syndrome (80% in Victoria) most couples have had screening during the CF affected pregnancy. Yet screening for CF carrier status is available, costs are similar to that for Down syndrome screening and CF carrier screening only ever needs to be done once. Waiting for couples to have a baby with CF before they are identified as carriers denies them choice. A national policy on CF carrier screening in Australia, and determination to equitably fund such a programme, is required.     

Parental attitudes to the identification of their infants as carriers of cystic fibrosis by newborn screening

AIM: To investigate parental attitudes to cystic fibrosis (CF) carrier detection of their infant by newborn screening (NBS). METHODS: Data were collected from a postal questionnaire sent to parents of infants identified as CF carriers by NBS in 1996-1997 (inclusive) and 2001 in Victoria, Australia (n = 66). RESULTS: Almost all parents remembered their child being identified as a CF carrier (97%: 1996/1997; 100%: 2001); yet the majority were unaware at the time that NBS could detect carriers (70%: 1996/1997; 49%: 2001). More parents in the later cohort reported having carrier testing compared with the earlier cohort (85% and 53% respectively) but recall was more uncertain in the earlier cohort when validated against health records. Cascade testing was not utilised frequently by other family members in either cohort. Residual risk of being a carrier if testing was negative was not well understood by parents. Some parents (28%: 1996/1997; 18%: 2001) had residual anxiety about the current health of their carrier child and their future reproductive decision making. Most parents were satisfied with the information provided to them at the time of the sweat test. Few differences were seen between the cohorts. CONCLUSION: Although the NBS process for CF in Victoria is working efficiently for the majority of families whose infant is identified as a carrier there are areas that can be improved. We recommend that greater attention should be given to informing parents that a consequence of NBS is CF carrier detection and strategies to improve utilisation of cascade testing should be developed.     

Screening for prediabetes in the general child population: maternal attitude to participation

Abstract: Screening to predict serious diseases in the general population has been regarded as unethical as it is supposed to make people anxious. Therefore we have evaluated whether mothers become anxious when their babies participate in a project to predict diabetes in the general child population. Out of 21 700 newborn children, 16 300 (75%) entered the ABIS project (All Babies in South‐east Sweden). The parents (usually the mothers) answered a questionnaire at the child's birth and then again after 1 yr. A total of 10 868 representative birth questionnaires had been analyzed. To the question, ‘How do you feel when you know that your child is participating in this study?’, only 2.5% of mothers of children with type 1 diabetes in the family answered ‘more anxious/much more anxious’, and even fewer (1.5%) of the mothers in the general population (p < 0.01). A total of 52.5% of the general population answered ‘calmer/more reassured’ (29.3% ‘calmer’ and 23.2% ‘much calmer’), while 43.3% felt unaffected. Those 1.5% of mothers who reported becoming more anxious were more likely to be in an unstable social situation (unemployed, p < 0.001; born abroad, p < 0.001; low education, p < 0.001). At the 1‐yr follow‐up, 4948 unselected questionnaires had been analyzed. Only 1.2% of the mothers felt ‘more anxious’, while the overwhelming majority felt either unaffected (58.7%) or calmer (38.6%). At this follow‐up, most of those who had felt ‘more anxious’ at birth did not feel that way any longer, and none of those with diabetes in the family. We conclude that large‐scale screening studies for the prediction of diabetes in the general population can be performed without causing increased anxiety. A few parents, most often found in the group with known social problems, might need extra information and support.     

Breaking the diagnosis of cystic fibrosis to parents: A process not a one-off event

Breaking the news to parents that their child has cystic fibrosis [CF] is most frequently given in the first few weeks of the baby’s life as a result of newborn screening. This is optimal to reduce morbidity but can have a significant impact on the parents’ mental wellbeing and the parent–child relationship. Parent feedback indicates that assimilating the diagnosis is not a one-off event but a process that takes time. CF professionals therefore need to be aware not only of how they communicate the diagnosis initially but also the ways in which families make sense of this throughout at least the following year. The parent–patient–team relationship is essential to good health outcomes. Key objectives of this paper are to enable: (1) understanding parental responses to the diagnosis which can indicate how well they are managing CF for their child, (2) improving the way in which the diagnosis is communicated and, (3) changing team management of CF in the early years to include parental collaboration to support better mental and physical outcomes.     

Newborn screening for cystic fibrosis

Early diagnosis of cystic fibrosis (CF) provides an opportunity to improve disease control and prevent early complications. Of patients with CF in the United States, 10% are identified early through newborn screening (including infants born in Colorado, Massachusetts, New Jersey, New York, Wisconsin, Wyoming, and parts of California, Connecticut, Pennsylvania, and Montana). Successful screening programs in these states have stimulated other states to consider adding CF screening to their newborn programs. Additionally, new technology permits expanded screening for numerous genetic conditions. Genetic screening, such as that used most frequently for CF, creates new challenges for the clinician, including atypical disease presentations and carrier detection. In this review, we examine the many advances in CF newborn screening and early care that were reported during the last few years.     

Evidence for newborn screening for cystic fibrosis

Different strategies are available for studying the effectiveness of newborn screening for cystic fibrosis (CF). Although observational studies suggest clinical benefits, their results are difficult to interpret because of the potential for several methodological problems. Randomised studies show that age at time of diagnosis is an important factor in the nutritional status of pancreatically insufficient patients and that a delayed diagnosis increases the risk of malnutrition in childhood. Effects on lung disease are more controversial. Advantages other than better clinical outcome or survival may be obtained by the implementation of CF neonatal screening, mainly the opportunity for presymptomatic trials and treatments and more informed reproductive choices for parents and relatives. Disadvantages of neonatal screening for CF include the detection of heterozygotes and the discovery of mild forms of disease.     

Inconclusive Cystic Fibrosis neonatal screening results: long-term psychosocial effects on parents

Aim:  Cystic Fibrosis (CF) Newborn Screening occasionally identifies neonates where a CF diagnosis can neither be confirmed nor excluded. To assess how parents of these infants cope with this ambiguous situation.
Methods:  Parents of 11 children with Ambiguous Diagnosis (group AD) were compared with parents of 11 children diagnosed with CF through neonatal screening [group Cystic Fibrosis Diagnosis (CFD)] and with parents of 11 Healthy Control children (group HC) matched for gender and age.
Results:  The emotional reaction to the inconclusive result was less pronounced in AD than in CFD (p = 0.003), and AD parents considered their infants as healthy as controls. Parents' anxiety about their child's health is stronger in CFD than in AD (p < 0.05) and HC (p < 0.001). Long-term emotional distress was rated similarly in AD and CFD, and greater than in HC (p = 0.0003). The parent/child relationship was less influenced in AD than in the CF group (p = 0.03). Seven AD and CFD parents changed their family planning projects.
Conclusion:  Inconclusive neonatal screening results appear to be understood and associated with lower anxiety levels than CF diagnosis. Concern about the child's health is similar to healthy controls and lower than in parents of CF children.     

Parent responses to participation in genetic screening for diabetes risk

Screening for type 1 diabetes (T1DM) risk in newborns has little negative emotional impact on mothers. In this study, the impact on the mother and the father was evaluated both in the general population and in families with diabetes. All parents with a newborn in Skane, Sweden, were invited to a screening for T1DM risk in their children (the Diabetes Prediction in Skane (DiPiS)). Blood was obtained at delivery from the mother and the child. When the child was 2 months old, parents gave written consent and filled out questionnaires, but were not informed about the genetic risk. Of the 10 538 invited families, 6831 (64.8%) consented and 806 (7.7%) declined participation. Five questions addressing both parents were filled out by 6676 (63.4%) mothers and 6099 (57.8%) fathers. In 146/6676 (2.2%) families, one family member had diabetes (D-families). Participation in DiPiS did not affect most parents and the majority was satisfied with the information. The majority of parents (28.9%) were reassured and only 1.1% (140/12,670) reported increased worries because of participation, compared to 2.8% of the mothers in D-families. Parents in D-families more often ascribed diabetes risk to their child as well as the risk being higher. Mothers and fathers differed in their answers on four of the five study questions, with mothers being more satisfied with the information, reporting more knowledge of diabetes, estimating lower risk of their child to get diabetes, but reporting more worries of possible future chronic disease in the child. Parents with lower education, being born abroad, or being younger who reported worries of chronic disease in the child were also reassured by participation in the study. These results confirm that screening for T1DM risk in newborns does not create worries in most parents, but stress that fathers differ from mothers in opinions and reactions, that parents' reactions are affected by diabetes in the family, and that demographic factors might be important for the parents' reports.     

Prenatal diagnosis for paediatricians

In Ontario, approximately 140,000 women deliver newborn infants each year. Of these women, 60,000 to 70,000 have multiple marker screening, 10,000 undergo amniocentesis or chorion villus sampling and virtually all have at least one prenatal ultrasound. Multiple marker screening is not used in every province and territory; however, amniocentesis and prenatal ultrasound are used throughout Canada. Most paediatric patients will have been exposed to some form of prenatal diagnosis. If an abnormality is found prenatally, parents may have concerns to discuss with the paediatrician after the child is born. Likewise, if a child with a problem is born following a normal pregnancy, the parents will want to know why the problem was missed prenatally. Paediatricians should be aware of prenatal tests that have been performed to understand better their patients and their families.     

Potential impact of newborn screening for cystic fibrosis on child survival: a systematic review and analysis

OBJECTIVE: To estimate the population impact of child mortality as a result of cystic fibrosis (CF) potentially preventable by newborn screening. STUDY DESIGN: A systematic literature review of mortality in children with classic CF without meconium ileus (MI) in screened and unscreened cohorts was extended by contacting investigators for unpublished data. In addition, survival in US states with and without newborn screening (NBS) programs for CF was compared using data from the Cystic Fibrosis Foundation Patient Registry (CFFPR). RESULTS: Among non-US studies, CF-related mortality risk to approximately 10 years of age was lower by 5 to 10 per 100 in screened cohorts. Unpublished US data from a trial of NBS for CF indicate no CF-related deaths to 10 years of age in either cohort. CFFPR data suggest improved survival among children with CF born in US states with NBS, with a CF-related mortality difference to 10 years of age between the screened and unscreened groups between 1.5 and 2 per 100 children with CF without MI. CONCLUSION: In addition to improving nutritional outcomes, newborn screening for CF may result in improved child survival. The absolute differential in mortality risk, although modest in size, appears comparable to NBS for certain other genetic disorders.     

Ethical issues with genetic testing in pediatrics

Advances in genetic research promise great strides in the diagnosis and treatment of many childhood diseases. However, emerging genetic technology often enables testing and screening before the development of definitive treatment or preventive measures. In these circumstances, careful consideration must be given to testing and screening of children to ensure that use of this technology promotes the best interest of the child. This statement reviews considerations for the use of genetic technology for newborn screening, carrier testing, and testing for susceptibility to late-onset conditions. Recommendations are made promoting informed participation by parents for newborn screening and limited use of carrier testing and testing for late-onset conditions in the pediatric population. Additional research and education in this developing area of medicine are encouraged.     

Analysis of the costs of diagnosing cystic fibrosis with a newborn screening program

OBJECTIVES: To compare the cost of diagnosing cystic fibrosis (CF) through a newborn screening program with the traditional method and to estimate the cost of CF diagnosis if a national newborn screening program is implemented. STUDY DESIGN: Surveys were conducted to determine the annual number of sweat tests in 1991 and in 2000 after implementation of statewide screening. A national survey of sweat test costs was used to estimate the annual expense for diagnosing CF in the United States through newborn screening. RESULTS: Since the introduction of newborn screening for CF, the numbers of sweat tests ordered annually have decreased from 1670 to 804 (including 134 follow-up tests from screening). The current estimated annual cost of Wisconsin CF newborn screening and diagnosis is $4.58 per newborn infant. The estimated annual cost per newly diagnosed CF infant using the traditional method is $4.97 per newborn infant. If no additional sweat tests were ordered outside of the newborn screening program, the estimated annual cost of a Wisconsin CF newborn screening and diagnosis is $2.66 per newborn and $2.47 per newborn for a national CF newborn screening program. CONCLUSIONS: A CF newborn screening program provides a potentially cost-saving alternative to the traditional method of diagnosis of CF.     

Neonatal screening for cystic fibrosis: present and future

Despite there being effective tests for detecting cystic fibrosis (CF) using newborn screening blood samples, screening in neonates has not had universal approval because of uncertainty about its benefits. After up to 18 y experience, at a recent conference in Caen several aspects attracted universal agreement. There is still major delay in clinical diagnosis after the onset of symptoms. There is short-term benefit in early diagnosis by screening, with reduced morbidity in the first 2 y, evidence of significant nutritional benefits up to the age of 10 y, and probable respiratory benefit over this time frame. There is great potential for research into treatment modalities and no evidence of significant psychological harm to CF babies from early diagnosis. With a screening protocol that includes a DNA test there is some unwanted carrier detection and careful genetic counselling is needed. There is no evidence yet that screening will extend the life of CF patients, so some doubts remain as to its overall effectiveness, and there have been no good studies on comparative costs in screened and unscreened cohorts. Even so, the weight of evidence suggests very worthwhile advantages for screened babies and their families. Because of this, it is unlikely that further trials will take place. It may be that the onus now is on those who do not support screening to justify this stance to parents who may favour it.     

Neonatal screening for cystic fibrosis: present and future

Despite there being effective tests for detecting cystic fibrosis (CF) using newborn screening blood samples, screening in neonates has not had universal approval because of uncertainty about its benefits. After up to 18 y experience, at a recent conference in Caen several aspects attracted universal agreement. There is still major delay in clinical diagnosis after the onset of symptoms. There is short-term benefit in early diagnosis by screening, with reduced morbidity in the first 2 y, evidence of significant nutritional benefits up to the age of 10 y, and probable respiratory benefit over this time frame. There is great potential for research into treatment modalities and no evidence of significant psychological harm to CF babies from early diagnosis. With a screening protocol that includes a DNA test there is some unwanted carrier detection and careful genetic counselling is needed. There is no evidence yet that screening will extend the life of CF patients, so some doubts remain as to its overall effectiveness, and there have been no good studies on comparative costs in screened and unscreened cohorts. Even so, the weight of evidence suggests very worthwhile advantages for screened babies and their families. Because of this, it is unlikely that further trials will take place. It may be that the onus now is on those who do not support screening to justify this stance to parents who may favour it.     

False negative results on newborn screening for cystic fibrosis

Over a 5 year period in Newcastle, 18 new cases of cystic fibrosis (CF) were diagnosed in children who had been screened in the newborn period. In six of these children, the screening programme failed. Four of these children had a normal screen and an additional two had elevated immunoreactive trypsin (IRT), but there were problems with the notification procedure. Three of the children missed by the screening process had a significantly delayed diagnosis; in all three cases the diagnosis of CF was suspected clinically, but a sweat test was delayed because of false reassurance from the fact that the child had been screened for CF. In a fourth case, multiple elevated sweat electrolyte levels were obtained, but the diagnosis of CF was considered to be in doubt because of the normal IRT assay. A sweat test should be performed on any child in whom there is clinical suspicion of CF.     

Oral glucose tolerance testing in children with cystic fibrosis

Ode KL, Frohnert B, Laguna T, Phillips J, Holme B, Regelmann W, Thomas W, Moran A. Oral glucose tolerance testing in children with cystic fibrosis. Background: Cystic fibrosis (CF) related diabetes is the most common comorbidity in persons with CF. International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines recommend annual oral glucose tolerance testing (OGTT) screening starting at age 10. The OGTT might be recommended in younger children if, as in adults, it provided clinically relevant prognostic information. A database review was performed to determine whether OGTT findings in children with CF predict subsequent clinical course. Methods: A retrospective matched‐pair cohort study was based on OGTTs performed during 1998–2003. Children aged 6–9 were classified as having normal glucose tolerance (NGT) or abnormal glucose tolerance (AGT). Children with AGT were matched by age and gender to those with NGT. Clinical status was assessed at baseline and 5 yr later. In a separate investigation, diabetes and prior AGT status of children aged 10–18 were used to assess predictions derived from the cohort study. Results: In 1998–2003, 39 of 94 children had AGT. Of these, 31 had sufficient follow‐up data to be included. Both at baseline and 5 yr later there was no significant difference in height, weight, body mass index ( BMI) or lung function between AGT and NGT. Diabetes developed in 13 AGT (42%) and one NGT (3%) [odds ratio (OR) 11, p = 0.0009]. Age of diabetes onset was 12 ± 1 yr in boys and 11 ± 1 yr in girls, compared to approximately 23 yr in the general CF population. Fifteen current children age 10–18 who had AGT before age 10 have diabetes, close to the prediction of 19. Conclusions: AGT in children with CF age 6–9 yr identifies those at high risk for progression to early onset diabetes.     

First information and support provided to parents of children with Down syndrome in Sweden: clinical goals and parental experiences

When parents are informed that their newborn child has Down syndrome (DS), they often respond with a traumatic crisis reaction. The aims of this study were to assess the clinical goals regarding the first information and support provided to parents of newborn children with DS at the Swedish paediatric departments, and to analyse the parents' experiences of how they were first informed and treated. Data were collected during 1992-1993 from all of the 51 departments of paediatrics in Sweden. Information on the parents' experiences, collected retrospectively in 1996, was based on recollection by 165 parents of 86 children with DS born between 1989 and 1993 at 10 of the paediatric departments considered representative for Sweden. Seventy-five percent of the families were informed about the diagnosis within 24 h post partum. Some parents felt they were informed too late, and a few parents that they were told too soon. Half of the parents were satisfied with the timing. About 70% of the parents considered the information insufficient and 60% felt that they had been unsupported. Seventy percent would have liked more frequent information. Parental criticisms concerning the way in which the information was provided were that they received too much negative information about DS and that both the communication skills and the basic knowledge of DS on the part of the professionals could have been better. Conclusion: The Swedish paediatric departments fall short of their reported strong clinical goals regarding the initial information in Sweden, and improvements in this area are desirable.     

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.     

Examination of long-lasting parental concern after false-positive results of neonatal hearing screening.

OBJECTIVE: To investigate whether false-positive outcomes on neonatal hearing screening cause long-lasting parental concerns. METHODS: A general population of parents whose children had participated in the universal neonatal hearing screening (UNHS) programme were examined. Parents filled out a questionnaire 6 months after UNHS. Outcomes were compared for all parents whose child tested positive or inconclusive in at least one of three tests but afterwards proved not to have hearing impairment (cases, n = 154) and a random sample of parents whose child passed the first test (controls, n = 288). Parental anxiety as measured with the State-Trait Anxiety Inventory (STAI), attitude towards the child (child health rating and experienced problems) and sensitivity to hearing problems were measured. RESULTS: Median STAI score was equal for cases and controls. Parental attitudes toward the child also did not differ. The difference in the proportion of parents who worried about their child's hearing was statistically significant between cases and controls (p = 0.001) and varied with the number of screens; 4% of controls were worried about the child's hearing, as compared to 10% of cases whose children were tested twice, and 15% of cases whose children were tested three times. CONCLUSIONS: False-positive UNHS test results do not cause long-term general parental anxiety. However, 6 months after screening, a considerable proportion of parents continued to experience hearing-specific worries regarding their child.