Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

Epidemiology of Robin sequence in the UK and Ireland: an active surveillance study.

BACKGROUND: Birth prevalence of Robin sequence (RS) is commonly reported as 1 case per 8000-14 000 live births. These estimates are based on single-source case ascertainment and may miss infants who did not require hospital admission or those without overt upper airway obstruction at birth. OBJECTIVES: To identify the true birth prevalence of RS with cleft palate in the UK and Ireland from a population-based birth cohort with high case ascertainment. METHODS: Active surveillance of RS with cleft palate was carried out in the UK/Ireland using dual sources of case ascertainment: British Paediatric Surveillance Unit (BPSU) reporting card and nationally commissioned cleft services. Clinical data were collected from notifying clinicians at two time points. RESULTS: 173 live-born infants met the surveillance case definition, giving a birth prevalence of 1 case per 5250 live births (19.1 per 100 000 (95% CI 16.2 to 21.9)), and 1:2690 in Scotland. 47% had non-isolated RS, with Stickler syndrome the most common genetic diagnosis (12% RS cases). Birth prevalence derived from the combined data sources was significantly higher than from BPSU surveillance alone. CONCLUSIONS: Birth prevalence of RS in the UK/Ireland derived from active surveillance is higher than reported by epidemiological studies from several other countries, and from UK-based anomaly registries, but consistent with published retrospective data from Scotland. Dual case ascertainment sources enabled identification of cases with mild or late-onset airway obstruction that were managed without hospital admission. Studies of aetiology and equivalent well-designed epidemiological studies from other populations are needed to investigate the identified geographical variability in birth prevalence.

Incidence, aetiology and neurodisability associated with severe microcephaly: a national surveillance study.

OBJECTIVE: To determine the incidence, causes and neurodevelopmental impact of severe microcephaly (head circumference <-3SD) up to age 2 years. DESIGN: Binational active paediatric surveillance study undertaken in 2017-2018 to identify and characterise new diagnoses of severe microcephaly. SETTING: UK and Ireland. PARTICIPANTS: Infants aged under 12 months at diagnosis. INTERVENTIONS: Observational study. MAIN OUTCOME MEASURES: Incidence, aetiology and neurodevelopmental outcomes at age 2 years. RESULTS: Fifty-nine infants met the case definition, of whom 30 (51%) were girls; 24 (41%) were born preterm (<37 weeks' gestation); and 34 (58%) were of 'white' ethnicity. Eight (14%) children died before 12 months of age. Incidence of severe microcephaly was 5.5 per 100 000 infants (95% CI 4.0 to 7.3). Higher relative risk (RR) was associated with preterm birth (RR 7.7, 95% CI 3.8 to 15.1) and British Asian ethnicity (RR 3.6, 95% CI 1.6 to 7.8). Microcephaly was mainly due to genetic causes (59%), brain ischaemia/hypoxia (10%) and congenital infection (8%), and 19% remained undetermined. Each child was referred on average to eight specialists, and 75% had abnormal brain imaging. By 2 years of age, 55 children experienced neurodevelopmental abnormalities, including feeding problems (68%), motor delay (66%), visual impairment (37%), hearing loss (24%) and epilepsy (41%). CONCLUSIONS: Although severe microcephaly is uncommon, it is associated with high mortality, complex multimorbidity and neurodisability, thus representing a significant ongoing burden for families and healthcare services. Potentially preventable causes include preterm birth, hypoxic/ischaemic brain injury and congenital infections. Clinical guidelines are essential to standardise aetiological investigation and optimise multidisciplinary management.

Maternal ethnicity and the prevalence of British pregnancies affected by neural tube defects.

BACKGROUND: Few data are available on the prevalence of neural tube defects (NTDs) within different ethnic communities of the United Kingdom. This study aimed to calculate prevalence estimates for NTD-affected pregnancies, classified by maternal ethnicity, and to explore why variations in prevalence might exist. METHODS: A cross-sectional study was performed with data from regional congenital anomaly registers in England and Wales, for NTD-affected pregnancies between 2006 and 2011. Using binomial regression models, we examined NTD-affected pregnancy prevalence estimates and rate ratios (PRRs), by maternal ethnicity. RESULTS: The prevalence of NTDs was 12.14 per 10,000 births, with no differences between study years. Anencephaly, encephalocele and spina bifida occurred at 4.98, 1.37 and 5.80 per 10,000 births respectively. Mothers of Indian ethnicity were 1.84 times more likely (95% CI: 1.24, 2.73) and Bangladeshi mothers 2.86 times more likely (95% CI: 1.48, 5.53) than White mothers to have an NTD-affected pregnancy, after adjusting for maternal deprivation and maternal age. The excess prevalence in Indian mothers was specifically for anencephaly (PRR 2.57; 95% CI: 1.52, 4.34), and in Bangladeshi mothers the trend was for increased spina bifida (PRR 3.86; 95% CI: 0.72, 8.69). Anencephaly in Indian mothers was especially associated with other congenital anomalies (non-isolated NTDs). CONCLUSIONS: Different British ethnic groups vary in NTD prevalence. The excess prevalence of anencephaly as a non-isolated NTD in pregnancies of Indian mothers could indicate involvement of genetic or other unmeasured behavioral factors. Future work is needed to seek etiological explanations for the ethnicity differences and to develop improved methods for primary prevention.

Challenges for funders in monitoring compliance with policies on clinical trials registration and reporting: analysis of funding and registry data in the UK.

OBJECTIVES: To evaluate compliance by researchers with funder requirements on clinical trial transparency, including identifying key areas for improvement; to assess the completeness, accuracy and suitability for annual compliance monitoring of the data routinely collected by a research funding body. DESIGN: Descriptive analysis of clinical trials funded between February 2011 and January 2017 against funder policy requirements. SETTING: Public medical research funding body in the UK. DATA SOURCES: Relevant clinical trials were identified from grant application details, post-award grant monitoring systems and the International Standard Randomised Controlled Trial Number (ISRCTN) registry. MAIN OUTCOME MEASURE: The proportion of all Medical Research Council (MRC)-funded clinical trials that were (a) registered in a clinical trial registry and (b) publicly reported summary results within 2 years of completion. RESULTS: There were 175 grants awarded that included a clinical trial and all trials were registered in a public trials registry. Of 62 trials completed for over 24 months, 42 (68%) had publicly reported the main findings by 24 months after trial completion; 18 of these achieved this within 12 months of completion. 11 (18%) trials took >24 months to report and 9 (15%) completed trials had not yet reported findings. Five datasets were shared with other researchers. CONCLUSIONS: Compliance with the funder policy requirements on trial registration was excellent. Reporting of the main findings was achieved for most trials within 24 months of completion; however, the number of unreported trials remains a concern and should be a focus for future funder policy initiatives. Identifying trials from grant management and grant monitoring systems was challenging therefore funders should ensure investigators reliably provide trial registries with information and regularly update entries with details of trial publications and protocols.

Risk factors for permanent childhood hearing impairment.

OBJECTIVE: While several perinatal risk factors for permanent childhood hearing impairment (PCHI) are known, association with gestational length remains unclear. We hypothesised that shorter gestational length predicts higher PCHI risk. DESIGN: 19 504 participants from the UK Millennium Cohort Study (born 2000-2002, prior to newborn screening). METHODS: Multivariable discrete-time survival analysis to examine associations between parent-reported PCHI by age 11 years and gestational length, plus other prespecified factors. RESULTS: PCHI affected 2.1 per 1000 children (95% CI 1.5 to 3.0) by age 11; however, gestational length did not predict PCHI risk (HR, 95% CI 1.00, 0.98 to 1.03 per day increase). Risk was increased in those with neonatal illness, with or without admission to neonatal care (6.33, 2.27 to 17.63 and 2.62, 1.15 to 5.97, respectively), of Bangladeshi or Pakistani ethnicity (2.78, 1.06 to 7.31) or born to younger mothers (0.92, 0.87 to 0.97 per year). CONCLUSION: Neonatal illness, rather than gestational length, predicts PCHI risk. Further research should explore associations with ethnicity.

Prevalence of permanent childhood hearing loss detected at the universal newborn hearing screen: Systematic review and meta-analysis.

CONTEXT: Permanent childhood hearing loss (PCHL) can affect speech, language, and wider outcomes. Adverse effects are mitigated through universal newborn hearing screening (UNHS) and early intervention. OBJECTIVE: We undertook a systematic review and meta-analysis to estimate prevalence of UNHS-detected PCHL (bilateral loss ≥26 dB HL) and its variation by admission to neonatal intensive care unit (NICU). A secondary objective was to report UNHS programme performance (PROSPERO: CRD42016051267). DATA SOURCES: Multiple electronic databases were interrogated in January 2017, with further reports identified from article citations and unpublished literature (November 2017). STUDY SELECTION: UNHS reports from very highly-developed (VHD) countries with relevant prevalence and performance data; no language or date restrictions. DATA EXTRACTION: Three reviewers independently extracted data and assessed quality. RESULTS: We identified 41 eligible reports from 32 study populations (1799863 screened infants) in 6195 non-duplicate references. Pooled UNHS-detected PCHL prevalence was 1.1 per 1000 screened children (95% confidence interval [CI]: 0.9, 1.3; I2 = 89.2%). This was 6.9 times (95% CI: 3.8, 12.5) higher among those admitted to NICU. Smaller studies were significantly associated with higher prevalences (Egger's test: p = 0.02). Sensitivity and specificity ranged from 89-100% and 92-100% respectively, positive predictive values from 2-84%, with all negative predictive values 100%. LIMITATIONS: Results are generalisable to VHD countries only. Estimates and inferences were limited by available data. CONCLUSIONS: In VHD countries, 1 per 1000 screened newborns require referral to clinical services for PCHL. Prevalence is higher in those admitted to NICU. Improved reporting would support further examination of screen performance and child demographics.

Ethnic-specific mortality of infants undergoing congenital heart surgery in England and Wales.

PURPOSE: To investigate ethnic differences in mortality for infants with congenital heart defects (CHDs) undergoing cardiac surgery or interventional catheterisation. DESIGN: Observational study of survival to age 1 year using linked records from routine national paediatric cardiac surgery and intensive care audits. Mortality risk was investigated using multivariable Poisson models with multiple imputation. Predictors included sex, ethnicity, preterm birth, deprivation, comorbidities, prenatal diagnosis, age and weight at surgery, preprocedure deterioration and cardiac diagnosis. SETTING: All paediatric cardiac surgery centres in England and Wales. PATIENTS: 5350 infants with CHDs born from 2006 to 2009. MAIN OUTCOME MEASURE: Survival at age 1 year. RESULTS: Mortality was 83.9 (95% CI 76.3 to 92.1) per 1000 infants, with variation by ethnic group. Compared with those of white ethnicity, infants in British Asian (Indian, Pakistani and Bangladeshi) and 'all other' (Chinese, mixed and other) categories experienced significantly higher mortality by age 1 year (relative risk [RR] 1.52[95% CI 1.19 to 1.95]; 1.62[95% CI 1.20 to 2.20], respectively), specifically during index hospital admission (RR 1.55 [95% CI 1.07 to 2.26]; 1.64 [95% CI 1.05 to 2.57], respectively). Further predictors of mortality included non-cardiac comorbidities, prenatal diagnosis, older age at surgery, preprocedure deterioration and cardiac diagnosis. British Asian infants had higher mortality risk during elective hospital readmission (RR 1.86 [95% CI 1.02 to 3.39]). CONCLUSIONS: Infants of British Asian and 'all other' non-white ethnicity experienced higher postoperative mortality risk, which was only partly explained by socioeconomic deprivation and access to care. Further investigation of case-mix and timing of risk may provide important insights into potential mechanisms underlying ethnic disparities.

Newborn Screening for Primary Congenital Hypothyroidism: Estimating Test Performance at Different TSH Thresholds.

Context: Active surveillance of primary congenital hypothyroidism (CH) in a multiethnic population with established newborn bloodspot screening. Objective: To estimate performance of newborn screening for CH at different test thresholds and calculate incidence of primary CH. Design: Prospective surveillance from June 2011 to June 2012 with 3-year follow-up of outcomes. Relative likelihood ratios (rLRs) estimated to compare bloodspot TSH test thresholds of 6 mU/L and 8 mU/L, with the nationally recommended standard of 10 mU/L for a presumptive positive result. Setting: UK National Health Service. Patients: Clinician notification of children aged <5 years investigated following clinical presentation or presumptive positive screening result. Main Outcome Measure(s): Permanent primary CH status determined by clinician report of continuing T4 requirement at 3-year follow-up. Results: A total of 629 newborns (58.3% girls; 58.7% white ethnicity) were investigated following presumptive positive screening result and 21 children (52.4% girls; 52.4% white) after clinical presentation; 432 remained on treatment at 3-year follow-up. Permanent CH incidence was 5.3 (95% CI, 4.8 to 5.8) per 10,000 infants. With use of locally applied thresholds, sensitivity, specificity, and positive predictive value were 96.76%, 99.97%, and 66.88%, respectively. Compared with a TSH threshold of 10 mU/L, positive rLRs for 8 mU/L and 6 mU/L were 1.20 (95% CI, 0.82 to 1.75) and 0.52 (95% CI, 0.38 to 0.72), and negative rLRs were 0.11 (95% CI, 0.03 to 0.36) and 0.11 (95% CI, 0.06 to 0.20), respectively. Conclusions: Screening program performance is good, but a TSH threshold of 8 mU/L appears superior to the current national standard (10 mU/L) and requires further evaluation. Further research should explore the implications of transient CH for screening policy.

Issues facing families of infants discharged after cardiac surgery: the perceptions of charity helpline staff.

AIM: To elicit the perceptions of helpline staff who talk to parents of children discharged after cardiac surgery in infancy about parents' key concerns. METHODS: A qualitative study involving semistructured interviews with 10 staff at four heart charities. Interviews were recorded, transcribed and analysed using Framework analysis. RESULTS: Staff identified the knowledge, communication and support needs of parents which they described in terms of the impact of patient and family factors, sources of support and systems. Staff perceptions of helplines, in terms of the function of a helpline and the roles of its staff, together with staff's personal views based on their experience of multiple encounters with many families, influenced how they viewed families' needs and responded to their requests. CONCLUSION: Helpline staff provided important, previously uncaptured evidence about the challenges faced by parents of children discharged after cardiac surgery in infancy. Staff have an important role in supporting communication, in terms of speaking to families about how to talk to professionals and talking to professionals directly to get or give information when parents are unable to do so. Capturing the perspective of helpline staff about communication issues has highlighted the need for interventions with professionals as well as parents.

Sharing and reuse of individual participant data from clinical trials: principles and recommendations.

OBJECTIVES: We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach. DESIGN AND METHODS: This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique. The consensus was reached in a series of three workshops held over 1 year, supported by exchange of documents and teleconferences within focused subgroups when needed. This work was set within the Horizon 2020-funded project CORBEL (Coordinated Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European. OUTCOME: We developed principles and practical recommendations on how to share data from clinical trials. RESULTS: The task force reached consensus on 10 principles and 50 recommendations, representing the fundamental requirements of any framework used for the sharing of clinical trials data. The document covers the following main areas: making data sharing a reality (eg, cultural change, academic incentives, funding), consent for data sharing, protection of trial participants (eg, de-identification), data standards, rights, types and management of access (eg, data request and access models), data management and repositories, discoverability, and metadata. CONCLUSIONS: The adoption of the recommendations in this document would help to promote and support data sharing and reuse among researchers, adequately inform trial participants and protect their rights, and provide effective and efficient systems for preparing, storing and accessing data. The recommendations now need to be implemented and tested in practice. Further work needs to be done to integrate these proposals with those from other geographical areas and other academic domains.

Ethnic and socioeconomic variation in incidence of congenital heart defects.

INTRODUCTION: Ethnic differences in the birth prevalence of congenital heart defects (CHDs) have been reported; however, studies of the contemporary UK population are lacking. We investigated ethnic variations in incidence of serious CHDs requiring cardiac intervention before 1 year of age. METHODS: All infants who had a cardiac intervention in England and Wales between 1 January 2005 and 31 December 2010 were identified in the national congenital heart disease surgical audit and matched with paediatric intensive care admission records to create linked individual child records. Agreement in reporting of ethnic group by each audit was evaluated. For infants born 1 January 2006 to 31 December 2009, we calculated incidence rate ratios (IRRs) for CHDs by ethnicity and investigated age at intervention, antenatal diagnosis and area deprivation. RESULTS: We identified 5350 infants (2940 (55.0%) boys). Overall CHD incidence was significantly higher in Asian and Black ethnic groups compared with the White reference population (incidence rate ratios (IRR) (95% CIs): Asian 1.5 (1.4 to 1.7); Black 1.4 (1.3 to 1.6)); incidence of specific CHDs varied by ethnicity. No significant differences in age at intervention or antenatal diagnosis rates were identified but affected children from non-White ethnic groups were more likely to be living in deprived areas than White children. CONCLUSIONS: Significant ethnic variations exist in the incidence of CHDs, including for specific defects with high infant mortality. It is essential that healthcare provision mitigates ethnic disparity, including through timely identification of CHDs at screening, supporting parental choice and effective interventions. Future research should explore the factors underlying ethnic variation and impact on longer-term outcomes.

Signs of deterioration in infants discharged home following congenital heart surgery in the first year of life: a qualitative study.

AIMS: To describe the ways in which parents recognise and make decisions about their child's symptoms following discharge home after congenital heart interventions in the first year of life and their experiences of seeking help. METHODS: This was a qualitative study involving semistructured interviews with parents. Twenty-one parents were recruited to the study. Parents all had a child who had congenital heart surgery in their first year of life between September 2009 and October 2013 at one of three UK cardiac centres; the children had either died or were readmitted as an emergency following initial discharge. RESULTS: Some parents were unable to identify any early warning signs. Others described symptoms of deterioration including changes in feeding and appearance, respiratory distress and subtle behavioural changes that may not be routinely highlighted to parents at discharge. Several barriers to accessing prompt medical assistance were identified including parents feeling that their concerns were not taken seriously, long wait times and lack of protocols at A&E. CONCLUSIONS: Our study highlights behavioural symptoms as being a potentially underemphasised sign of deterioration and identifies a number of barriers to parents accessing support when they are concerned. It is important that parents are encouraged to seek advice at the earliest opportunity and that those health professionals at the front line have access to the information they need in order to respond in an appropriate and timely way. A role for home monitoring was also noted as potentially useful in identifying at risk children who appear clinically well.

Unexpected deaths and unplanned re-admissions in infants discharged home after cardiac surgery: a systematic review of potential risk factors.

BACKGROUND: Babies with CHDs are a particularly vulnerable population with significant mortality in their 1st year. Although most deaths occur in the hospital within the early postoperative period, around one-fifth of postoperative deaths in the 1st year of life may occur after hospital discharge in infants who have undergone apparently successful cardiac surgery. Aim To systematically review the published literature and identify risk factors for adverse outcomes, specifically deaths and unplanned re-admissions, following hospital discharge after infant surgery for life-threatening CHDs. METHODS: A systematic search was conducted in MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Knowledge, and PsycINFO electronic databases, supplemented by manual searching of conference abstracts. RESULTS: A total of 15 studies were eligible for inclusion. Almost exclusively, studies were conducted in single US centres and focussed on children with complex single ventricle diagnoses. A wide range of risk factors were evaluated, and those more frequently identified as having a significant association with higher mortality or unplanned re-admission risk were non-Caucasian ethnicity, lower socio-economic status, co-morbid conditions, age at surgery, operative complexity and procedure type, and post-operative feeding difficulties. CONCLUSIONS: Studies investigating risk factors for adverse outcomes post-discharge following diverse congenital heart operations in infants are lacking. Further research is needed to systematically identify higher risk groups, and to develop interventions targeted at supporting the most vulnerable infants within an integrated primary and secondary care pathway.

Modelling survival and mortality risk to 15 years of age for a national cohort of children with serious congenital heart defects diagnosed in infancy.

BACKGROUND: Congenital heart defects (CHDs) are a significant cause of death in infancy. Although contemporary management ensures that 80% of affected children reach adulthood, post-infant mortality and factors associated with death during childhood are not well-characterised. Using data from a UK-wide multicentre birth cohort of children with serious CHDs, we observed survival and investigated independent predictors of mortality up to age 15 years. METHODS: Data were extracted retrospectively from hospital records and death certificates of 3,897 children (57% boys) in a prospectively identified cohort, born 1992-1995 with CHDs requiring intervention or resulting in death before age one year. A discrete-time survival model accounted for time-varying predictors; hazards ratios were estimated for mortality. Incomplete data were addressed through multilevel multiple imputation. FINDINGS: By age 15 years, 932 children had died; 144 died without any procedure. Survival to one year was 79.8% (95% confidence intervals [CI] 78.5, 81.1%) and to 15 years was 71.7% (63.9, 73.4%), with variation by cardiac diagnosis. Importantly, 20% of cohort deaths occurred after age one year. Models using imputed data (including all children from birth) demonstrated higher mortality risk as independently associated with cardiac diagnosis, female sex, preterm birth, having additional cardiac defects or non-cardiac malformations. In models excluding children who had no procedure, additional predictors of higher mortality were younger age at first procedure, lower weight or height, longer cardiopulmonary bypass or circulatory arrest duration, and peri-procedural complications; non-cardiac malformations were no longer significant. INTERPRETATION: We confirm the high mortality risk associated with CHDs in the first year of life and demonstrate an important persisting risk of death throughout childhood. Late mortality may be underestimated by procedure-based audit focusing on shorter-term surgical outcomes. National monitoring systems should emphasise the importance of routinely capturing longer-term survival and exploring the mechanisms of mortality risk in children with serious CHDs.

Patient-reported quality of life outcomes for children with serious congenital heart defects.

OBJECTIVE: To compare patient-reported, health-related quality of life (QoL) for children with serious congenital heart defects (CHDs) and unaffected classmates and to investigate the demographic and clinical factors influencing QoL. DESIGN: Retrospective cohort study. SETTING: UK National Health Service. PATIENTS: UK-wide cohort of children with serious CHDs aged 10-14 years requiring cardiac intervention in the first year of life in one of 17 UK paediatric cardiac surgical centres operating during 1992-1995. A comparison group of classmates of similar age and sex was recruited. MAIN OUTCOME MEASURES: Child self-report of health-related QoL scores (Pediatric Quality of Life Inventory, PedsQL) and parental report of schooling and social activities. RESULTS: Questionnaires were completed by 477 children with CHDs (56% boys; mean age 12.1 (SD 1.0) years) and 464 classmates (55%; 12.0 (SD 1.1) years). Children with CHDs rated QoL significantly lower than classmates (CHDs: median 78.3 (IQR 65.0-88.6); classmates: 88.0 (80.2-94.6)) and scored lower on physical (CHDs: 84.4; classmates: 93.8; difference 9.4 (7.8 to 10.9)) and psychosocial functioning subscales (CHDs: 76.7, classmates: 85.0; difference 8.3 (6.0 to 10.6)). Cardiac interventions, school absence, regular medications and non-cardiac comorbidities were independently associated with reduced QoL. Participation in sport positively influenced QoL and was associated with higher psychosocial functioning scores. CONCLUSIONS: Children with serious CHDs experience lower QoL than unaffected classmates. This appears related to the burden of clinical intervention rather than underlying cardiac diagnosis. Participation in sports activities is positively associated with increased emotional well-being. Child self-report measures of QoL would be a valuable addition to clinical outcome audit in this age group.

Late clinical presentation of congenital adrenal hyperplasia in older children: findings from national paediatric surveillance.

OBJECTIVES: To describe the clinical presentation and sequelae, including salt-wasting crises of newly-diagnosed congenital adrenal hyperplasia (CAH) in children aged over 1 year in a contemporary population without screening. To appraise the potential benefit of newborn screening for late-presenting CAH. DESIGN: Active national surveillance undertaken in Great Britain prospectively from 2007-2009 through the British Paediatric Surveillance Unit. SETTING: England, Wales and Scotland. PATIENTS: Children first presenting aged 1-15 years with clinical features of CAH and elevated 17-hydroxyprogesterone. RESULTS: Fifty-eight children (26 [45%] boys) aged 1-15 years were reported; 50 (86%) had 21-hydroxylase deficiency. Diagnosis was precipitated by secondary sexual characteristics (n=38 [66%]; median age 5.8 [IQR] 4.8, 7.6) years, genital virilisation (8 girls; 3.2 [IQR 1.3, 7.3] years) or an affected sibling (n=8; 10.0 [IQR 7.4, 13.3] years). At least 33 (57%) children had advanced bone age and 13 (30%) were obese (body mass index ≥ 95 th centile). No child had experienced a salt-wasting crisis. CONCLUSIONS: In Great Britain, 30 children aged 1-15 years present annually for the first time with CAH. Older children frequently manifest prematurely advanced epiphyseal and pubertal maturation and genital virilisation, which are often irreversible and likely to have long-lasting consequences for adult health and wellbeing. Almost one-third of affected children are obese before commencing steroid therapy. Newborn screening offers the potential to avoid serious clinical manifestations in older children with unrecognised CAH; however, it may also detect some children who would otherwise remain asymptomatic and for whom the benefit from treatment is uncertain.

Mortality with congenital heart defects in England and Wales, 1959-2009: exploring technological change through period and birth cohort analysis.

BACKGROUND: Technological advances in surgery, intensive care and medical support have led to substantial decrease in mortality for children with congenital heart defects (CHDs) over the last 50 years. METHODS: Using routinely-collected mortality and population data for England and Wales from 1959 to 2009, the authors investigated age, period and birth cohort trends in child mortality attributable to CHDs. RESULTS: The total number of deaths with CHDs at all ages between 1959 and 2009 was 61 903 (33 929 (55%) males). Absolute numbers of CHD-related deaths in children (under age 15 years) fell from 1460 in 1959 to 154 in 2009. Infants (aged under 1 year) comprised over 60% of all deaths due to CHD during the 5-year period 1959-1963, but this fell to 22% by 2004-2008. Age-standardised death rates have declined for both sexes but, despite narrowing sex differences, males continue to have higher death rates. Successive birth cohorts have experienced improved death rates in the first year of life; however, declining mortality across all age-groups has only been observed for birth cohorts originating after 1989. Poisson regression modelling predicts continuing generational decline in mortality. CONCLUSIONS: Death rates attributable to CHDs have fallen dramatically with advances in paediatric cardiac surgery and intensive care, largely due to decreased mortality in infants aged under 1 year. Initially, mortality in later childhood rose as infant deaths fell, suggesting death was delayed beyond infancy. Children born within the last 20 years experienced lower mortality throughout childhood.

Incidence and clinical features of congenital adrenal hyperplasia in Great Britain.

OBJECTIVES: To estimate the incidence of clinically diagnosed congenital adrenal hyperplasia (CAH), clinical features and age at first presentation. To assess the potential benefit of newborn screening for CAH. DESIGN: Active surveillance through the British Paediatric Surveillance Unit of all children aged under 16 years with newly diagnosed CAH, undertaken prospectively between August 2007 and August 2009. Twelve laboratories testing for CAH reported new diagnoses between August 2007 and January 2009. Reporting clinicians completed clinical questionnaires. SETTING: England, Wales and Scotland. RESULTS: 144 children with CAH were reported, of whom 132 (92%) had 21-hydroxylase deficiency. Thirty-six (25%) children were Asian and 62 (43%; 95% CI 35% to 51%) were boys. Incidence of new diagnoses in children ≤ 16 years was 0.60 (95% CI 0.50 to 0.71) per 100,000. Eighty-six (59%; 36 boys) children were diagnosed in the first year of life (estimated birth prevalence 5.48 (95% CI 4.42 to 6.81) per 100,000), most (77; 89%) of whom presented in the first month of life. Virilised genitalia were found in three-quarters of girls. Twenty-seven newborns first presented with salt-wasting crises, of whom 18 (67%; 16 boys) presented on or after 14 days of age. CONCLUSIONS: Approximately one child in every 18 000 born in Great Britain has CAH. Similar numbers of boys and girls present clinically in the first year of life, but boys present with more severe manifestations, such as salt-wasting crises. Around 70% of newborns who first present with salt-wasting crisis would be detected earlier through newborn screening.

Surveillance of rare diseases: a public health evaluation of the British Paediatric Surveillance Unit.

BACKGROUND: The British Paediatric Surveillance Unit (BPSU), a joint undertaking between the Royal College of Paediatrics and Child Health, Institute of Child Health and Health Protection Agency, undertakes nationwide surveillance of rare paediatric disorders. In 2007-09, formal evaluation to examine its effectiveness commenced. METHODS: Centres of Disease Control guidelines for appraising public health surveillance systems were applied. Data sources included BPSU databases, published and unpublished reports. Questionnaires were sent to 600 participating paediatricians and 27 researchers. Half of the questionnaires were administered online to assess the feasibility of electronic reporting. RESULTS: Three thousand UK paediatricians report monthly to the BPSU (94% return) and eighty BPSU studies have been published. These studies have influenced immunization and screening policy, altered clinical practice and informed health service configuration. Surveillance operations are simple, stable, representative and responsive to changing demands. Returns from the paediatricians' survey were 75%; investigators 89%. Paediatricians valued the BPSU and did not find participation burdensome. Most supported online questionnaires (56%) but not monthly electronic reporting (35%). CONCLUSIONS: Evaluation demonstrated the effectiveness of the BPSU as a valuable resource for clinicians and policy-makers. Opportunities identified for future development include secure online reporting, improved responsiveness to urgent health threats and promoting public involvement.