Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide.

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations.

Twenty-year trends in diagnosis of life-threatening neonatal cardiovascular malformations.

BACKGROUND: Infants with cardiovascular malformations are usually asymptomatic at birth. Earlier diagnosis is likely to improve outcome. OBJECTIVE: To examine trends in the diagnosis of potentially life-threatening cardiovascular malformations. METHODS: Ascertainment of all cardiovascular malformations diagnosed in infancy in the resident population of one English health region between 1985 and 2004. Infants with life-threatening cardiovascular malformations were all with hypoplastic left heart, pulmonary atresia with intact ventricular septum, transposition of the great arteries or interruption of the aortic arch; and those dying or undergoing operation within 28 days with coarctation of the aorta, aortic stenosis, pulmonary stenosis, tetralogy of Fallot, pulmonary atresia with ventricular septal defect or total anomalous pulmonary venous connection. RESULTS: Cardiovascular malformations were diagnosed in infancy in 4444 of 690,215 live births (6.4 per 1000) and were potentially life threatening in 669 (15%). Overall, 55 (8%) were recognised prenatally, 416 (62%) postnatally before discharge from hospital, 168 (25%) in living infants after discharge and 30 (5%) after death. Antenatal diagnoses increased from 0 to around 20% and no case was first diagnosed after death in the past 6 years. However, the proportion going home without a diagnosis remains around 25%. Malformations most likely to remain undiagnosed at discharge were coarctation of the aorta (54%), interruption of the aortic arch (44%), aortic valve stenosis (40%) and total anomalous pulmonary venous connection (37%). CONCLUSIONS: One in three infants with a potentially life-threatening cardiovascular malformation left hospital undiagnosed. Better early diagnosis is likely to be achieved by further improvements in antenatal diagnosis and more widespread use of routine pulse oximetry.

Newborn screening for congenital heart defects: a systematic review and cost-effectiveness analysis.

OBJECTIVES: To provide evidence to inform policy decisions about the most appropriate newborn screening strategy for congenital heart defects, identifying priorities for future research that might reduce important uncertainties in the evidence base for such decisions. DATA SOURCES: Electronic databases. Groups of parents and health professionals. REVIEW METHODS: A systematic review of the published medical literature concerning outcomes for children with congenital heart defects was carried out. A decision analytic model was developed to assess the cost-effectiveness of alternative screening strategies for congenital heart defects relevant to the UK. A further study was then carried out using a self-administered anonymous questionnaire to explore the perspectives of parents and health professionals towards the quality of life of children with congenital heart defects. The findings from a structured review of the medical literature regarding parental experiences were linked with those from a focus group of parents of children with congenital heart defects. RESULTS: Current newborn screening policy comprises a clinical examination at birth and 6 weeks, with specific cardiac investigations for specified high-risk children. Routine data are lacking, but under half of affected babies, not previously identified antenatally or because of symptoms, are identified by current newborn screening. There is evidence that screen-positive infants do not receive timely management. Pulse oximetry and echocardiography, in addition to clinical examination, are alternative newborn screening strategies but their cost-effectiveness has not been adequately evaluated in a UK setting. In a population of 100,000 live-born infants, the model predicts 121 infants with life-threatening congenital heart defects undiagnosed at screening, of whom 82 (68%) and 83 (69%) are detected by pulse oximetry and screening echocardiography, respectively, but only 39 (32%) by clinical examination alone. Of these, 71, 71 and 34, respectively, receive a timely diagnosis. The model predicts 46 (0.5%) false-positive screening diagnoses per 100,000 infants with clinical examination, 1168 (1.3%) with pulse oximetry and 4857 (5.4%) with screening echocardiography. The latter includes infants with clinically non-significant defects. Total programme costs are predicted of pound 300,000 for clinical examination, pound 480,000 for pulse oximetry and pound 3.54 million for screening echocardiography. The additional cost per additional timely diagnosis of life-threatening congenital heart defects ranges from pound 4900 for pulse oximetry to pound 4.5 million for screening echocardiography. Including clinically significant congenital heart defects gives an additional cost per additional diagnosis of pound 1500 for pulse oximetry and pound 36,000 for screening echocardiography. Key determinants for cost-effectiveness are detection rates for pulse oximetry and screening echocardiography. Parents and health professionals place similar values on the quality of life outcomes of children with congenital heart defects and both are more averse to neurological than to cardiac disability. Adverse psychosocial effects for parents are focused around poor management and/or false test results. CONCLUSIONS: Early detection through newborn screening potentially can improve the outcome of congenital heart defects; however the current programme performs poorly, and lacks monitoring of quality assurance, performance management and longer term outcomes. Pulse oximetry is a promising alternative newborn screening strategy but further evaluation is needed to obtain more precise estimates of test performance and to inform optimal timing, diagnostic and management strategies. Although screening echocardiography is associated with the highest detection rate, it is the most costly strategy and has a 5% false-positive rate. Improving antenatal detection of congenital heart defects increases the cost per timely postnatal diagnosis afforded by any newborn screening strategy but does not alter the relative effects of the strategies. An improvement of timely management of screen positive infants is essential. Further research is required to refine the detection rate and other aspects of pulse oximetry, to evaluate antenatal screening strategies more directly, and to investigate the psychosocial effects of newborn screening for congenital heart defects.

Guidelines and adenosine dosing in supraventricular tachycardia.

This retrospective review of present practice of administration of adenosine by paediatricians shows that current guidelines recommend starting doses that are effective in only 9% of infants and children.

A case control study to examine the pharmacological factors underlying ventricular septal defects in the North of England.

BACKGROUND: Amphetamine exposure is associated with congenital cardiac abnormalities in animals. We previously reported an association between recreational use of 2,4-methylenedioxymethamphetamine (ecstasy, MDMA) and ventricular septal defect in babies born to users. We have carried out a case control study to investigate risks in the occurrence of ventricular septal defect in a cohort of babies born in the North East of England. METHODS: Cases were identified from paediatric cardiology units in Newcastle upon Tyne and Leeds, and controls were recruited from the mothers of babies born in the same hospital as the index case. Research nurses carried out interviews using a structured questionnaire. RESULTS: A total of 296 case control pairs were studied. There was insufficient exposure to ecstasy to test the primary hypothesis. Increased risk of ventricular septal defect was found to be associated with consumption of cough and cold remedies [pre-conception OR 2.2, 95% CI 1.41, 3.51; pregnancy OR 5.1, 95% CI 2.56, 11.27; exposure in either OR 2.83, 95% CI 1.85, 4.45; P<0.005] and in the case of non-steroidals for exposures in pregnancy (OR 4.2, 95% CI 1.54, 14.26; P<0.005). CONCLUSIONS: These findings suggest that ventricular septal defect is associated with consuming the medications identified. They are also compatible with the hypothesis that sympathomimetics (pseudoephedrine, phenylephrine and phenylpropanolamine) present in cough mixtures cause the increased risk, and with our original hypothesis that sympathomimetics and amphetamines are potentially cardiotoxic in utero.

Variability of four limb blood pressure in normal neonates.

AIMS: To assess the variation in blood pressure (BP) between limbs in normal neonates. To assess whether comparison of arm and leg BP in neonates is reproducible enough to allow the difference to raise suspicion of coarctation of the aorta. METHODS: Infants recruited from the postnatal wards and the postnatal murmur clinic underwent echocardiography and BP measurement in each limb using a Dinamap Compact T 482210. The method of BP measurement was guided by a telephone survey of 40 UK neonatal units. RESULTS: Forty healthy neonates underwent echocardiography and all had a normal aortic arch. BP was measured in 39. In three, BP in the arms was 20 mm Hg higher than in the legs. This gave a specificity of comparison of the upper and lower limb BPs of 92 (36/39) or a false positive rate of 8% (3/39). The standard deviation in BPs was 15.7 mm Hg between arms, 14.5 mm Hg between legs, and 11 mm Hg when the nearest arm and leg were compared. CONCLUSIONS: With current measurement techniques, normal neonates may have a wide variation in BP between limbs. A difference of 20 mm Hg in isolation is more likely to be due to random variability in measurement than to coarctation of the aorta. If coarctation of the aorta is suspected, it can only be excluded or confirmed by echocardiography.

Cardiovascular malformations in infants of diabetic mothers.

OBJECTIVE: To compare the prevalence at live birth and the spectrum of cardiovascular malformations in infants born to diabetic mothers with pre-existing diabetes with that in infants of non-diabetic mothers. DESIGN: Prospective study of all live births in the resident population of one health region, with recording of details of the outcome of all pregnancies of women with pre-existing diabetes and of all live born babies with cardiovascular malformations. RESULTS: In the six years 1995-2000 there were 192 618 live births in the study population. Cardiovascular malformations were confirmed in 22 of 609 (3.6%) babies with diabetic mothers and in 1417 of 192 009 (0.74%) babies with non-diabetic mothers. The odds ratio for a cardiovascular malformation with maternal diabetes was 5.0 (95% confidence interval 3.3 to 7.8). Combination of these results with previous reports and comparison with the spectrum of cardiovascular malformations in infants of non-diabetic mothers shows a greater than threefold excess of transposition of the great arteries, truncus arteriosus, and tricuspid atresia. CONCLUSIONS: Pre-existing maternal diabetes is associated with a fivefold increase in risk of cardiovascular malformations. Transposition of the great arteries, truncus arteriosus, and tricuspid atresia are overrepresented to produce a substantial excess of these malformations.

The influence of congenital heart disease on survival of infants with oesophageal atresia.

OBJECTIVE: To examine the prevalence of congenital heart disease in babies with oesophageal atresia and its influence on outcome. DESIGN: Retrospective analysis. SETTING: The resident population of one health region. RESULTS: A total of 153 babies with oesophageal atresia were identified from 509 975 live births (0.30 per 1000); 26 (17%) had cardiac defects. Survival of babies with normal hearts was 97%, 97%, and 95% at one week, one month, and one year. Survival of babies with congenital heart disease was 85%, 85%, and 67% at one week, one month, and one year, but only one of ten deaths was the result of the congenital heart disease. The remaining deaths were due to other congenital malformations, respiratory disease, or chromosome abnormalities. CONCLUSIONS: There is a high prevalence of congenital heart disease in babies with oesophageal atresia. Congenital heart disease is associated with a higher mortality in oesophageal atresia but it is not the cause of it.

Survival with congenital heart disease and need for follow up in adult life.

OBJECTIVE: To predict the growth in demand for long term follow up of adults with congenital heart disease. DESIGN: Observed diagnoses of congenital heart disease in infancy and childhood were adjusted for observed infant survival, predicted further survival to age 16 years, underascertainment in older childhood, and predicted need for long term follow up. SETTING: The resident population of one health region in the UK. PATIENTS: All confirmed cardiovascular malformations diagnosed in 1985 to 1999 in children born in 1985 to 1994. RESULTS: 1942 cases of congenital heart disease were diagnosed in infancy in a population of 377 310 live births (5.2/1000). 1588 (82%) survived to 1 year and 1514 were predicted to survive to age 16. 605 further diagnoses were made in childhood-678 when adjusted for underascertainment. Thus, 2192 children were predicted to reach age 16, of whom 784 would require long term follow up in adult life. The adult population would comprise 28% complex, 54% significant, and 18% minor congenital heart disease. These figures predict the need for adult follow up of congenital heart disease of over 200 extra cases per 100 000 live births each year or over 1600 extra cases a year every year in the UK. CONCLUSIONS: The need for follow up of congenital heart disease in adult life is likely to grow linearly, with increasing complexity and increasing need for reinvestigation and reintervention with time. Appropriate provision should be made for adequate manpower, resources, and facilities for care of these patients.

Early diagnosis of congenital heart disease.

Routine examination of apparently healthy newborn babies detects less than half of those with congenital cardiac malformations because they are asymptomatic and without signs. More severe cardiac malformations are not detected more easily. A normal clinical examination does not exclude serious congenital cardiac malformation. Left heart obstruction is easily overlooked but often causes serious deterioration in less than 3 weeks. It is important to arrange early echocardiography of babies with signs and to consider cardiac malformation in a sick baby even if a previous routine examination was normal. All babies with Down syndrome should have early expert cardiological assessment.

Recommendations of the British Paediatric Cardiac Association for therapeutic cardiac catheterisation in congenital cardiac disease.

The aims of these recommendations are to improve the outcome for patients after, and to provide acceptable standards of practice of therapeutic cardiac catheterisation performed to treat congenital cardiac disease. The scope of the recommendations includes all interventional procedures, recognising that for some congenital malformations, surgical treatment is equally as effective as, or occasionally preferable to, interventional treatment. The limitations of the recommendations are that, at present, no data are available which compare the results of interventional treatment with surgery, and certainly none which evaluate the numbers and types of procedures that need to be performed for the maintenance of skills. Thus, there is a recognised need to collect comprehensive data with which these recommendations could be reviewed in the future, and re-written as evidence-based guidelines. Such a review will have to take into account the methods of collection of data, their effectiveness, and the latest developments in technology. The present recommendations should, therefore, be considered as consensus statements, and as describing accepted practice, which could be used as a basis for ensuring and improving the quality of future care.

Natural and unnatural history of pulmonary atresia.

OBJECTIVE: To investigate mortality, cause of death, survival, and quality of life in all types of cardiac malformation with congenital pulmonary atresia. DESIGN: Retrospective analysis. SETTING: The resident population of one health region with a single tertiary referral centre. PATIENTS: All babies with pulmonary atresia live born in 1980 to 1995. MAIN OUTCOME MEASURES: Anatomical classification, total mortality, cause of death, duration of survival, exercise ability. All cases were classified as pulmonary atresia with intact septum (PA-IVS), pulmonary atresia with ventricular septal defect (PA-VSD), or pulmonary atresia with complex cardiac malformation (complex pulmonary atresia). RESULTS: 129 cardiac malformations with congenital pulmonary atresia were identified from 601 635 live births (21.4/100 000): 29 had PA-IVS, 60 had PA-VSD, and 40 had complex pulmonary atresia. Total mortality was 72/129 (56%), with 15 deaths in the first week and 49 in the first year. There were 23 surgical deaths, 33 hospital deaths (not related to surgery), and 16 sudden deaths, 12 of which remained unexplained. The sudden death rate was 29/1000 patient years of follow up. Of the 57 survivors, 39% have exercise ability I or II and 61% III or IV. Definitive surgical repair produced better exercise ability. CONCLUSIONS: Early mortality is high in all types of pulmonary atresia, although survival has improved in recent years. Most children who have not undergone definitive repair have significant exercise limitation.

Sudden death in children and adolescents.

OBJECTIVE: To identify the incidence, causes, and characteristics of sudden death at age 1-20 years. DESIGN: A review of all deaths at age 1-20 years. Death certificates were obtained from the Office for National Statistics, and further information, where appropriate, from coroners, paediatricians, physicians, and pathologists. SETTING: The resident population of one English health region in 1985-1994. RESULTS: In a population of 806 500 children and adolescents aged 1-20 years there were 2523 deaths in 10 years. Medical causes accounted for 1017 deaths (40%); 1236 (49%) were unnatural, and 270 (11%) were sudden. These sudden deaths comprised 142 with a previous diagnosis, the commonest being epilepsy 49 (34%), cardiovascular disease 33 (23%), and asthma 30 (21%); 87 attributed to a cause discovered at necropsy, which was respiratory infection in 32 (37%), other infections in 17 (20%), and unsuspected cardiovascular abnormalities in 26 (30%); 41 remained unexplained. CONCLUSIONS: Half of all sudden deaths in children or adolescents were attributed to an already diagnosed condition. Abnormalities identified at necropsy accounted for one third of sudden deaths. Undiagnosed hypertrophic cardiomyopathy caused less than one death per million person years in the population aged 1-20 years. Unexplained sudden death, which may be caused by primary cardiac arrhythmia, is probably about 10 times more common.

Temporal variability in birth prevalence of cardiovascular malformations.

OBJECTIVE: To investigate changes over time in the prevalence at live birth of cardiovascular malformations and to compare "anatomical" and "physiological" diagnostic hierarchies within a population. DESIGN: Retrospective and prospective ascertainment of all congenital cardiovascular malformations diagnosed in infancy. SETTING: The resident population of one health region. PATIENTS: All infants live born from 1985 to 1997 with cardiovascular malformations confirmed by echocardiography, cardiac catheterisation, surgery or autopsy. MAIN OUTCOME MEASURES: Year to year variation in prevalence of individual malformations and of "complex", "significant", and "minor" groups. RESULTS: 2671 babies with cardiovascular malformations were confirmed in a denominator population of 477 960 live births (5.6 per 1000). There was no change over 13 years in the birth prevalence of "complex" or "significant" defects, but a highly significant increase in "minor" defects (p < 0.0001), mainly small ventricular septal defects. Termination of pregnancy increased from no cases in 1985 to 16 in 1997 with no demonstrable effect on live born babies with heart defects. A one dimensional "anatomical" diagnostic hierarchy led to under ascertainment of pulmonary atresia by 27%, coarctation of the aorta by 39%, and interruption of the aorta by 100%. CONCLUSIONS: The apparent increase in live born cardiovascular malformations results mainly from improved diagnosis of minor defects. There has been no change over time in birth prevalence of more serious defects. Spontaneous year to year variation in numbers will make it difficult to ascribe any short term changes to any particular intervention. A two dimensional diagnostic hierarchy is offered as a standard.