EUGLOREH project




9.1. Newborns and perinatal health.

9.1.2. Congenital Malformations

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9.1.2. Congenital Malformations Introduction


Collectively, congenital anomalies represent an important public health issue in terms of

·          impact on the quality of life of affected children and adults and their families

·          contribution to foetal and infant mortality, both in terms of loss of potential years of life and emotional costs to the family

·          provision, quality and financial cost of medical, social and educational services to improve the participation and quality of life of affected individuals and their families

·          provision, quality and financial cost of prenatal screening in the population and its psychological cost to pregnant women.


Congenital (“present from birth”) anomalies which involve structural malformations diagnosed prenatally, at birth or within the first year of life are the focus of epidemiological surveillance through congenital anomaly registers, and the focus of this section. Many registers also include cases diagnosed later in infancy or childhood. “Majorcongenital anomalies are those with serious medical or functional consequences; some of these may also be lethal. Many affected pregnancies are spontaneously aborted, often in the first trimester (these are not included in the figures). Many rare genetic disorders are diagnosed later in childhood and these are discussed elsewhere in this Report (see Chapter 5). Metabolic diseases diagnosed through neonatal screening may be included in congenital anomaly registers, but are not included here. Some behavioural and neurological conditions also have a congenital origin but are not diagnosed or confirmed until after infancy.


The development of the organs occurs in the first trimester of pregnancy (brain development continues later), including the first six weeks before many pregnancies have been recognized. In terms of preventive action regarding environmental risk factors, this places a great importance on directing promotion of a healthy environment and protection from adverse exposures to the entire community, or women of childbearing age, rather than pregnant women only, and on developing an effective system of preconceptional care. Moreover, protecting the health of adults and children is not necessarily enough to protect the health of the foetus; thus, foetuses and pregnant women must have a special status in public health policy.


Within Europe, there are geographic and socioeconomic inequalities in the prevalence of congenital anomalies. These are now of two main typesvariation in the prevalence of risk factors affecting total prevalence, and additional variation in prenatal detection and termination of pregnancy rates affecting live-birth prevalence. As well as these inequalities, congenital anomalies are often ignored in the wider public health agenda due to their individual rarity. Thus, there are inequalities between congenital anomalies and more common diseases for what concerns access to preventive treatment and rehabilitative research, policy and services. Data sources


EUROCAT (European Surveillance of Congenital Anomalies) is the principal source of information on the epidemiology of congenital anomalies in Europe. EUROCAT is a network of population-based congenital anomaly registers, using multiple sources of information to collect high quality data (both in terms of case ascertainment and diagnostic detail). Registries cover affected livebirths, stillbirths and fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly (TOPFA) following prenatal diagnosis (whether before or after 20 weeks gestation). Registries may cover only diagnoses made prenatally and in infancy, or extend registration to new diagnoses made during childhood.


EUROCAT started in 1979. There are currently 38 registers in 20 countries (see Table, covering in total 1.4 million births per year. Annual birth coverage is 23.4% of births of the EU-15 countries, 35.0% of the EU-NMS countries and 25.6% of EU-27. In addition to the EU-27 countries, Norway, Switzerland, and Croatia participate in EUROCAT (Table 1), as well as the Ukraine since 2007. The only EU countries with established registers of congenital anomalies not participating in EUROCAT are Czech Republic and Slovak Republic, both of which are working towards full membership in 2009.


Table Coverage of the European Population by EUROCAT Full or Associate Member Registries


Maintaining high quality data usually requires a limit to the total size of the population to be covered by a register, thus the preference in larger nations for regional rather than national registries, networked nationally and at a European level by EUROCAT. The proportion of national births covered by registers in each country is shown in Table 1, ranging among those countries participating from 3% (Germany) to 100% (Norway, Sweden, Finland, Malta, Hungary). Although complete coverage of the European population may be an ideal, this should not replace deeper investment of resources in areas already coveredexcellent data from one quarter of Europe will give us more meaningful information than poor data from all of Europe.


Collaboration of registers within a European network has greatly improved data comparability between countries. A standard set of minor or poorly defined anomalies are excluded (EUROCAT, 2005a), although it can be difficult to apply the criteria precisely as there is not always enough information in health service records to distinguish between different severities of the same anomaly. Data quality can also be influenced by health service factors (e.g. the proportion of stillbirths with postmortem carried out, or the proportion of multiply malformed cases where a karyotype has been performed ) and registry factors (e.g. specificity of coding and completeness of ascertainment of TOPFA or postneonatally diagnosed anomalies among livebirths).


Other sources of epidemiological information about congenital anomalies in Europe include the following:


a) The WHO HFA database contains data on infant mortality due to congenital anomalies. Their data can be seen in Chapter 4.1. Such infant mortality data from infant death registrations is dependent on the quality of death certification, but is particularly useful for countries with no current congenital anomaly registers. The data are limited with regard to type of congenital anomaly. Differences between countries in infant mortality due to congenital anomaly can reflect one or more of the following factors: a) the risk of pregnancies being affected by a congenital anomaly in that country b) the level of investigation by autopsy in case of infant death c) the likelihood that an affected pregnancy will be prenatally diagnosed leading to termination of pregnancy d) the quality of treatment for congenital anomalies (e.g. surgery for congenital heart disease) and e) practices regarding registration of a baby as a stillbirth or livebirth where the congenital anomaly is so severe that the baby is not viable.   


b) Hospital Episode or Discharge Data. These data are potentially particularly useful for major congenital anomalies where livebirth is the most common outcome, infant survival is high, and surgery is routinely indicated e.g. hypospadias, gastroschisis and orofacial clefts. Such data usually do not include terminations of pregnancy following prenatal diagnosis (TOPFA), or stillbirths, and usually do not cover health service episodes on an outpatient basis. In some countries, private hospitals do not make their data available, or hospitals do not use a standard coding system. It can be difficult to link several episodes for the same individual together, particularly across years. Many congenital anomaly registers nevertheless now use HE/HD data as one of their sources of information.


c) International Clearinghouse for Birth Defect Surveillance and Research ( Many of the EUROCAT registers belong to ICBDSR also, as well two EU non-EUROCAT registers in Czech Republic and Slovak Republic. Data description and analysis


Prevalence of congenital anomalies


EUROCAT records a total prevalence of major congenital anomalies of 23.8 per 1 000 births for 2000-2004 (Table Total prevalence includes live-births, stillbirths, and terminations of pregnancy due to foetal anomaly (TOPFA) following prenatal diagnosis. The live-birth prevalence is 19.9 per 1 000 births.


Table Prevalence per 1 000 births of EUROCAT congenital anomaly subgroups 2000-2004


The average prevalence of different subgroups in Europe is shown in Table The prevalence of chromosomal anomalies is 3.4 per 1 000 births. In the data shown in Table, these cases have been excluded from other subgroups (i.e. a child with an abdominal wall defect and a chromosomal anomaly is recorded only under chromosomal anomalies). Congenital heart disease is the most common subgroup, at 6.4 per 1 000 births, followed by limb defects (3.6 per 1 000), urinary system (2.8 per 1 000) and nervous system defects (2.0 per 1 000). EUROCAT updates each year prevalence figures on 95 subgroups of congenital anomaly, available on its website (EUROCAT, 2007). Those with a total prevalence above 0.1 per 1 000 births are shown in Table


There has been a slight increase in recent years in the overall prevalence of congenital anomalies (followed by the usual dip in the most recent years due to late case registration). This increase is seen to be in part due to an increase in the prevalence of congenital heart disease (Figure, but an overall improvement in data quality and increases in risk factors may represent other possible partial explanations. Despite the steady rise in the overall prevalence of terminations of pregnancy for foetal anomaly (TOPFA), live-birth prevalence has increased.


Figure Trends in the total and live birth prevalence per 1 000 births of All Anomalies and Cardiac Anomalies, 1992-2004.


Perinatal mortality and termination of pregnancy.


Congenital anomalies are an important contributor to perinatal mortality. The overall recorded rate of stillbirths with congenital anomaly is 0.43 per 1 000 births, and deaths in the first week 0.55 per 1 000 births, giving a total perinatal mortality rate associated to congenital anomaly of 0.99 per 1 000 births (Table The main congenital anomaly subgroups contributing to perinatal mortality are congenital heart disease (23% of perinatal deaths with anomaly), nervous system anomalies (19% of perinatal deaths with anomaly), and chromosomal anomalies (21%) (Table


Chromosomal anomalies contribute more to stillbirths than first week deaths, while congenital heart disease contributes more to first week deaths than stillbirths. Nervous system defects contribute equally in both categories.


Table Perinatal mortality due to congenital anomalies, 2000-2004.


Perinatal mortality due to congenital anomaly varies per country (Table The lowest rates are recorded in Italy (0.2 per 1 000) but there is a known problem with recording of the cause of death for stillbirths and neonatal deaths, thus, this figure is probably considerably underascertained. The highest rates of perinatal mortality associated to congenital anomaly are recorded in Ireland (2.4 per 1 000) and Malta (2.3 per 1 000). These are both countries where TOPFA is illegal, and thus the perinatal mortality rate includes affected foetuses with a lethal or high mortality anomaly which would have been prenatally diagnosed in other countries leading to termination of pregnancy (and exclusion from mortality statistics).


Table Ratio of Terminations of Pregnancy for Foetal Anomaly following prenatal diagnosis (TOPFA) to all births, and Perinatal Mortality per 1 000 births, by country, 2000-2004


The ratio of TOPFA to births varies from 0 (Ireland and Malta) to 11.4 (France) per 1 000 births. Differing prenatal screening policies and practices, differences in uptake of screening and diagnosis due to cultural and organisational factors, and differences in TOPFA laws, influence the rate of TOPFA in the population, as discussed in detail elsewhere (EUROCAT, 2005b). In Poland, TOPFA is not encouraged, and done only in case of lethal anomaly. Some countries allow TOPFA at any gestational age (Austria, Belgium, Croatia, England & Wales, France, Germany). Others have an upper gestational age limit (Finland, Italy, Spain, Sweden, Switzerland, Czech Republic), while others have an upper gestational age limit but allow TOPFA for lethal anomalies beyond this limit (Netherlands, Norway, Portugal, Denmark).


Table shows TOPFA before and after 20 weeks gestation. The highest TOPFA ratio both before and after 20 weeks gestation is recorded in France (5.6 and 5.8 per 1 000 births respectively). Comparison between countries is complicated by different laws and practices regarding the recording of late terminations. Late TOPFA, where legal, may be recorded as stillbirth or as live-birth with neonatal death in some countries, and practice may also vary within countries.


TOPFA in most countries far outnumber stillbirths and neonatal deaths with congenital anomaly (Table Up to 0.8% (Switzerland) of foetuses die due to the presence of a congenital anomaly, whether as a TOPFA, stillbirth or neonatal death (but excluding spontaneous abortions), while 5 countries record a rate above 0.5% (Table The differences in total mortality (TOPFA plus perinatal) between countries probably mainly reflects the frequency with which TOPFA is carried out for non-lethal anomalies, but is also influenced by differences between countries in the prevalence of anomalies such as neural tube defects and Down syndrome and, as previously mentioned, the completeness of ascertainment of stillbirths, neonatal deaths and TOPFA.


Despite the important mortality consequences of congenital anomaly, the vast majority of cases of congenital anomaly across Europe are live born children who survive infancy, but who may have important medical, social or educational needs.


Congenital heart disease


The live birth prevalence of congenital heart disease is 6.1 per 1 000 births (Table, the largest group of congenital anomalies. This average figure is almost certainly under-ascertained, as registries collecting data on diagnoses after the neonatal period, and with full access to echography data report a prevalence of 8-10 per 1 000. The reported prevalence of congenital heart disease has been increasing (Figure, probably associated with greater referral of babies with a heart murmur for early echography. Severe heart defects are quite commonly prenatally diagnosed e.g. 39% of transposition of great vessels, and 73% of hypoplastic left heart (EUROCAT, 2007). TOPFA is not common for congenital heart disease, unless the heart defect is associated with other congenital anomalies or is lethal.


Down Syndrome


Risk of Down Syndrome is strongly associated with advanced maternal age. The increase in average maternal age in Europe is documented in Chapter 8. Figure shows the resulting increase in the total prevalence of Down Syndrome across Europe, to 2.2 per 1 000 births. Geographical variation in total prevalence corresponds to differences in maternal age profile between countries (Dolk et al, 2005a). For example, the registries in France and Switzerland, where the proportion of births to mothers over 35 is high, recorded a total prevalence (including LB, SB and TOPFA) of 3.4 per 1 000.


Figure Trends in the total and live birth prevalence per 1 000 births of Down Syndrome, 1992-2004


Prenatal screening for Down Syndrome has resulted in the prenatal detection of an increasing proportion of cases, among both older and younger mothers. This is associated to an increasing number of TOPFA. Overall in Europe, as represented by EUROCAT registers, the live birth prevalence of Down Syndrome has slightly declined (Figure to 1.0 per 1 000 births as the increase in TOPFA has outweighed the increase in maternal age. In 2000-2004, differences in policy and practice regarding prenatal screening and TOPFA, as well as maternal age differences, resulted in an over four-fold variation in live birth prevalence of Down Syndrome in Europe, ranging from 0.4 per 1 000 to 2.0 per 1 000 (the high rates being in Ireland and Malta).


Table Total and live birth prevalence per 1 000 births of Neural Tube Defects and Down syndrome per country, 2000-2004


Neural Tube Defects


In 1991, results of a randomised trial of peri-conceptional folic acid supplementation (MRC, 1991) established that raising folic acid status could be an effective measure to prevent neural tube defects (MRC, 1991), potentially more than halving the prevalence in Europe. The prevalence of NTD in Europe has, however, not declined over the subsequent decade (Figure This has represented a failure in preventive policy.


Figure Trends in the total and live birth prevalence per 1 000 births of Neural Tube Defects, 1992-2004


During the 1980s and previously, a strong decline in the rates of neural tube defects occurred in the British Isles, where rates have always traditionally been high (Busby et al, 2005a; Busby et al, 2005b; EUROCAT, 1991). During the 1990s, a shallow further decline was experienced in the British Isles (Busby et al, 2005a; Busby et al, 2005b). In the 2000-2004 period, the total prevalence in the British Isles was not higher than in many continental European areas. The most apparent geographic differences are represented by the lower prevalence experienced by Southern European countries, particularly Italy. Diet and/or genetic factors may explain this low prevalence.


In many countries, most cases of neural tube defects are prenatally diagnosed leading to TOPFA, while in others TOPFA is rare (see above). This has resulted in a very wide variation in live birth prevalence rates, from 0.1 per 1 000 in France and Spain to 1.0 per 1 000 in Poland (Table


Orofacial clefts


Cleft palate and cleft lip occur in 1.3 per 1 000 births in Europe (Table Cleft lip with or without palate is aetiologically different from cleft palate and accounts for nearly two thirds of cases. Geographic variation within Europe has consistently been shown for cleft lip with or without palate (EUROCAT, 2002a; EUROCAT, 2002b). Some Northern European countries have higher rates, for example Germany, the Netherlands and Denmark had rates between 1.3 and 1.6 per 1 000 for 2000-2004 (EUROCAT, 2007), while rates of 0.6 per 1 000 or below were recorded in Italy, Spain and Ireland.




Gastroschisis is an anomaly of the abdominal wall, with an average prevalence of 0.2 per 1 000 births in 2000-2004 (Table It is associated to low socioeconomic status and young maternal age (less than 20 years). A strong increase in gastroschisis prevalence has occurred both in Europe (Loane et al, 2007) and elsewhere in the world. Particularly high rates and increases have been experienced in Britain, only part of which is associated to high rates of teenage pregnancy (Loane et al, 2007). In Italy however, rates are lower and an increase in prevalence has not been experienced (Loane et al, 2007). The great majority of cases of gastroschisis are prenatally diagnosed (EUROCAT, 2007), but TOPFA is rare as the prognosis is good with surgery.




Hypospadias, where the urethral opening in boys is misplaced, has a prevalence of a minimum of 1.3 per 1 000 births (Table Individual registries report prevalence rates up to 2.5 per 1 000 in the period 2000-2004, and two areas report a higher prevalenceSicily at 3.0 per 1 000, and Malta at 4.2 per 1 000. It is difficult to produce a valid prevalence estimate unless data regarding surgery in the first three years of life are accessed (Dolk et al, 2004). Criteria may vary over the diagnosis of milder cases. Hypospadias is of particular current interest in relation to the possibility that it can be caused by exposure to endocrine disrupting chemicals. The high rate of hypospadias in Sicily is under investigation in relation to industrial and agricultural chemical exposures (Bianchi et al, 2006). Risk factors


For main risk factors see Table 9.1a.


Table 9.1a. Main risk factors for newborns and perinatal health



High maternal age at delivery.  Maternal demographic characteristics affect rates of perinatal mortality and morbidity (Maher and Macfarlane, 2004). Older mothers and nulliparas both face increased risks of stillbirth (Canterino et al, 2004; Raymond et al, 1994; Reddy et al, 2006). Studies report higher rates of antepartum, intrapartum and neonatal complications including pregnancy induced hypertension, preterm labor, caesarean births and neonatal intensive care unit admissions in older women (Clearly-Goldman et al, 2005; Luke and Brown, 2007a; Prysak et al, 1995). Parity is known to be associated with maternal and neonatal conditions such as hypertension, pre-eclampsia and fetal growth restriction. Parity also impacts the use of services and intervention during pregnancy, labour, and delivery (Bai et al, 2002; Cnattingius et al, 1993; Huang et al, 2000). Multiple pregnancies also carry a much higher fetal and neonatal mortality risk than singleton pregnancies (Kahn et al, 2003; Luke and Brown, 2007b; Magee 2004). This increased risk is mostly due to the higher preterm birth rate in multiple pregnancies (Ananth et al, 2005; Garite et al, 2004).  Figures 9.T1.1 and 9.T1.2. present data on the proportion of childbearing women in the EU who are aged under 20 years and 35 years and older. The relationship between maternal age and perinatal health outcomes is U-shaped and it is thus pertinent to compare the extremes of the age distribution. The risk of many adverse outcomes begins to increase at approximately 35 years of age. For younger mothers, the increased risk of perinatal mortality is  associated with social and health care factors, including lack on antenatal care (Olausson et al, 1997).


Figure 9.T1.1. Percentage of mothers under 20 in 2005 or most recent year


Figure 9.T1.2a. Percent of mothers 35 years and older in EU15 and Norway


Figure 9.T1.2b. Percent of mothers 35 years and older in new members States


Differences between the new and old member States are also apparent with respect to childbearing at older ages. There is a trend towards later childbearing in the 15 old member States, while this trend is much less evident in the new member States. Although many fewer women bear children late in life in the new member states, there is a large variation in both groups.


Smoking during pregnancy. The harmful effects of smoking on perinatal outcomes, in particular their birthweight and fetal mortality, are well documented in the scientific literature (Stillman et al, 1986; Castles et al, 1999; Cnattingius, 2004). These effects concern not only the perinatal period but also the infant’s long-term development. Smoking cessation may be the most effective intervention to improve both short- and long-term outcome for mothers and children and is an indicator of effective antenatal preventive health services. Finally, perinatal health outcomes are linked to social factors (Kaminski et al, 2000; Kramer et al, 2000b). Mortality and morbidity rates are higher among socially disadvantaged population groups, defined by educational status or parental occupation as well as neighbourhood deprivation scores. The rate of smoking among women of childbearing age varies across Europe, as Figure 9.1c illustrates. This information is not sufficient for monitoring the impact of smoking on perinatal outcomes, however, because many women stop smoking during pregnancy, as shown by the data from the EUROPERISTAT project on smoking during pregnancy. In the countries that could provide data, the proportion of women smoking during pregnancy varies from under 10% to almost 25%.


Figure 9.T1.3. Rates of Smoking Among all Women 25-34 vs Women During 3rd Trimester of Pregnancy


Drinking alcohol during pregnancy. Prenatal exposure to alcohol can be associated with a distinctive pattern of intellectual deficits  that become apparent later in childhood, including reductions in general intellectual functioning and academic skills as well as deficits in verbal learning, spatial memory and reasoning, reaction time, balance and other cognitive  and motor skills. There is a typical constellation of facial features and developmental delay and learning disability, and diagnosis is often made in early childhood rather than the first year of life. Special surveys are therefore needed to supplement congenital anomaly registers to determine numbers. Trends regarding alcohol drinking among young women in some countries, especially binge drinking, are of great concern. The effects of binge drinking on the fetus are largely unknown.


Congenital anomalies

In the majority of individual cases of congenital anomaly, the cause of the condition is unknown, but suspected to be an interaction of multiple environmental and genetic factors. For about 15% of cases, there is an identifiable chromosomal abnormality. Under 5% of cases can be attributed to a known single gene mutation, and under 5% to exposure to a single environmental teratogen (such as a drug taken during early pregnancy). Congenital anomalies are usually grouped under “medical genetics”, but the study of socioeconomic differences emphasizes the importance of environmental factors as causes, and these are at present the most amenable to prevention. Genetic susceptibility to environmental exposures is likely to vary importantly in the population.

Motherslow folic acid status in the peri-conceptional period is an established risk factor for neural tube defects (MRC, 1991) and probably a range of other anomalies (Botto et al, 2006). Other nutrients are most probably important. Particular attention has been paid also to vitamin B12, but generally a healthy diet is to be promoted for the prevention of congenital anomalies. Some dietary elements in excess, such as vitamin A, are teratogenic and high dose dietary supplements should not be promoted.


Some women are at higher risk of delivering babies with congenital anomaly due to chronic disease status. Diabetes and epilepsy are both associated with higher congenital anomaly risk (EUROCAT, 2004; Macintosh et al, 2006), and there is increasing evidence that obesity is also associated with a higher risk (Waller, 2007; EUROCAT, 2004).  In the case of epilepsy and diabetes, appropriate clinical care can reduce the risk, and there is still much to do in European countries to ensure that all women with these conditions receive the highest standard of care (Macintosh et al, 2006). The rising prevalence of obesity and diabetes are of concern in relation to the burden of congenital anomalies in the population


Rubella vaccination programmes for babies and/or young girls are an essential continuing measure to prevent congenital rubella syndrome, associated with deafness, eye defects and congenital heart disease. Monitoring of vaccination uptake rate, as well as attention to vaccination status of immigrants, is needed. Additional information systems are needed to capture all cases of congenital rubella syndrome, as some do not present with structural malformations diagnosed at birth.


The thalidomide (softenon) tragedy turned the world’s attention to the potential dangers of therapeutic drugs taken during early pregnancy. A number of drugs are now known to be teratogenic (Schaefer et al, 2001). Some of these are to be avoided during pregnancy, others are necessary (such as antiepileptic drugs) but a careful selection of the type of drug is needed to balance risks and benefits. Pharmacovigilance or postmarketing surveillance of drugs taken during pregnancy is not systematic, and it is possible that there are more drugs currently on the market which carry a risk of congenital anomaly when taken during pregnancy.


Assisted reproductive technology (ART) is being used with increasing frequency, with new techniques being developed over time (e.g. intracytoplasmic sperm injection) to add to the range already available. Currently, there is controversy about the level of risk of congenital anomaly associated with ART (Hansen et al, 2005). Particularly stringent data confidentiality in relation to ART makes this area particularly difficult to research.


Recreational drugs such as cocaine and solvent abuse also carry teratogenic risks. These are particularly difficult to study, as the drug use may be illegal and there are often many coexisting risk factors such as smoking, alcohol, poor nutrition and other risk factors associated with deprivation.


Older maternal age is a risk factor for chromosomal anomalies such as Down syndrome. Trends towards older age at childbearing are a complex social phenomenon, but are associated with poorer reproductive outcomes.


Our knowledge of the risks of exposure to chemicals, in the occupational, domestic and community environment is very incomplete (Cordier, 1992; Cordier et al, 1997; Dolk and Vrijheid, 2003; EUROCAT, 2004). To protect the fetus, we need to adopt a precautionary approach in reducing exposure particularly to byproducts of chlorination in drinking water, releases from waste disposal sites, endocrine disrupting chemicals, pesticides and solvents.


References cited in the section on congenital anomalies are listed in Chapter 9.1.2; references cited in the other paragraphs are listed in Chapter 9.1.1


 Control tools and policies


Primary Prevention


Primary prevention of congenital anomalies has not been an area of overall improvement in Europe, as evidenced by the lack of decline in prevalence since 1992.


Very little data is available about socioeconomic differences in congenital anomaly risk at European level, but the evidence to date generally suggests a substantial socioeconomic gradient (Vrijheid et al, 2000). Socio-economic deprivation may be associated to a number of environmental risk factors for congenital anomaly such as maternal nutrition, maternal infection, maternal drug exposure, occupational exposures and environmental pollution. Minority ethnic groups may experience higher risks due to deprivation, as well as some specific risks due to genetic or cultural factors. Measures to alleviate family poverty should help to reduce congenital anomaly risk, as well as specific measures should help to reduce known risk factors.


The potential to prevent neural tube defects, and possibly other anomalies also (Botto et al, 2006) by raising the folate status of women preconceptionally has not been fulfilled (Busby et al, 2005a; Busby et al, 2005b; Abramsky et al, 2007; EUROCAT, 2005) and is the major primary prevention opportunity. Experience has shown that peri-conceptional folic acid supplementation (i.e. recommending that women start taking supplements from before conception to the first trimester) is an unsuccessful population prevention strategy, since it is difficult to reach women preconceptionally, particularly if they do not plan their pregnancy. Socio-economic inequalities in neural tube defect prevalence are likely to be widening because of the uneven uptake of supplementation (De Walle and de Jong van den Berg, 2007). Some European countries are considering folic acid fortification of a staple food, such as flour, following the example of countries in North and South America, where such a strategy has demonstrated to be successful in preventing neural tube defects (De Wals et al, 2007). For example, this has recently been recommended by the British Food Standards Agency. Research has suggested a role for folic acid in protecting against cardiovascular disease, an additional argument for food fortification.


Secondary prevention


Developments in surgical treatments and neonatal intensive care have improved the outcome in terms of survival and long-term morbidity, for example for congenital heart defects, diaphragmatic hernia and gastroschisis. Developments have concerned both surgical procedures and organization of services within centres of excellence treating a sufficient volume of cases. However, information on improvement of outcomes over time tends to come from individual specialized clinics, rather than from populations experiencing the full range of care (Garne et al, 1999)


Prenatal diagnosis can help in the preparation for postnatal surgery, and there is suggestive evidence for example that survival of babies with Transposition of Great Arteries is improved if diagnosis is prenatal (Garne et al, 2007). This is a potentially important area for future developments.


Prenatal screening and diagnosis


The two main types of prenatal screening are biochemical screening and ultrasound scanning for structural malformations and “soft markers”. For Down Syndrome, a combined approach is increasingly used, but screening developments are unevenly diffused across Europe (EUROCAT, 2005). Screening policies vary between European countries (EUROCAT, 2005), and even countries with a similar policy may vary considerably in its implementation (EUROCAT, 2005).


An increasing proportion of affected pregnancies are prenatally diagnosed, with prenatal diagnosis rates are particularly high for some anomalies as presented in section Comparisons of the proportion of cases prenatally diagnosed, the average gestational age at diagnosis, diagnostic methods used and the proportion of cases resulting in termination of pregnancy have shown enormous variation between and within countries (Garne et al, 2004; Garne et al, 2005). Such variation may result from cultural differences underlying policy or individual uptake, from different interpretations of the scientific evidence in the design and implementation of screening, or from differences in organization, resources and systems in place to put changes in the health services into effect.


However, prenatal screening also presents to the healthcare system significant challenges in terms of increasingmedicalisation” of pregnancy, ethical questions, and giving women fully informed choices during pregnancy (Green et al, 2004). The option of pregnancy termination necessitates decisions on which anomalies justify this and how late in pregnancy. Pregnant women need to be given full information on the likely outcome for the anomaly which has been diagnosed, information which is only partially available for many rare anomalies. Inevitably, screening involves both false positives and false negatives, either of which can cause distress (Green et al, 2004).


Public health initiatives and policies


Congenital anomalies straddle different public health agendasrare diseases, peri-natal and child health, environmental health and major health determinants. Funding for EUROCAT network co-ordination currently comes from the European Commission’s Directorate General for Health and Consumer Protection, under its Public Health Programme, as a component of the European information system for rare diseases. The added value of European collaboration is particularly great for congenital anomalies, coming from the opportunity to pool data on rare anomalies and/or exposures, compare data between regions and countries, give a common response to European public health questions and share expertise and resources, including computing tools in an area which is generally under-resourced. Nevertheless, there are currently no plans for a sustainable European information systemdecisions on funding are short-term. Moreover, national and regional funding for registers is insufficient and short-term. In 2005, approximately 4 million euro was being spent on congenital anomaly registers by European Union countries. This equates to approximately 3 euro per birth in a registry area, or 1 euro per birth in the European Union.


The majority of congenital anomalies are rare (as defined by prevalence less than 5 per 10 000 in the EU), depending on how one delimits the clinical or disease entities. Most rare diseases (see Chapter 5.15) are congenital. The rare disease public health agenda, however, is mainly oriented towards genetic diseases and towards developing drug treatments for genetic diseases. Full attention should in addition be paid to reducing environmental risk factors for congenital anomalies, and to further development of non-drug treatments e.g. improved shunts for hydrocephalus.


Registries provide syntheses across a variety of data sources generated by the health system. There are many areas therefore where improvement in underlying health information systems across Europe would improve the quality or efficiency of registries: a) full coding of cause of death on stillbirth and infant death certificates b) the potential to link registry cases to death notifications in order to ascertain survival c) greater accuracy and accessibility of hospital episode data d) electronic access to birth registrations and medical records for diagnostic detail and core risk factor information e) full information on terminations of pregnancy following prenatal diagnosis f) linkage between different health information systems using unique patient identifiers. EUROCAT is working with EURO-PERISTAT towards better peri-natal information across Europe. Each registry follows national practice in relation to data confidentiality (Busby et al, 2005c). Registers in some countries are currently in a difficult position because of national interpretations of the European directive regarding patient consent. Although a reasonable requirement in theory, experience shows that while parental refusals are very rare, obtaining informed parental consent for registration is logistically difficult and requires resources much greater than those made available. The issue of consent and confidentiality is central to the creation of European public health information.


Little information is currently available on long term outcome for the child and family in terms of survival, morbidity, quality of life and participation. Longitudinal and retrospective follow-up studies of children with congenital anomalies need support. There has been no recent economic evaluation of the “burden” of congenital anomalies in Europe. Such an evaluation is needed to help give them their place in the public health agenda.


Risk factors for congenital anomalies amenable to primary prevention have been presented in Table 9.1a. The following would form elements of a preventive strategy:


a) Many majorlifestyledeterminants of ill health in the population, such as alcohol, recreational drugs, smoking and obesity, are also risk factors for congenital anomalies. Any strategy to tackle these health determinants should pay special attention to women in childbearing age, remembering that the harm is often done before the pregnancy is recognized and that the foetus may have special susceptibility.


b) Policies aimed at ensuringhealthy pregnancy” can pay attention to congenital anomalies as part of a range of outcomes including birth weight and neuro-developmental outcomes. However, for congenital anomalies a system of pre-conceptional care is needed, as reduction of risk factors needs to start very early or even before pregnancy.


c) Folic acid fortification of a staple food is the single most promising preventive strategy and may have other health benefits.


d) Public health measures should have regard to the “precautionary principle” as well as “evidence-based practice”, protecting the foetus despite scientific uncertainty, particularly with regard to complex exposures such as environmental pollution.


e) Public health measures aimed at migrants between European countries, or immigrants from non-European countries should pay special attention to women in childbearing age, for example in relation to poverty, rubella vaccination and specific genetic risks.


f) The phenomenon of older maternal age at childbirth and its reproductive risks needs to be understood at social level, in order to create an appropriate policy response.


g) Much greater investment is needed in systematic follow-up of medicinal drugs and assisted reproduction technologies, in relation to their potential to affect the foetus. The recent initiation of the EnCePP pharmacovigilance network by the European Medicines Agency is an important step forward. It should be a priority to ensure safe use of medicine during pregnancy.


h) More research should be funded into the environmental causes of congenital anomalies. Future developments


The last few decades have not seen increasing success in congenital anomaly prevention, as evidenced by the lack of decline in prevalence. Implementation of current knowledge with effective policies, as well as research into the causes of congenital anomalies, have the potential to change this situation.


Prenatal screening and diagnosis have seen a rapid development. The near future will bring less invasive technologies for the detection of chromosomal anomalies, and greater sensitivity and specificity of diagnosis of anomalies. Variation in the quality of screening services within Europe requires further examination. The challenge for European countries is also to reduce the number of women having to consider termination of pregnancy as an option by achieving effective primary prevention, and improving the outcome of affected children and their families in terms of health, quality of life and participation. References


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TOPFA            Terminations of Pregnancy for Foetal Anomaly