Collectively, congenital anomalies represent an important
public health issue in terms of
on the quality of life of affected children and adults and their families
to foetal and infant mortality, both in terms of loss of potential years of life
and emotional costs to the family
quality and financial cost of medical, social and educational services to
improve the participation and quality of life of affected individuals and their
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. “Major” congenital 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 types – variation 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.
220.127.116.11. 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 18.104.22.168.1), 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
Table 22.214.171.124.1. 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 covered – excellent 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
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 (www.icbdsr.org). Many of the EUROCAT
registers belong to ICBDSR also, as well two EU non-EUROCAT registers in Czech Republic and Slovak Republic.
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 126.96.36.199). 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 188.8.131.52. Prevalence per 1 000
births of EUROCAT congenital anomaly subgroups 2000-2004
The average prevalence of different subgroups in Europe is shown in Table 184.108.40.206. The prevalence of chromosomal anomalies is 3.4 per 1 000
births. In the data shown in Table 220.127.116.11, 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 18.104.22.168.
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 22.214.171.124), 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 126.96.36.199. Trends in the total
and live birth prevalence per 1 000 births of All Anomalies and Cardiac
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 188.8.131.52). 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 184.108.40.206).
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
Table 220.127.116.11. Perinatal mortality due
to congenital anomalies, 2000-2004.
Perinatal mortality due to congenital anomaly varies per
country (Table 18.104.22.168). 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 22.214.171.124. 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 126.96.36.199 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 188.8.131.52). 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 184.108.40.206). 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 220.127.116.11), 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
18.104.22.168), 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
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 22.214.171.124 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 126.96.36.199. 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 188.8.131.52) 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 184.108.40.206. 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 220.127.116.11). This has represented a failure in preventive policy.
Figure 18.104.22.168. 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
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 22.214.171.124).
Cleft palate and cleft lip occur in 1.3 per 1 000 births
in Europe (Table 126.96.36.199). 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 188.8.131.52). 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
184.108.40.206). Individual registries report prevalence rates up to 2.5 per 1 000 in the period 2000-2004, and two areas report a higher prevalence – Sicily 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,
For main risk factors see Table 9.1a.
Table 9.1a. Main risk factors for newborns and perinatal health
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
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.
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
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.
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
low 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
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.
(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.
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
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
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
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.
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
tools and policies
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
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.
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
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
An increasing proportion of affected pregnancies are
prenatally diagnosed, with prenatal diagnosis rates are particularly high for
some anomalies as presented in section 220.127.116.11. 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 increasing
“medicalisation” 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
agendas – rare 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 system – decisions 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
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 major “lifestyle” determinants 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 ensuring “healthy 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
h) More research should be funded into the environmental
causes of congenital anomalies.
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
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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
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TOPFA Terminations of Pregnancy for