ICBDSR Report 2024

England NCARDRS, 2015 to 2019

total births in the 5-year period: 2,036,067 (livebirths: 2,027,968)
average births per year: 407,210 (livebirths: 405,590)
terminations of pregnancy legal in country: Yes
data include terminations of pregnancy: Yes
source structure: Population-based

A word from the program about the program

The NCARDRS program is population-based and now includes all birth outcomes in England. Data prior to 2018 was a regional subset based on 21% to 49% of births in England. From 2018, registration covered all of England but regions were in different stages of development of registration and ascertainment continued to vary regionally, particularly for conditions most commonly detected postnatally.
In 2018, NCARDRS achieved its goal of national data collection.It receives electronic submissions from every cytogenetic laboratory in England, from hospital trusts, diagnostic laboratories and have access to custom-built data extracts from neonatal and hospital patient management systems and fetal medicine software systems.
The denominator for England varied for reporting years. For 2016 it was 329,301 total births, 2017 it was 320,013 total births, 2018 it was 628,171 total births and 2019 it was 614,952 total births.
NCARDRS does not collect undescended testes, and has information on the position of polydactyly for only a small subset of babies with polydactyly.

Selected data highlights

Programs share aggregated information on selected major congenital anomalies for joint monitoring and evaluation. Programs may include additional anomalies in their activities. The following tables highlight key findings on the congenital anomalies selected for joint monitoring.

Top Ten by Frequency

Because of their frequency, these conditions impact the largest number of individuals and their families and are the most likely to be encountered in clinical practice. These top ten conditions are selected among those with significant clinical and public health impact. Ffor example, undescended testis is not included in this list.

Condition	Cases	Yearly Avg	Prevalence
Top 10 Conditions by Frequency
among specific diagnoses with major health impact, England NCARDRS, 2015-2019 shown are total cases for the reporting period, yearly average cases, and prevalence per 10,000
Down syndrome	5263	1053	25.8
Neural tube defects, total	2593	519	12.7
Cleft lip with or without cleft palate	1942	388	9.5
Trisomy 18	1485	297	7.3
Cystic kidney	1402	280	6.9
Hypospadias	1274	255	6.3
Cleft palate without cleft lip	1261	252	6.2
Spina bifida	1205	241	5.9
Omphalocele	1126	225	5.5
Anencephaly	1090	218	5.4
Note: not considered here are microcephaly, undescended testis, and unspecified conditions. However, microcephaly and undescended testis are included in the full table below. The green bar visually compares the prevalence (rows) relative to the most common condition in the table.

Notable Seven

These conditions were selected based on prior knowledge of their overall health impact (morbidity and mortality), regardless of frequency. This selection is the same for all programs. For example, neural tube defects and critical congenital heart disease are included as they may account in some programs for nearly half of all infant deaths associated with congenital anomalies.

Modifiable risk factors are well established for several of these conditions. This implication, as the potential for primary prevention, is unpacked in a later section (‘what if scenario’).

	Yearly cases		Percent liveborn	Prevalence per 10,000
Seven highly impactful conditions
selected on the basis of high morbidity and mortality, and potential for primary prevention England NCARDRS, 2015-2019
	Program	Country	Percent liveborn	Prevalence per 10,000
Neural tube defects (NTD)
Neural tube defects, total	519	861	22	12.7
Spina bifida	241	400	37	5.9
Anencephaly	218	366	6	5.4
Orofacial
Cleft lip with or without cleft palate	388	644	83	9.5
Cleft palate without cleft lip	252	420	91	6.2
Heart
Tetralogy of Fallot	190	319	80	4.7
Transposition of great vessels	165	278	82	4.1
Hypoplastic left heart syndrome	130	217	46	3.2
Estimated from program prevalence extrapolated to total country births. United Kingdom births for 2022 from World Bank. The green bar visually compares the prevalence (rows) relative to the most common condition in the table.

The full table

This more expansive set of major congenital anomalies, internal and external, includes most conditions of significant clinical and public health impact. Most programs include these conditions, and some even more. Note that a child with multiple anomalies will be counted in all pertinent rows.

A later section provides a more detailed analysis of trisomy 21 (Down syndrome).

	All births			Livebirths
Selected congenital conditions by system
number of cases and prevalence (prev) per 10,000, for all births and livebirths England NCARDRS, 2015-2019
	Cases	Prev	95% CI	Cases	Prev	95% CI
Neural tube defects (NTD)
Neural tube defects, total	2593	12.7	12.2 - 13.2	571	2.8	2.6 - 3.0
Spina bifida	1205	5.9	5.6 - 6.3	440	2.2	2.0 - 2.4
Anencephaly	1090	5.4	5.0 - 5.7	66	0.3	0.2 - 0.4
Encephalocele	298	1.5	1.3 - 1.6	65	0.3	0.2 - 0.4
Other brain
Hydrocephaly	912	4.5	4.2 - 4.8	551	2.7	2.5 - 2.9
Holoprosencephaly	386	1.9	1.7 - 2.1	53	0.3	0.2 - 0.3
Microcephaly	227	1.1	1.0 - 1.3	167	0.8	0.7 - 0.9
Eye and Ear
Microphthalmos	86	0.4	0.3 - 0.5	70	0.3	0.3 - 0.4
Anophthalmos	27	0.1	0.1 - 0.2	14	0.1	0.0 - 0.1
Anotia	17	0.1	0.0 - 0.1	13	0.1	0.0 - 0.1
Microtia	-	-	-	-	-	-
Orofacial
Cleft lip with or without cleft palate	1942	9.5	9.1 - 10.0	1620	8.0	7.6 - 8.4
Cleft palate without cleft lip	1261	6.2	5.9 - 6.5	1152	5.7	5.4 - 6.0
Choanal atresia bilateral	145	0.7	0.6 - 0.8	130	0.6	0.5 - 0.8
Heart
Tetralogy of Fallot	951	4.7	4.4 - 5.0	761	3.8	3.5 - 4.0
Coarctation of aorta	950	4.7	4.4 - 5.0	826	4.1	3.8 - 4.4
Transposition of great vessels	827	4.1	3.8 - 4.3	678	3.3	3.1 - 3.6
Hypoplastic left heart syndrome	652	3.2	3.0 - 3.5	300	1.5	1.3 - 1.6
Gastrointestinal
Anorectal atresia/stenosis	801	3.9	3.7 - 4.2	636	3.1	2.9 - 3.4
Esophageal atresia	639	3.1	2.9 - 3.4	584	2.9	2.6 - 3.1
Small intestinal atresia/stenosis	255	1.3	1.1 - 1.4	247	1.2	1.1 - 1.4
Genitourinary
Cystic kidney	1402	6.9	6.5 - 7.3	1079	5.3	5.0 - 5.6
Hypospadias	1274	6.3	5.9 - 6.6	1258	6.2	5.9 - 6.5
Renal agenesis	997	4.9	4.6 - 5.2	630	3.1	2.9 - 3.3
Indeterminate sex	124	0.6	0.5 - 0.7	102	0.5	0.4 - 0.6
Bladder exstrophy	72	0.4	0.3 - 0.4	37	0.2	0.1 - 0.2
Epispadias	18	0.1	0.1 - 0.1	17	0.1	0.0 - 0.1
Undescended testis	-	-	-	-	-	-
Limb
Limb deficiency, total	508	2.5	2.3 - 2.7	309	1.5	1.4 - 1.7
Limb deficiency, transverse	277	1.4	1.2 - 1.5	190	0.9	0.8 - 1.1
Polydactyly preaxial	100	0.5	0.4 - 0.6	90	0.4	0.4 - 0.5
Limb deficiency, unspec.	100	0.5	0.4 - 0.6	58	0.3	0.2 - 0.4
Limb deficiency, mixed	62	0.3	0.2 - 0.4	28	0.1	0.1 - 0.2
Limb deficiency, preaxial	51	0.3	0.2 - 0.3	19	0.1	0.1 - 0.1
Limb deficiency, postaxial	22	0.1	0.1 - 0.2	12	0.1	0.0 - 0.1
Limb deficiency, intercalary	21	0.1	0.1 - 0.2	13	0.1	0.0 - 0.1
Limb deficiency, axial	-	-	-	-	-	-
Abdominal
Omphalocele	1126	5.5	5.2 - 5.9	318	1.6	1.4 - 1.7
Diaphragmatic hernia	774	3.8	3.5 - 4.1	549	2.7	2.5 - 2.9
Gastroschisis	682	3.3	3.1 - 3.6	608	3.0	2.8 - 3.2
Omphalocele/Gastroschisis, unspec.	145	0.7	0.6 - 0.8	14	0.1	0.0 - 0.1
Prune belly sequence	16	0.1	0.0 - 0.1	12	0.1	0.0 - 0.1
Chromosomal
Down syndrome	5263	25.8	25.2 - 26.6	2319	11.4	11.0 - 11.9
Trisomy 18	1485	7.3	6.9 - 7.7	181	0.9	0.8 - 1.0
Trisomy 13	547	2.7	2.5 - 2.9	63	0.3	0.2 - 0.4
Note a dash (-) indicates data not available or not provided

A deeper look: comments from the program leads

The program leads provide their insights on data, operations, and recent achievements. Their interpretation of the data is particularly valuable because of their local experience and knowledge.

NCARDRS receive electronic submissions from every cytogenetic laboratory in England, from hospital trusts, diagnostic laboratories and have access to custom-built data extracts from neonatal and hospital patient management systems and fetal medicine software systems. All birth outcomes should be represented.
Data prior to 2018 was a regional subset based on 21% to 49% of births in England. From 2018, registration covered all of England but regions were in different stages of development of registration and ascertainment continued to vary regionally, particularly for conditions most commonly detected postnatally. The Denominator for England varied for reporting years due to this. For 2016 it was 329,301 total births, 2017 it was 320,013 total births, 2018 it was 628,171 total births and 2019 it was 614,952 total births. In 2018, NCARDRS achieved its goal of national data collection. When NCARDRS was formed in 2015 we reported on 21% of births in England. In both the 2016 and 2017 submissions, datafrom seven NCARDRS reporting regions, representing 49% coverage of births, were presented. Since 2018 data collection has covered the whole of England.
NCARDRS does not collect undescended testes and these prevalence estimates should not be reported. NCARDRS has information on the position of polydactyly for only a small subset of babies with polydactyly.

Down syndrome (trisomy 21)

By far the most common chromosomal anomaly, Down syndrome is known to occur more frequently (has a higher risk of occurrence) in births of women with higher maternal age

This pattern is universally observed, provided there is no significant bias toward missing pregnancies with Down syndrome in older women (e.g., because of unreported pregnancy terminations)

	All cases			Livebirths
Down syndrome, overall and by maternal age
separately for all births and livebirths, prevalence per 10,000 (Poisson exact confidence intervals) England NCARDRS, 2015-2019
	Cases	Prev	95% CI	Cases	Prev	95% CI
All maternal ages	5263	25.8	25.2 - 26.6	2319	11.4	11.0 - 11.9
< 20 years	59	9.4	7.2 - 12.2	38	6.1	4.1 - 8.0
20 to 24	233	7.9	6.9 - 9.0	167	5.7	4.8 - 6.5
25 to 29	539	9.5	8.7 - 10.3	282	5.0	4.4 - 5.5
30 to 34	1149	17.7	16.7 - 18.7	513	7.9	7.2 - 8.6
35 to 39	1926	52.2	49.9 - 54.5	761	20.6	19.1 - 22.1
40 to 44	1233	154.5	146.0 - 163.4	503	63.0	57.5 - 68.5
45+ years	116	173.7	143.5 - 208.3	54	80.9	59.4 - 102.3
Age unspec.	8	-	-	1	-	-
Age unspec. = maternal age unknown or unspecified

Down syndrome - maternal age pyramid

Because of the relation between prevalence of Down syndrome and maternal age, the maternal age distribution in the population is a major determinant of the number of conceptions with Down syndrome in the population.

For programs that have maternal age specific data, one can compare the maternal-age ‘pyramid’ for all births in the population with that of births with Down syndrome. Typically, the distribution is skewed, with a relative excess of births with Down syndrome among the more advanced maternal age groups.

Down syndrome - birth rates matter

Despite the considerably higher risk (rates) of Down syndrome in mothers over 40 or 45 years, these age groups contribute comparatively fewer affected births than younger age groups. This is because birth rates matter: fewer births in the more advanced age groups mean fewer cases overall from those age groups.

A Pareto chart helps highlight the cumulative contribution of different age groups to the total number of cases. This information can help inform strategies for testing and counseling.

Linking risk factor profile and congenital anomalies

The term triple surveillance refers to a model of public health surveillance that births includes the full causal chain, from a) risk factors, which influence the number of affected pregnancies; to b) the affected pregnancies themselves, that are vulnerable to adverse health outcomes; and to c) the health outcomes in affected individuals. The burden of risk becomes expressed eventually in the burden of disease.

Historically, birth defect surveillance has focused on the second element, the occurrence of congenital anomalies.

However, improving outcomes (morbidity, mortality, disability) requires understanding and tracking risk factors (to improve primary prevention) and health outcomes (to improve care). Triple surveillance advocates integrating the tracking of all three elements in this causal chain. Together, these three domains provide clinicians, public health professionals, and policy makers with information to act.

To highlight such context, the next sections provide elements of country demographics, outcomes (mainly early mortality), and selected risk factors. These data, particularly those on risk factors and outcomes, are sometimes directly measured, and sometimes estimated. Birth defect programs with their partners can supplement these data with local assessments.

Country demographics

A surveillance program operates within its country’s demographic situation and trends. This information adds meaning and context to birth defect surveillance information.

Key Indicator	2022 data
Demographic Indicators, United Kingdom
on population, births, life expectancy
Total population	67,791,000
Number of births	677,910
Birth rate (per 1000 pop)	10.0
Fertility (births per woman)	1.6
Life expectancy at birth (years)	82.1
Source: World Bank (accessed Sept 2024)

From program to country

Many (though not all) programs cover a proportion of the country in which they operate. In this setting, a common question is what the program can tell use about the impact of congenital anomalies country-wide, under the assumption that the program information is a good estimator for the country itself. This assumption, of course, needs to be carefully examined, and the program staff typically has the local knowledge to help frame such estimates within the strengths and limitations of the data.

The table below uses the prevalence measured within the program to estimate the number of births with selected congenital anomalies for the entire country. These extrapolations have limitations, and in most cases are illustrative. However, at times a program that covers a proportion of the population may be the only practical window into congenital anomalies country-wide.

	All cases	liveborn
A window into the country: United Kingdom, 2022 estimates
Country-wide estimates for selected conditions (677,910 births), extrapolating from program data
Neural tube defects (NTD)
Neural tube defects, total	863	191
Spina bifida	401	147
Anencephaly	363	22
Encephalocele	99	22
Other brain
Hydrocephaly	304	184
Holoprosencephaly	129	18
Microcephaly	76	56
Eye and Ear
Microphthalmos	29	23
Anophthalmos	9	5
Anotia	6	4
Orofacial
Cleft lip with or without cleft palate	647	542
Cleft palate without cleft lip	420	385
Choanal atresia bilateral	48	43
Heart
Tetralogy of Fallot	317	254
Coarctation of aorta	316	276
Transposition of great vessels	275	227
Hypoplastic left heart syndrome	217	100
Gastrointestinal
Anorectal atresia/stenosis	267	213
Esophageal atresia	213	195
Small intestinal atresia/stenosis	85	83
Genitourinary
Cystic kidney	467	361
Hypospadias	424	421
Renal agenesis	332	211
Indeterminate sex	41	34
Bladder exstrophy	24	12
Epispadias	6	6
Limb
Limb deficiency, total	169	103
Limb deficiency, transverse	92	64
Polydactyly preaxial	33	30
Limb deficiency, unspec.	33	19
Limb deficiency, mixed	21	9
Limb deficiency, preaxial	17	6
Limb deficiency, postaxial	7	4
Limb deficiency, intercalary	7	4
Abdominal
Omphalocele	375	106
Diaphragmatic hernia	258	184
Gastroschisis	227	203
Omphalocele/Gastroschisis, unspec.	48	5
Prune belly sequence	5	4
Chromosomal
Down syndrome	1752	775
Trisomy 18	494	61
Trisomy 13	182	21
Note: includes conditions with at least 5 estimated cases. Assumes that prevalence estimates from program are valid country-wide.

Outcomes - early mortality

The relative impact of congenital anomalies on early mortality (neonatal, infant, and under 5 years) tends to increase as infant mortality due to other causes falls. This pattern has been observed worldwide. These general indicators of early mortality are tracked regularly by public health agencies.

Key Indicator	2022 data
Mortality Indicators, United Kingdom
Neonatal mortality (per 1000)	2.7
Infant mortality (per 1000)	3.6
Under 5 mortality (per 1000)	4.1
Source: World Bank, accessed Sept 2024. The green bar visually compares the indicators (rows) relative to the indicator with the highest value.

Outcomes - mortality with congenital anomalies

A more specific indicator (infant deaths due to congenital anomalies) is more challenging to document accurately. Missed diagnoses, especially of internal anomalies, can lead to massive underestimates, especially in settings where diagnoses rely only or mostly on an external exam. The table below summarizes data and estimates from systematic public sources. However, local assessments from birth defect surveillance program can help improve the quality of this key indicator.

Age group	Percent	Deaths / 100k pop
Deaths due to birth defects, United Kingdom
among infants (< 1 year old) and from first to fifth birthday
1 to < 5 yrs	15.4	1.8
Infants	9.2	34.1
Source: WHO mortality data for 2020 \| who.int. The green bar visually compares the indicators (rows) relative to the indicator with the highest value.

Risk factors

Some modifiable exposures are well-established risk factors for congenital anomalies. Reducing these exposures is the basis for effective primary prevention. Here we focus specifically on smoking, diabetes, and folate insufficiency. These factors, both common and modifiable, increase the risk of major contributors to morbidity and mortality, including orofacial clefts, neural tube defects, and serious congenital heart disease. The impact of these risk factors depend on their frequency in the population. The following tables show frequency estimates for the country. In another section, these data are used to estimate the number of cases in the country potentially preventable by eliminating the risk factors.

Smoking

Smoking is associated with increased risk for many adverse pregnancy outcomes and several congenital anomalies, including orofacial clefts and probably congenital heart disease. The increased risk is relatively modest (odds ratios tipically less than 1.5) but the effect size, or number of cases due to smoking, depends on the rate of smoking among women who become pregnant. Here we used country-specific estimates of smoking in women of reproductive age (see table for references). Rates of smoking during pregnancy tend to be lower, but by the time many women know they are pregnant, the at-risk period for congenital anomalies has often already passed.

Women	Frequency (%)
Smoking in women
Frequency in two different groups, United Kingdom
Of reproductive age	24.4 ( 21.0 - 28.3 )
During pregnancy	23.3 ( 19.6 - 27.3 )
Source: IHME \| www.healthdata.org \| and Lange 2018

Diabetes

Maternal pregestational diabetes is associated with increased risk for many serious congenital anomalies, including spina bifida, several critical congenital heart defects, and multiple congenital anomalies, among others. In some cases the relative risk (or odds ratio) can be quite high, above 4 or 5 in some cases. The effect size (number of cases due to diabetes) depends on the frequency of diabetes, which tipically increases with age.

Age Group	Percent
Diabetes in women
Frequency by age group, United Kingdom
15 to 19	0.3
20 to 24	0.4
25 to 29	0.6
30 to 34	0.9
35 to 39	1.5
40 to 44	2.4
45 to 49	3.4
Source: IHME \| www.healthdata.org

Folate insufficiency

Folate insufficiency is associated with increased risk for neural tube defects and perhaps other congenital anomalies. On a population-basis, well-implemented folic acid fortification is estimated to decrease the prevalence of neural tube defects below 6 per 10,000 or perhaps even lower. Folic acid fortification is most effective when it is mandatory and universal, meaning that it involves foods commonly consumed by large parts of the population (e.g., wheat, maize, rice, depending on culture and geography).

Mandatory	Food vehicle	Year started
Folic acid fortification
Status of mandatory fortification in United Kingdom
No	-	-
Source: Country program and FFI \| fortificationdata.org

What if - prevention scenarios

What follows is a tricky but important exercise. By combining information about risk factors and prevalence of congenital anomalies, one can attempt to estimate the number of cases attributable to risk factors. This is illustrated in the table below, which uses prevalence information from the program and risk factor information (e.g., diabetes frequency in women) from country data. These estimates also require knowing the relative risk of disease given the exposure. Here we use odds ratios derived from high quality studies and metanalyses. These data then are fed into the Levine estimator of attributable fraction to generate the scenarios that you see in the table. For neural tube defects, we used a different approach. We used 6 per 10,000 as the (conservative) estimate of the birth prevalence achievable by fully implemented folate fortification, and postulated that a prevalence in excess of this value consists of cases attributable to folate insufficiency (as relates to neural tube defect prevention).

	Prevalence per 10,000	attributable cases			Risk factor parameters
Attributable cases for selected risk factors
yearly estimates in program and in country, and per million births England NCARDRS, 2015-2019
	Prevalence per 10,000	Program	Country	per 1M births	Risk factor parameters
Neural tube defects (NTD)
Neural tube defects, total	12.7	273	454	670	Presumed folate insufficiency, prevalence > 6
Orofacial
Cleft lip with or without cleft palate	9.5	30	49	73	smoking, freq: 24.4%, OR: 1.34
Cleft palate without cleft lip	6.2	13	21	32	smoking, freq: 24.4%, OR: 1.22
Heart
Tetralogy of Fallot	4.7	4	7	11	diabetes, freq: 0.6%, OR: 4.89
Transposition of great vessels	4.1	2	4	6	diabetes, freq: 0.6%, OR: 3.34
Hypoplastic left heart syndrome	3.2	3	5	7	diabetes, freq: 0.6%, OR: 4.58
Odds ratios from literature, exposure frequencies from country estimates (see methods for details). Estimates for neural tube defects are provided only when reported prevalence is greater than 6 per 10,000. Note that for programs that do not include stillbirths or terminations of pregnancy, these may be underestimates.

Arguably, these estimates are simplistic. For one, they assume accurate inputs and lack of interactions between risk factors. For neural tube defects, for example, the assumption is that the reported prevalence is accurate (e.g., that it includes stillbirths and pregnancy terminations) and that the excess prevalence is entirely due to (or preventable by) the folate status of the population.

For smoking and diabetes, these estimates assume, for example, that the reported smoking rates in women reflect the smoking rates in the at-risk period, typically the periconceptional period. Smoking rates in pregnancy are typically lower than rates among women of childbearing age, but many women realize they are pregnant after the at-risk period for many congenital anomalies. One may argue that the true smoking rates in the at-risk period are somewhere between these two estimates .

Finally, the computation of attributable cases in these scenarios considers risk factors ‘one at the the time’ and does not account, for example, for multiple exposures (e.g., diabetes and smoking) or interactions among multiple exposures. And so on.

Nevertheless, even rough estimates provide an important message. Some instances, perhaps many, of major and even lethal congenital anomalies are preventable by reducing the burden of risk in populations and individuals. Moreover, for many risk factors (smoking and diabetes in particular), the benefits of exposure mitigation extend beyond the prevention of congenital anomalies to the prevention of many other health conditions, for the fetus as well as for parents.