ICBDSR Report 2024

Canada Alberta ACASS, 2015 to 2020

total births in the 6-year period: 317,752 (livebirths: 315,613)
average births per year: 52,960 (livebirths: 52,600)
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 ACASS program covers the province of Alberta in western Canada. The program covers livebirths and stillbirths, as well as pregnancy terminations less than 20 weeks of gestation. The birth population was about 50,000 births per year for the period covered by the report.
While aiming for complete and timely ascertainment, the ACASS system is primarily passive, relying on others for case notifications. Data for 2019 and 2020 may not be complete, as the COVID-19 pandemic required a significant public health response with impacts across and beyond the health system.
ACASS continues to publish a dedicated congenital anomaly surveillance report approximately every two years, which provides context to the data with reference to the most current literature. The most recent ACASS report was published in March 2024, with data to 2021. This report can be accessed here: www.albertahealthservices.ca/assets/info/cmg/if-cmg-ab-congenital-abnormalities-fourteenth-report.pdf
ACASS is currently leveraging a relatively new electronic provincial clinical information system to enhance congenital anomalies surveillance (e.g., increase active case ascertainment for completeness; streamline for efficiency, accuracy, and timeliness
ACASS continues to promote awareness of congenital anomalies through various platforms, including local presentations, international conferences, and publications.
Collaborative opportunities have increased to determine the impact of congenital anomalies (e.g., public healthcare costs), a better understanding of rare conditions (e.g., arthrogryposis multiplex congenita, recurrent constellations of embryonic malformations/RCEM conditions), and increased participation in national and international networks (e.g., Canadian Congenital Anomalies Surveillance Network, EUROCAT-World Affiliate Member).

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, Canada Alberta ACASS, 2015-2020 shown are total cases for the reporting period, yearly average cases, and prevalence per 10,000
Hypospadias	875	146	27.5
Down syndrome	763	127	24.0
Polydactyly preaxial	686	114	21.6
Limb deficiency, total	405	68	12.7
Limb deficiency, unspec.	405	68	12.7
Cleft lip with or without cleft palate	378	63	11.9
Cystic kidney	260	43	8.2
Cleft palate without cleft lip	226	38	7.1
Trisomy 18	226	38	7.1
Neural tube defects, total	215	36	6.8
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 Canada Alberta ACASS, 2015-2020
	Program	Country	Percent liveborn	Prevalence per 10,000
Orofacial
Cleft lip with or without cleft palate	63	417	82	11.9
Cleft palate without cleft lip	38	249	86	7.1
Neural tube defects (NTD)
Neural tube defects, total	36	238	44	6.8
Spina bifida	20	130	54	3.7
Anencephaly	10	63	24	1.8
Heart
Transposition of great vessels	22	147	80	4.2
Hypoplastic left heart syndrome	19	123	62	3.5
Tetralogy of Fallot	12	84	73	2.4
Estimated from program prevalence extrapolated to total country births. Canada 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 Canada Alberta ACASS, 2015-2020
	Cases	Prev	95% CI	Cases	Prev	95% CI
Neural tube defects (NTD)
Neural tube defects, total	215	6.8	5.9 - 7.7	95	3.0	2.4 - 3.6
Spina bifida	119	3.7	3.1 - 4.5	64	2.0	1.5 - 2.5
Anencephaly	58	1.8	1.4 - 2.4	14	0.4	0.2 - 0.7
Encephalocele	38	1.2	0.8 - 1.6	17	0.5	0.3 - 0.8
Other brain
Hydrocephaly	109	3.4	2.8 - 4.1	65	2.1	1.6 - 2.6
Microcephaly	107	3.4	2.8 - 4.1	91	2.9	2.3 - 3.5
Holoprosencephaly	87	2.7	2.2 - 3.4	33	1.0	0.7 - 1.4
Eye and Ear
Microtia	84	2.6	2.1 - 3.3	82	2.6	2.0 - 3.2
Microphthalmos	53	1.7	1.2 - 2.2	29	0.9	0.6 - 1.3
Anotia	4	0.1	0.0 - 0.3	3	0.1	0.0 - 0.3
Anophthalmos	3	0.1	0.0 - 0.3	2	0.1	0.0 - 0.2
Orofacial
Cleft lip with or without cleft palate	378	11.9	10.7 - 13.2	309	9.8	8.7 - 10.9
Cleft palate without cleft lip	226	7.1	6.2 - 8.1	194	6.1	5.3 - 7.0
Choanal atresia bilateral	40	1.3	0.9 - 1.7	37	1.2	0.8 - 1.6
Heart
Coarctation of aorta	156	4.9	4.2 - 5.7	134	4.2	3.5 - 5.0
Transposition of great vessels	134	4.2	3.5 - 5.0	107	3.4	2.7 - 4.0
Hypoplastic left heart syndrome	112	3.5	2.9 - 4.2	69	2.2	1.7 - 2.7
Tetralogy of Fallot	75	2.4	1.9 - 3.0	55	1.7	1.3 - 2.2
Gastrointestinal
Anorectal atresia/stenosis	149	4.7	4.0 - 5.5	114	3.6	2.9 - 4.3
Esophageal atresia	95	3.0	2.4 - 3.7	86	2.7	2.1 - 3.3
Small intestinal atresia/stenosis	53	1.7	1.2 - 2.2	48	1.5	1.1 - 2.0
Genitourinary
Undescended testis	936	29.5	27.6 - 31.4	936	29.7	27.8 - 31.6
Hypospadias	875	27.5	25.7 - 29.4	874	27.7	25.9 - 29.5
Cystic kidney	260	8.2	7.2 - 9.2	198	6.3	5.4 - 7.1
Indeterminate sex	70	2.2	1.7 - 2.8	58	1.8	1.4 - 2.3
Renal agenesis	48	1.5	1.1 - 2.0	21	0.7	0.4 - 0.9
Bladder exstrophy	15	0.5	0.3 - 0.8	11	0.3	0.1 - 0.6
Epispadias	6	0.2	0.1 - 0.4	6	0.2	0.0 - 0.3
Limb
Polydactyly preaxial	686	21.6	20.0 - 23.3	620	19.6	18.1 - 21.2
Limb deficiency, total	405	12.7	11.5 - 14.0	230	7.3	6.3 - 8.2
Limb deficiency, unspec.	405	12.7	11.5 - 14.0	230	7.3	6.3 - 8.2
Limb deficiency, transverse	-	-	-	-	-	-
Limb deficiency, preaxial	-	-	-	-	-	-
Limb deficiency, postaxial	-	-	-	-	-	-
Limb deficiency, axial	-	-	-	-	-	-
Limb deficiency, intercalary	-	-	-	-	-	-
Limb deficiency, mixed	-	-	-	-	-	-
Abdominal
Omphalocele	131	4.1	3.4 - 4.9	41	1.3	0.9 - 1.7
Diaphragmatic hernia	107	3.4	2.8 - 4.1	77	2.4	1.9 - 3.0
Gastroschisis	93	2.9	2.4 - 3.6	83	2.6	2.1 - 3.2
Prune belly sequence	4	0.1	0.0 - 0.3	2	0.1	0.0 - 0.2
Chromosomal
Down syndrome	763	24.0	22.3 - 25.8	405	12.8	11.6 - 14.1
Trisomy 18	226	7.1	6.2 - 8.1	42	1.3	0.9 - 1.7
Trisomy 13	86	2.7	2.2 - 3.3	12	0.4	0.2 - 0.6
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.

Comments by Dr. Mary Ann Thomas. During the reporting period, 2015-2020, the prevalence of gastroschisis reached a high per 10,000 total births of 3.83 in 2018 to a low of 1.6 in 2020. The overall prevalence is 2.93. The overall prevalence of omphalocele during the same period is 4.12, with the prevalence ranging from 3.50 in 2020 to 5.06 in 2017. Whereas there is a statistically significantly increasing trend in Alberta for omphalocele from 1997-2021 (p=0.0005), there is no significant change for gastroschisis for the same period (p=0.3032) (Alberta Congenital Anomalies Surveillance System, 2024). A contributing factor may be the changing demographics of the Alberta population, particularly the decrease in the percent of births to mothers <20 years, which was 8% in 1990 and remained relatively high through the 90s and early 2000s. In 2015, the rate was 2.7% and has subsequently declined to 1.5% in 2021. There has also been an increase in births to mothers >35 years, from 15% in 2000 to 19% in 2015 and subsequently increasing to 25% in 2021.
It is likely that this shift will contribute to changes in frequencies of congenital anomalies that are associated with maternal age, especially those associated with the <20 years and >35 years maternal age groups.
For more information, ACASS continues to publish a dedicated congenital anomaly surveillance report, approximately every two years, which provides context to the data with reference to the most current literature. The last published report can be accessed with the following link:

www.albertahealthservices.ca/assets/info/cmg/if-cmg-ab-congenital-abnormalities-fourteenth-report.pdf

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) Canada Alberta ACASS, 2015-2020
	Cases	Prev	95% CI	Cases	Prev	95% CI
All maternal ages	763	24.0	22.3 - 25.8	405	12.8	11.6 - 14.1
< 20 years	2	3.0	0.4 - 10.7	2	3.0	0.4 - 10.9
20 to 24	23	6.4	4.1 - 9.6	19	5.3	2.9 - 7.7
25 to 29	102	11.3	9.2 - 13.7	59	6.6	4.9 - 8.2
30 to 34	181	15.6	13.4 - 18.1	100	8.7	7.0 - 10.4
35 to 39	275	47.9	42.4 - 53.9	127	22.3	18.4 - 26.2
40 to 44	164	148.5	126.7 - 173.1	89	81.6	64.7 - 98.5
45+ years	16	230.5	131.8 - 374.4	9	131.8	46.2 - 217.3
Age unspec.	0	-	-	0	-	-
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, Canada
on population, births, life expectancy
Total population	38,939,056
Number of births	350,452
Birth rate (per 1000 pop)	9.0
Fertility (births per woman)	1.3
Life expectancy at birth (years)	81.3
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: Canada, 2022 estimates
Country-wide estimates for selected conditions (350,452 births), extrapolating from program data
Neural tube defects (NTD)
Neural tube defects, total	237	105
Spina bifida	131	71
Anencephaly	64	16
Encephalocele	42	19
Other brain
Hydrocephaly	120	72
Microcephaly	118	101
Holoprosencephaly	96	37
Eye and Ear
Microtia	93	91
Microphthalmos	58	32
Orofacial
Cleft lip with or without cleft palate	417	343
Cleft palate without cleft lip	249	215
Choanal atresia bilateral	44	41
Heart
Coarctation of aorta	172	149
Transposition of great vessels	148	119
Hypoplastic left heart syndrome	124	77
Tetralogy of Fallot	83	61
Gastrointestinal
Anorectal atresia/stenosis	164	127
Esophageal atresia	105	95
Small intestinal atresia/stenosis	58	53
Genitourinary
Undescended testis	1032	1039
Hypospadias	965	970
Cystic kidney	287	220
Indeterminate sex	77	64
Renal agenesis	53	23
Bladder exstrophy	17	12
Epispadias	7	7
Limb
Polydactyly preaxial	757	688
Limb deficiency, total	447	255
Limb deficiency, unspec.	447	255
Abdominal
Omphalocele	144	46
Diaphragmatic hernia	118	85
Gastroschisis	103	92
Chromosomal
Down syndrome	842	450
Trisomy 18	249	47
Trisomy 13	95	13
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, Canada
Neonatal mortality (per 1000)	3.3
Infant mortality (per 1000)	4.3
Under 5 mortality (per 1000)	4.9
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, Canada
among infants (< 1 year old) and from first to fifth birthday
Infants	19.6	80.5
1 to < 5 yrs	13.7	2.4
Source: WHO mortality data for 2022 \| 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, Canada
Of reproductive age	16.6 ( 13.2 - 20.3 )
During pregnancy	20.9 ( 17.8 - 24.2 )
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, Canada
15 to 19	0.6
20 to 24	0.9
25 to 29	1.3
30 to 34	1.9
35 to 39	2.7
40 to 44	3.7
45 to 49	5.1
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 Canada
Yes	Wheat flour	2021
Yes	Rice	2021
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 Canada Alberta ACASS, 2015-2020
	Prevalence per 10,000	Program	Country	per 1M births	Risk factor parameters
Orofacial
Cleft lip with or without cleft palate	11.9	3	22	64	smoking, freq: 16.6%, OR: 1.34
Cleft palate without cleft lip	7.1	1	9	25	smoking, freq: 16.6%, OR: 1.22
Neural tube defects (NTD)
Neural tube defects, total	6.8	4	28	80	Presumed folate insufficiency, prevalence > 6
Heart
Transposition of great vessels	4.2	1	4	12	diabetes, freq: 1.3%, OR: 3.34
Hypoplastic left heart syndrome	3.5	1	5	16	diabetes, freq: 1.3%, OR: 4.58
Tetralogy of Fallot	2.4	1	4	12	diabetes, freq: 1.3%, OR: 4.89
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.