Barbara Sibbald

Spina bifida before and after folic acid fortification in Canada.

BACKGROUND In 1998, fortification of a large variety of cereal products with folic acid became mandatory in Canada. A multicentric study was carried out to assess the impact of this policy on the frequency of NTDs. The present analysis focused on spina bifida. METHODS The study population included approximately 2 million livebirths, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces, from 1993 to 2002. Spina bifida cases were divided according to the upper limit of the defect: upper (cranial, cervical, or thoracic) and lower (lumbar or sacral) defects. Based on published results of red blood cell folate tests, the study period was divided into prefortification, partial fortification, and full fortification periods. RESULTS A total of 1,286 spina bifida cases were identified: 51% livebirths, 3% stillbirths, and 46% terminations. Prevalence decreased from 0.86/1,000 in the prefortification to 0.40 in the full fortification period, while the proportion of upper defects decreased from 32% to 13%. Following fortification, regional variations in the prevalence and distribution of sites almost disappeared. CONCLUSIONS Results confirmed the etiologic heterogeneity of spina bifida and the more pronounced effect of folic acid in decreasing the risk of the more severe clinical presentations.

Prevalence of multiple congenital contractures including arthrogryposis multiplex congenita in Alberta, Canada, and a strategy for classification and coding†

BACKGROUND The population prevalence of multiple congenital contractures, many of which have either arthrogryposis multiplex congenita or amyoplasia congenita, ranges from 1/3300 to 1/56,000. Three other studies report a range of 1/4500 to 1/12,500. Classification and coding of these disorders in the International Classification of Diseases, tenth edition, (ICD-10) is less than satisfactory, even when augmented by the Royal College of Pediatrics and Child Health (RCPCH). expansion. METHODS The database of the Alberta Congenital Anomalies Surveillance System (ACASS) was used to review all cases (1980-2007) of the previously named disorders with special emphasis on the 1997-2007 cohort. The latter period was chosen because more complete ascertainment was likely due to the addition of terminations of pregnancy data beginning in 1997. This cohort was further analyzed into the three practical groups: I, limb only; II, limb plus non-central nervous system anomalies; and III, limb plus lethality, central nervous system anomalies, or both, with further syndrome identification in groups II and III. The ICD-10-RCPCH classification and codes were reviewed. RESULTS The prevalence for multiple congenital contractures in Alberta is 1/8700 for 1980-1996 and 1/4300 for 1997-2007. Rates for the three groups were calculated. Specific diagnostic categories were found in groups II and III of 43% and 65%, respectively. Mortality is high, especially in the first month of life (45% total losses). New classification and coding systems are proposed.

Anophthalmia and microphthalmia in the Alberta Congenital Anomalies Surveillance System.

BACKGROUND A higher than expected rate of anophthalmia/microphthalmia (A/M) for 1999 was noted in both the Alberta Congenital Anomalies Surveillance System (ACASS) and the Canadian Congenital Anomalies Surveillance System (CCASS). Since this increase was at variance with the previous 19 years, we performed a review to determine whether the increase was true and, if so, the possible explanation. METHODS We reviewed the records of the cases of A/M in the ACASS together with the accompanying attachments (e.g., consultant, autopsy and chromosome reports) for 1991-2001. In addition, we contacted all 91 registered ophthalmologists in Alberta. Letters were also written to the Edmonton and Calgary offices of the Canadian National Institute for the Blind (CNIB). RESULTS Sixty cases of A/M were ascertained over the study period. Of the 88 active ophthalmologists in the province, 21 (24%) replied, but no new cases were ascertained from this source. No replies were received from the CNIB. We constructed five categories of clinical phenotypes for the 60 cases: 20 had a chromosomal etiology, 13 had a recognized syndrome or association, 16 had extraocular malformations, 5 had other eye anomalies, and 6 had A/M only. Pregnancy terminations were not included. The higher rate in 1999 was mainly due to cases with a chromosomal etiology or a recognized syndrome or association. There was no indication that a teratogen was causing a cluster of A/M cases, as our annual rates were comparable to those for other jurisdictions not only in Canada but also in other countries. INTERPRETATION Our review confirmed that the rate of A/M in Alberta in 1999 was high but that the increase was mainly due to five cases of trisomy 13 together with one case associated with a syndrome (Meckel-Gruber). Our findings provide reassurance that there was no environmental cause of clustering of anophthalmia or microphthalmia. This review demonstrates the importance of ongoing population-based surveillance in providing baseline birth prevalence rates for evaluating trends and clusters.

Validation of congenital anomaly coding in Canada's administrative databases compared with a congenital anomaly registry

BACKGROUND Congenital anomaly (CA) surveillance provides epidemiologic data that are necessary for health planning. Approaches to CA surveillance vary; however, an increasing number of jurisdictions rely on administrative health databases for case ascertainment. This study aimed to assess the validity of CA coding in three administrative databases compared with a CA registry. METHODS A cohort of 5862 live and stillborn infants from Calgary Alberta Canada was created through linking 12 clinical and administrative databases. Diagnostic codes for all health care contacts (hospitalizations, emergency room visits, out-patient physician visits) in the first 3 months of life were examined for relevant International Classification of Disease codes. Sensitivity, positive predictive values, and kappa coefficients were calculated, and data from the Alberta Congenital Anomalies Surveillance System was used as the reference standard. RESULTS The ability of administrative data to accurately ascertain CAs varied by data source and the specificity of the diagnosis. Consistently, hospitalization data out-performed other administrative data sources in terms of sensitivity, positive predictive values, and kappa. Kappa scores for CAs easily visible at birth ranged from moderate (0.62 for emergency room visits and 0.65 for out-patient physician claims) to good (0.83 for hospitalization data) depending on the data source. CONCLUSION The validity of CA coding in administrative databases compared with a CA registry varies by database used and by CA studied. This has important implications for national surveillance efforts. Condition-specific validity should be assessed locally before use of these data sources for research or planning purposes.

Congenital heart defects and major structural noncardiac anomalies in Alberta, Canada, 1995–2002

BACKGROUND Although the majority of congenital heart defects (CHDs) occur in isolation, a significant number occur with noncardiac anomalies. This study determined the proportion of noncardiac anomalies among CHD cases in Alberta. METHODS Records of infants and children born in Alberta between January 1, 1995, to December 31, 2002, were searched using multiple sources of ascertainment in addition to the Alberta Congenital Anomalies Surveillance System (ACASS) (Alberta Health and Wellness, 2012). Each case was assigned to one CHD category and was further categorized into one of the following groups: isolated CHD, syndromes, chromosomal, associations and sequences, teratogens, Mendelian, neoplasia, heterotaxy, multiple minor anomalies, and multiple major anomalies. RESULTS Of all 3751 CHD cases (prevalence 12.42/1000 total births: confidence interval, 12.03-12.83), 75% were isolated, 10% had a chromosomal etiology, and 9% had multiple major anomalies. All other categories accounted for <2% each. The most commonly associated major noncardiac anomalies were musculoskeletal (MSK) (24%) followed by anomalies of the urinary tract (14%), gastrointestinal system (GI) (11%), and central nervous system (CNS) (11%). CONCLUSIONS This is both a population-based and clinical study using a classification scheme that could help to determine possible etiologic factors contributing to CHD. By eliminating known etiologies such as chromosomal and single gene, future studies can focus on the remainder to evaluate possible preventive measures. The most commonly associated major noncardiac anomalies involve the MSK system, followed by the urinary, GI, and CNS systems.

Folic acid fortification and the birth prevalence of congenital heart defect cases in Alberta, Canada.

BACKGROUND Congenital heart defects (CHDs) are the most common type of congenital anomaly. The precise etiology is unknown and the development of successful primary prevention strategies is challenging. Folic acid may have a protective role; however published results have been inconsistent. This study examines the impact of mandatory folic acid fortification (FAF) on the prevalence of CHDs. METHODS CHD cases were ascertained using the Alberta Congenital Anomalies Surveillance System, Pediatric Cardiology Clinics, Pathology, and hospital records. The birth prevalence and odds ratios (OR) of isolated CHD cases (i.e., without noncardiac anomalies) were calculated comparing pre-FAF (1995-1997) with post-FAF (1999-2002). RESULTS The prevalence of isolated CHD cases remained relatively unchanged when pre-FAF (9.34, 95% confidence interval [CI] 8.79-9.92) was compared with post-FAF (9.41, 95% CI, 8.93-9.91). Left ventricular outflow tract obstruction (LVOTO) decreased post-FAF (OR, 0.76; 95% CI, 0.61-0.94). Coarctation of the aorta contributed to this decline (OR, 0.55; 95% CI, 0.32-0.92). Atrial septal defect (ASD) (OR, 1.42; 95% CI, 1.13-1.80) and ASD with ventricular septal defect (OR, 1.52; 95% CI, 1.10-2.10) increased post-FAF. The remaining types of CHDs were unchanged. CONCLUSION FAF alone does not have an impact on the prevalence of CHDs as a group and the majority of selected types of CHDs in Alberta. The decrease in LVOTO, particularly coarctation of the aorta, may be due to FAF or other environmental factors. The increase in ASD and ASD with ventricular septal defect may reflect an increase in diagnosis and ascertainment.

Comment to the paper: Multiple neural tube defects may not be very rare by S.K. Mahalik et al

Dear Sir, The report by Mahalik et al. [8] of the high prevalence of multiple site neural tube defects (NTDs) in Chandigarh, India prompted us to review data from the Alberta Congenital Anomalies Surveillance System (ACASS) [1].We report NTD rates in a hierarchical manner with the highest defect being the only one recorded. These reflect cases and not just anomalies so that the concurrence of anencephaly and spina bifida in a single casewill be counted once as anencephaly. Nevertheless, we have the capability of retrieving the actual written record and can determine whether there are multiple site NTDs in a single case. We reviewed all NTD cases for 1995–2005 from ACASS. We excluded seven cases where there is a continuous defect such as craniorachischisis, one case each of occipital encephalocele and spinal dysraphism where the details are unclear and one case of anencephaly and thoracolumbar diplomyelia. That left nine cases where the infant had two separate NTDs (see Table 1). Terminations of pregnancy are included from 1997 in the numerator but are not in the denominator. Our multiple site rate is more than 15 times lower than that of Mahalik et al. which is 0.38/1,000. High rates of NTDs in the Sikh population have been reported previously especially in Chandigarh (8.8/1,000) and Amritsar (8.0/1,000) [14]. These rates are among the highest in the world and comparable with early rates in Belfast and South Wales [13] before the advent of folic acid supplementation. Mahalik et al. comment that multiple site NTDs may be commoner in populations with a high prevalence of NTDs. In British Columbia (BC) Baird [2], in a Registry study, noted that the prevalence of NTDs was twice as high in the Sikhs compared to the general population of BC (1/350 vs 1/795). The clinical and genetic study of Hall et al. [6] on 512 NTD probands in BC found a higher frequency of both high level spina bifida and multiple site NTDs in their Sikh population compared to the non Sikh. High level spina bifida was found in 31 % of Sikh probands vs 14.7 % in non Sikh probands and of those with multiple site NTDs 25 % were Sikhs. The frequency of nonNTD congenital anomalies was higher among siblings of Sikh probands (8.8 %) than among siblings of other probands (2.4 %; P<.05). The excess was due to hydrocephalus. It would appear that the Sikh population carries their high risk of NTDs even when they emigrate to another country which was also shown by Searle [11]. In reviewing our cases, none of the parents had Sikh names or even Indian names. Alberta has a low prevalence of NTD cases and this plus the relative absence of a Sikh population may account for our much lower prevalence of multiple site NTDs than in Chandigarh. Neurulation is the process by which a closed neural tube forms from the preceding embryonic neural folds. Primary and secondary neurulation are recognized. Primary neurulation occurs by the dorsal bending of the two sides of the flat neuroepithelial placode. This placode or plate follows gastrulation and the formation of the primitive streak and notochordal process; this forms a midline and establishes a longitudinal axis and bilateral symmetry as the body plan of all vertebrate embryos. The two sides of the neural folds come together and fuse in the dorsal midline in the future cervical region, then extending the closure rostrally to the anterior neuropore and caudally to the posterior neuropore, which close at 24 and 28 days, respectively, the posterior closing later because the R. B. Lowry (*) : B. Sibbald Alberta Congenital Anomalies Surveillance System, Alberta Health, Calgary, Canada e-mail: brian.lowry@albertahealthservices.ca