Godwin KA, Sibbald B, Bedard T, Kuzeljevic B, Lowry RB, Arbour L. Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry. Canadian Journal of Public Health. 2008; 99: 271-275.
PubMed ID: 18767269
To use the Canada-based Alberta Congenital Anomalies Surveillance System (ACASS) to examine changes in birth prevalence of select structural congenital anomalies between pre- and post-folic acid fortification of grain products (1992 to 1996 vs. 1999 to 2003).
- Live birth or stillbirth in the province of Alberta, Canada between 1992 to 1996 or 1999 to 2003
- One or more congenital anomaly diagnosed up to one year of age, including anencephaly, spina bifida, cleft palate, cleft lip, obstructive defects of the renal pelvis and ureter, reduction deformities of the upper or lower limb, bulbus cordis anomalies and anomalies of cardiac septal closure, common truncus, transposition of great vessels, tetralogy of Fallot, ventricular septal defect, ostium secundum type atrial septal defect, anomalies of the abdominal wall, omphalocele, gastroschisis or hypertrophic pyloric stenosis
- Neither informed consent processes nor IRB review were mentioned in the article.
- Live birth or stillbirth prior to 1992, between 1997 and 1998 or after 2003
- Aborted pregnancy.
- All live births and stillbirths in Alberta, Canada during the target periods were recorded in the Alberta Congenital Anomalies Surveillance System (ACASS)
- Infants diagnosed with a congenital anomaly at birth, hospital admission or death had a notification form completed and submitted to ACASS by trained hospital personnel.
- The surveillance system relied on vital records to ascertain live births and stillbirths
- As a trend design, the study compared frequencies of congenital anomalies pre- and post-folic acid fortification of grain products
- Infants with one or more anomaly were counted in multiple categories.
- The number of live births and stillbirths constituted the denominator for each time period. The numerator was both the individual number of each congenital anomaly, but also the total number of anomalies for each time period
- Odds ratios were determined using the chi-square approximation
- The Bonferroni correction was applied to adjust for multiple testing, so a P-value of less than 0.003 was required for statistical significance.
Timing of Measurements
Ascertainment of a congenital anomaly could occur up to one year after birth. How diagnoses were determined was not described.
Folic acid-linked congenital anomalies, including anencephaly, spina bifida, cleft palate, cleft lip, obstructive defects of the renal pelvis and ureter, reduction deformities of the upper or lower limb, bulbus cordis anomalies and anomalies of cardiac septal closure, common truncus, transposition of great vessels, tetralogy of Fallot, ventricular septal defect, ostium secundum type atrial septal defect, anomalies of the abdominal wall, omphalocele, gastroschisis or hypertrophic pyloric stenosis.
Pre-folic acid fortification (1992 to 1996) vs. post-folic acid fortification (1999 to 2003) of grain products.
- Initial N: 389,349
- 198,321 in 1992 to 1996
- 191,028 in 1999 to 2003
- Location: Alberta, Canada.
- From pre- to post-fortification, there were significant decreases in birth prevalence of spina bifida and ostium secundum type atrial septal defects. Prevalence also decreased for anencephaly, cleft lip, cleft lip and palate, bulbus cordis anomalies and anomalies of caridac septal closure, common truncus and tetralogy of fallot, but not significantly
- Prevalence increased significantly for obstructive defects of the renal pelvis and ureter, anomalies of the abdominal wall, gastroschisis and hypertrophic pyloric stenosis. Non-significant increases were observed for cleft palate, reduction limb deformities, transposition of the great vessels and omphalocele.
|N||Per 1,000 Births||N||Per 1,000 Births|
|Anencephaly||38||0.19||27||0.14||0.74||0.45 to 1.21||0.2759|
|Spina bifida||97||0.49||48||0.25||0.51||0.36 to 0.73||0.0002|
|Cleft palate||146||0.74||159||0.83||1.12||0.90 to 1.42||0.3102|
|Cleft lip||84||0.42||75||0.39||0.93||0.68 to 1.27||0.6924|
|Cleft palate and cleft lip||155||0.78||140||0.73||0.94||9.75 to 1.18||0.6215|
|Obstructive defects of the renal pelvis and ureter||267||1.35||373||1.95||1.45||1.24 to 1.70||<0.0001|
|Reduction deformities of the upper limb||121||0.61||127||0.66||1.10||0.85 to 1.40||0.5400|
|Reduction deformities of the lower limb||63||0.32||72||0.38||1.19||0.85 to 1.64||0.3647|
|Bulbus cordis anomalies plus anomalies of cardiac septal closure||1,183||6.00||1,107||5.80||0.97||0.89 to 1.06||0.5009|
|Common truncus||14||0.07||10||0.05||0.74||0.33 to 1.67||0.6026|
|Transposition of great vessels||64||0.32||72||0.38||1.17||0.83 to 1.64||0.4128|
|Tetralogy of Fallot||63||0.32||56||0.29||0.92||0.64 to 1.32||0.7295|
|Ventricular septal defect||536||2.70||528||2.76||1.02||0.91 to 1.15||0.7372|
|Ostium secundum type atrial septal defect||412||2.10||319||1.70||0.80||0.69 to 0.93||0.0037|
|Anomalies of the abdominal wall||77||0.39||104||0.54||1.40||1.04 to 1.88||0.0289|
|Omphalocele||30||0.15||43||0.23||1.49||0.03 to 2.37||0.1176|
|Gastroschisis||38||0.19||70||0.37||1.91||1.29 to 2.84||0.0015|
|Hypertrophic pyloric stenosis||119||0.60||171||0.90||1.49||1.18 to 1.89||0.0009|
|Total||3,507||18.00||3,501||18.00||1.02||0.99 to 1.00||0.1300|
- This provincial registry-based analysis supports previously recognized reductions in spina bifida and anencephaly attributable to folic acid fortification
- The fact that there was no overall increase in septal defects and a significant reduction in atrial septal defects was observed may support the hypothesis that folic acid is at least one of the critical nutrients responsible for the reduction in heart defects associated with multivitamin use
- Gastroschisis, a defect presumably caused by vascular disruption, is increasing, especially in younger women. The rising rate seems to pre-date folic acid fortification, and likely reflects a pre-existing, unrelated trend.
- Even after folic acid awareness campaigns, fewer than 50% of women take folic acid-containing multi-vitamins. Thus, fortified grain products remain an important source of folic acid for the majority of women.
- The authors identified the following limitations:
- A registry analysis can only reveal associations between the timing of fortification and trends in birth defects rates
- Since elective abortion data were not recorded in the pre-fortification time period, they could not be used in the analyses
- Changing demographics were not assessed; demographic shifts between the time periods may account for the increasing prevalence observed with some of the anomalies
- The association between the observed trends and folic acid fortification must be considered carefully. Individuals' folate and folic acid intake were not measured, so ecological observations should not be applied to individuals within the population
- Although the article notes that hospital personnel reporting congenital anomalies to ACASS were trained and supervised, it is unclear whether anomalies were reported consistently across hospitals in the province (including both case identification as well as any potential non-response issues). Any differences in consistency between hospitals and overtime may confound the study findings.
Research Design and Implementation Criteria Checklist: Primary Research
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