Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vaccine in Quebec.

CONTEXT: An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe. OBJECTIVE: To assess narcolepsy risk following administration of a similar vaccine in Quebec. DESIGN: Retrospective population-based study. SETTING: Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre. POPULATION: Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry. MAIN OUTCOME MEASURES: Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method. RESULTS: A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12). RR was 2.07 (0.70-6.17) in the SCCS, and 1.48 (0.37-7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases. CONCLUSIONS: Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.

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.

Impact of folic acid food fortification on the birth prevalence of lipomyelomeningocele in Canada.

BACKGROUND: Recent studies reported no reduction in the frequency of lipomeningomyelocele (LMMC) in Hawaii and Nova Scotia after the implementation of a folic acid food fortification policy in 1998, while a marked reduction in the prevalence of other NTDs was observed. This study was performed to assess the prevalence of LMMC in Canada in relation to the timing of food fortification. METHODS: The study population included livebirths, stillbirths, and terminations of pregnancies because of fetal anomaly to women residing in seven Canadian provinces, from 1993 to 2002. In each province, the ascertainment of NTD cases relied on multiple sources, and in addition all medical charts were reviewed. The study period was divided into pre-, partial, and full fortification periods, based on results of red cell folate tests published in the literature. RESULTS: A total of 86 LMMC cases were recorded among approximately 1.9 million live births. The average birth prevalence rate was 0.05/1,000, ranging from a minimum of 0.01/1,000 in 2002 to a maximum of 0.08/1,000 in 1999. There was statistical heterogeneity between years (p = .01), but no pattern compatible with a decrease following fortification. Comparing the full fortification period with the prefortification period, there was a slight but not statistically significant decrease in LMMC birth prevalence. CONCLUSIONS: LMMC seems to be pathogenically distinct from myelomeningocele and more studies are needed to understand the embryologic mechanisms leading to this condition, and the environmental and genetic factors involved in its etiology.

Reduction in neural-tube defects after folic acid fortification in Canada.

BACKGROUND: In 1998, folic acid fortification of a large variety of cereal products became mandatory in Canada, a country where the prevalence of neural-tube defects was historically higher in the eastern provinces than in the western provinces. We assessed changes in the prevalence of neural-tube defects in Canada before and after food fortification with folic acid was implemented. METHODS: The study population included live births, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces from 1993 to 2002. On the basis of published results of testing of red-cell folate levels, the study period was divided into prefortification, partial-fortification, and full-fortification periods. We evaluated the relationship between baseline rates of neural-tube defects in each province and the magnitude of the decrease after fortification was implemented. RESULTS: A total of 2446 subjects with neural-tube defects were recorded among 1.9 million births. The prevalence of neural-tube defects decreased from 1.58 per 1000 births before fortification to 0.86 per 1000 births during the full-fortification period, a 46% reduction (95% confidence interval, 40 to 51). The magnitude of the decrease was proportional to the prefortification baseline rate in each province, and geographical differences almost disappeared after fortification began. The observed reduction in rate was greater for spina bifida (a decrease of 53%) than for anencephaly and encephalocele (decreases of 38% and 31%, respectively). CONCLUSIONS: Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high.

Trend in prevalence of neural tube defects in Quebec.

BACKGROUND: In Canada, the first recommendations on the use of folic acid (FA) supplements by women planning a pregnancy or capable of becoming pregnant were issued in 1993. In 1998, fortification of flour with FA became mandatory. The objective of this study was to assess the impact of these measures on the prevalence of neural tube defects (NTDs) in the province of Quebec. METHODS: The study population included stillbirths, live births, and elective terminations for fetal malformations that were reported in 1992-2000 for women residing in the province of Quebec. NTD cases were identified from stillbirth certificates and hospital discharge summaries. RESULTS: There was a marked decrease in the total NTD rate after 1997. The average NTD rate was 1.89 per 1000 total births during the period of 1992-1997, and 1.28 per 1000 in 1998-2000, a 32% reduction (p < 0.001). CONCLUSIONS: Fortification of flour, which began in early 1997 and gradually became widespread, is a very plausible explanation for the timing, shape, and magnitude of the decrease in NTD prevalence observed in Quebec and other Canadian provinces. An increase in FA supplement use may have played only a minor role. Birth Defects Research (Part A) 67:000-000, 2003.

Pregnancy planning and folic acid supplement use: results from a survey in Quebec.

BACKGROUND: To decrease the risk of neural tube defects, all women planning pregnancy or capable of becoming pregnant should take folic acid supplements. The aim of the study was to describe the association between pregnancy planning and vitamin supplement use. METHODS: A total of 1,858 pregnant women registered for a prenatal ultrasound examination in the Montérégie region, Province of Quebec, Canada, completed a questionnaire between November 1997 and May 1998. Pregnancy planning was described by six ordinal variables, which were included in a nonlinear principal component analysis. The main dimension representing the intensity of pregnancy planning was used as the dependent variable in a multivariate linear regression model, and as a basis for assessing vitamin use according to four levels of planning. RESULTS: A majority of women scored high for intensity of pregnancy planning. Planning intensity score increased with age and was higher among women who attended university, had a family income greater than CAD $30,000, and were married. Vitamin use in the period prior to conception occurred with a frequency of 27.5%, increasing moderately with planning intensity scores. Overall, only 13.5% of fetuses were exposed to adequate doses of folic acid. CONCLUSION: A promotion campaign selectively targeting women likely to plan a pregnancy could have a significant impact in reducing neural tube defect incidence.

Pregnancy planning: a determinant of folic acid supplements use for the primary prevention of neural tube defects.

OBJECTIVE: Daily consumption of supplements containing 400 micrograms of folic acid in the periconception period may reduce the risk of neural tube defects (NTDs) by as much as 70%. However, despite explicit recommendations, folic acid consumption among women likely to become pregnant remains low. The objectives of this study were: to evaluate women's knowledge and beliefs with regard to folic acid; to estimate the frequency of vitamin supplement consumption; and to identify its determinants during the periconception period. METHODS: In 1999-2000, a questionnaire was completed by 1,240 pregnant women in 10 Quebec hospitals. RESULTS: Seventy percent of the respondents were aware of the preventive role of folic acid but only 25% had taken the recommended dose of supplements during the periconception period. Supplement consumption is associated with the pregnancy planning intensity score (OR: 1.06; 95% CI: 1.02-1.11), knowledge score (OR: 1.11; 95% CI: 1.07-1.16) and belief in the usefulness of supplements (OR: 1.56; 95% CI: 1.02-2.39). CONCLUSION: These results indicate that further efforts are needed to inform the population and promote the optimal use of folic acid supplements.