Folic acid cuts baby heart defects

“Folic acid in bread can reduce risk of heart defects in babies,” The Daily Telegraph has reported. The newspaper says that new Canadian research has shown that adding the vitamin to bread and pasta can cut the risk of congenital heart defects (CHDs) in babies. In the UK there is said to be concern about the addition since increased folic acid intake can potentially mask vitamin B12 deficiency in the elderly.

Folic acid supplements are valuable in the weeks prior to conception and in the first 12 weeks of pregnancy, as they reduce the risk of neural tube defects such as spina bifida. This new, thorough analysis of Canada’s CHD rates also suggests that the addition of folic acid to grain products since 1998 has reduced the prevalence of CHD. In years before fortification the prevalence of severe CHDs was 1.64 cases per 1,000 births, but in the years following the change rates fell to 1.47 per 1,000. Although the research has several important limitations, this unique study supports previous evidence of an association between CHDs and folic acid, and should be considered in the debate over fortification of food products.

Where did the story come from?

This research was conducted by Raluca Ionescu-Ittu of the Department of Epidemiology, Biostatistics and Occupational Health and other colleagues of McGill University, Canada. Funding for the study was provided by the Heart and Stroke Foundation of Canada and the Fonds de la Recherche en Santé du Québec. The study was published in the peer-reviewed British Medical Journal.

What kind of scientific study was this?

This was a time-trend analysis investigating whether there has been a reduction in the prevalence of severe CHDs since the Canadian government introduced mandatory fortification of flour and pasta products with folate in 1998.

Although an association between folic acid supplementation and reduced neural tube defects (such as spina bifida) is firmly established, other research has suggested that it may also reduce the number of babies born with CHDs.

The researchers focused on the province of Quebec, identifying all infants born with severe CHDs between 1990 and 2005 using a database of medical records since 1983. They used codes to identify babies with a severe CHD identified at birth or within the first three years of life. They also looked at the Quebec death registry to find babies who had died or been stillborn as a result of severe CHDs. Information on the annual number of live births in Quebec for the 16-year period was retrieved from Statistics Canada reports.

The severe CHDs analysed in this study included those with tetralogy of Fallot, endocardial cushion defects, univentricular hearts, truncus arteriosus and transposition complexes. Analysis was restricted to severe defects only, due to the possibility of inaccuracy in detecting mild defects.

The researchers examined the trends for birth prevalence of severe CHDs before and after the 1998 implementation of folic acid fortification of grain products. The researchers cut their analysis into two time periods: births prior to, and after, January 1999. This was to allow a 15-month lag time between announcement of the policy and its implementation and a lag time between conception and birth.

What were the results of the study?

During the period of 1990 to 2005 there were 1,324,440 births in Quebec and 2,083 of these infants were born with severe CHDs. The average birth prevalence of severe CHDs in years before fortification was slightly higher than that for the period after fortification. Prior to fortification the average rate was 1.64 cases per 1,000 births (95% confidence interval 1.55 to 1.73), while after fortification there were 1.47 cases per 1,000 births (confidence interval 1.37 to 1.58).

Separate analysis of types of defects showed that the birth prevalence of defects involving abnormal connections between the heart chambers or blood vessels (conotruncal defects) and other types of CHD (non-conotruncal) were both reduced in the years after fortification.

Time-trend analysis showed that there was no yearly change in the birth prevalence of severe CHDs in the nine years prior to fortification (rate ratio 1.01, 95% confidence interval 0.99 to 1.03). In the seven years after fortification there was a significant decrease in prevalence, falling by 6% every year (rate ratio 0.94, 95% confidence interval 0.90 to 0.97).

What interpretations did the researchers draw from these results?

The researchers conclude from their study that the Canadian fortification of grain products with folic acid was followed by a significant decrease in the prevalence of severe CHDs. This supports the theory that folic acid supplementation in the period around conception reduces the number of babies born with severe CHDs.

What does the NHS Knowledge Service make of this study?

This thorough analysis has examined the changing prevalence of severe CHDs in the years surrounding mandatory folic acid fortification of grain products in 1998. The study has found that birth prevalence of severe CHDs has reduced from 1.64 per 1,000 births in years prior to fortification compared to 1.47 per 1,000 in the following seven years, with a gradual reduction in prevalence every year.

There are several points to bear in mind regarding this research:

• Although there is a clear association between fortification and reduced birth prevalence of severe CHDs, it is difficult to conclude that the decrease is definitely as a result of fortification of flour and pasta. There is no information available on women’s consumption of these grain products (that is, whether they consumed them and how much they consumed) both in women whose babies were born with CHDs and those born without.
• Women may also have been continuing to take folic acid tablets in the conception period, and not relying solely on that found in grain products. The paper says the target daily intake with the fortification policy was significantly lower than that with multivitamin supplementation.
• In this study it was not possible to adjust for the many other factors that might potentially increase the risk of CHDs, for example genetics, maternal infections, illnesses and drug exposure, father’s health and environmental factors.
• Although accurate databases were used to obtain data on severe CHDs there is the possibility for inaccurate recording and misclassification in the databases. It is also not possible to comment on any pregnancy terminations that may have been carried out as a result of CHDs being detected.
• The researchers say they did not think it feasible to detect all the milder cases of CHD. This means a large number of babies with other congenital conditions have not been included in the analysis.
• Although the researchers allowed for a time lag for implementation of the fortification policy (based on US estimates from implementation of their own policy), there is the possibility that the cut-off period that they used of January 1999 may be out by several months.

Nevertheless, this is reportedly the first population-based study to investigate the association between grain fortification with folic acid and birth prevalence of severe CHDs. It supports previous evidence of an association between CHDs and folic acid, and it will add to the debate about the values and drawbacks of nationwide fortification of grain products.