Joe Mulinare: The Early Years of Folic Acid Research
Categories: General
April 27th, 2012 2:02 pm ET - Curt Shannon
Editor’s Note: In 2012 we will mark the 20th anniversary of the US Public Health Service recommendation that women of childbearing age should consume 400 micrograms (mcg) of folic acid every day to help prevent certain neural tube defects (NTDs) – spina bifida and anencephaly. Several CDC scientists were involved in the research that led up to the recommendation, or contributed to the subsequent work on folic acid that continues today, including Joseph Mulinare, Robert J. Berry, J. David Erickson, and Godfrey Oakley. The four blogs in this series tell their stories.
When Joseph (Joe) Mulinare, MD, MSPH, came to CDC in 1981 he immediately began to work on researching the role of folic acid in preventing the neural tube defects (NTDs) anencephaly and spina bifida, serious birth defects of the brain and spine. He helped conduct an early CDC study of babies born in metro Atlanta between 1968-1980,that found a reduced risk for having a baby with a neural tube defect among mothers who had taken folic acid around the time of conception.
During the mid-1980s, it was decided that the case control studies that CDC was conducting and other observational studies from the United Kingdom and elsewhere, were not sufficient to show that folic acid really prevented NTDs,” says Mulinare. There was consensus that a randomized controlled trial was needed.
A randomized controlled trial among women who had already had a child with an NTD was conducted during the 1980s and its results were reported in 1991 by the British Medical Research Council (MRC) with principal investigator Nicholas Wald—which showed that folic acid alone prevented NTDs among women who had had a previous NTD-affected pregnancy.
“With that randomized trial and evidence from a couple of other studies that were unpublished at the time, including a randomized trial from Hungary that found that a multi-vitamin containing folic acid actually prevented NTDs among women who had not had a previous NTD-affected pregnancy, we set the stage for writing the September 1992 recommendation for the prevention of the occurrence of NTDs—that all women of childbearing age consume 400 micrograms (mcg) daily,” said Mulinare. “Part of that recommendation also included a repeat of the one we had done earlier in August 1991, which said that all women who had had a previous affected pregnancy should take 4,000 micrograms, 10 times the amount, because the MRC study actually used 4,000 micrograms, not 400.”
The recommendation pointed out three ways that women can get folic acid: from diet, from supplements, and through fortification. There was general agreement that getting 400 mcg of folic acid solely from naturally-occurring food sources was impractical—women would have to eat a lot of it, it’s expensive, and it’s not readily available in many communities. “We knew that only 20 percent of women were consuming a supplement containing 400 micrograms of folic acid, so our plan from 1992 to 1999 was to work to get required folic acid fortification of cereal grain products and to do promotions saying that women of childbearing age should take 400 micrograms in a supplement,” explains Mulinare.
However, there were problems with supplementation. Gallup conducted polls from 1995-2005 that showed little change in the use of 400 mcg of folic acid through supplementation. “From the surveillance that we did—we never saw the percentage of use of 400 micrograms of folic acid (through supplements) go above about 35 percent,” says Mulinare. This information further justified and reinforced the whole approach to move forward with fortification of flour.
From 1992-1996, Mulinare and others worked with the March of Dimes, the American Academy of Pediatrics, the Teratology Society, and the Food and Drug Administration (FDA) to determine the amount of folic acid that would be put into enriched foods. The required amount of 140 mcg of folic acid /100 grams was officially implemented in January 1998. “At that point, we had what we thought was the best possible coverage of women of child-bearing age to get folic acid for the prevention of spina bifida and anencephaly,” says Mulinare.
Prior to fortification in 1998, CDC estimated that there were approximately 4,000 NTD-affected pregnancies every year. Following fortification, a study showed a decrease of NTD-affected pregnancies by more than 1,000. “So, 1,000 babies who otherwise would have been born with an NTD were born without an NTD. That was a pretty decent public health achievement, for which we got some credit recently as one of the 10 most effective prevention campaigns in the US,” states Mulinare. “The National Birth Defects Prevention Network Surveillance System has indicated that by the end of 2006 there was about a 36 percent overall reduction in the rates of NTDs.” That means than over the past 10 years, more than 10,000 pregnancies have occurred that have not been affected by an NTD.
According to the NHANES (National Health and Nutrition Examination Survey) only about 20-25 percent of women in the US consume a supplement of 400 mcg. After fortification had been in effect for several years, it was suggested that women of reproductive age who did not take supplements also had a similar reduction in the prevalence of NTDs. The 140 mcg (in fortified foods) taken on a regular basis appeared to be enough to prevent many NTDs among non-supplement users. “Unlike supplements, in which you have to ask people to change behavior, fortification is there—and, hopefully, will always be there,” says Mulinare. “The positive thing is that we are in a place where it is felt by many that the folic acid that is being put in food now is safe and effective.”
For more information about CDC’s folic acid success story, go Folic Acid: Helping to Prevent Birth Defects. For more detailed information on folic acid, visit the CDC Folic Acid Web Page on the CDC Works For You 24/7 web site. Thanks to Faye McDonald Smith of CDC who wrote the original article on which this blog was based.
Joe Mulinare (l) and Dave Erickson collaborated closely during the 1980s and 1990s as part of the CDC team that studied the role of folic acid in preventing certain types of NTDs. Photo courtesy of Godfrey Oakley
During the mid-1980s, it was decided that the case control studies that CDC was conducting and other observational studies from the United Kingdom and elsewhere, were not sufficient to show that folic acid really prevented NTDs,” says Mulinare. There was consensus that a randomized controlled trial was needed.
A randomized controlled trial among women who had already had a child with an NTD was conducted during the 1980s and its results were reported in 1991 by the British Medical Research Council (MRC) with principal investigator Nicholas Wald—which showed that folic acid alone prevented NTDs among women who had had a previous NTD-affected pregnancy.
“With that randomized trial and evidence from a couple of other studies that were unpublished at the time, including a randomized trial from Hungary that found that a multi-vitamin containing folic acid actually prevented NTDs among women who had not had a previous NTD-affected pregnancy, we set the stage for writing the September 1992 recommendation for the prevention of the occurrence of NTDs—that all women of childbearing age consume 400 micrograms (mcg) daily,” said Mulinare. “Part of that recommendation also included a repeat of the one we had done earlier in August 1991, which said that all women who had had a previous affected pregnancy should take 4,000 micrograms, 10 times the amount, because the MRC study actually used 4,000 micrograms, not 400.”
An important part of the recommendation was that women needed to start taking 400 mcg prior to conception–at least a month before they conceive. “What we also knew then–and is still true now—is that about 50 percent of pregnancies are unplanned in the US,” says Mulinare. “So that made us write the recommendation in a way that said all women of childbearing age should be consuming 400 micrograms of folic acid daily because we wanted to cover the 50 percent of women who don’t plan to become pregnant.” Since NTDs occur very early in pregnancy, within the first 28 days, adequate consumption of folic acid prior to pregnancy is critical.
The recommendation pointed out three ways that women can get folic acid: from diet, from supplements, and through fortification. There was general agreement that getting 400 mcg of folic acid solely from naturally-occurring food sources was impractical—women would have to eat a lot of it, it’s expensive, and it’s not readily available in many communities. “We knew that only 20 percent of women were consuming a supplement containing 400 micrograms of folic acid, so our plan from 1992 to 1999 was to work to get required folic acid fortification of cereal grain products and to do promotions saying that women of childbearing age should take 400 micrograms in a supplement,” explains Mulinare.
However, there were problems with supplementation. Gallup conducted polls from 1995-2005 that showed little change in the use of 400 mcg of folic acid through supplementation. “From the surveillance that we did—we never saw the percentage of use of 400 micrograms of folic acid (through supplements) go above about 35 percent,” says Mulinare. This information further justified and reinforced the whole approach to move forward with fortification of flour.
From 1992-1996, Mulinare and others worked with the March of Dimes, the American Academy of Pediatrics, the Teratology Society, and the Food and Drug Administration (FDA) to determine the amount of folic acid that would be put into enriched foods. The required amount of 140 mcg of folic acid /100 grams was officially implemented in January 1998. “At that point, we had what we thought was the best possible coverage of women of child-bearing age to get folic acid for the prevention of spina bifida and anencephaly,” says Mulinare.
Prior to fortification in 1998, CDC estimated that there were approximately 4,000 NTD-affected pregnancies every year. Following fortification, a study showed a decrease of NTD-affected pregnancies by more than 1,000. “So, 1,000 babies who otherwise would have been born with an NTD were born without an NTD. That was a pretty decent public health achievement, for which we got some credit recently as one of the 10 most effective prevention campaigns in the US,” states Mulinare. “The National Birth Defects Prevention Network Surveillance System has indicated that by the end of 2006 there was about a 36 percent overall reduction in the rates of NTDs.” That means than over the past 10 years, more than 10,000 pregnancies have occurred that have not been affected by an NTD.
According to the NHANES (National Health and Nutrition Examination Survey) only about 20-25 percent of women in the US consume a supplement of 400 mcg. After fortification had been in effect for several years, it was suggested that women of reproductive age who did not take supplements also had a similar reduction in the prevalence of NTDs. The 140 mcg (in fortified foods) taken on a regular basis appeared to be enough to prevent many NTDs among non-supplement users. “Unlike supplements, in which you have to ask people to change behavior, fortification is there—and, hopefully, will always be there,” says Mulinare. “The positive thing is that we are in a place where it is felt by many that the folic acid that is being put in food now is safe and effective.”
For more information about CDC’s folic acid success story, go Folic Acid: Helping to Prevent Birth Defects. For more detailed information on folic acid, visit the CDC Folic Acid Web Page on the CDC Works For You 24/7 web site. Thanks to Faye McDonald Smith of CDC who wrote the original article on which this blog was based.
.png)
No hay comentarios:
Publicar un comentario