5 p.m., June 24, 1991: The beginning of the end of spina bifida F and anencephaly F (2020)

At 5 p.m., June 24, 1991, I experienced the most exciting moment of my long career in teratology and birth defects epidemiology. I returned a phone call to now Sir Nicholas Wald. He told me that the UK Medical Research Council (MRC) randomized controlled trial had ended early because it conclusively showed that folic acid alone would prevent 72% of spina bifida and anencephaly occurrence among women who previously delivered a child with spina bifida and/or anencephaly. Spina bifida and anencephaly are common, severe, often fatal, neural tube birth defects affecting pregnancies worldwide. Figure 1 is a photo of the original note I wrote down during the call with Sir Nicholas Wald at 5 p.m., June 24, 1991. I quickly jotted down what I was hearing from Dr. Wald in the hotel light pink note pad by the phone. I knew at this moment that we had the science to eliminate a likely large proportion of spina bifida and anencephaly. I knew that to prevent spina bifida F and anencephaly F (F stands for folic acid-preventable spina bifida and anencephaly), the world required that food be fortified with sufficient folic acid. I gave this goal my highest priority since then, and it continues to be a priority in my work as the Director of the Center for Spina Bifida Prevention at Emory University until this day, because over 100 countries are failing to require folic acid fortification of staples. I fear, as I approach my 80th birthday, I will not see the end of the preventable spina bifida F and anencephaly F pandemic. On June 24, 1991, I was exceedingly happy and excited. I had to catch a boat to go to a dinner being held by the Teratology Society. So I wanted to share the news I received from Sir Nicholas Wald with Drs. Dave Erickson (seen in Figure 2) and Jose Cordero, two close colleagues at the US Centers for Disease Control and Prevention (CDC), but did not want to do so at the meeting. The three of us did not meet until 9 p.m. that day in my room. It had been very difficult not to tell them this confidential, wonderful, game changing result from the MRC trial until then. Insightful, as always, Dave reminded me that Dr. Robert J. Berry was scheduled to fly out of Atlanta the same week Friday to take his wife Jane and his four sons to China to conduct a randomized controlled trial among women who had not had a child with spina bifida or anencephaly. Dave said it was no longer ethical to do such a study and we should not let Dr. Berry and his family leave for China unless my boss, Dr. Vernon Houk knew of findings of the UK MRC study and approved Dr. Berry carrying on a different kind of study in China. Thank you, Dave, you saved my bacon again. I made an appointment and Dave and I met with Dr. Houk and Mr. Jack Jackson on June 25, 1991. Vern listened and said send Dr. Berry to China. Dave and I returned for the last 2 days of the meeting. Dr. Berry departed on that Friday and worked with our colleague Dr. Li Zhu to complete and publish, in the New England Journal of Medicine, findings from the community intervention trial that they did, which showed that the Recommended Daily Allowance (RDA) dose of 400 μg/day was fully effective in preventing spina bifida and anencephaly among study participants. It, therefore, was not necessary to use 4,000 μg/day dose that had been used in the UK MRC randomized controlled trial. I had refused to tell Dr. Houk's secretary the agenda for the meeting. It was so confidential I did not think appropriate to discuss on the phone. When we arrived, both she and then Dr. Houk were not very happy that I had not given the agenda. Fortunately, Dr. Houk did not let his displeasure with me get in the way of his very proper decision. In August, we published in the Morbidity and Mortality Weekly Reports CDC recommendations for women who had had a child with either of the two birth defects (i.e., spina bifida and anencephaly). On September 11, 1992, CDC published the United States Public Health Service recommendation that all women of reproductive age consume daily 400 μg of folic acid to prevent spina bifida and anencephaly. The US FDA subsequently issued regulations requiring all enriched grains to be fortified at 140 μg per 100 g of grain, which resulted in most Americans consuming about 150 μg daily and the reduction of spina bifida and anencephaly to 5 per 10,000 births, establishing the nonfolic acid preventable rate of spina bifida and anencephaly. The Society for Birth Defects Research and Prevention (formerly Teratology Society) passed a resolution (see the editorial on it in this issue) calling on all governments to fortify grains with at least 150 μg per 100 g of grain. Sadly, the European Teratology Society refused to pass a similar resolution contributing to the continuing preventable pandemic of spina bifida F and anencephaly F. Getting the FDA to require folic acid fortification was not easy. When I first discussed the idea with them the senior FDA official, I am told, said we will never fortify with folic acid. The final essential push to get fortification required in the United States was Dr. Jennifer Howse and Dr. Richard Johnston, Jr.'s finest hour while at the March of Dimes. After the FDA had decided in May of 1995 not to permit or require folic acid fortification, they brought the political pressure that led Dr. David Kessler, the Commissioner, to issue regulations in March 1996 that required fortification by January 1, 1998. The CDC has noted that in the last decade of the last century and first decade of this century folic acid fortification is one of the top 10 actions in public health. In the first decade of this century, folic acid fortification programs saved $4.5 billion in the US health care expenses alone that can be diverted toward addressing other health issues. Finally, there was an important collateral benefit—fortification with folic acid also eliminated folate deficiency anemia in the US population. The authors declare no conflicts of interest. NA