We are failing to prevent birth defects caused by preexisting maternal diabetes mellitus! In this issue, Correa et al report strong case-control data that suggest that, among women who took a vitamin that contained folic acid periconceptionally, those with preexisting diabetes mellitus are 6 times more likely to have a baby with a congenital heart defect than women without diabetes mellitus. For truncus arteriosus, the increase is 25-fold. For noncardiac birth defects, the risk is increased 3-fold. For holoprosencephaly, the increase is 9-fold. These are simply enormous increases in risk. Something about maternal diabetes mellitus is responsible, and it is not being adequately addressed by the research, clinical, public health, and political worlds. There is an urgent need to prevent these birth defects.

If prevention were easy, we would have already accomplished it. Although the evidence from randomized, controlled trials is sparse, there is strong observational evidence that good glycemic control lowers the risk. There is a nice dose-response curve with HgbA1c. It is reasonable to assume that better preconception control of glycemia will prevent a significant proportion, if not all, of the excess birth defects among the children of women with preexisting diabetes mellitus. Because such control must precede conception, all women with diabetes mellitus who could become pregnant must be in control.

Programs for all women of reproductive age are much more difficult to implement successfully than programs that can be implemented after conception, but they can be done. We have prevented the congenital rubella syndrome through routine immunization of boys and girls and folic acid–preventable spina bifida and anencephaly through mandatory fortification of enriched cereal grains, such as flour. The data in the article by Correa et al suggest that folic acid fortification has removed the excess risk of spina bifida and anencephaly among the children of women with preexisting diabetes mellitus but has done little, if anything, to reduce risk for other birth defects. Their work is consistent with the idea that regular consumption of folic acid supplements, even in the postfortification era, may reduce some of the risk for certain birth defects, but this idea is not proved. Even if there is protection, there still would remain risk. Simply put: there is no easy magic bullet. We can and must do better.

The prevention of these birth defects requires, or at least we should assume it requires, all women with diabetes mellitus who could become pregnant to be in good glycemic control when they become pregnant. This is an extremely tall order. It would be easier if one could rely on a program only for women who planned their pregnancies. Unfortunately, such a program would not work for the 60% of unplanned pregnancies among women with diabetes mellitus. In addition, as Correa et al point out, approximately one-third of women of reproductive age with diabetes mellitus have yet to be diagnosed. Does this mean we need to screen all women of reproductive age for diabetes mellitus every 5 years? If so, another tall order.

What new steps should be taken to accelerate the prevention? I think we should markedly increase our effort to prevent birth defects among women with juvenile diabetes mellitus. These women are almost all known to the clinical care system. We need clinical research programs that seek to determine what sort of support for these women will increase the likelihood of good glycemic control when pregnancy occurs. Lessons learned here are likely to be applicable to other women with diabetes mellitus. Such a program would start in the pediatric community. One of the keys to successful research will be collaborative studies that will involve many centers. One of the great contributions to pediatrics in the last 50 years has been the success at curing acute lymphocytic leukemia. The key to this success was that the pediatric research community realized that no single center would accumulate cases fast enough to solve this problem in a reasonable time, which led to large multicenter study groups that gradually whittled away at finding the successful treatments for leukemia.

Multicenter studies would be helped by population-based registries of children with juvenile diabetes mellitus. Correa et al used data from the National Birth Defects Prevention Study, which was built on existing population-based birth defects surveillance systems that amassed the children with birth defects who were born among 3,000,000 births. Correa et al knew that getting sufficient data from which to make reasonable inferences about birth defects and preexisting diabetes mellitus required very large numbers. Maybe a practical place to start for registries of children with juvenile diabetes mellitus is in the locations that already have population-based birth defects surveillance programs.

We must establish a reasonable prevention goal and then achieve it. I suggest that we have as a goal a 50% reduction by 2020 of birth defects among the children of women with juvenile diabetes mellitus. To achieve this goal will take contributions from many sectors. If there is the political will to achieve such a goal, I suggest that Congress, the Juvenile Diabetes Foundation, the March of Dimes, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and the National Institutes of Health combine resources to commission the Institute of Medicine to produce a plan rapidly that could be expected to achieve the 50% reduction and that would require the pertinent appropriations committees of Congress to be prepared to move rapidly to provide the resources that will be needed to implement the plan. Such actions should accelerate the pace of the prevention of birth defects that are associated with preexisting diabetes mellitus and thereby improve the lives of children and families while reducing infant mortality rates.

I suggest that the National Birth Defects Prevention Study gather information on HgbA1c. Perhaps women with diabetes mellitus, in their interviews, can give a reliable report of their HgbA1c near conception. Alternatively, the surveillance programs could be asked to abstract this information on a routine basis. A special study might be conducted to obtain these values for the women with diabetes mellitus in the current study. The addition of this biomarker would improve the inferences that can be made from these data.

Those researchers around the world who want to do something immediately to prevent birth defects that are associated with maternal diabetes mellitus should promote mandatory folic-acid fortification of flours. We know that not only will this action prevent spina bifida and anencephaly among children of women with diabetes mellitus, but it will also prevent these serious birth defects for the children of women in the general population. It has been 20 years since the definitive study that proved that folic acid will prevent spina bifida and anencephaly. It is a major, tragic failure of public health policy that no country in Europe has yet to require fortification and that the Prime Minister of New Zealand has, for a political favor, delayed implementation of mandatory folic-acid fortification. I remind you that Rosenberg wrote that folic acid fortification is the “… most important science-driven intervention in nutrition and public health in decades.” It is sad that these preventable birth defects continue to occur because of a failure of political will.

On a happy note, there was the political will for folic acid fortification in the United States. I hope there will also be the political will here to accelerate the pace of the prevention of the birth defects that are associated with preexisting diabetes mellitus.