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August 2003
Dear members,
The mission of the March of Dimes Birth Defects Foundation is to improve the health of babies by preventing birth defects and infant mortality. March of Dimes Global Programs builds on the Foundation's strengths by developing and implementing innovative programs to promote perinatal health worldwide.
This electronic newsletter provides you with announcements about resources and activities of the March of Dimes and its partners, promising new research results, upcoming conferences and other useful topics.
Recommended Levels of Folic Acid and Vitamin B12 Fortification
A Technical Consultation of the Pan American Health Organization (PAHO), March of Dimes and Centers for Disease Control and Prevention (CDC)
Neural tube defects (NTDs) are common congenital malformations originating when the open neural tube, present at very early stages in the development of the human embryo, fails to close on or before the 29th day after conception. Approximately 200,000 children worldwide die from folic acid-preventable NTDs every year. NTDs, therefore, constitute one of the most common forms of congenital malformations, with varying prevalence depending on genetic and environmental conditions.
There is overwhelming evidence linking folate insufficiency to increased risk of NTDs, and increased intake of synthetic folic acid (the more bioavailable form of folate) to reduction of NTD risk. The findings lend support to the recommendation by the U.S. Public Health Service in 1992 that all women of childbearing age should consume 0.4 mg (400 µg) of synthetic folic acid daily, in addition to folate from a varied diet, in order to reduce their risk of an NTD-affected pregnancy. All women who are capable of becoming pregnant should consume this same level of folic acid so that body levels of folate are adequate before and after conception.
Providing folic acid supplementation to all women of childbearing age, however, poses major logistical challenges. Thus, increasing folate levels through folic acid fortification of foods is an important public health strategy for most countries, including those of the Americas. In January 1998, the United States, followed by Canada, began folic acid fortification of grains. In the following years, other countries in the Americas began to implement mandatory fortification of grains with folic acid. Currently, 16 countries in the Americas are fortifying wheat flour with folic acid, in addition to iron, at levels that vary between 1.5 and 3.4 mg/kg flour. Unfortunately, countries have adopted different levels of fortification without any standardized criteria for determining these fortification levels. Thus, clear guidelines for selecting the optimal level of folic acid fortification are necessary, and these need to take into consideration the nutritional requirement, consumption level of the food vehicle, technological issues and costs.
A concern often raised when considering folic acid fortification of foods is that it will result in some people’s consuming average daily levels above the upper limit of 1mg recommended by the Institute of Medicine. Although health effects of consuming high levels of folic acid are not fully known, a concern is delay in the diagnosis of hematological and neurological impairments due to vitamin B12 deficiency, with possible acceleration of neurological manifestations of vitamin B12 deficiency. Vitamin B12 deficiency can occur in individuals with dietary patterns that exclude animal or fortified foods, and in some adults—usually 50 years of age and older—who are unable to absorb vitamin B12 in food. Given that the diet in Latin America and the Caribbean is generally based on corn, rice, wheat, beans and potatoes, with relatively low intakes of foods of animal origin, vitamin B12 deficiency is a major concern and should be considered. There are yet no recommendations or guidelines in relation to food fortification with vitamin B12.
Responding to this need, the Food and Nutrition Program of the Pan American Health Organization, the March of Dimes and the Centers for Disease Control and Prevention convened a Technical Consultation in January 2003 to develop guidelines on folic acid and vitamin B12 fortification for the populations of the Americas. The Consultation addressed the following topics: (1) the physiology of folate and vitamin B12 in health and disease; (2) the role of folate and vitamin B12 in population health; (3) the dietary intake recommendations of folate and vitamin B12; (4) indicators of folate and vitamin B12 status; (5) benefits and limitations of folic acid supplementation; (6) folate and vitamin B12 status in the Americas; (7) folic acid fortification experiences in Canada, Chile, Costa Rica, and the U.S.; and (8) issues around technological feasibility, food vehicles and cost of fortification.
A special supplement of the Nutrition Reviews containing the proceedings and the guidelines from the Consultation will be published later this summer. A Web link to the supplement will be published in the next copy of the newsletter. The guidelines are expected to serve as an impetus to a broader process of promoting and strengthening programs on optimal food fortification, specifically with respect to folic acid and vitamin B12, in the Americas and around the world.
Medical Genetics and Cancer Prevention in the Countries of the Eastern Mediterranean
The revolution in perinatal health practice and medical genetics during the past two decades has profoundly benefited health in many populations of the industrialized world. Unfortunately, these benefits have had little or no impact in developing countries where more than 80 percent of the world’s population—4.8 billion people—lives. Each year, more than 5 million children worldwide are born with serious birth defects that cause death or lifelong disability for the individual and hardship for entire families. More than 4.6 million of these infants (or 93 percent) are born in developing nations.
The success of the Human Genome Project has contributed to knowledge that can help reduce birth defects mortality and disability worldwide. Project findings have led to the identification of the genes responsible for an increasing number of monogenic disorders and the active investigation in large population cohorts of the genetic bases of the more common polygenic disorders. There is a pressing need to transfer this rapidly increasing knowledge to new generations of biomedical researchers, health care providers and other specialists in the developing world.
The European Genetics Foundation (EGF) was founded in 1995 to train young medical geneticists in genomics and to promote the public understanding of genetics. EGF manages the European School of Genetic Medicine, the only initiative in Europe that has established a tradition in the organization of advanced training in these fields.
Last year, EGF was awarded a grant of 1.1 million Euros to conduct a project entitled Euro-Mediterranean Cancer Prevention and Genetic Medicine Network within the framework of the Euro-Mediterranean Information Society (EUMEDIS) of the European Commission. The principal objective of the project is to create a Euro-Mediterranean network that shares scientific expertise and resources and improves health care in the areas of genetic medicine and cancer prevention.
The aims of the project are to: (1) train health care professionals from the 12 Mediterranean (MEDA) countries (Algeria, Cyprus, Egypt, Israel, Jordan, Lebanon, Malta, Morocco, the Palestinian autonomous territories, Syria, Tunisia and Turkey) in genetic medicine and cancer prevention; (2) establish a Euro-Mediterranean Network of clinical geneticists and laboratory specialists who share current knowledge in the diagnosis and treatment of genetic disorders, including cancers, through the use of Internet technology; and (3) test and compare new technologies (in particular, diagnostic DNA chips) for laboratory diagnosis. The course content will focus on those genetic diseases—e.g., the thalassemias—and cancers that occur most commonly in Mediterranean countries.
The following courses are being offered by EGF as part of the EUMEDIS project:
- 8th Course in Cancer Genetics – Bertinoro, Italy, 5-9 September 2003 (15 fellowships for MEDA scientists available)
- 1st Course in Genetic and Acquired Thrombophilia: Investigation and Management – Cyprus, 29 November-2 December 2003 (15 fellowships for MEDA scientists available).
In addition, EGF is offering the following two courses:
- 5th Course in Molecular Cytogenetics and DNA arrays - Bertinoro, 10-14 September 2003 (10 fellowships available)
- 3rd Course in From Developmental Genes to Dysmorphology- Bertinoro, 4-7 October 2003 (10 fellowships available).
For information on how to register for these courses and apply for fellowships, and for additional information on EGF or the EUMEDIS project, please visit: www.eurogene.org.
The March of Dimes-de Waal Mission Alliance
Despite considerable advances in the reduction of infant mortality in Central and South America over the past two decades, infant mortality rates (IMR) in a number of countries remain high. Rates currently range from 10/1000 in Chile to 67/1000 in Bolivia.
Strengthening education of health care providers and the public in prenatal health is one strategy for supporting the continued decline in the IMR in Latin America. March of Dimes Global Programs collaborated with the Netherlands-based de Waal Foundation to develop and implement a broad-based prenatal education curriculum for Latin America. The curriculum is being taught to health care providers, educators and community leaders who, in turn, are educating pregnant women, adolescents and the broader community about best practices in promoting healthy birth outcomes. The curriculum is currently administered through non-governmental organizations established in each target country for this purpose.
Since the program's inception in 2000, over 10,000 professionals in six countries (Ecuador, Peru, Honduras, Nicaragua, El Salvador and Guatemala) have been trained, and the program continues to expand. Program staff in each target country also are charged with developing strategies for raising program funds from outside sources. The goal for each national program is to become self-supporting after five years of operation, and this goal is being realized. Last year the program office in Ecuador raised more than $100,000 dollars in outside support of its activities.
The success of the March of Dimes-de Waal Foundation partnership demonstrates that organizations with distinct capacities, but sharing a common mission, can cooperate to create successful and sustainable prenatal health programs. For more information on the de Waal-March of Dimes prenatal program, visit the PreNatal Web site.
Hormone Treatment Reported To Lower Preterm Birth Rate
"The incidence of preterm birth in developing countries is higher than in developed countries," according to a recent report by Eduardo B. da Fonseca and colleagues at Brazil's University of São Paolo Medical School. "In Brazil, preterm birth is a public health problem because of the striking social differences in the population." They cite a preterm birth rate of 22.5 percent at their hospital, as compared with rates of 7-12 percent in developed countries.
In February, the São Paolo team published one of two recent studies suggesting that treating selected women at high risk for preterm birth (i.e., women with a previous preterm birth) with progesterone during the latter half of pregnancy can reduce preterm births by one-third to one-half.
In their study, 72 high-risk women used vaginal suppositories containing 100 mg of natural progesterone, applied every night from the 24th week until delivery or the 34th week of gestation. 70 matched controls used placebos in the same way. Assignment to the two groups was randomized and blinded.
All women had single fetuses. Nearly all had at least one prior, spontaneous preterm birth. A few in each group were at risk because of a uterine malformation or incompetent cervix. All were screened for common genital tract infections. Those with positive cultures were given specific antibiotics, and repeat cultures verified success of that treatment.
In the progesterone and placebo groups respectively, preterm birth rates were 13.8 percent versus 28.5 percent for births before 37 weeks, and more strikingly, 2.8 percent versus 18.6 percent for the more worrisome births before 34 weeks.
It is of interest that among the 20-30 percent of women in both groups who were hospitalized for preterm labor, tocolytic treatment with beta-mimetic drugs delayed delivery for more than 72 hours in 85.7 percent of the progesterone group versus 36.4 percent of the placebo group. Delay of only a few days offers the chance for corticosteroid treatment to speed maturation of the fetal lungs.
In June, a collaborating group of 19 United States medical centers reported a similar study in which 310 women received weekly injections of 250 mg of 17 alpha-hydroxyprogesterone caproate (17P), a weak but long-acting semi-synthetic form of the hormone, starting in the 16th to 20th week and continuing until delivery or the 36th week. There were 153 matched controls. All women had single fetuses, and at least one prior preterm birth (averaging 1.4 in the 17P group and 1.6 in the placebo group).
In the 17P and placebo groups, preterm birth rates were 36.3 percent versus 54.9 percent for birth before 37 weeks, 20.6 percent versus 30.7 percent before 35 weeks, and 11.4 percent versus 19.6 percent before 32 weeks.
Babies in the 17P group had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage and need for supplemental oxygen.
How progesterone treatment can reduce risk of preterm birth is unclear. Small studies of treatment with 17P started at least three decades ago, when the "progesterone withdrawal" mechanism that leads to labor and delivery in various other mammals was suspected of a similarly strong role in primates. Such studies had mixed results, although a meta-analysis in 1990 pointed to about a 50 percent reduction in preterm labor, preterm birth and low birthweight. The two new studies may revive the notion of progesterone withdrawal as part of what triggers labor in humans, and should lead to further clinical trials to further elucidate the potential effects of pregesterone on pregnancy and preterm delivery.
Until next time,
The March of Dimes
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