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Summary: July 20, 2021 marked the 30th anniversary of the publication of the landmark trial by the British Medical Research Council showing unequivocally that maternal intake of folic acid (vitamin B9) starting before pregnancy prevents most cases of infant spina bifida and anencephaly—two major neural tube defects that are severe, disabling, and often fatal. Mandatory food fortification with folic acid is a safe, cost-effective, and sustainable intervention to prevent spina bifida and anencephaly. Yet few countries implement fortification with folic acid; only a quarter of all preventable spina bifida and anencephaly cases worldwide are currently avoided by food fortification. We summarise scientific evidence supporting immediate, mandatory fortification with folic acid to prevent the development of spina bifida and anencephaly. We make an urgent call to action for the World Health Assembly to pass a resolution for universal mandatory folic acid fortification. Such a resolution could accelerate the slow pace of spina bifida and anencephaly prevention globally, and will assist countries to reach their 2030 Sustainable Development Goals on child mortality and health equity. The cost of inaction is profound, and disproportionately impacts susceptible populations in low-income and middle-income countries.

Background: Spina bifida and anencephaly are largely preventable birth defects through mandatory folic acid fortification. Our objective was to estimate the proportion of folic acid‐preventable spina bifida and anencephaly (FAP SBA) prevented worldwide through mandatory fortification of wheat and/or maize flour with folic acid during the year 2017. Methods: Using existing data, we identified countries with mandatory fortification policies that added at least 1.0 ppm folic acid to wheat and/or maize flour and had information on percentage of industrially milled flour that is fortified. We assumed mandatory folic acid fortification at 200 μg/day of folic acid fully protects against FAP SBA, reducing the prevalence of spina bifida and anencephaly to 0.5 per 1,000 live births. Results: Overall, 59 countries met our criteria for implementing mandatory folic acid fortification of wheat and/or maize flour in 2017. These countries prevented about 50,270 out of 280,500 FAP SBA births in 2017. Thus, we have only achieved 18% prevention of FAP SBA worldwide. Several countries in Africa and Asia with a high number of FAP SBA‐affected births do not have mandatory fortification. Conclusion: About 230,000 children unnecessarily developed FAP SBA globally in 2017. There is an urgent need for all countries to implement mandatory folic acid fortification, a proven, safe public health intervention that saves money and prevents infant mortality and disability. Prevention of FAP SBA can play an important role in helping countries to achieve their Sustainable Development Goals for health. [ABSTRACT FROM AUTHOR]

Background: The United States implemented mandatory folic acid fortification of enriched cereal grains in 1998. Although several studies have documented the resulting decrease in anemia and folate deficiency, to our knowledge, no one has determined the prevalence of folate-deficiency anemia after fortification. Objective: We determined the prevalence of folate deficiency and folate-deficiency anemia within a sample of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Design: The REGARDS cohort is a prospective cohort of 30,239 black and white participants living in the contiguous United States. We measured serum folate concentrations in a random sample of 1546 REGARDS participants aged ≥50 y with baseline hemoglobin and red blood cell mean corpuscular volume measurements. Folate deficiency was defined as a serum folate concentration < 6.6 nmol/L (<3.0 ng/mL), and anemia was defined as a hemoglobin concentration,13 g/dL in men and <12 g/dL in nonpregnant women (WHO criteria). Folate-deiciency anemia was defined as the presence of both folate deficiency and anemia. Results: The mean hemoglobin concentration was 13.6 g/dL, and 15.9% of subjects had anemia. The median serum folate concentration was 34.2 nmol/L (15.1 ng/mL), and only 2 of 1546 participants 0.1%) were folate deficient. Both subjects were African American women with markedly elevated C-reactive protein concentrations, macrocytosis, and normal serum cobalamin concentrations; only one subject was anemic. Overall, the prevalence of folate-deficiency anemia was <0.1% (1 of 1546 subjects). Conclusion: Our data suggest that, after mandatory folic acid fortification, the prevalence of folate-deficiency anemia is nearly nonexistent in a community-dwelling population in the United States. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To describe the prevalence of biochemical B12 deficiency in adults with type 2 diabetes taking metformin compared with those not taking metformin and those without diabetes, and explore whether this relationship is modified by vitamin B12 supplements. RESEARCH DESIGN AND METHODS--Analysis of data on U.S. adults ≥50 years of age with (n = 1,621) or without type 2 diabetes (n = 6,867) from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Type 2 diabetes was defined as clinical diagnosis after age 30 without initiation of insulin therapy within 1 year. Those with diabetes were classified according to their current metformin use. Biochemical B12 deficiency was defined as serum B12 concentrations ≤148 pmol/L and borderline deficiency was defined as >148 to ≤221 pmol/L. RESULTS--Biochemical B12 deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002). Among those with diabetes, metformin use was associated with biochemical B12 deficiency (adjusted odds ratio 2.92; 95% CI 1.26-6.78). Consumption of any supplement containing B12 was not associated with a reduction in the prevalence of biochemical B12 deficiency among those with diabetes, whereas consumption of any supplement containing B12 was associated with a two-thirds reduction among those without diabetes. CONCLUSIONS--Metformin therapy is associated with a higher prevalence of biochemical B12 deficiency. The amount of B12 recommended by the Institute of Medicine (IOM) (2.4 µg/day) and the amount available in general multivitamins (6 µg) may not be enough to correct this deficiency among those with diabetes. [ABSTRACT FROM AUTHOR]

Objective: To explore the association between vitamin B12 (B12)-containing supplement use, low B12 concentrations and biochemically defined B12 deficiency in US adults. Design: A cross-sectional study with adjustment for survey design. Prevalence ratios for two age groups (18-50 and >50 years) were estimated using unconditional logistic models. Outcome measures included prevalence of low serum B12 concentration (<148 pmol/l) and biochemical B12 deficiency (serum B12<148 pmol/l with concomitant homocysteine<10 μmol/l). Setting: A population survey of health and nutritional measures. Subjects: Subjects were non-institutionalized adults, aged 18 years and older, who participated in Phase 2 of NHANES III (Third National Health and Nutrition Examination Survey). Results: Low B12 concentrations were less prevalent among persons consuming B12-containing supplements (P=0·001) with an adjusted prevalence ratio of 0·6 (95% CI 0·3, 1·0). Biochemical B12 deficiency showed a similar trend (P=0·0002), with an adjusted prevalence ratio of 0·3 (95% CI 0·1, 0·8). Prevalence ratios were similar in adults <50 years of age, although the prevalence of low B12 and biochemical deficiency was proportionally higher. Conclusions: Consumption of B12-containing supplements was associated with at least 50% lower prevalence of both low serum B12 and biochemical B12 deficiency in a nationally representative sample of US adults, suggesting increased consumption of B12 from supplements or from fortified foods may reduce the prevalence of B12 deficiency. Additionally, the current Recommended Daily Allowance for B12 of 2·4μg may be insufficient for those aged .50 years. [ABSTRACT FROM AUTHOR]

The article investigates the prevalence of a diabetic condition and adhesive capsulitis of the shoulder. It analyzes an anonymous database for diabetic condition. The article shows that the prevalence of diabetes in patients with adhesive capsulitis was 38.6 percent, while the prevalence of prediabetes was 32.95 percent. It discusses the risk of diabetes and prediabetes in patients presenting with adhesive capsulitis of the shoulder.

Oral supplements of synthetic folic acid and vitamin B12 are very effective in increasing blood levels of the vitamins and are known to prevent birth defects and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Presents letters on medical subjects as of October 15, 2002. Reactions to previous article on the decline of family medicine; Evidence of parallel problems with stroke care and postoperative care for geriatric patients with hip fractures; Interaction of certain drugs and grapefruit; Importance of folic acid fortification; Other issues.

Research during the last 5 years has made it clear that people who do not take folie acid supplements are at increased risk for functional folate deficiency, which has been proven to cause spina bifida and anencephaly and also has been associated with an increased risk for occlusive cardiovascular disease. The overriding folate policy issue is how to increase dramatically the folate consumption of 75% of the pop ulation who are not now consuming 0.4 mg of folie acid in a supplement. The most expeditious way to increase consumption is through fortification of a food staple. Public health programs are also needed to edu cate people about the vital importance of increased consumption of folie acid vitamin supplements and of foods rich in natural folates. It is urgent that fortifica tion of cereal-grain products be implemented now. The level proposed by FDA would accomplish some preven tion, but much more prevention would occur if the forti fication were 2.5 times that level. Fortification at the higher level would prevent about 1000 spina bifida and anencephaly birth defects each year and perhaps as many as 50,000 premature deaths each year from cor onary disease. Available data have not demonstrated that increasing consumption of folie acid by 0.1 to 0.25 mg of folie acid a day is harmful. If a policy needs to be established on the assumption that people who take vitamin supplements could be harmed, a good policy option is available: require that all folie acid vita min supplements also contain 0.4 mg of vitamin B- 12. J. Nutr. 126: 751S-755S, 1996. [ABSTRACT FROM AUTHOR]

Abstract: During the 1970s, the crude incidence of Rh hemolytic disease of the newborn (RhHDN) in the United States dropped 65 per ¢--from 40.5/10,000 total births in 1970 to 14.3/10,000 total births in 1979. Since the risk of RhHDN is directly associated with birth order, changes both in birth order-specific RhHDN incidence rates and in the birth order distribution would be expected to influence crude RhHDN incidence. Review of birth order-specific incidences ascertained in Connecticut, 1972-1977, shows that incidence was stable for first and second births, whereas it dropped significantly for third and fourth births. Due to the nearly complete use of Rh immune globulin (RhIG) in Connecticut during these years, the drop in these specific rates is best attributed to this prevention strategy. Nationwide, during the 1970s, the annual percentages of fourth and higher order births decreased from 18 per ¢ to 10 per ¢. We estimate that some 30 per ¢ to 40 per ¢ of the 1970-1979 drop in the crude rate is attributed to changes in the birth order distribution, whereas 60 per ¢ to 70 per ¢ of the drop is attributed to RhIG. However, comparison of pooled incidences for 1972-1974 and 1975-1977 observed in Connecticut for first births and births to 15-19 year olds showed significant increases for both groups in 1975-1977, Further study of specific trends from other areas is needed to confirm these observations. Also needed is investigation of likely causes of sensitization among these teenaged, primiparous women. [ABSTRACT FROM AUTHOR]

Abstract: The prenatal detection of fetal neural tube defects (NTD)is now possible by means of a multi-tiered program utilizing maternal serum alpha-fetoprotein (MSAFP) screening coupled with ultrasonography and amniocentesis where indicated. This paper considers the economic consequences of screening for fetal NTD a theoretical cohort of 100,000 pregnant women at risk of having an affected fetus who would elect to terminate their pregnancies if an affected fetus were found. The cost of the program was balanced against the benefits of the program, such as the averted costs of institutionalization, medical care, and the like. The total cost of the program to screen 100,000 such women was calculated to be $2,047,780, or slightly over $20 per woman screened, while the total economic benefits exceeded $4,000,000. (Ant. J. Public Health 69:566-573, 1979.) [ABSTRACT FROM AUTHOR]

Comments on a report on the survival and severity of neural tube defects during the period that the U.S. Food and Drug Administration mandated folic acid fortification of grains. Clinical impact of the research findings; Review of related literature; Appeal to the U.S. Congress to increase the budget of the Centers for Disease Control and Prevention.

This article proposes that the U.S. Food and Drug Administration must require the addition of more folic acid in enriched flour and other grains in 2005. In 1991 Wald and his colleagues first provided unambiguous evidence that synthetic folic acid in a pill would prevent most children from getting spina bifida and anencephaly. Sufficient folic acid fortification of food eaten by most women of reproductive age would prevent almost all folic acid-preventable spina and anencephaly. In this regard, the Centers for Disease Control and Prevention and in state health departments have tracked the continuing occurrence of spina bifida and anencephaly before and after folic acid fortification of enriched grains. Unfortunately, the agency estimates that 2000 cases of folic acid-preventable spina bifida and anencephaly pregnancies continue to occur yearly in the country.

Dr. Thomas H. Shepard died on October 3, 2016 at the age of 93. He was a major figure in the fields of teratology, embryonic and fetal pathology, and pediatrics. He was beloved by his colleagues as he was by the many students and fellows whom he taught, mentored and befriended. His contributions to teratology are extraordinary and he is greatly missed. [ABSTRACT FROM AUTHOR]

The article discusses how the Eastern Mediterranean Region (EMR) could have been the first to achieve total prevention of folic acid preventable-spina bifida and anencephaly (FAP SBA) with Oman as the first country in the world to successfully implement a country-wide folic acid fortification program. It cites the possible approaches to show total prevention including spina bifida and anencephaly surveillance programs and conducting case-control studies.

Mandatory vitamin B12 fortification of enriched grain products is long overdue in the United States and Canada. Fortification would help provide the 2.4 μg of synthetic vitamin B12 that the US Institute of Medicine recommends for all persons 50 years and older. The findings of Ray and colleagues1 in this issue suggest that B12 may also help to prevent neural tube defects. If recommendations for B12 fortification were followed, it is possible that cases of spina bifida and anencephaly would be prevented. Two hundred twenty thousand children each year acquire folic acid-preventable spina bifida because many governments, including all in Europe, have yet to implement mandatory folic acid fortification. Fortification with folic acid and vitamin B12 is safe and should be implemented in all countries. [ABSTRACT FROM AUTHOR]

A letter to the editor featuring the authors' acknowledgement of the contributions of the journal in educating its readers about the positive effects of folic acid dietary supplementation in preventing neural tube defects is presented.

Comments on a study about pregnant women who consume enough synthetic folic acid before and during the early weeks of pregnancy. Recommendations for increasing the pace for prevention of folic acid-preventable spina bifida and other folic acid-preventable diseases; Discussion on consumption of wheat and corn flour in the U.S.; Overview of the decision of the Food and Drug Administration to require folic acid-enriched grain products.

Presents an overview of the research on the identification of the preventive attribute of folic acid against spina bifida and anencephaly (SBA). Birth prevalence of SBA; Medical Research Council trial; Public Health Service's recommendation of daily folic acid intake for women; Folic-acid fortified food staple; Advice on consumption of folic acid below 1,0 milligrams per day.

Reviews the computer software 'PC Mass-Psychiatry.'

Focuses on the Birth Defects Monitoring Program (BDMP) by the National Institute of Child Health and Human Development, Centers for Disease Control and Prevention, the March of Dimes Birth Defects Foundation and the Commission on Professional and Hospital Activities in the U.S. Purpose of the program to monitor the incidence of birth defects and other conditions of the newborn; Data used in the BDMP which represents the largest single source of uniformly collected and coded discharge data on birth defects among newborns; Charts depicting rates of malformations among newborns between 1970 to 1980.

Editorial. Comments on the US Food and Drug Administration's issuance of regulation requiring all enriched cereal grains be fortified with folic acid. Benefits of increasing consumption of folic acid; Safeness of increasing consumption of folic acid; Speculation on the harm of fortifying cereal grains with folic acid; Suggestion on the fortification of cereal grains with vitamin B-12.

The article presents a response to a letter to the editor about the concentration of folic acid in food.

Presents a letter to the editor in response to the article "Lessons from the withdrawal of rofecoxib," by P. Dieppe and colleagues in the October 16, 2004 issue.