Comparison of National Policies onPericonceptional Use of Folic Acid toPrevent Spina Bifida andAnencephaly (SBA)MARTINAC. CORNEL1,2 AND J. DAVID ERICKSON1,3*1International Clearinghouse for Birth Defects Monitoring Systems, Rome, Italy2Department of Medical Genetics, University of Groningen, 9713 AW Groningen, The Netherlands3Centers for Disease Control and Prevention, Atlanta, Georgia 30333

In 1991 the British Medical Research Council-fundedrandomized controlled trial (RCT) (MRCVitamin StudyResearch Group, ’91), demonstrated that folic acidsupplements used before conception and during earlypregnancy (i.e., the periconceptional period) will pre-vent some but not all of the neural tube defects, spinabifida and anencephaly (SBA); in 1992 similar resultswere reported from an RCT in Hungary by Czeizel andDudas (’92). Following the release of these results,health agencies in several countries established poli-cies concerning the use of folic acid during the pericon-ceptional period to prevent SBA. The development ofthese policies has been followed closely by the Interna-tional Clearinghouse for Birth Defects Monitoring Sys-tems, an organization of birth defects monitoring pro-grams from many countries around the world.Prevention of birth defects is an important goal of theClearinghouse.

METHODS

We have collected published information from 12countries known to have issued official policies. Wehave determined which countries have establishedpolicies from (1) contacts with Health Ministries byClearinghouse programs, (2) by a literature search ofMEDLINE, and (3) by contact with UNICEF. In thispaper we compare those official policies in effect as ofMarch 1997.The policies of all countries are accompanied by

specific recommendations for action for the preventionof SBA. There are two general kinds of recommenda-tions: ‘‘recurrence’’ and ‘‘occurrence.’’ Recurrence recom-mendations suggest actions that can be taken bywomenwho already have had a pregnancy affected by SBA.Occurrence recommendations suggest actions forwomenin the general population, women who have not had aprior affected pregnancy. In most countries the risk inthe general population (i.e., the occurrence risk) isbetween 0.5 and 3 per 1,000 births. Women who havehad an earlier SBA-affected pregnancy are at increasedrisk (10–50 per 1,000 births) of having an affected fetusin a subsequent pregnancy (recurrence). Of all SBA-affected pregnancies, less than 5% occur in families

where there has been an earlier SBA-affected preg-nancy. The impact of occurrence recommendations onthe frequency of SBA, therefore, will be much greaterthan the impact of recurrence recommendations.‘‘Folic acid’’ refers to pteroylmonoglutamic acid, a

synthetic compound that is used in dietary supple-ments and fortified foods. The term ‘‘folate’’ refers to allcompounds that have the vitamin properties of folicacid; folates include folic acid and naturally occurringcompounds in food. Folic acid is more readily absorbedthan are most naturally occurring food folates.

RESULTS

Countries whose national health agencies have maderecommendations regarding the prevention of SBA byincreasing the consumption of folic acid or naturallyoccurring food folates are listed in Table 1. In mostcountries the recommendation for recurrence specifiesa high daily consumption of folic acid (4.0–5.0 mg) inthe periconceptional period, whereas a lower intake,usually in the range of 0.4–0.5 mg per day, is advised forthe prevention of first occurrences of SBA (Table 2). InSpain, the Ministry of Health has issued advisoriesonly on recurrence prevention. In China and Hungary,no distinction is made between occurrence and recur-rence, and all women planning pregnancies are beingadvised to take lower-dose folic acid supplements. InNew Zealand, for both occurrence and recurrence,women were advised on an interim basis to take 5.0 mgfolic acid daily, but now a 0.8 mg folic acid tablet isavailable and is recommended for occurrence preven-tion.

DISCUSSION

The development of official policies indicates thatseveral countries consider the primary prevention ofSBAan important public health goal. Although the goalis the same in all countries, there are some importantdifferences in the policies formulated. In some coun-tries, all women of childbearing age who are capable of

*Correspondence to: J. David Erickson, MS-F45, Centers for DiseaseControl and Prevention, Atlanta GA30333.

Received 6 June 1996; accepted 12 February 1997

TERATOLOGY 55:134–137 (1997)

r 1997 WILEY-LISS, INC.

becoming pregnant are advised to consume adequateamounts of folic acid, whereas in other countries thisadvice is directed only at women planning pregnancy.The difference may be related in part to the proportionof planned pregnancies in the countries involved. Forexample, in Ireland many pregnancies are unplanned(Department of Health, Ireland, ’93). Similarly, in theUnited States it is estimated that more than 50% ofpregnancies are unplanned (Centers for Disease Con-trol and Prevention, ’92). Hence, the recommendationsin these countries are directed at all women of reproduc-tive age. In China, however, where there are relativelyfew unplanned pregnancies, the recommendation isdirected at women planning to become pregnant (Minis-try of Public Health, China, ’93). In the recommenda-tions from the other countries, information on theplanning of pregnancies is not given. Helping to pre-vent SBA by instituting a policy aiming at all women ofchildbearing age may be harder to realize than preven-tion through a policy aiming only at women planningpregnancy, since women who are planning pregnancymay be better motivated, and the period during whichthey have to follow the advice is much shorter. On theother hand, if a large proportion of pregnancies areunplanned, many infants will not benefit from a pri-

mary preventive measure aimed only at women whoare planning pregnancies.Fortification of a staple foodstuff, such as flour, might

be the most efficient way to increase the folic acidconsumption of a large proportion of women in somecountries, but not in others. In China, where 80% of thepopulation lives in rural areas, food production anddistribution is generally local. Therefore, centralizedfortification of staple foods is not considered feasible inChina at this time. However, health authorities in atleast five countries (Australia, South Africa, The Neth-erlands, the United Kingdom, and the United States)have considered fortification of staple foodstuffs. InJune 1995, the Australian National Food Authorityamended its Food Standards Code to permit the volun-tary fortification of a number of foods, including flours,with folic acid. In September 1995, The NetherlandsCabinet approved an amendment of the Food andDrugs Act allowing the addition of folic acid to certainfoods to compensate for losses during processing (‘‘resto-ration’’). In March 1996, the U.S. Food and DrugAdministration mandated that enriched cereal grainflours will be fortified with 0.14 mg folic acid per 100 gflour. This action will result in the addition of folic acidto most flour-based foods, such as breads and pastas.Manufacturers must comply with this mandate byJanuary 1, 1998. This fortification will increase the folicacid consumption of most U.S. women, but only anadditional 2–3% of womenwill consume theU.S. recom-mended 0.4mg folic acid per day directly as the result offlour fortification; the average reproductive-age womanwill increase her daily folic acid consumption by only0.1 mg (Centers for Disease Control and Prevention,’93).Currently, limited types of food fortified with folic

acid are available only in a few countries included inthis study—breakfast cereals, bread, and milk in Ire-land; breakfast cereals and bread in the United King-dom; breakfast cereals in the United States. NewZealand is now considering whether extra folic acidshould be added to specific foods such as breakfastcereals.Although most countries recommend a folate intake

of 0.4 mg per day for women without a previousSBA-affected pregnancy, there are some variations. TheHungarian recommendation suggests a range of con-sumption for women planning a pregnancy from 0.4–1.0 mg folic acid per day, and the Canadian recommen-dation suggests consideration of 0.8 mg per day.Australia advises a supplement of 0.5 mg daily becausesupplements containing folic acid alone are only avail-able in 0.5 mg pills; in The Netherlands only 0.5 mgpills were available when the advisory was issued, butnow 0.4 mg pills are available.Although the daily intake of folates recommended by

Norwegian health authorities for occurrence preven-tion may appear very similar to the recommendedamount in other countries (Table 2), the advice differsin that the consumption should be achieved by eating

TABLE 1. Countries that have national policies onprevention of spina bifida and anencephaly through

periconceptional folic acid consumption

CountryAgency that issued recommendation/

reference

Australia National Health and Medical ResearchCouncil (’94)

Canada Department of Health and Welfare;Health Protection Branch (McCourt,’93)

China Ministry of Public Health (’93)Denmark National Food Agency (’97)Hungary National Health Promotion Institute

(’95)Ireland Health Promotion Unit, Department of

Health (’93)New Zealand Public Health Commission (’93)Norway Directorate of Health (’93)South Africa Department of National Health and

Population Development (’93)Spain Ministry of Health (’92)The Netherlands Inspectorate of Public Health (’93)1United Kingdom Department of Health (’92)

Scottish Office Home and Health Depart-ment

Welsh OfficeDepartment of Health and Social Ser-vices, Northern Ireland

United States US Department of Health and HumanServices; Public Health Service (’91,’92)

1Several governmental agencies were involved: The FoodCouncil and Health Council together gave advice to theMinistry of Health, which then communicated it to healthworkers in a letter from the Inspectorate of Public Health. Therecommendations differ somewhat. We included only theInspectorate’s advice in this survey.

POLICIES ON USE OF FOLIC ACID TO PREVENT SBA 135

folate-rich foods only; the advice in Canada also speci-fies folate-rich foods for women not planning a preg-nancy, but does not indicate a desired amount for dailyintake. In all other countries that have made occur-rence recommendations, folic acid supplements areindicated as a source of folate. Because most naturallyoccurring folates in foods are less readily absorbed thanis folic acid, the Norwegian and Canadian advice willlead to a lower absorbed dose. However, the Canadianadvice for women planning pregnancies to consider theuse of supplements could lead to higher intakes than inNorway.The occurrence recommendation advanced in the

United States differs from the recommendations ofsome other countries in that the consumption of 0.4 mgof folates can come from foods or from fortified foods orsupplements. Other countries recommend that thesupplements be added to the diet. However, should anAmerican woman consume a diet containing sufficientfolate-rich foods, her intake of 0.4 mg of folates wouldresult in consumption of bioavailable folates that islower thanwhen 0.4mg of folic acid is added to any diet.We have discussed governmental recommendations

concerning folic acid intake to prevent SBA, but obvi-ously governmental advisories alone are not sufficientto achieve a major decrease in the occurrence of SBA.We have not investigated what actions have been taken

to inform health workers and women of childbearingages about these recommendations. In some countrieswhere no governmental advisories have been issued,some professional groups have issued recommenda-tions. In addition, voluntary groups, such as the Associa-zione Studio Malformazioni in Italy, the March ofDimes Birth Defects Foundation in the United States,and organizations of parents and patients have startedcampaigns. Although we have not included a review ofthese efforts here, we recognize that these activitiesmight have an impact similar to, or greater than, thatof a governmental advisory.When the information that folic acid decreases the

risk for SBA reaches women of childbearing age, theywill have to change their behaviour and follow theadvice. We have not investigated what proportion ofpregnancies occur after periconceptional use of folicacid. Doing so would be the best way to measure howeffective a policy, program, or campaign is. In the futurethe International Clearinghouse for BirthDefectsMoni-toring Systems will collect data on the periconceptionaluse of folic acid from different countries.Spina bifida and anencephaly are common and seri-

ous birth defects, and a substantial fraction are prevent-able simply by increasing women’s consumption of folicacid. Promoting the prevention of SBA by increasing

TABLE 2. Summary of spina bifida and anencephaly occurrenceprevention recommendations

Country

Directed at allfertile women or atwomen planninga pregnancy

Recommendeddaily

consumptionof folates (mg)

How to achieve dailyconsumption

Australia Planning or likely tobecome pregnant

.0.5 Folate-rich foods 1 fortifiedfoods 1 0.5 mg supplementdaily

Canada All Not specified Folate-rich foodsPlanning .0.4/0.81 Supplement daily

China Planning .0.4 Supplement dailyDenmark Planning 0.4 Folate-rich foods; supplement if

neededHungary Planning 0.4–1.0 Supplement dailyIreland Women who are

likely to becomepregnant

.0.4 Folate-rich foods 1 fortifiedfoods 1 0.4 mg supplementdaily

New Zealand Planning 0.8 0.8 mg tablet per day. A diet con-taining extra folates aroundthe time of conception is recom-mended, to add to but notreplace daily folic acid by tablet

Norway All 0.4 Folate-rich foodsSouth Africa All 0.4 Supplement dailyThe Netherlands Planning .0.5 0.5 mg supplement dailyUnited Kingdom Planning .0.4 Folate-rich foods 1 fortified

food 1 0.4 mg supplementdaily

United States All 0.4 Food and/or fortified food and/orsupplements

1The Canadian recommendations state that women planning a pregnancy should consulttheir physician about folic acid supplements. In the information to physicians, it is statedthat ‘‘a dose of 0.4 mg daily is likely to be beneficial,’’ but ‘‘Individuals may choose to use dosesup to 0.8 mg, as the evidence for a preventive effect on occurrence is strongest at that dose.’’

136 M.C. CORNEL AND J.D. ERICKSON

folic acid consumption represents an opportunity forpublic health action in many countries.

LITERATURE CITEDCenters for Disease Control (USA) (1991) Use of folic acid forprevention of spina bifida and other neural tube defects 1983–1991.M.M.W.R., 40:513–6.

Centers for Disease Control and Prevention (USA) (1992) Recommen-dations for the use of folic acid to reduce the number of cases of spinabifida and other neural tube defects. M.M.W.R., 41:1–7.

Centers forDiseaseControl andPrevention (USA) (1993)Positionpaper onfolic acid food fortification and the prevention of aspina bifida andanencephaly.WorkingGroup onFolicAcid, unpublishedmanuscript.

Czeizel A, Dudas I (1992) Prevention of first occurrence of neural tubedefects by periconceptional vitamin supplementation. N.E.J.M.,327:1832–5.

Department of Health (Ireland) (1993) What every woman needs toknow about the prevention of neural tube defects spina bifida andanencephaly. The Health Promotion Unit.

Department of Health (United Kingdom) (1992) Expert AdvisoryGroup (United Kingdom). Folic Acid and the Prevention of NeuralTube Defects.

Department of National Health and Population Development (SouthAfrica) (1993) The prevention of neural tube defects by folic acidsupplementation. Recommendation from the Department of NationalHealth andPopulationDevelopment. SouthAfricanMed. J., 83:914.

Directorate of Health (Norway) (February 1993) Measures aiming atthe reduction of neural tube defects.

General Directorate of Pharmacy and Sanitary Products (Spain)(1992) Recommendations regarding the use of supplemental folicacid to prevent damage to the neural tube. Circular 1/92. Ministry ofHealth, Madrid.

Inspectorate of Public Health (The Netherlands) (November 1993)Prevention of neural tube defects.

McCourt C. (1993) Primary prevention of neural tube defects: noticefrom the HPB (Canada). Can. Med. Assoc. J., 148:1451.

Ministry of Public Health (People’s Republic of China) The Ministry ofHealth promulgates the third batch of recommendations (Septem-ber 13, 1993). Jian Kang Bao, October 1993, vol. 1, p. 1. And:Recommendation of using folic acid supplements to prevent neuraltube defects.

MRC Vitamin Study Research Group (1991) Prevention of neural tubedefects: Results of the Medical Research Council Vitamin Study.Lancet, 338:131–7.

National Food Agency (Denmark) (1997) Folate and neural tubedefects.

National Health and Medical Research Council (Australia) (1994)Revised statement on the relationship between dietary folic acid andneural tube defects such as spina bifida. J. Paediatr. Child Health,30:476–477.

National Health Promotion Institute (Hungary) (1995) Congenitalanomalies are preventable.

Public Health Commission (New Zealand) (September 28, 1993)Reducing the chances of spina bifida by taking folic acid.

POLICIES ON USE OF FOLIC ACID TO PREVENT SBA 137