Primary prevention of congenital anomalies was identified as an important action in the field of rare diseases by the European Commission in 2008, but it was not included in the Council Recommendation on an action in the field of rare diseases in 2009. However, primary prevention of congenital anomalies is feasible because scientific evidence points to several risk factors (e.g., obesity, infectious and toxic agents) and protective factors (e.g., folic acid supplementation and glycemic control in diabetic women). Evidence-based community actions targeting fertile women can be envisaged, such as risk-benefit evaluation protocols on therapies for chronic diseases, vaccination policies, regulations on workplace and environmental exposures as well as the empowerment of women in their lifestyle choices. A primary prevention plan can identify priority targets, exploit and integrate ongoing actions and optimize the use of resources, thus reducing the health burden for the new generation. The EUROCAT-EUROPLAN recommendations for the primary prevention of congenital anomalies endorsed in 2013 by the European Union Committee of Experts on Rare Diseases present an array of feasible and evidence-based measures from which national plans can adopt and implement actions based on country priorities. Primary prevention of congenital anomalies can be achieved here and now and should be an integral part of national plans on rare diseases.

Keywords:
Congenital anomalies, EUROCAT, EUROPLAN, Health policies, Periconceptional service, Preconception care, Preconception counseling, Prevention of congenital abnormalities, Primary prevention, Public health
1.
World Health Organization: Congenital anomalies. Fact sheet No. 370, updated January 2014. http://www.who.int/mediacentre/factsheets/fs370/en/# (accessed August 28, 2014).
2.
Whitworth M, Dowswell T: Routine pre-pregnancy health promotion for improving pregnancy outcomes. Cochrane Database Syst Rev 2009;CD007536.
3.
Gilbert-Barness E: Teratogenic causes of malformations. Ann Clin Lab Sci 2010;40:99-114.
4.
WHO Guidelines on Preventing Early Pregnancy and Poor Reproductive Outcomes among Adolescents in Developing Countries. Systematic Review. Geneva, WHO, 2011.
5.
Taruscio D, Arriola L, Baldi F, Barisic I, Bermejo-Sánchez E, Bianchi F, Calzolari E, Carbone P, Curran R, Garne E, Gatt M, Latos-Bieleńska A, Khoshnood B, Irgens L, Mantovani A, Martínez-Frías ML, Neville A, Rissmann A, Ruggeri S, Wellesley D, Dolk H: European recommendations for primary prevention of congenital anomalies: a joined effort of EUROCAT and EUROPLAN projects to facilitate inclusion of this topic in the National Rare Disease Plans. Public Health Genomics 2014;17:115-123.
6.
Taruscio D, Carbone P, Granata O, Baldi F, Mantovani A: Folic acid and primary prevention of birth defects. Biofactors 2011;37:280-284.
7.
Honein MA, Rasmussen SA, Reefhuis J, Romitti PA, Lammer EJ, Sun L, Correa A: Maternal smoking and environmental tobacco smoke exposure and the risk of orofacial clefts. Epidemiology 2007;18:226-233.
8.
Hackshaw A, Rodeck C, Boniface S: Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update 2011;17:589-604.
9.
Ungerer M, Knezovich J, Ramsay M: In utero alcohol exposure, epigenetic changes, and their consequences. Alcohol Res 2013;35:37-46.
10.
Boyd PA, Haeusler M, Barisic I, Loane M, Garne E, Dolk H: Paper 1: the EUROCAT network - organization and processes. Birth Defects Res A Clin Mol Teratol 2011;91(suppl 1):S2-S15.
11.
Dolk H: EUROCAT: 25 years of European surveillance of congenital anomalies. Arch Dis Child Fetal Neonatal Ed 2005;90:F355-F358.
12.
Khoshnood B, Greenlees R, Loane M, Dolk H; EUROCAT Project Management Committee; EUROCAT Working Group: Paper 2: EUROCAT public health indicators for congenital anomalies in Europe. Birth Defects Res A Clin Mol Teratol 2011;91(suppl 1):S16-S22.
13.
EU Council Recommendation of June 8, 2009 on a European action in the field of rare diseases. Off J Eur Union 2009;C151:7-10.
14.
Taruscio D, Gentile AE, De Santis M, Ferrelli RM, Posada de la Paz M, Hens M, Huizer J, Fregonese L, Stefanov R, Bottarelli V, Weinman A, Le Cam Y, Gavhed D, Mincarone P, Bushby K, Frazzica RG, Donati C, Vittozzi L, Jessop E: EUROPLAN: a project to support the development of national plans on rare diseases in Europe. Public Health Genomics 2013;16:278-287.
15.
EUROCAT Working Group 2012: EUROCAT special report: congenital anomalies are a major group of mainly rare diseases. EUROCAT Central Registry, University of Ulster. http://www.eurocat-network.eu/content/Special-Report-Major-Group-of-Mainly-Rare-Diseases.pdf (accessed August 28, 2014).
16.
Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on Rare Diseases: Europe's challenges (COM(2008)679 final). http://ec.europa.eu/health/ph_threats/non_com/docs/rare_com_en.pdf (accessed August 28, 2014).
17.
Rasmussen SA, Erickson JD, Reef SE, Ross DS: Teratology: from science to birth defects prevention. Birth Defects Res A Clin Mol Teratol 2009;85:82-92.
18.
Czeizel AE: Birth defects are preventable. Int J Med Sci 2005;2:91-92.
19.
Irani P, Bohn C, Halasan C, Landen M, McCusker D: Community health assessment: driving the need for current, easily accessible population health data. J Public Health Manag Pract 2006;12:113-118.
20.
Johnson K, Posner SF, Biermann J, Cordero JF, Atrash HK, Parker CS, Boulet S, Curtis MG; CDC/ATSDR Preconception Care Work Group; Select Panel on Preconception Care: Recommendations to improve preconception health and health care - United States. A report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. MMWR Recomm Rep 2006;55:1-23.
21.
Earl R, Crowther CA, Middleton P: Interventions for hyperthyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev 2013;11:CD008633.
22.
Reid SM, Middleton P, Cossich MC, Crowther CA, Bain E: Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev 2013;5:CD007752.
23.
Mahmud M, Mazza D: Preconception care of women with diabetes: a review of current guideline recommendations. BMC Womens Health 2010;10:5.
24.
Wahabi HA, Alzeidan RA, Esmaeil SA: Pre-pregnancy care for women with pre-gestational diabetes mellitus: a systematic review and meta-analysis. BMC Public Health 2012;12:792.
25.
Tieu J, Middleton P, Crowther CA: Preconception care for diabetic women for improving maternal and infant health. Cochrane Database Syst Rev 2010;12:CD007776.
26.
Tieu J, Bain E, Middleton P, Crowther CA: Interconception care for women with a history of gestational diabetes for improving maternal and infant outcomes. Cochrane Database Syst Rev 2013;6:CD010211.
27.
Browne ML, Rasmussen SA, Hoyt AT, Waller DK, Druschel CM, Caton AR, Canfield MA, Lin AE, Carmichael SL, Romitti PA; National Birth Defects Prevention Study: Maternal thyroid disease, thyroid medication use, and selected birth defects in the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol 2009;85:621-628.
28.
European Food Safety Authority: Scientific opinion on dietary reference values for iodine. EFSA J 2014;12:3660.
29.
van Zuuren EJ, Albusta AY, Fedorowicz Z, Carter B, Pijl H: Selenium supplementation for Hashimoto's thyroiditis. Cochrane Database Syst Rev 2013;6:CD010223.
30.
Kitzmiller JL, Wallerstein R, Correa A, Kwan S: Preconception care for women with diabetes and prevention of major congenital malformations. Birth Defects Res A Clin Mol Teratol 2010;88:791-803.
31.
Shriraam V, Mahadevan S, Anitharani M, Selvavinayagam, Sathiyasekaran B: National health programs in the field of endocrinology and metabolism - miles to go. Indian J Endocrinol Metab 2014;18:7-12.
32.
Koloverou E, Esposito K, Giugliano D, Panagiotakos D: The effect of Mediterranean diet on the development of type 2 diabetes mellitus: a meta-analysis of 10 prospective studies and 136,846 participants. Metabolism 2014;63:903-911.
33.
Popkin BM, Slining MM: New dynamics in global obesity facing low- and middle-income countries. Obes Rev 2013;14(suppl 2):11-20.
34.
Karoutsou E, Polymeris A: Environmental endocrine disruptors and obesity. Endocr Regul 2012;46:37-46.
35.
Opray N, Grivell RM, Deussen AR, Dodd JM: Directed preconception health programs and interventions for improving pregnancy outcomes for women who are overweight or obese (protocol). Cochrane Database Syst Rev 2014;1:CD010932.
36.
Sotres-Alvarez D, Siega-Riz AM, Herring AH, Carmichael SL, Feldkamp ML, Hobbs CA, Olshan AF; National Birth Defects Prevention Study: Maternal dietary patterns are associated with risk of neural tube and congenital heart defects. Am J Epidemiol 2013;177:1279-1288.
37.
Haider BA, Bhutta ZA: Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev 2006;4:CD004905, update in Cochrane Database Syst Rev 2012;11:CD004905.
38.
Czeizel AE, Dudás I, Vereczkey A, Bánhidy F: Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects. Nutrients 2013;5:4760-4775.
39.
De-Regil LM, Fernández-Gaxiola AC, Dowswell T, Peña-Rosas JP: Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2010;10:CD007950.
40.
Obeid R, Holzgreve W, Pietrzik K: Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? J Perinat Med 2013;41:469-483.
41.
Denny KJ, Jeanes A, Fathe K, Finnell RH, Taylor SM, Woodruff TM: Neural tube defects, folate, and immune modulation. Birth Defects Res A Clin Mol Teratol 2013;97:602-609.
42.
Guan Z, Wang J, Guo J, Wang F, Wang X, Li G, Xie Q, Han X, Niu B, Zhang T: The maternal ITPK1 gene polymorphism is associated with neural tube defects in a high-risk Chinese population. PLoS One 2014;9:e86145.
43.
Bitzer J, von Stenglin A, Bannemerschult R: Women's awareness and periconceptional use of folic acid: data from a large European survey. Int J Womens Health 2013;5:201-213.
44.
Stamm RA, Houghton LA: Nutrient intake values for folate during pregnancy and lactation vary widely around the world. Nutrients 2013;5:3920-3947.
45.
Fajardo V, Varela-Moreiras G: Efficacy of adding folic acid to foods. Int J Vitam Nutr Res 2012;82:177-186.
46.
Wei SQ: Vitamin D and pregnancy outcomes. Curr Opin Obstet Gynecol 2014;26:438-447.
47.
Harvey NC, Holroyd C, Ntani G, Javaid K, Cooper P, Moon R, Cole Z, Tinati T, Godfrey K, Dennison E, Bishop NJ, Baird J, Cooper C: Vitamin D supplementation in pregnancy: a systematic review. Health Technol Assess 2014;18:1-190.
48.
Huber JC Jr, Brender JD, Zheng Q, Sharkey JR, Vuong AM, Shinde MU, Griesenbeck JS, Suarez L, Langlois PH, Canfield MA, Romitti PA, Weyer PJ; National Birth Defects Prevention Study: Maternal dietary intake of nitrates, nitrites and nitrosamines and selected birth defects in offspring: a case-control study. Nutr J 2013;12:34.
49.
Latini G, Knipp G, Mantovani A, Marcovecchio ML, Chiarelli F, Söder O: Endocrine disruptors and human health. Mini Rev Med Chem 2010;10:846-855.
50.
Nieuwenhuijsen MJ, Dadvand P, Grellier J, Martinez D, Vrijheid M: Environmental risk factors of pregnancy outcomes: a summary of recent meta-analyses of epidemiological studies. Environ Health 2013;12:6.
51.
European Food Safety Authority: Scientific opinion on the risk for public health related to the presence of mercury and methylmercury in food. EFSA J 2012;10:2985.
52.
European Food Safety Authority: Scientific opinion on the developmental neurotoxicity potential of acetamiprid and imidacloprid. EFSA J 2013;11:3471.
53.
Barouki R, Gluckman PD, Grandjean P, Hanson M, Heindel JJ: Developmental origins of non-communicable disease: implications for research and public health. Environ Health 2012;11:42.
54.
European Food Safety Authority: Scientific opinion on lead in food. EFSA J 2010;8:1570.
55.
Rinaudo P, Wang E: Fetal programming and metabolic syndrome. Annu Rev Physiol 2012;74:107-130.
56.
Juul A, Almstrup K, Andersson AM, Jensen TK, Jørgensen N, Main KM, Rajpert-De Meyts E, Toppari J, Skakkebæk NE: Possible fetal determinants of male infertility. Nat Rev Endocrinol 2014;10:553-562.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.