Background: As nutritional deficiencies are known to lead to adverse pregnancy outcomes, a woman's nutritional status should be assessed preconceptionally with the goal of optimizing maternal, fetal and infant health. Worldwide micronutrient intakes do not fit pregnancy requirements, so that their supplementation is recommended from the beginning of pregnancy in most of the low- and middle-income countries. Conversely, data on multiple supplementation in developed countries appear few and controversial. Key Message: Although a balanced diet is generally accessible in industrialized countries, a switch to a high-fat and low-quality diet has led to an inadequate vitamin and mineral intake during pregnancy, so that recent data show the micronutrient intake and supplementation to be lower than recommended even in high-income countries, particularly for iron, folic acid, calcium and vitamin D. Conclusions: Currently, even if there is insufficient evidence to support routine supplementation at the population level, except for periconceptional folate supplementation, these results need to be evaluated at an individual level in order to avoid nutritional deficiencies and to encourage women to establish healthful dietary practices prior to conception. The new goal in industrialized countries needs to be an individualized approach that takes account of the phenotypic, genotypic and metabolic differences among individuals of the same population.

Buckley AJ, Jaquiery AL, Harding JE: Nutritional programming of adult disease. Cell Tissue Res 2005;322:73-79.
De Boo H, Harding JE: The development origins of adult disease (Barker) hypothesis. Aust NZ J Obstet Gynaecol 2006;46:4-14.
Haider BA, Bhutta ZA: Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev 2012;11: CD004905.
Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW; Nutrition Impact Model Study Group (anaemia): Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ 2013;346:f3443.
Peña-Rosas JP, Viteri FE: Effects and safety of preventive oral iron or iron + folic acid supplementation for women during pregnancy. Cochrane Database Syst Rev 2009;12: CD004736.
Berti C, Biesalski HK, Gärtner R, Lapillonne A, Pietrzik K, Poston L, Redman C, Koletzko B, Cetin I: Micronutrients in pregnancy: current knowledge and unresolved questions. Clin Nutr 2011;30:689-701.
Institute of Medicine, Food and Nutrition Board, Committee on Nutritional Status during Pregnancy: Part II. Dietary intake and nutrient supplements. Washington, National Academy, 1990.
Moos MK, Dunlop AL, Jack BW, Nelson L, Coonrod DV, Long R, Boggess K, Gardiner PM: Healthier women, healthier reproductive outcomes: recommendations for the routine care of all women of reproductive age. Am J Obstet Gynecol 2008;199:S280.
ACOG: Nutrition and women. ACOG Educ Bull 229. Washington, ACOG, 1996.
King JC: Physiology of pregnancy and nutrient metabolism. Am J Clin Nutr 2000;71 (suppl 5):1218S-1225S.
Berti C, Cetin I, Agostoni C, Desoye G, Devlieger R, Emmett PM, Ensenauer R, Hauner H, Herrera E, Hoesli I, Krauss-Etschmann S, Olsen SF, Schaefer-Graf U, Schiessl B, Symonds ME, Koletzko B: Pregnancy and infants' outcome: nutritional and metabolic implications. Crit Rev Food Sci Nutr 2014, Epub ahead of print.
Luan H, Meng N, Liu P, Feng Q, Lin S, Fu J, Davidson R, Chen X, Rao W, Chen F, Jiang H, Xu X, Cai Z, Wang J: Pregnancy-induced metabolic phenotype variations in maternal plasma. J Proteome Res 2014;13:1527-1536.
Zhang Z, Yuan E, Liu J, Lou X, Jia L, Li X, Zhang L: Gestational age-specific reference intervals for blood copper, zinc, calcium, magnesium, iron, lead, and cadmium during normal pregnancy. Clin Biochem 2013;46:777-780.
Alvarez SJ, Castanon SG, Ruata MLC, Aragues EF, Terraz PB, Irazabal YG, et al: Updating of normal levels of copper, zinc and selenium in serum of pregnant women. J Trace Elem Med Biol 2007;21:49-52.
Cetin I, Berti C, Calabrese S: Role of micronutrients in the periconceptional period. Hum Reprod Update 2010;16:80-95.
Koletzko B, Bauer CP, Bung P, Cremer M, Flothkötter M, Hellmers C, Kersting M, Krawinkel M, Przyrembel H, Rasenack R, Schäfer T, Vetter K, Wahn U, Weissenborn A, Wöckel A: German national consensus recommendations on nutrition and lifestyle in pregnancy by the ‘Healthy Start - Young Family Network'. Ann Nutr Metab 2013;63:311-322.
WHO: Iodine deficiency in Europe: a continuing public health problem. Geneva, WHO, 2009.
WHO: The challenge of obesity in the WHO European region and the strategies for response. Geneva, WHO, 2007.
Yeh J, Shelton JA: Increasing prepregnancy body mass index: analysis of trends and contributing variables. Am J Obstet Gynecol 2005;193:1994-1998.
Mansour D: Implications of the growing obesity epidemic on contraception and reproductive health. J Fam Plann Reprod Health Care 2004;30:209-211.
Mojtabai R: Body mass index and serum folate in childbearing age women. Eur J Epidemiol 2004;19:1029-1036.
Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA: Maternal obesity and risk for birth defects. Pediatrics 2003;111:1152-1158.
Anderson JL, Waller DK, Canfield MA, Shaw GM, Watkins ML, Werler MM: Maternal obesity, gestational diabetes, and central nervous system birth defects. Epidemiology 2005;16:87-92.
Blumfield ML, Hure AJ, Macdonald-Wicks L, Smith R, Collins CE: A systematic review and meta-analysis of micronutrient intakes during pregnancy in developed countries. Nutr Rev 2013;71:118-132.
Bothwell TH: Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr 2000;72(suppl 1):257S-264S.
Alwan NA, Greenwood DC, Simpson NAB, McArdle HJ, Godfrey KM, Cade JE: Dietary iron intake during early pregnancy and birth outcomes in a cohort of British women. Hum Reprod 2011;26:911-919.
Milman N: Iron in pregnancy: how do we secure an appropriate iron status in the mother and child? Ann Nutr Metab 2011;59:50-54.
Cetin I, Berti C, Mandò C, Parisi F: Placental iron transport and maternal absorption. Ann Nutr Metab 2011;59:55-58.
Stevens G, Finucane M, De-Regil L, Paciorek C, Flaxman S, Branca F, et al: Global, regional, and national trends in total and severe anaemia prevalence in children and pregnant and non-pregnant women. Lancet Glob Health 2013;1:e16-e25.
WHO: Micronutrient deficiencies: iron deficiency anaemia. 2014.
Peña-Rosas JP, De-Regil LM, Dowswell T, Viteri FE: Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev 2012;7:CD009997.
Zaim M, Piselli L, Fioravanti P, Kanony-Truc C: Efficacy and tolerability of a prolonged release ferrous sulphate formulation in iron deficiency anaemia: a non-inferiority controlled trial. Eur J Nutr 2012;51:221-229.
Devrim E, Tarhan I, Ergüder IB, Durak I: Oxidant/antioxidant status of placenta, blood, and cord blood samples from pregnant women supplemented with iron. J Soc Gynecol Investig 2006;13:502-505.
IOM: Dietary reference intakes for calcium and vitamin D. 2010.
Buppasiri P, Lumbiganon P, Thinkhamrop J, Ngamjarus C, Laopaiboon M: Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes. Cochrane Database Syst Rev 2011;10:CD007079.
WHO: Calcium supplementation in pregnant women. Geneva, WHO, 2013.
Lee JM, Smith JR, Phillip BL, Chen TC: Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr 2007;46:42-44.
Brannon PM, Picciano MF: Vitamin D in pregnancy and lactation in humans. Annu Rev Nutr 2011;31:89-115.
Park EA: The therapy of rickets. J Am Med Assoc 1940;115:370-379.
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA: The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011;96:53-58.
Ginde AA, Scragg R, Schwartz RS, Camargo CA Jr: Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older US adults. J Am Geriatr Soc 2009;57:1595-1603.
Johnson DD, Wagner CL, Hulsey TC, Mc-Neil RB, Ebeling M, Hollis BW: Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinatol 2011;28:7-12.
Biesalski HK: Vitamin D recommendations: beyond deficiency. Ann Nutr Metab 2011;59:10-16.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society: Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-1930.
Fekete K, Berti C, Trovato M, Lohner S, Dullemeijer C, Souverein Ow, Cetin I, Decsi T: Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation. Nutr J 2012;11:75.
Hovdenak N, Haram K: Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol 2012;164:127-132.
USPSTF: Folic acid for the prevention of neural tube defects: US Preventive Services Task Force recommendation statement. Ann Intern Med 2009;150:626-631.
Berti C, Fekete K, Dullemeijer C, Trovato M, Souverein O W, Cavelaars A, Dhonukshe-Rutten R, Massari M, Decsi T, Van't Veer P, Cetin I: Folate intake and markers of folate status in women of reproductive age, pregnant and lactating women: a meta-analysis. J Nutr Metab 2012;2012:470656.
Lamers Y, Prinz-Langenohl R, Brämswig S, Pietrzik K: Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr 2006;84:156-161.
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.
Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM: Folate levels and neural tube defects. Implications for prevention. JAMA 1995;274:1698-1702.
Lassi ZS, Salam RA, Haider BA, Bhutta ZA: Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev 2013;3:CD006896.
van Uitert E, van Ginkel S, Willemsen S, Lindemans J, Koning A, Eilers P, Exalto N, Laven J, Steegers E, Steegers-Theunissen R: An optimal periconception maternal folate status for embryonic size: the Rotterdam Predict study. BJOG 2014;121:821-829.
Vollset SE, Clarke R, Lewington S, Ebbing M, Halsey J, Lonn E, Armitage J, Manson JE, Hankey GJ, Spence JD, Galan P, Bønaa KH, Jamison R, Gaziano JM, Guarino P, Baron JA, Logan RF, Giovannucci EL, den Heijer M, Ueland PM, Bennett D, Collins R, Peto R; B-Vitamin Treatment Trialists' Collaboration: Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet 2013;381:1029-1036.
Yang QH, Carter HK, Mulinare J, Berry RJ, Friedman JM, Erickson JD: Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001-2002. Am J Clin Nutr 2007;85:1409-1416.
Branum AM, Bailey R, Singer BJ: Dietary supplement use and folate status during pregnancy in the United States. J Nutr 2013;143:486-492.
Lamers Y: Folate recommendations for pregnancy, lactation, and infancy. Ann Nutr Metab 2011;59:32-37.
Bestwick JP, Huttly WJ, Morris JK, Wald NJ: Prevention of neural tube defects: a cross-sectional study of the uptake of folic acid supplementation in nearly half a million women. PLoS One 2014;9:e89354.
Agodi A, Barchitta M, Valenti G, Quattrocchi A, Marchese AE, Oliveri Conti G, Fallico R, Sciacca S, Ferrante M: Dietary folate intake and blood biomarkers reveal high-risk groups in a Mediterranean population of healthy women of childbearing potential. Ann Nutr Metab 2013;63:179-185.
Cafolla A, Dragoni F, Girelli G, Tosti ME, Costante A, Pastorelli D, Bedogni G, Scott S: Folate status in Italian blood donors: relation to gender and smoking. Haematologica 2000;85:694-698.
Hertrampf E, Cortés F, Erickson JD, Cayazzo M, Freire W, Bailey LB, Howson C, Kauwell GP, Pfeiffer C: Consumption of folic acid-fortified bread improves folate status in women of reproductive age in Chile. J Nutr 2003;133:3166-3169.
Dhonukshe-Rutten RA, de Vries JH, de Bree A, van der Put N, van Staveren WA, de Groot LC: Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations. Eur J Clin Nutr 2009;63:18-30.
Sofi F, Vecchio S, Giuliani G, Martinelli F, Marcucci R, Gori AM, Fedi S, Casini A, Surrenti C, Abbate R, Gensini GF: Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy Italian population: the ‘Florence' diet is not Mediterranean. Eur J Clin Nutr 2005;59:584-591.
Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH: The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999;340:1449-1454.
Zappacosta B, Persichilli S, Iacoviello L, Di Castelnuovo A, Graziano M, Gervasoni J, Leoncini E, Cimino G, Mastroiacovo P: Folate, vitamin B12 and homocysteine status in an Italian blood donor population. Nutr Metab Cardiovasc Dis 2013;23:473-480.
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