title: Micronutrient fortification of food and its impact on woman and child health: a systematic review.
abstract: BACKGROUND
  Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.
  
  
  METHODS
  A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.
  
  
  RESULTS
  Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.
  
  
  CONCLUSIONS
  Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality.
authors: Centre of Excellence in Women & Child Health, Aga Khan University, Karachi 74800, Pakistan. zulfiqar.bhutta@aku.edu.
authors: Jai K
authors: JK
authors: Das
authors: Rehana A
authors: RA
authors: Salam
authors: Rohail
authors: R
authors: Kumar
authors: Zulfiqar A
authors: ZA
authors: Bhutta
mesh_terms: D001827:Body Height; D001835:Body Weight; D002648:Child; D002657:Child Development; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005527:Food, Fortified; D006801:Humans; D007455:Iodine / Q000008:administration & dosage; D019266:Iron, Dietary / Q000008:administration & dosage; D018977:Micronutrients / Q000008:administration & dosage*; D009752:Nutritional Status; D014801:Vitamin A / Q000008:administration & dosage; D014807:Vitamin D / Q000008:administration & dosage; D016387:Women's Health; D015032:Zinc / Q000008:administration & dosage
chemical_list: D019266:Iron, Dietary; D018977:Micronutrients; D014801:Vitamin A; D014807:Vitamin D; D005492:Folic Acid; D007455:Iodine; D015032:Zinc
references: Am J Clin Nutr. 1985 Feb;41(2):254-63
references: 3838218
references: J Clin Endocrinol Metab. 2007 Aug;92(8):3122-7
references: 17504896
references: J Pediatr Gastroenterol Nutr. 2004 Oct;39(4):346-53
references: 15448423
references: Am J Clin Nutr. 1993 Apr;57(4):506-11
references: 8460605
references: Nutrition. 2004 Feb;20(2):177-80
references: 14962682
references: Asia Pac J Clin Nutr. 2007;16(3):505-11
references: 17704033
references: Am J Clin Nutr. 2004 Oct;80(4):952-9
references: 15447905
references: Am J Clin Nutr. 2010 Dec;92(6):1406-15
references: 20962160
references: J Nutr. 2010 Jan;140(1):49-53
references: 19889805
references: Eur J Epidemiol. 2011 Aug;26(8):629-35
references: 21660518
references: Br J Nutr. 2009 Nov;102(9):1362-9
references: 19653920
references: Birth Defects Res A Clin Mol Teratol. 2011 Sep;91(9):831-5
references: 21630426
references: Eur J Nutr. 2013 Mar;52(2):695-703
references: 22618893
references: Public Health. 2009 Dec;123(12):794-9
references: 19914671
references: J Hum Nutr Diet. 2009 Apr;22(2):156-65
references: 19226352
references: Nutr J. 2006 Dec 05;5:32
references: 17147795
references: Public Health Nutr. 2010 Nov;13(11):1923-30
references: 20529401
references: Br J Nutr. 2009 Oct;102(7):962-6
references: 19519975
references: Am J Clin Nutr. 2005 May;81(5):1168-75
references: 15883444
references: Public Health Nutr. 2008 Jul;11(7):720-8
references: 18096105
references: Birth Defects Res A Clin Mol Teratol. 2004 Dec;70(12):948-52
references: 15562514
references: Am J Clin Nutr. 2008 Jun;87(6):1715-22
references: 18541560
references: Eur J Nutr. 2009 Feb;48(1):45-53
references: 19030908
references: CMAJ. 2002 Aug 6;167(3):241-5
references: 12186168
references: J Nutr. 2003 Oct;133(10):3166-9
references: 14519804
references: Am J Clin Nutr. 2005 Dec;82(6):1276-82
references: 16332661
references: Am J Clin Nutr. 1999 Sep;70(3):391-404
references: 10479202
references: Paediatr Perinat Epidemiol. 2003 Oct;17(4):378-83
references: 14629320
references: Am J Clin Nutr. 2008 Mar;87(3):734-43
references: 18326613
references: J Bone Miner Res. 2001 Sep;16(9):1704-9
references: 11547841
references: Public Health Nutr. 2010 May;13(5):623-30
references: 19912674
references: Asia Pac J Clin Nutr. 2002;11(2):123-7
references: 12074178
references: Osteoporos Int. 2003 Oct;14(10):828-34
references: 12915959
references: Pediatrics. 2006 Mar;117(3):803-13
references: 16510661
references: BMJ. 2009 May 12;338:b1673
references: 19436079
references: Eur J Endocrinol. 2002 Dec;147(6):747-53
references: 12457449
references: J Nutr. 2010 Mar;140(3):635-41
references: 20107144
references: J Nutr. 2006 Jul;136(7):1814-20
references: 16772442
references: Indian J Pediatr. 2002 Jul;69(7):617-23
references: 12173703
references: Pediatrics. 1959 Sep;24:404-12
references: 14421495
references: Br J Nutr. 2011 Jun;105(11):1652-9
references: 21303569
references: Saudi Med J. 2007 Aug;28(8):1227-9
references: 17676207
references: J Clin Endocrinol Metab. 2008 Jul;93(7):2616-21
references: 18413422
references: Am J Clin Nutr. 1994 May;59(5):985-9
references: 8172105
references: Nutrition. 2005 Jan;21(1):20-4
references: 15661474
references: Am J Clin Nutr. 2009 Jul;90(1):76-87
references: 19458014
references: BMJ. 2008 Apr 26;336(7650):924-6
references: 18436948
references: Public Health Nutr. 2010 Sep;13(9):1462-71
references: 20412603
references: Nutr Rev. 2004 Jun;62(6 Pt 2):S40-3
references: 15298447
references: Birth Defects Res A Clin Mol Teratol. 2008 Jul;82(7):527-32
references: 18481813
references: Food Nutr Bull. 2010 Mar;31(1 Suppl):S86-93
references: 20629355
references: Am J Clin Nutr. 2007 Feb;85(2):538-47
references: 17284755
references: Arch Latinoam Nutr. 2001 Mar;51(1 Suppl 1):48-53
references: 11688082
references: Pediatrics. 2000 Mar;105(3):E38
references: 10699140
references: Asia Pac J Clin Nutr. 2011;20(1):118-24
references: 21393119
references: Food Nutr Bull. 2010 Mar;31(1 Suppl):S3-6
references: 20629348
references: Eur J Endocrinol. 2006 Jan;154(1):21-8
references: 16381987
references: J Pediatr Gastroenterol Nutr. 2008 Nov;47(5):660-6
references: 18979587
references: Obstet Gynecol. 2005 Apr;105(4):757-62
references: 15802402
references: J Nutr. 2012 Nov;142(11):1997-2003
references: 23014487
references: Lancet. 2008 Jan 19;371(9608):243-60
references: 18207566
references: Am J Med Genet A. 2005 Jun 1;135(2):120-5
references: 15846825
references: Br J Nutr. 2012 Feb;107(4):556-66
references: 21733297
references: Asia Pac J Clin Nutr. 2008;17(1):68-71
references: 18364329
references: Acta Paediatr. 2002;91(2):119-24
references: 11951995
references: J Trop Pediatr. 2012 Oct;58(5):370-4
references: 22345330
references: J Nutr. 2010 Dec;140(12):2241-7
references: 20980657
references: Br J Nutr. 2001 May;85 Suppl 2:S193-7
references: 11509110
references: Acta Paediatr. 2001 Jul;90(7):724-31
references: 11519973
references: J Clin Endocrinol Metab. 2002 Jun;87(6):2809-15
references: 12050255
references: Am J Clin Nutr. 1988 Jan;47(1):108-12
references: 3337028
references: J Nutr. 2010 Dec;140(12):2221-6
references: 20980643
references: BMC Public Health. 2012 Jul 06;12:506
references: 22770558
references: BMJ. 1999 Mar 13;318(7185):693-7
references: 10074011
references: J Nutr Sci Vitaminol (Tokyo). 2008 Dec;54(6):440-7
references: 19155581
references: J Clin Invest. 1997 Mar 15;99(6):1287-94
references: 9077538
references: S Afr Med J. 1974 Aug 24;48(41):1763-6
references: 4213309
references: Am J Clin Nutr. 1977 Jul;30(7):1185-95
references: 879081
references: J Clin Endocrinol Metab. 2007 Apr;92(4):1397-401
references: 17264188
references: Public Health Nutr. 2009 Dec;12(12):2329-34
references: 19105864
references: Am J Clin Nutr. 2005 Nov;82(5):1032-9
references: 16280435
references: Food Nutr Bull. 2007 Mar;28(1):100-8
references: 17718017
references: Food Nutr Bull. 2005 Sep;26(3):259-65
references: 16222916
references: BMC Med Res Methodol. 2005 Apr 20;5:13
references: 15840177
references: J Nutr. 2006 Oct;136(10):2633-7
references: 16988138
references: East Mediterr Health J. 2010 Nov;16(11):1148-52
references: 21222324
references: J Clin Endocrinol Metab. 2007 Feb;92(2):437-42
references: 17118996
references: Am J Clin Nutr. 2003 Apr;77(4):891-8
references: 12663288
references: Clin Endocrinol (Oxf). 2011 Jun;74(6):762-8
references: 21521276
references: Nutr Rev. 2004 Jun;62(6 Pt 2):S35-9
references: 15298446
references: Am J Med Genet A. 2003 Jun 1;119A(2):137-40
references: 12749051
references: J Reprod Med. 2004 Sep;49(9):707-12
references: 15493560
references: Am J Clin Nutr. 2006 Oct;84(4):822-9
references: 17023709
references: Thyroid. 1999 Jun;9(6):545-56
references: 10411116
references: J Nutr. 2003 Apr;133(4):1075-80
references: 12672922
references: Am J Clin Nutr. 2007 Aug;86(2):412-20
references: 17684213
references: J Am Coll Nutr. 2005 Apr;24(2):107-14
references: 15798077
references: Br J Nutr. 2006 Dec;96(6):1140-8
references: 17181890
references: Eur J Endocrinol. 2006 Aug;155(2):219-28
references: 16868134
references: Arch Dis Child. 1999 Sep;81(3):247-52
references: 10451399
references: Pediatrics. 2006 Sep;118(3):906-15
references: 16950980
references: J Am Coll Nutr. 1998 Apr;17(2):187-94
references: 9550463
references: Nutrition. 2011 Apr;27(4):428-34
references: 20605698
references: East Mediterr Health J. 2010 May;16(5):533-8
references: 20799554
references: Am J Clin Nutr. 1988 Feb;47(2):265-9
references: 3341258
references: Am J Clin Nutr. 1999 Mar;69(3):497-503
references: 10075336
references: Asia Pac J Clin Nutr. 2008;17(2):250-7
references: 18586644
references: Asia Pac J Clin Nutr. 2008;17(2):264-9
references: 18586646
references: Am J Clin Nutr. 1989 Jan;49(1):162-9
references: 2492140
references: Eur J Clin Nutr. 2004 Feb;58(2):376-85
references: 14749760
references: Birth Defects Res A Clin Mol Teratol. 2008 Aug;82(8):547-52
references: 18496833
references: Clin Endocrinol (Oxf). 2011 Jul;75(1):120-6
references: 21521277
references: Food Nutr Bull. 2009 Mar;30(1 Suppl):S79-107
references: 19472603
references: Am J Clin Nutr. 2004 Nov;80(5):1291-8
references: 15531678
references: Am J Clin Nutr. 1992 Sep;56(3):491-8
references: 1503059
references: Birth Defects Res A Clin Mol Teratol. 2005 Oct;73(10):679-89
references: 16240378
references: Asia Pac J Clin Nutr. 2008;17 Suppl 1:147-50
references: 18296324
references: Bone. 2010 Mar;46(3):759-67
references: 19895912
references: BMJ. 2008 May 17;336(7653):1106-10
references: 18483053
references: Am J Clin Nutr. 2007 Apr;85(4):1127-33
references: 17413115
references: Am J Clin Nutr. 2010 Jul;92(1):93-100
references: 20444958
references: J Am Diet Assoc. 1979 Feb;74(2):112-8
references: 105029
references: Pediatrics. 2006 Jun;117(6):2014-21
references: 16740843
references: Curr Opin Clin Nutr Metab Care. 2008 May;11(3):309-14
references: 18403929
references: Pediatrics. 1993 May;91(5):976-82
references: 8474819
references: Lancet. 2007 May 26;369(9575):1799-1806
references: 17531887
references: Am J Clin Nutr. 2000 Sep;72(3):738-44
references: 10966892
references: J Nutr. 2009 May;139(5):1013-21
references: 19321576
references: J Nutr. 2005 Nov;135(11):2596-601
references: 16251617
references: Food Nutr Bull. 2008 Jun;29(2 Suppl):S38-51
references: 18709880
references: Public Health Nutr. 2008 Jan;11(1):30-40
references: 17565762
references: JAMA. 2001 Jun 20;285(23):2981-6
references: 11410096
references: J Clin Endocrinol Metab. 2009 Jul;94(7):2400-5
references: 19366844
references: PLoS One. 2010 Aug 13;5(8):e12167
references: 20730057
references: Ann Trop Paediatr. 2001 Dec;21(4):319-33
references: 11732150
references: Am J Clin Nutr. 1981 Jan;34(1):41-9
references: 7446457
references: Am J Clin Nutr. 2004 Oct;80(4):973-81
references: 15447908
references: Am J Clin Nutr. 2010 Nov;92(5):1094-104
references: 20844068
references: Osteoporos Int. 2011 Oct;22(10):2721-31
references: 21170641
references: Public Health. 2008 Mar;122(3):313-21
references: 17645902
references: Southeast Asian J Trop Med Public Health. 1998 Mar;29(1):50-7
references: 9740268
references: Birth Defects Res A Clin Mol Teratol. 2004 Sep;70(9):559-64
references: 15368553
references: J Pediatr Gastroenterol Nutr. 1993 Jul;17(1):97-104
references: 8350219
references: Rev Saude Publica. 2009 Aug;43(4):565-71
references: 19488664
references: Nutr Rev. 2011 Apr;69(4):186-204
references: 21457264
references: Arch Dis Child. 1995 Sep;73(3):216-20
references: 7492158
references: Br J Nutr. 2008 Jul;100(1):166-73
references: 18208635
references: Am J Clin Nutr. 2010 Jul;92(1):170-6
references: 20444956
references: Am J Clin Nutr. 1996 Aug;64(2):142-51
references: 8694013
references: J Nutr Educ Behav. 2007 Nov-Dec;39(6):302-10
references: 17996625
references: J Pediatr Gastroenterol Nutr. 2006 Oct;43(4):525-32
references: 17033530
references: Asia Pac J Clin Nutr. 2010;19(2):195-9
references: 20460232
references: Birth Defects Res A Clin Mol Teratol. 2008 Apr;82(4):211-6
references: 18338391
references: J Am Diet Assoc. 2008 Dec;108(12):2090-4
references: 19027414
references: Am J Clin Nutr. 1976 Oct;29(10):1114-21
references: 788494
references: J Nutr. 2008 Apr;138(4):782-6
references: 18356335
references: Am J Clin Nutr. 2006 Dec;84(6):1357-64
references: 17158417
references: Am J Med Genet A. 2003 Jul 30;120A(3):309-13
references: 12838547
references: Teratology. 2002 Jul;66(1):33-9
references: 12115778
references: Am J Clin Nutr. 2010 Feb;91(2):431-9
references: 20016011
references: J Am Coll Nutr. 2010 Apr;29(2):122-9
references: 20679147
references: Food Nutr Bull. 2008 Jun;29(2):140-9
references: 18693478
references: Am J Clin Nutr. 2008 Nov;88(5):1378-87
references: 18996875
references: Reprod Toxicol. 2008 Aug;25(4):408-12
references: 18550330
references: Am J Clin Nutr. 1979 Dec;32(12):2532-9
references: 506975
references: BMJ. 2008 May 10;336(7652):1049-51
references: 18467413
references: Acta Paediatr. 1997 Jul;86(7):683-9
references: 9240873
references: Nutrition. 2006 Nov-Dec;22(11-12):1120-8
references: 17030114
references: Osteoporos Int. 2005 Dec;16(12):1907-16
references: 16133646
references: Am J Clin Nutr. 2003 Aug;78(2):284-90
references: 12885710
references: J Clin Endocrinol Metab. 1998 Nov;83(11):3817-25
references: 9814452
references: Int J Prev Med. 2012 Mar;3(Suppl 1):S124-30
references: 22826754
references: Rev Assoc Med Bras (1992). 2012 Jan-Feb;58(1):118-24
references: 22392326
references: BJOG. 2000 Jul;107(7):885-9
references: 10901560
references: Public Health Nutr. 2005 Aug;8(5):461-7
references: 16153327
references: Pediatrics. 2003 May;111(5 Pt 1):1002-9
references: 12728080
references: Am J Clin Nutr. 2001 Dec;74(6):791-5
references: 11722961
references: Am J Clin Nutr. 2004 May;79(5):805-11
references: 15113718
references: Eur J Nutr. 2011 Aug;50(5):341-9
references: 21153900
references: Public Health Nutr. 2009 Feb;12(2):244-8
references: 18789173
references: Am J Clin Nutr. 1993 Feb;57(2):190-4
references: 8424387
references: Asia Pac J Clin Nutr. 2009;18(3):326-34
references: 19786380
references: Am J Clin Nutr. 2003 Feb;77(2):425-32
references: 12540404
references: Am J Clin Nutr. 2003 Mar;77(3):663-7
references: 12600858
references: Food Nutr Bull. 2005 Mar;26(1):32-8
references: 15810797
references: J Pediatr Gastroenterol Nutr. 1998 Feb;26(2):167-71
references: 9481631
references: Am J Clin Nutr. 2001 Jun;73(6):1034-9
references: 11382656
references: Zhonghua Er Ke Za Zhi. 2011 Dec;49(12):926-32
references: 22336361
references: Am J Clin Nutr. 1982 Jul;36(1):87-93
references: 7091038
references: J Trop Pediatr. 2012 Dec;58(6):475-80
references: 22643708
references: Paediatr Perinat Epidemiol. 2010 Jul 1;24(4):349-51
references: 20618724
references: Med J Aust. 2007 Jan 15;186(2):69-71
references: 17223766
references: J Nutr. 2011 May;141(5):935-43
references: 21411608
references: Am J Clin Nutr. 1996 Dec;64(6):903-7
references: 8942415
references: Am J Clin Nutr. 2011 Aug;94(2):578-84
references: 21697075
references: Clin Endocrinol (Oxf). 2009 Sep;71(3):440-5
references: 19067717
references: Lancet. 2008 Feb 2;371(9610):417-40
references: 18206226
references: J Nutr. 2012 Oct;142(10):1836-42
references: 22915294
references: Med J Aust. 2007 Jun 4;186(11):574-6
references: 17547546
references: BMJ. 2008 May 3;336(7651):995-8
references: 18456631
references: Am J Clin Nutr. 1998 Aug;68(2 Suppl):499S-508S
references: 9701168
references: Public Health Nutr. 2005 Sep;8(6):572-81
references: 16236186
references: J Nutr. 2010 Jun;140(6):1146-54
references: 20410083
references: Br J Nutr. 2004 Jul;92(1):159-68
references: 15230999
references: BMC Pregnancy Childbirth. 2004 Sep 27;4(1):20
references: 15450123
references: Am J Clin Nutr. 2012 Aug;96(2):309-24
references: 22760566
references: J Pediatr Gastroenterol Nutr. 1984 Jun;3(3):421-5
references: 6737187
references: J Nutr. 2006 Jan;136(1):123-7
references: 16365070
references: Eur J Endocrinol. 2008 Sep;159(3):293-9
references: 18586897
references: Public Health Nutr. 2001 Dec;4(6):1201-9
references: 11796083
references: J Nutr. 2006 Jun;136(6):1617-23
references: 16702330
references: Br J Nutr. 2008 Aug;100(2):418-23
references: 18275625
references: Am J Clin Nutr. 1988 Nov;48(5):1271-6
references: 3189216
references: Food Nutr Bull. 2005 Jun;26(2):177-86; discussion 187-9
references: 16060219
references: J Nutr. 2008 Feb;138(2):379-88
references: 18203907