Prevention and control of micronutrient deficiencies in developing countries: current perspectives

Figures & data

Table 1 Iron: evidence of effects on iron status and/or related health outcomes via different interventions in developing countries

Author, year	Intervention	Study design, population	Impact on biomarkers and health outcomes (intervention versus control)
Imdad and Bhutta, 2012^Citation13	Daily supplementation	Systematic review and meta-analysis (30 trials) Pregnant women	At-term anemia incidence and IDA Incidence of LBW Incidence of preterm birth, SGA	+ + No effect
Peña-Rosas et al, 2012^Citation14	Daily oral iron supplements	Cochrane review (60 trials) Pregnant women	Hb levels at term and postpartum Risk of at-term anemia and iron deficiency Risk of LBW babies Side effects Risk of Hb > 130 g/L in pregnancy and at term Placental malaria	+ + + − with ≥60 mg iron − No effect
Pasricha et al, 2013^Citation15	Daily supplementation	Systematic review and meta-analysis (35 RCTs) Children (4–23 months)	Risk for anemia, iron deficiency and IDA Mental and psychomotor development Length, length-for-age, weight, weight-for-age Prevalence of vomiting and fever	+ No effect No effect −
Sachdev et al, 2005^Citation16	Supplementation; fortified formula milk/cereals	Systematic review (17 RCTs) Children (≤ 15 years)	Motor development score	No convincing effect
Sachdev et al, 2006^Citation17	Supplementation; fortified formula milk/cereals	Systematic review (25 RCTs) Children (≤13.5 years)	Weight-for-age, weight-for-height, height-for-age, MAC, skinfold thickness, HC	No effect
Gera et al, 2007^Citation18	Supplementation; fortified formula milk/cereals	Systematic review (55 RCTs)	Hb concentration	+
Vuele et al, 2013^Citation19	Fortified foods, fortified formula, supplements	Systematic review and meta-analysis (28 RCTs) Pediatric population and pregnant women	Pediatric population (21 RCTs): Length, HC Weight, MAC	No effect + with doses of 40–66 mg in children ≥6 years
			Pregnant women (7 RCTs): Birth weight, length of gestation	No effect
Assunção and Santos, 2007^Citation20	Fortified foods, fortified formula	Systematic review (21 trials) Children and adolescents	Iron status biomarkers Anemia prevalence	+ Inconclusive results due to important methodological limitations
Assunção et al, 2012^Citation21	Flour fortification	Population-based surveys Children <6 years	Anemia prevalence Hb levels	− in children <24 months − in children <24 months
Dutra-de-Oliveira et al, 2011^Citation22	Water with or without ascorbic acid	Review Children and their families	Anemia and number of iron-deficient Hb and serum ferritin	+ in children + in adults and children
Miglioranza et al, 2009^Citation23	Fortified sweet and salty corn flourderived products	Before and after study	Prevalence of iron deficiency and IDA	+
Das et al, 2013^Citation24	Fortification Formula milk, complementary baby foods, milk, condiments, drinking water, food bars, candies, noodles, fruit juices, cereals, flours, processed flour-based products	Systematic review (201 studies) Pediatric population; women of reproductive age, pregnant and postmenopausal women	Children (41 studies): Serum ferritin Anemia Women (13 studies): Hb and serum ferritin Prevalence of anemia	+ + + +
Gera et al, 2012^Citation25	Fortification; biofortification	Systematic review, meta-analysis and metaregression (60 RCTs) Children and adults	Hb and serum ferritin Risk of anemia and iron deficiency Other indicators of iron nutriture Serum zinc, infections, physical growth, mental and motor development	+ + + No effect

Notes: + beneficial effect; – adverse effect.

Abbreviations: Hb, hemoglobin; HC, head circumference; IDA, iron deficiency anemia; LBW, low birth weight; MAC, mid-arm circumference; RCTs, randomized controlled trials; SGA, small-for-gestational-age.

Table 2 Folic acid and iodine: evidence of effects on biomarkers of status and/or related health outcomes via different interventions in developing countries

Author, year	Intervention	Study design, population	Impacts on biomarkers and health outcomes (intervention versus control)
Folic acid
Fekete et al, 2012^Citation26	Supplementation	Systematic review and metaanalysis (10 RCTs) Pregnant women	Birth weight Placental weight, length of gestation	+ No effect
Das et al, 2013^Citation24	Fortification Mass fortification of flour and processed flour-based products	Systematic review (201 studies) Pediatric population; WRA, pregnant and postmenopausal women	Women (31 studies) Neural-tube defects, spina bifida, and anencephaly RBC folate, serum folate	+ No effect
Iodine
Das et al, 2013^Citation24	Mass salt fortification programs	Systematic review (201 studies) Pediatric population; wRA, pregnant and postmenopausal women	Children (7 studies): Urinary iodine Serum thyroxin levels Women (16 studies): Urinary iodine Incidence of hypothyroidism Serum thyroxin Women (13 RCTs): Serum 25-hydroxy-D3 and parathyroid hormone Serum levels of bone resorption markers Maternal death or serious morbidity Risk of preterm birth Risk of stillbirth or death before discharge from hospital	+ No effect + + No effect + in postmenopausal women + in wRA and postmenopausal women + + No effect

Note: + beneficial effect.

Abbreviations: RBC, red blood cell; RCTs, randomized controlled trials; WRA, women of reproductive age.

Table 3 Zinc: evidence of effects on biomarkers of status and/or related health outcomes via different interventions in developing countries

Author, year	Intervention	Study design, population	Impacts on biomarkers and health outcomes (intervention vs control)
Luabeya et al, 2007^Citation27	Daily supplementation of vitamin A alone vs (vitamin A plus zinc) vs (vitamin A plus zinc plus MMN)	RCT Children (6–24 months)	Diarrhea and respiratory disease morbidity	No effect
Walker and Black, 2010^Citation28	Supplementation (alone or in combination)	Systematic review Infants and children (1–59 months)	Proportion of diarrheal episodes beyond 7 days; risk of hospitalization; all-cause mortality; diarrhea mortality	+
Chaffee and King, 2012^Citation29	Daily supplementation	Meta-analysis Pregnant women	Risk of preterm birth Parameter of fetal growth (risk of LBW, birth weight, length at birth, or HC at birth)	+ No effect
Aggarwal et al, 2007^Citation30	Supplementation	Meta-analysis Infants and children (≤41 months)	Episodes of diarrhea, severe diarrhea or dysentery, persistent diarrhea Episodes of respiratory tract infection or pneumonia	+ +
Roth et al, 2010^Citation31	Routine (ie, daily or weekly) supplementation	Meta-analysis Children (<5 years)	Incidence of ALRI defined by specific clinical criteria	+
Soofi et al, 2013^Citation32	Provision of two micronutrient powder formulations, with or without zinc	Cluster randomized trial Children (6–18 months)	Risk of iron deficiency anemia at 18 months Height Proportion of days with diarrhea, incidence of bloody diarrhea, reported chest indrawing Incidence of febrile episodes or admission to hospital for diarrhea, respiratory problems, or febrile episodes	+ for both MNP groups + mainly in MNP-zinc group − in both MNP groups No effect
Das et al, 2013^Citation24	Fortification Infant formula feeds or milk; porridge, bread	Systematic review (201 studies) Pediatric population; women of reproductive age, pregnant and postmenopausal women	Children (10 studies): Serum zinc Height velocity, weight, Hb levels, serum copper levels	+ No effect
Rosado et al, 2009^Citation33	Biofortification of wheat	Short-term, cross-sectional study Women	Zinc absorption	+

Notes: + beneficial effect; – adverse effect.

Abbreviations: ALRI, acute lower respiratory infection; Hb, hemoglobin; HC, head circumference; LBW, low birth weight; MMN, multiple micronutrient; MNP, micronutrient powders (sprinkles); RCTs, randomized controlled trials; vs, versus.

Table 4 Vitamin A: evidence of effects on biomarkers of status and/or related health outcomes via different interventions in developing countries

Reference	Intervention	Study design and population	Biomarkers and health outcomes (intervention versus control)
Mayo-Wilson et al, 2011^Citation34	Prophylactic supplementation	Systematic review and meta-analysis (43 RCTs) Children (6 months to 5 years)	All causes of mortality Incidence of diarrhea, measles Prevalence of vision problems (including night blindness, xerophthalmia) Risk of vomiting within 48 hours	+ + +
Haider and Bhutta, 2011^Citation35	Supplementation	Cochrane review (7 trials) Term neonates	Risk of infant mortality Cause-specific mortality and morbidity, vitamin A deficiency, anemia and adverse events	+ at 6 months of age Limited data available
Thapa et al, 2005^Citation36	Nepal national vitamin A supplement program: female community health volunteers providing one high-dose capsule twice/year, and nutrition education	Nationally representative survey Children (12–59 months)	Coverage Child mortality	57% +
Semba et al, 2010^Citation37	India national vitamin A supplement program	Nationally representative survey Children (12–59 months)	Coverage within the last 6 months Prevalence of stunting, severe stunting, underweight, severe underweight Under-5 child mortality rate	20.2% Maternal education related + Inversely proportional
Grover et al, 2008^Citation38	Cambodian national vitamin A supplement program	Nationally representative survey Preschool children (12–59 months)	Coverage within the last 6 months	42.8% Maternal education associated
Das et al, 2013^Citation24	Fortification Monosodium glutamate, sugar, flour, processed based-flour products	Systematic review (201 studies) Pediatric populations; WRA, pregnant and postmenopausal women	Children (8 studies): Serum retinol and Hb levels Prevalence of vitamin A deficiency	+ No effect
Hotz et al, 2012^Citation35	Biofortification; programs to promote production and consumption of β-carotenerich orange sweet potato at household level Components: agriculture, demand creation/behavior change, marketing, through training with household members and broader, area-wide activities and promotions	Randomized, controlled, cluster-design effectiveness study Children 6 months to 5 years of age, and women	Orange sweet potato intake Prevalence of inadequate vitamin A intake Prevalence of serum retinol < 1.05 μmol/L for children.	+ Accounting for 44%–60% of vitamin A intake at follow-up + in children and women +
Hotz etal, 2012^Citation40	Biofortification; large-scale intervention to promote orange sweet potato production and consumption at household level	Large-scale intervention; see Hotz et al, 2012^Citation39 Children (6–35 months) and their mothers or other female caretakers	Orange sweet potato and vitamin A intakes among children and women	+ Accounting for 47%–60% of all sweet potatoes consumed, providing 80% of total vitamin A intakes in children

Notes: + beneficial effect; – adverse effect.

Abbreviations: Hb, hemoglobin; RCTs, randomized controlled trials; WRA, women of reproductive age.

Table 5 Multiple micronutrients: evidence of effects on biomarkers of status and/or related health outcomes via different interventions in developing countries

Author, year	Intervention	Study design and population	Biomarkers and health outcomes (intervention vs control)
Bhutta et al, 2012^Citation41	MMN supplementation vs standard IFA supplements	Systematic review (7 RCTs) Pregnant women	Anemia in the third trimester and Hb levels	No difference
Fall et al, 2009^Citation42	MMN supplementation vs IFA supplementation	Meta-analysis (12 RCTs) Pregnant women	Duration of gestation and incidence of preterm birth Mean birth weight Prevalence of LBW and SGA	No effect + +
Ronsmans et al, 2009^Citation43	MMN supplementation vs IFA supplementation	Meta-analysis (12 RCTs) Pregnant women	Stillbirths; neonatal deaths	No effect
Eichler et al, 2012^Citation44	Fortification of milk and cereal foods vs non-fortified foods	Systematic review and meta-analysis (18 RCTs) Infants and children (6–23 months)	Hematologic outcomes Risk of anemia Serum retinol Functional health outcomes; morbidity	+ with iron plus MMN being the most effective + + Inconclusive results
De-Regil et al, 2011^Citation45	Home fortification of foods with MNP	Cochrane review (8 trials) Infants and children <2 years	Risk of anemia; iron deficiency Growth Anemia and Hb levels	+ No effect Similar results vs daily iron supplementation
Best et al, 2011^Citation46	Fortified foods	Review (12 trials) School-age children (6–18 years)	Hb, iron, vitamin A, iodine, folate status Anemia prevalence Anthropometric status Morbidity (incidence or duration of diarrhea and respiratory-related diseases) Cognitive performance	+ + Equivocal results Equivocal results Inconsistent results
Salam et al, 2013^Citation47	Home fortification with MNPs	Systematic review and meta-analysis (16 RCTs) Children	Prevalence of anemia, IDA, retinol deficiency Hb levels Serum ferritin and zinc deficiency Anthropometric outcomes including stunting, wasting, underweight, HAZ, WAZ, WHZ Diarrhea Fever and URI	+ + No effect No effect No effect
Suchdev et al, 2011^Citation48	Home fortification of foods	Systematic review* Pregnant women	Maternal and newborn health outcomes
Radhika et al, 2011^Citation49	Premix rice-based meal	Double-blind, RCT 5- to 11-year-old schoolchildren (national “midday meal program” of the government of India)	Serum ferritin Hb levels Prevalence of anemia and iron deficiency anemia Prevalence of iron deficiency	+ No effect No effect +
Makola et al, 2003^Citation50	Fortified beverage	Double-blind RCT Pregnant women (gestational ages of 8 to 34 weeks)	Hb and serum ferritin Risk of anemia and iron deficiency anemia Risk of iron deficiency	+ + + in women with both iron deficiency and adequate stores
Das et al, 2013^Citation24	Fortification vs no fortification Complementary baby foods, milk, seasoning powder, cereals, flours, processed flour-based products	Systematic review (201 studies) Pediatric populations; women of reproductive age, pregnant and postmenopausal women	Children (34 studies): Hb, serum ferritin, anemia prevalence Serum zinc and retinol, vitamin A deficiency HAZ, WAZ and WHZ Overall morbidity (including fever, UTI, diarrhea, respiratory infections) Women (5 RCTs): Hb, serum ferritin, zinc, retinol Anemia prevalence	+ No effect No effect No effect + +

Notes: + beneficial effect; – adverse effect;

* No studies satisfied the inclusion criteria; ie, there have been no studies evaluating the effects in pregnant women.

Abbreviations: HAZ. height for age z- score; Hb, hemoglobin; IDA, iron deficiency anemia; IFA, iron-folic acid; LBW, low birth weight; MMN, multiple micronutrient; MNP, micronutrient powders (sprinkles); RCTs, randomized controlled trials; SGA, small-for-gestational-age; URI, upper respiratory infections; UTI, urinary tract infections; vs, versus; WAZ, weight for age z-score; WHZ, weight for height z-score.

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