Fortification of condiments and seasonings with iron for preventing anaemia and improving health.

BACKGROUND: Anaemia affects approximately 1.8 billion people worldwide; over 60% of anaemia cases globally are due to iron deficiency (ID). Iron deficiency and anaemia contribute to the global burden of disease and affect physical and cognitive development in children, and work productivity and economic well-being in adults. Fortification of food with iron, alone or in combination with other nutrients, is an effective intervention to control ID. Condiments and seasonings are ideal food vehicles for iron fortification in countries where they are commonly used. OBJECTIVES: To determine the effects and safety of condiment and seasoning fortification with iron alone or iron plus other micronutrients on iron deficiency, anaemia, and health-related outcomes in the general population. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and other databases up to 24 January 2023. We also searched the International clinical trials registry platform (ICTRP) for any ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) (randomisation at individual or cluster level), non-randomised controlled trials, interrupted time series with at least three measure points both before and after intervention, and controlled before-after studies. Participants were populations of any age (including pregnant women), from any country, excluding those with critical illness or severe co-morbidities. We included interventions in which condiments or seasonings have been fortified with any combination of iron and other vitamins and minerals, irrespective of the fortification technology used. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and assessed the eligibility of studies. Disagreements were resolved through discussion or input from a third review author. Two review authors extracted the data and assessed the risk of bias in all the included studies. We followed the methods laid out by Cochrane and used GRADE criteria for assessing certainty of the evidence. MAIN RESULTS: Our search identified 15,902 records after removal of duplicates. We included 16 studies with 20,512 participants (18,410 participants after adjusting for clustering effects). They were all carried out in upper-middle- and lower-middle-income countries. Three studies were controlled before-after studies, one was non-randomised trial, and 12 were RCTs (including three cluster RCTs). Six studies took place in schools; seven in communities; and one each in a nursery/kindergarten, tea estate, and factory. Three studies involved only women, one study involved both women and their children, and all other studies focused on children and/or adolescents. Nine studies used salt as a vehicle for iron fortification, three used fish sauce, two used soy sauce, one used curry powder, and one a "seasoning powder". The dose of iron received by participants ranged from 4.4 mg to 55 mg/day. The sample sizes in the trials ranged from 123 to 14,398, and study durations ranged from three months to two years. Twelve RCTs contributed data for meta-analysis. Six trials compared iron-fortified condiments versus the unfortified condiment, and six trials provided data comparing iron fortification in combination with other micronutrients versus the same condiment with other micronutrients, but no added iron. In one trial, the fortificant contained micronutrients that may have affected the absorption of iron. Overall no studies were assessed as having a low risk of bias. All included studies were assessed to have a high overall risk of bias, with the most concerns being around allocation concealment, blinding, and random sequence generation. There was very high heterogeneity amongst studies in almost all examined outcomes. Condiments/seasonings fortified with iron versus unfortified condiments/seasonings We are uncertain about whether consuming condiments/seasonings fortified with iron in comparison to the same unfortified condiment reduces anaemia at the end of intervention (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.18 to 0.65; 2328 participants; 4 studies; very low-certainty of evidence). We are uncertain about whether consuming iron-fortified condiments increases haemoglobin concentrations (mean difference (MD) 6.40 (g/L), 95% CI -0.62 to 13.41; 2808 participants; 5 studies; very low-certainty evidence). Fortification of condiments/seasonings with iron probably slightly reduces ID (RR 0.33, 95% CI 0.11 to 1.01; 391 participants; 2 studies; moderate-certainty evidence). We are uncertain about whether fortification with iron increases ferritin concentration (MD 14.81 (µg/L), 95% CI 5.14 to 24.48; 4459 participants; 6 studies; very low-certainty evidence). Condiments/seasonings fortified with iron plus other micronutrients versus condiments/seasonings fortified with other micronutrients except iron Consuming condiments/seasonings fortified with iron plus other micronutrients may reduce anaemia (RR 0.59, 95% CI 0.40 to 0.89; 1007 participants; 4 studies; low-certainty evidence). We are uncertain about whether fortification of condiments/seasonings with iron plus other micronutrients will improve haemoglobin concentration (MD 6.22 g/dL, 95% CI 1.60 to 10.83; 1270 participants; 5 studies; very low-certainty evidence). It may reduce ID (RR 0.36, 95% CI 0.19 to 0.69; 1154 participants; 4 studies; low-certainty evidence). We are uncertain about whether fortification with iron plus other micronutrients improves ferritin concentration (MD 10.63 µg/L, 95% CI 2.40 to 18.85; 1251 participants; 5 studies; very low -certainty evidence). Condiments/seasonings fortified with iron versus no intervention No trial reported data on this comparison. No studies reported adverse effects. Funding sources do not appear to have distorted the results in any of the assessed trials. AUTHORS' CONCLUSIONS: We are uncertain whether consuming iron-fortified condiments/seasonings reduces anaemia, improves haemoglobin concentration, or improves ferritin concentration. It may reduce ID. Findings about ferritin should be interpreted with caution since its concentrations increase during inflammation. Consuming condiments/seasonings fortified with iron plus other micronutrients may reduce anaemia, and we are uncertain whether this will improve haemoglobin concentration or ferritin concentration. More studies are needed to determine the true effect of iron-fortified condiments/seasonings on preventing anaemia and improving health. The effects of this intervention on other health outcomes like malaria incidence, growth and development are unclear.

ANTECEDENTES: La anemia afecta aproximadamente a 1800 millones de personas en todo el mundo; más del 60% de los casos de anemia en el mundo se deben a la deficiencia de hierro (DH). La deficiencia de hierro y la anemia contribuyen a la carga mundial de morbilidad y afectan al desarrollo físico y cognitivo de los niños, así como a la productividad laboral y el bienestar económico de los adultos. El enriquecimiento de los alimentos con hierro, solo o en combinación con otros nutrientes, es una intervención eficaz para controlar la DH. Los condimentos y sazonadores son vehículos alimentarios ideales para el enriquecimiento con hierro en los países donde se utilizan habitualmente. OBJETIVOS: Determinar los efectos y la seguridad del enriquecimiento de condimentos y aderezos con hierro solo o hierro más otros micronutrientes sobre la deficiencia de hierro, la anemia y los desenlaces relacionados con la salud en la población general. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL, MEDLINE, Embase, CINAHL y otras bases de datos hasta el 24 de enero de 2023. También se realizaron búsquedas de ensayos en curso en la Plataforma de registros internacionales de ensayos clínicos (ICTRP). CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados aleatorizados (ECA) (asignación aleatoria a nivel individual o grupal), ensayos controlados no aleatorizados, series temporales interrumpidas con al menos tres puntos de medición tanto antes como después de la intervención, y estudios controlados del tipo antes­después. Los participantes fueron poblaciones de cualquier edad (incluidas mujeres embarazadas), de cualquier país, excluidos aquellos con enfermedades críticas o comorbilidades graves. Se incluyeron las intervenciones en las que los condimentos o sazonadores se han enriquecido con cualquier combinación de hierro y otras vitaminas y minerales, independientemente de la tecnología de enriquecimiento utilizada. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión seleccionaron y evaluaron de forma independiente la elegibilidad de los estudios. Los desacuerdos se resolvieron mediante debate o aporte de material de un tercer autor de la revisión. Dos autores de la revisión extrajeron los datos y evaluaron el riesgo de sesgo en todos los estudios incluidos. Se siguieron los métodos establecidos por Cochrane y se utilizó el método GRADE para evaluar la certeza de la evidencia. RESULTADOS PRINCIPALES: La búsqueda identificó 15 902 registros tras eliminar los duplicados. Se incluyeron 16 estudios con 20 512 participantes (18 410 participantes después de ajustar los efectos del conglomerado). Todos ellos se llevaron a cabo en países de ingresos medios­bajos y medios­altos. Tres estudios fueron controlados del tipo antes­después, uno fue un ensayo no aleatorio y 12 fueron ECA (incluidos tres ECA grupales). Seis estudios tuvieron lugar en escuelas, siete en comunidades y uno en una guardería, uno en una plantación de té y uno en una fábrica. En tres estudios participaron solo mujeres, en un estudio participaron tanto mujeres como sus hijos, y todos los demás estudios se centraron en niños y/o adolescentes. Nueve estudios utilizaron la sal como vehículo para el enriquecimiento con hierro, tres la salsa de pescado, dos la salsa de soja, uno el curry en polvo y otro un "sazonador en polvo". La dosis de hierro recibida por los participantes osciló entre 4,4 mg y 55 mg/día. El tamaño muestral de los ensayos osciló entre 123 y 14 398, y la duración de los estudios, entre tres meses y dos años. Doce ECA aportaron datos para el metanálisis. Seis ensayos compararon condimentos enriquecidos con hierro versus el condimento no enriquecido, y seis ensayos proporcionaron datos que comparaban el enriquecimiento con hierro en combinación con otros micronutrientes versus el mismo condimento con otros micronutrientes, pero sin hierro agregado. En un ensayo, el fortificante contenía micronutrientes que podrían haber afectado la absorción del hierro. En general, no se evaluó ningún estudio como de riesgo de sesgo bajo. Se evaluó que todos los estudios incluidos tenían un riesgo de sesgo general alto, y las mayores preocupaciones se centraron en la ocultación de la asignación, el cegamiento y la generación de secuencias al azar. Hubo una heterogeneidad muy alta entre los estudios en casi todos los desenlaces examinados. Condimentos/sazonadores enriquecidos con hierro versus condimentos/sazonadores no enriquecidos Es incierto si el consumo de condimentos/sazonadores enriquecidos con hierro en comparación con el mismo condimento no enriquecido reduce la anemia al finalizar la intervención (razón de riesgos [RR] 0,34; intervalo de confianza [IC] del 95%: 0,18 a 0,65; 2328 participantes; cuatro estudios; evidencia de certeza muy baja). Es incierto si el consumo de condimentos enriquecidos con hierro aumenta las concentraciones de hemoglobina (diferencia de medias [DM] 6,40 g/l; IC del 95%: ­0,62 a 13,41; 2808 participantes; cinco estudios; evidencia de certeza muy baja). El enriquecimiento de condimentos/sazonadores con hierro probablemente reduce ligeramente la DH (RR 0,33; IC del 95%: 0,11 a 1,01; 391 participantes; dos estudios; evidencia de certeza moderada). Es incierto si el enriquecimiento con hierro aumenta la concentración de ferritina (DM 14,81 µg/L; IC del 95%: 5,14 a 24,48; 4459 participantes; seis estudios; evidencia de certeza muy baja). Condimentos/sazonadores enriquecidos con hierro y otros micronutrientes versus condimentos/sazonadores enriquecidos con otros micronutrientes excepto hierro El consumo de condimentos/sazonadores enriquecidos con hierro más otros micronutrientes podría reducir la anemia (RR 0,59; IC del 95%: 0,40 a 0,89; 1007 participantes; cuatro estudios; evidencia de certeza baja). Es incierto si el enriquecimiento de condimentos/sazonadores con hierro más otros micronutrientes mejorará la concentración de hemoglobina (DM 6,22 g/dL; IC del 95%: 1,60 a 10,83; 1270 participantes; cinco estudios; evidencia de certeza muy baja). Podría reducir la DH (RR 0,36; IC del 95%: 0,19 a 0,69; 1154 participantes; cuatro estudios; evidencia de certeza baja). Es incierto si el enriquecimiento con hierro más otros micronutrientes mejora la concentración de ferritina (DM 10,63 µg/L; IC del 95%: 2,40 a 18,85; 1251 participantes; cinco estudios; evidencia de certeza muy baja). Condimentos/sazonadores enriquecidos con hierro versus ninguna intervención Ningún ensayo informó datos sobre esta comparación. Ningún estudio informó efectos adversos. Las fuentes de financiación no parecen haber distorsionado los resultados en ninguno de los ensayos evaluados. CONCLUSIONES DE LOS AUTORES: Es incierto si el consumo de condimentos/sazonadores enriquecidos con hierro reduce la anemia, mejora la concentración de hemoglobina o mejora la concentración de ferritina. Podría reducir la DH. Los resultados sobre la ferritina deben interpretarse con cautela, ya que sus concentraciones aumentan durante la inflamación. El consumo de condimentos/sazonadores enriquecidos con hierro más otros micronutrientes podría reducir la anemia, y no se sabe con certeza si mejorará la concentración de hemoglobina o de ferritina. Se necesitan más estudios para determinar el verdadero efecto de los condimentos/sazonadores enriquecidos con hierro en la prevención de la anemia y la mejora de la salud. Los efectos de esta intervención en otros desenlaces sanitarios como la incidencia del paludismo, el crecimiento y el desarrollo son inciertos.

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age.

BACKGROUND: Vitamin and mineral deficiencies, particularly those of iron, vitamin A, and zinc, affect more than two billion people worldwide. Young children are highly vulnerable because of rapid growth and inadequate dietary practices. Multiple micronutrient powders (MNPs) are single-dose packets containing multiple vitamins and minerals in powder form, which are mixed into any semi-solid food for children six months of age or older. The use of MNPs for home or point-of-use fortification of complementary foods has been proposed as an intervention for improving micronutrient intake in children under two years of age. In 2014, MNP interventions were implemented in 43 countries and reached over three million children. This review updates a previous Cochrane Review, which has become out-of-date. OBJECTIVES: To assess the effects and safety of home (point-of-use) fortification of foods with MNPs on nutrition, health, and developmental outcomes in children under two years of age. For the purposes of this review, home fortification with MNP refers to the addition of powders containing vitamins and minerals to semi-solid foods immediately before consumption. This can be done at home or at any other place that meals are consumed (e.g. schools, refugee camps). For this reason, MNPs are also referred to as point-of-use fortification. SEARCH METHODS: We searched the following databases up to July 2019: CENTRAL, MEDLINE, Embase, and eight other databases. We also searched four trials registers, contacted relevant organisations and authors of included studies to identify any ongoing or unpublished studies, and searched the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs with individual randomisation or cluster-randomisation. Participants were infants and young children aged 6 to 23 months at the time of intervention, with no identified specific health problems. The intervention consisted of consumption of food fortified at the point of use with MNP formulated with at least iron, zinc, and vitamin A, compared with placebo, no intervention, or use of iron-containing supplements, which is standard practice. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, and assessed the risk of bias of included studies. We reported categorical outcomes as risk ratios (RRs) or odds ratios (ORs), with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) and 95% CIs. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 29 studies (33,147 children) conducted in low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean, where anaemia is a public health problem. Twenty-six studies with 27,051 children contributed data. The interventions lasted between 2 and 44 months, and the powder formulations contained between 5 and 22 nutrients. Among the 26 studies contributing data, 24 studies (26,486 children) compared the use of MNP versus no intervention or placebo; the two remaining studies compared the use of MNP versus an iron-only supplement (iron drops) given daily. The main outcomes of interest were related to anaemia and iron status. We assessed most of the included studies at low risk of selection and attrition bias. We considered some studies to be at high risk of performance and detection bias due to lack of blinding. Most studies were funded by government programmes or foundations; only two were funded by industry. Home fortification with MNP, compared with no intervention or placebo, reduced the risk of anaemia in infants and young children by 18% (RR 0.82, 95% CI 0.76 to 0.90; 16 studies; 9927 children; moderate-certainty evidence) and iron deficiency by 53% (RR 0.47, 95% CI 0.39 to 0.56; 7 studies; 1634 children; high-certainty evidence). Children receiving MNP had higher haemoglobin concentrations (MD 2.74 g/L, 95% CI 1.95 to 3.53; 20 studies; 10,509 children; low-certainty evidence) and higher iron status (MD 12.93 µg/L, 95% CI 7.41 to 18.45; 7 studies; 2612 children; moderate-certainty evidence) at follow-up compared with children receiving the control intervention. We did not find an effect on weight-for-age (MD 0.02, 95% CI -0.03 to 0.07; 10 studies; 9287 children; moderate-certainty evidence). Few studies reported morbidity outcomes (three to five studies each outcome) and definitions varied, but MNP did not increase diarrhoea, upper respiratory infection, malaria, or all-cause morbidity. In comparison with daily iron supplementation, the use of MNP produced similar results for anaemia (RR 0.89, 95% CI 0.58 to 1.39; 1 study; 145 children; low-certainty evidence) and haemoglobin concentrations (MD -2.81 g/L, 95% CI -10.84 to 5.22; 2 studies; 278 children; very low-certainty evidence) but less diarrhoea (RR 0.52, 95% CI 0.38 to 0.72; 1 study; 262 children; low-certainty of evidence). However, given the limited quantity of data, these results should be interpreted cautiously. Reporting of death was infrequent, although no trials reported deaths attributable to the intervention. Information on side effects and morbidity, including malaria and diarrhoea, was scarce. It appears that use of MNP is efficacious among infants and young children aged 6 to 23 months who are living in settings with different prevalences of anaemia and malaria endemicity, regardless of intervention duration. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups. AUTHORS' CONCLUSIONS: Home fortification of foods with MNP is an effective intervention for reducing anaemia and iron deficiency in children younger than two years of age. Providing MNP is better than providing no intervention or placebo and may be comparable to using daily iron supplementation. The benefits of this intervention as a child survival strategy or for developmental outcomes are unclear. Further investigation of morbidity outcomes, including malaria and diarrhoea, is needed. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups.

Including 60 mg Elemental Iron in a Multiple Micronutrient Supplement Blunts the Increase in Serum Zinc after 12 Weeks of Daily Supplementation in Predominantly Anemic, Nonpregnant Cambodian Women of Reproductive Age.

BACKGROUND: Multiple micronutrient (MMN) supplementation may result in interaction effects due to competing absorptive pathways of trace elements. OBJECTIVES: The aim of this study was to investigate the effect of MMN supplementation with or without iron on serum zinc, selenium, and copper concentrations in Cambodian women. METHODS: In a 2 × 2 factorial double-blind randomized 12-wk trial, predominantly anemic, nonpregnant women (aged 18-45 y) received daily 60 mg of iron (Fe; n = 201); 14 other micronutrients including zinc (15 mg), selenium (65 µg), and copper (2 mg), but no iron (MMN; n = 202); 60 mg iron plus MMN (Fe + MMN; n = 206); or a placebo (n = 200). Fasting morning blood was collected at baseline and 12 wk from women in 26 villages in Kampong Chhnang province. Serum zinc, selenium, and copper concentrations (secondary outcomes of the randomized controlled trial) were measured using inductively coupled plasma mass spectrometry. Generalized linear regression was used to estimate intervention effects [ß coefficient (95% CI)] for Fe (with or without MMN) and MMN (with or without Fe) after testing for the presence of an Fe × MMN interaction. RESULTS: A total of 760 women completed the trial. Zinc deficiency prevalence at baseline was 45% (inflammation-adjusted serum zinc <10.7 µmol/L). A significant Fe × MMN interaction (P = 0.02) was detected in the 2 × 2 analysis with serum zinc concentration as the outcome: the MMN group had a higher mean serum zinc concentration at 12 wk (12.3 µmol/L; 95% CI: 12.2, 12.4 µmol/L) compared with all other groups, and the Fe + MMN group had a higher mean serum zinc concentration (11.6 µmol/L; 95% CI: 11.5, 11.7 µmol/L) compared with the Fe group (11.0 µmol/L; 95% CI: 10.9, 11.0 µmol/L) and the placebo group (11.2 µmol/L; 95% CI: 11.1, 11.4 µmol/L). CONCLUSIONS: The inclusion of 60 mg iron in the daily MMN formulation may be interfering with the absorption and/or metabolism of supplemental zinc in Cambodian women. This is of particular concern when MMN supplementation is implemented in populations with risk of zinc deficiency. This trial was registered at clinicaltrials.gov as NCT-02481375.

Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women.

BACKGROUND: Anaemia is a condition in which the number of red blood cells is insufficient to meet physiologic needs; it is caused by many conditions, particularly iron deficiency. Traditionally, daily iron supplementation has been a standard practice for preventing and treating anaemia. However, its long-term use has been limited, as it has been associated with adverse side effects such as nausea, constipation, and teeth staining. Intermittent iron supplementation has been suggested as an effective and safer alternative to daily iron supplementation for preventing and reducing anaemia at the population level, especially in areas where this condition is highly prevalent. OBJECTIVES: To assess the effects of intermittent oral iron supplementation, alone or in combination with other nutrients, on anaemia and its associated impairments among menstruating women, compared with no intervention, a placebo, or daily supplementation. SEARCH METHODS: In February 2018, we searched CENTRAL, MEDLINE, Embase, nine other databases, and two trials registers. In March 2018, we also searched LILACS, IBECS and IMBIOMED. In addition, we examined reference lists, and contacted authors and known experts to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs with either individual or cluster randomisation. Participants were menstruating women; that is, women beyond menarche and prior to menopause who were not pregnant or lactating and did not have a known condition that impeded the presence of menstrual periods. The intervention was the use of iron supplements intermittently (one, two or three times a week on non-consecutive days) compared with placebo, no intervention, or the same supplements provided on a daily basis. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy, assessed the risk of bias of the included studies, and rated the quality of the evidence using GRADE. MAIN RESULTS: We included 25 studies involving 10,996 women. Study methods were not well described in many of the included studies and thus assessing risk of bias was difficult. The main limitations of the studies were lack of blinding and high attrition. Studies were mainly funded by international organisations, universities, and ministries of health within the countries. Approximately one third of the included studies did not provide a funding source.Although quality across studies was variable, the results consistently showed that intermittent iron supplementation (alone or with any other vitamins and minerals) compared with no intervention or a placebo, reduced the risk of having anaemia (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.49 to 0.87; 11 studies, 3135 participants; low-quality evidence), and improved the concentration of haemoglobin (mean difference (MD) 5.19 g/L, 95% CI 3.07 to 7.32; 15 studies, 2886 participants; moderate-quality evidence), and ferritin (MD 7.46 µg/L, 95% CI 5.02 to 9.90; 7 studies, 1067 participants; low-quality evidence). Intermittent regimens may also reduce the risk of having iron deficiency (RR 0.50, 95% CI 0.24 to 1.04; 3 studies, 624 participants; low-quality evidence), but evidence was inconclusive regarding iron deficiency anaemia (RR 0.07, 95% CI 0.00 to 1.16; 1 study, 97 participants; very low-quality evidence) and all-cause morbidity (RR 1.12, 95% CI 0.82 to 1.52; 1 study, 119 participants; very low-quality evidence). Women in the control group were less likely to have any adverse side effects than those receiving intermittent iron supplements (RR 1.98, 95% CI 0.31 to 12.72; 3 studies, 630 participants; moderate-quality evidence).In comparison with daily supplementation, results showed that intermittent supplementation (alone or with any other vitamins and minerals) produced similar effects to daily supplementation (alone or with any other vitamins and minerals) on anaemia (RR 1.09, 95% CI 0.93 to 1.29; 8 studies, 1749 participants; moderate-quality evidence). Intermittent supplementation may produce similar haemoglobin concentrations (MD 0.43 g/L, 95% CI -1.44 to 2.31; 10 studies, 2127 participants; low-quality evidence) but lower ferritin concentrations on average (MD -6.07 µg/L, 95% CI -10.66 to -1.48; 4 studies, 988 participants; low-quality evidence) compared to daily supplementation. Compared to daily regimens, intermittent regimens may also reduce the risk of having iron deficiency (RR 4.30, 95% CI 0.56 to 33.20; 1 study, 198 participants; very low-quality evidence). Women receiving iron supplements intermittently were less likely to have any adverse side effects than those receiving iron supplements daily (RR 0.41, 95% CI 0.21 to 0.82; 6 studies, 1166 participants; moderate-quality evidence). No studies reported on the effect of intermittent regimens versus daily regimens on iron deficiency anaemia and all-cause morbidity.Information on disease outcomes, adherence, economic productivity, and work performance was scarce, and evidence about the effects of intermittent supplementation on these outcomes unclear.Overall, whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or given to populations with different degrees of anaemia at baseline did not seem to affect the findings. Furthermore, the response did not differ in areas where malaria was frequent, although very few trials were conducted in these settings. AUTHORS' CONCLUSIONS: Intermittent iron supplementation may reduce anaemia and may improve iron stores among menstruating women in populations with different anaemia and malaria backgrounds. In comparison with daily supplementation, the provision of iron supplements intermittently is probably as effective in preventing or controlling anaemia. More information is needed on morbidity (including malaria outcomes), side effects, work performance, economic productivity, depression, and adherence to the intervention. The quality of this evidence base ranged from very low to moderate quality, suggesting that we are uncertain about these effects.

Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition.

BACKGROUND: Rice fortification with vitamins and minerals has the potential to increase the nutrition in rice-consuming countries where micronutrient deficiencies exist. Globally, 490 million metric tonnes of rice are consumed annually. It is the dominant staple food crop of around three billion people. OBJECTIVES: To determine the benefits and harms of rice fortification with vitamins and minerals (iron, vitamin A, zinc or folic acid) on micronutrient status and health-related outcomes in the general population. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and 16 other databases all up to 10 December 2018. We searched ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) on 10 December 2018. SELECTION CRITERIA: We included randomised and quasi-randomised trials (with either individual or cluster randomisation) and controlled before-and-after studies. Participants were populations older than two years of age (including pregnant women) from any country. The intervention was rice fortified with at least one micronutrient or a combination of several micronutrients (iron, folic acid, zinc, vitamin A or other vitamins and minerals) compared with unfortified rice or no intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened studies and extracted data. MAIN RESULTS: We included 17 studies (10,483 participants) and identified two ongoing studies. Twelve included studies were randomised-controlled trials (RCTs), with 2238 participants after adjusting for clustering in two cluster-RCTs, and five were non-randomised studies (NRS) with four controlled before-and-after studies and one cross-sectional study with a control (8245 participants). Four studies were conducted in India, three in Thailand, two in the Philippines, two in Brazil, one each in Bangladesh, Burundi, Cambodia, Indonesia, Mexico and the USA. Two studies involved non-pregnant, non-lactating women and 10 involved pre-school or school-age children. All 17 studies reported fortification with iron. Of these, six studies fortified rice with iron only; 11 studies had other micronutrients added (iron, zinc and vitamin A, and folic acid). One study had one arm each with vitamin A alone and carotenoid alone. Elemental iron content ranged from 0.2 to 112.8 mg/100 g uncooked rice given for a period varying from two weeks to 48 months. Thirteen studies did not clearly describe either sequence generation or allocation concealment. Eleven studies had a low attrition rate. There was no indication of selective reporting in the studies. We considered two RCTs at low overall risk of bias and 10 at high overall risk of bias. One RCT was at high or unclear risk of bias for most of the domains. All controlled before-and-after studies had a high risk or unclear risk of bias in most domains. The included studies were funded by Government, private and non-governmental organisations, along with other academic institutions. The source of funding does not appear to have altered the results. We used the NRS in the qualitative synthesis but we excluded them from the quantitative analysis and review conclusions since they provided mostly contextual information and limited quantitative information. Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added) Fortification of rice with iron (alone or in combination with other micronutrients) may make little or no difference in the risk of having anaemia (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.54 to 0.97; I2 = 74%; 7 studies, 1634 participants; low-certainty evidence) and may reduce the risk of iron deficiency (RR 0.66, 95% CI 0.51 to 0.84; 8 studies, 1733 participants; low-certainty evidence). Rice fortification may increase mean haemoglobin (mean difference (MD) 1.83, 95% CI 0.66 to 3.00; I2 = 54%; 11 studies, 2163 participants; low-certainty evidence) and it may make little or no difference to vitamin A deficiency (with vitamin A as one of the micronutrients in the fortification arm) (RR 0.68, 95% CI 0.36 to 1.29; I2 = 37%; 4 studies, 927 participants; low-certainty evidence). One study reported that fortification of rice (with folic acid as one of the micronutrients) may improve serum or plasma folate (nmol/L) (MD 4.30, 95% CI 2.00 to 6.60; 215 participants; low-certainty evidence). One study reported that fortification of rice with iron alone or with other micronutrients may slightly increase hookworm infection (RR 1.78, 95% CI 1.18 to 2.70; 785 participants; low-certainty evidence). We are uncertain about the effect of fortified rice on diarrhoea (RR 3.52, 95% CI 0.18 to 67.39; 1 study, 258 participants; very low-certainty evidence). Rice fortified with vitamin A alone or in combination with other micronutrients versus unfortified rice (no micronutrients added) One study had one arm providing fortified rice with vitamin A only versus unfortified rice. Fortification of rice with vitamin A (in combination with other micronutrients) may increase mean haemoglobin (MD 10.00, 95% CI 8.79 to 11.21; 1 study, 74 participants; low-certainty evidence). Rice fortified with vitamin A may slightly improve serum retinol concentration (MD 0.17, 95% CI 0.13 to 0.21; 1 study, 74 participants; low-certainty evidence). No studies contributed data to the comparisons of rice fortification versus no intervention. The studies involving folic acid and zinc also involved iron in the fortification arms and hence we reported them as part of the first comparison. AUTHORS' CONCLUSIONS: Fortification of rice with iron alone or in combination with other micronutrients may make little or no difference in the risk of having anaemia or presenting iron deficiency and we are uncertain about an increase in mean haemoglobin concentrations in the general population older than 2 years of age. Fortification of rice with iron and other micronutrients such as vitamin A or folic acid may make little or no difference in the risk of having vitamin A deficiency or on the serum folate concentration. There is limited evidence on any adverse effects of rice fortification.

Prevalence thresholds for wasting, overweight and stunting in children under 5 years.

OBJECTIVE: Prevalence ranges to classify levels of wasting and stunting have been used since the 1990s for global monitoring of malnutrition. Recent developments prompted a re-examination of existing ranges and development of new ones for childhood overweight. The present paper reports from the WHO-UNICEF Technical Expert Advisory Group on Nutrition Monitoring. DESIGN: Thresholds were developed in relation to sd of the normative WHO Child Growth Standards. The international definition of 'normal' (2 sd below/above the WHO standards median) defines the first threshold, which includes 2·3 % of the area under the normalized distribution. Multipliers of this 'very low' level (rounded to 2·5 %) set the basis to establish subsequent thresholds. Country groupings using the thresholds were produced using the most recent set of national surveys. SETTING: One hundred and thirty-four countries. SUBJECTS: Children under 5 years. RESULTS: For wasting and overweight, thresholds are: 'very low' (≈6 times 2·5 %). For stunting, thresholds are: 'very low' (≈12 times 2·5 %). CONCLUSIONS: The proposed thresholds minimize changes and keep coherence across anthropometric indicators. They can be used for descriptive purposes to map countries according to severity levels; by donors and global actors to identify priority countries for action; and by governments to trigger action and target programmes aimed at achieving 'low' or 'very low' levels. Harmonized terminology will help avoid confusion and promote appropriate interventions.

Fortification of maize flour with iron for controlling anaemia and iron deficiency in populations.

BACKGROUND: Approximately 800 million women and children have anaemia, a condition thought to cause almost 9% of the global burden of years lived with disability. Around half this burden could be amenable to interventions that involve the provision of iron. Maize (corn) is one of the world's most important cereal grains and is cultivated across most of the globe. Several programmes around the world have fortified maize flour and other maize-derived foodstuffs with iron and other vitamins and minerals to combat anaemia and iron deficiency. OBJECTIVES: To assess the effects of iron fortification of maize flour, corn meal and fortified maize flour products for anaemia and iron status in the general population. SEARCH METHODS: We searched the following international and regional sources in December 2017 and January 2018: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; MEDLINE (R) In Process; Embase; Web of Science (both the Social Science Citation Index and the Science Citation Index); CINAHL Ebsco; POPLINE; AGRICOLA (agricola.nal.usda.gov); BIOSIS (ISI); Bibliomap and TRoPHI; IBECS; Scielo; Global Index Medicus - AFRO (includes African Index Medicus); EMRO (includes Index Medicus for the Eastern Mediterranean Region); LILACS; PAHO (Pan American Health Library); WHOLIS (WHO Library); WPRO (includes Western Pacific Region Index Medicus); IMSEAR, Index Medicus for the South-East Asian Region; IndMED, Indian medical journals; and the Native Health Research Database. We searched clinicaltrials.gov and the International Clinical Trials Registry Platform (ICTRP) for any ongoing or planned studies on 17 January 2018 and contacted authors of such studies to obtain further information or eligible data if available.For assistance in identifying ongoing or unpublished studies, we also contacted relevant international organisations and agencies working in food fortification on 9 August 2016. SELECTION CRITERIA: We included cluster- or individually randomised controlled trials and observational studies. Interventions included (central/industrial) fortification of maize flour or corn meal with iron alone or with other vitamins and minerals and provided to individuals over 2 years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies for inclusion, extracted data from included studies and assessed the risk of bias of the included studies. Trial designs with a comparison group were included to assess the effects of interventions. Trial designs without a control or comparison group (uncontrolled before-and-after studies) were included for completeness but were not considered in assessments of the overall effectiveness of interventions or used to draw conclusions regarding the effects of interventions in the review. MAIN RESULTS: Our search yielded 4529 records. After initial screening of titles and abstracts, we reviewed the full text of 75 studies (80 records). We included 5 studies and excluded 70. All the included studies assessed the effects of providing maize products fortified with iron plus other vitamins and minerals versus unfortified maize flour. No studies compared this intervention to no intervention or looked at the relative effect of flour and products fortified with iron alone (without other vitamins and minerals). Three were randomised trials involving 2610 participants, and two were uncontrolled before-and-after studies involving 849 participants.Only three studies contributed data for the meta-analysis and included children aged 2 to 11.9 years and women. Compared to unfortified maize flour, it is uncertain whether fortifying maize flour or corn meal with iron and other vitamins and minerals has any effect on anaemia (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.58 to 1.40; 2 studies; 1027 participants; very low-certainty evidence), or on the risk of iron deficiency (RR 0.75, 95% CI 0.49 to 1.15; 2 studies; 1102 participants; very low-certainty evidence), haemoglobin concentration (mean difference (MD) 1.25 g/L, 95% CI -2.36 to 4.86 g/L; 3 studies; 1144 participants; very low-certainty evidence) or ferritin concentrations (MD 0.48 µg/L, 95% CI -0.37 to 1.33 µg/L; 1 study; 584 participants; very low-certainty evidence).None of the studies reported on any adverse effects. We judged the certainty of the evidence to be very low based on GRADE, so we are uncertain whether the results reflect the true effect of the intervention. We downgraded evidence due to high risk of selection bias and unclear risk of performance bias in one of two included studies, high heterogeneity and wide CIs crossing the line of no effect for anaemia prevalence and haemoglobin concentration. AUTHORS' CONCLUSIONS: It is uncertain whether fortifying maize flour with iron and other vitamins and minerals reduces the risk of anaemia or iron deficiency in children aged over 2 years or in adults. Moreover, the evidence is too uncertain to conclude whether iron-fortified maize flour, corn meal or fortified maize flour products have any effect on reducing the risk of anaemia or on improving haemoglobin concentration in the population.We are uncertain whether fortification of maize flour with iron reduces anaemia among the general population, as the certainty of the evidence is very low. No studies reported on any adverse effects.Public organisations funded three of the five included studies, while the private sector gave grants to universities to perform the other two. The presence of industry funding for some of these trials did not appear to positively influence results from these studies.The reduced number of studies, including only two age groups (children and women of reproductive age), as well as the limited number of comparisons (only one out of the four planned) constitute the main limitations of this review.

Applying international guidelines for calcium supplementation to prevent pre-eclampsia: simulation of recommended dosages suggests risk of excess intake in Ethiopia.

OBJECTIVE: To simulate impact of Ca supplementation on estimated total Ca intakes among women in a population with low dietary Ca intakes, using WHO recommendations: 1·5-2·0 g elemental Ca/d during pregnancy to prevent pre-eclampsia. DESIGN: Single cross-sectional 24 h dietary recall data were adjusted using IMAPP software to simulate proportions of women who would meet or exceed the Estimated Average Requirement (EAR) and Tolerable Upper Intake Level (UL) assuming full or partial adherence to WHO guidelines. SETTING: Nationally and regionally representative data, Ethiopia's 'lean' season 2011. SUBJECTS: Women 15-45 years (n 7908, of whom 492 pregnant). RESULTS: National mean usual Ca intake was 501 (sd 244) mg/d. Approximately 89, 91 and 96 % of all women, pregnant women and 15-18 years, respectively, had dietary Ca intakes below the EAR. Simulating 100 % adherence to 1·0, 1·5 and 2·0 g/d estimated nearly all women (>99 %) would meet the EAR, regardless of dosage. Nationally, supplementation with 1·5 and 2·0 g/d would result in intake exceeding the UL in 3·7 and 43·2 % of women, respectively, while at 1·0 g/d those exceeding the UL would be <1 % (0·74 %) except in one region (4·95 %). CONCLUSIONS: Most Ethiopian women consume insufficient Ca, increasing risk of pre-eclampsia. Providing Ca supplements of 1·5-2·0 g/d could result in high proportions of women exceeding the UL, while universal consumption of 1·0 g/d would meet requirements with minimal risk of excess. Appropriately tested screening tools could identify and reduce risk to high Ca consumers. Research on minimum effective Ca supplementation to prevent pre-eclampsia is also needed to determine whether lower doses could be recommended.

Multiple micronutrient supplements in pregnancy: Implementation considerations for integration as part of quality services in routine antenatal care. Objectives, results, and conclusions of the meeting.

Health promotion, screening, diagnosis, and disease prevention are essential services of quality routine antenatal care for pregnant adult and adolescent women. Supplementation programmes in pregnancy, generally implemented in the context of antenatal care services, have had less than optimal results in many countries, generally attributed to limited access, low coverage, and reduced adherence to the recommended regimens and counselling. The World Health Organization Department of Nutrition for Health and Development, in collaboration with the United Nations Children's Fund and Nutrition International, convened the technical consultation "Multiple micronutrient supplements in pregnancy: Implementation considerations for successful incorporation into existing programmes." The objectives of the technical consultation were to (a) examine implementation experiences of micronutrient supplementation interventions in pregnant women, lessons learnt, and best practices; (b) discuss programmatic and technical considerations of interventions on multiple micronutrient supplementation in pregnant women in low-, middle-, and high-income countries; and (c) identify implementation considerations that can be useful to scaling up efforts by national policymaker and their advisors considering multiple micronutrient supplementation in pregnant women as part of existing antenatal care programmes as well as other delivery platforms. The consultation was based on presentations of background papers, case studies, and plenary discussions. Country representatives were asked to discuss the context of micronutrient supplementation for their countries and share implementation challenges they faced. This paper provides the background and rationale of the technical consultation, synopsises the presentations, and provides a summary of the main considerations and conclusions reached during plenary discussions.

Barriers and enablers for iron folic acid (IFA) supplementation in pregnant women.

In order to inform large scale supplementation programme design, we review and summarize the barriers and enablers for improved coverage and utilization of iron and folic acid (IFA) supplements by pregnant women in 7 countries in Africa and Asia. Mixed methods were used to analyse IFA supplementation programmes in Afghanistan, Bangladesh, Indonesia, Ethiopia, Kenya, Nigeria, and Senegal based on formative research conducted in 2012-2013. Qualitative data from focus-group discussions and interviews with women and service providers were used for content analysis to elicit common themes on barriers and enablers at internal, external, and relational levels. Anaemia symptoms in pregnancy are well known among women and health care providers in all countries, yet many women do not feel personally at risk. Broad awareness and increased coverage of facility-based antenatal care (ANC) make it an efficient delivery channel for IFA; however, first trimester access to IFA is hindered by beliefs about when to first attend ANC and preferences for disclosing pregnancy status. Variable access and poor quality ANC services, including insufficient IFA supplies and inadequate counselling to encourage consumption, are barriers to both coverage and adherence. Community-based delivery of IFA and referral to ANC provides earlier and more frequent access and opportunities for follow-up. Improving ANC access and quality is needed to facilitate IFA supplementation during pregnancy. Community-based delivery and counselling can address problems of timely and continuous access to supplements. Renewed investment in training for service providers and effective behaviour change designs are urgently needed to achieve the desired impact.

Integrating nutrition into health systems at community level: Impact evaluation of the community-based maternal and neonatal health and nutrition projects in Ethiopia, Kenya, and Senegal.

Maternal undernutrition and mortality remain high in several African countries. Key nutrition and health interventions improve maternal and birth outcomes. Evidence is scarce on how to strengthen health systems to ensure pregnant women and newborns are reached with these interventions. We conducted three quasi-experimental nonrandomized Community Based Maternal and Neonatal Health and Nutrition projects in regions of Ethiopia, Senegal, and Kenya to demonstrate how proven nutrition interventions could be integrated into health programs to improve knowledge and practices during pregnancy, birth, and postpartum. We evaluated impact on knowledge and practices related to maternal and neonatal care using logistic regression and repeated-measures models with districts as a fixed variable and adjusted for covariates. Combined country analyses show significant positive effects of the intervention on women receiving first antenatal care visit (ANC) during first trimester (OR = 1.44; p < .001), those consuming any iron and folic acid supplement during their latest pregnancy (OR = 1.60; p = .005), those whose <6 months infants were exclusively breastfed (OR = 2.01; p=.003), those whose delivery was facility based (OR = 1.48; p=.031), and those whose postnatal care was facility based (OR = 2.15; p<.001). There was no significant differences between intervention and control groups regarding one or more and four or more ANC visits, women consuming iron and folic acid for ≥90 days, and early initiation of breastfeeding. We conclude that integrating proven nutrition interventions into health programs at community level improved components of access to and use of ANC, delivery services, and postnatal care by women in three African countries.

Design and implementation of a health systems strengthening approach to improve health and nutrition of pregnant women and newborns in Ethiopia, Kenya, Niger, and Senegal.

Maternal and neonatal mortality are unacceptably high in developing countries. Essential nutrition interventions contribute to reducing this mortality burden, although nutrition is poorly integrated into health systems. Universal health coverage is an essential prerequisite to decreasing mortality indices. However, provision and utilization of nutrition and health services for pregnant women and their newborns are poor and the potential for improvement is limited where health systems are weak. The Community-Based Maternal and Neonatal Health and Nutrition project was established as a set of demonstration projects in 4 countries in Africa with varied health system contexts where there were barriers to safe maternal health care at individual, community and facility levels. We selected project designs based on the need, context, and policies under consideration. A theory driven approach to programme implementation and evaluation was used involving developing of contextual project logic models that linked inputs to address gaps in quality and uptake of antenatal care; essential nutrition actions in antenatal care, delivery, and postnatal care; delivery with skilled and trained birth attendant; and postnatal care to outcomes related to improvements in maternal health service utilization and reduction in maternal and neonatal morbidity and mortality. Routine monitoring and impact evaluations were included in the design. The objective of this paper is to describe the rationale and methods used in setting up a multi-country study that aimed at designing the key maternal and neonatal health interventions and identifying indicators related to inputs, outcomes, and impact that were measured to track change associated with our interventions.

Effect of iodized salt on organoleptic properties of processed foods: a systematic review.

Despite the global recommendation for fortification of salt with iodine, including salt used in food processing, most salt iodization programs have focussed only on iodization of household salt. Food manufacturers are frequently concerned about the potential instability of iodine and changes in organoleptic properties of their products if iodized salt is used instead of non-iodized salt. To address these concerns, this paper provides a comprehensive review of studies conducted to assess the effect of iodized salt on the organoleptic properties of processed foods and condiments. A comprehensive review was conducted of eligible studies identified by searching electronic databases (PubMed, Medline) and open Internet searches for studies examining the effect of salt iodized with either potassium iodide (KI) or potassium iodate (KIO3) on processed foods. A total of 34 studies on the effect of iodized salt on 38 types of processed foods are summarized. There is no evidence that the use of iodized salt in production of processed foods or condiments causes adverse organoleptic changes that will affect consumer acceptability or product quality. Universal salt iodization is widely recognized as the most cost-effective intervention to eliminate iodine deficiency. Taking into account increases in the proportion of dietary salt consumed through processed foods, and declines in salt consumed as household salt, iodized salt should be used in the production of processed foods as a means of assuring optimal iodine nutrition without the risk of affecting the organoleptic properties of foods.

Point-of-use fortification of foods with micronutrient powders containing iron in children of preschool and school-age.

BACKGROUND: Approximately 600 million children of preschool and school age are anaemic worldwide. It is estimated that at least half of the cases are due to iron deficiency. Point-of-use fortification of foods with micronutrient powders (MNP) has been proposed as a feasible intervention to prevent and treat anaemia. It refers to the addition of iron alone or in combination with other vitamins and minerals in powder form, to energy-containing foods (excluding beverages) at home or in any other place where meals are to be consumed. MNPs can be added to foods either during or after cooking or immediately before consumption without the explicit purpose of improving the flavour or colour. OBJECTIVES: To assess the effects of point-of-use fortification of foods with iron-containing MNP alone, or in combination with other vitamins and minerals on nutrition, health and development among children at preschool (24 to 59 months) and school (five to 12 years) age, compared with no intervention, a placebo or iron-containing supplements. SEARCH METHODS: In December 2016, we searched the following databases: CENTRAL, MEDLINE, Embase, BIOSIS, Science Citation Index, Social Science Citation Index, CINAHL, LILACS, IBECS, Popline and SciELO. We also searched two trials registers in April 2017, and contacted relevant organisations to identify ongoing and unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs trials with either individual or cluster randomisation. Participants were children aged between 24 months and 12 years at the time of intervention. For trials with children outside this age range, we included studies where we were able to disaggregate the data for children aged 24 months to 12 years, or when more than half of the participants were within the requisite age range. We included trials with apparently healthy children; however, we included studies carried out in settings where anaemia and iron deficiency are prevalent, and thus participants may have had these conditions at baseline. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of trials against the inclusion criteria, extracted data from included trials, assessed the risk of bias of the included trials and graded the quality of the evidence. MAIN RESULTS: We included 13 studies involving 5810 participants from Latin America, Africa and Asia. We excluded 38 studies and identified six ongoing/unpublished trials. All trials compared the provision of MNP for point-of-use fortification with no intervention or placebo. No trials compared the effects of MNP versus iron-containing supplements (as drops, tablets or syrup).The sample sizes in the included trials ranged from 90 to 2193 participants. Six trials included participants younger than 59 months of age only, four included only children aged 60 months or older, and three trials included children both younger and older than 59 months of age.MNPs contained from two to 18 vitamins and minerals. The iron doses varied from 2.5 mg to 30 mg of elemental iron. Four trials reported giving 10 mg of elemental iron as sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), chelated ferrous sulphate or microencapsulated ferrous fumarate. Three trials gave 12.5 mg of elemental iron as microencapsulated ferrous fumarate. Three trials gave 2.5 mg or 2.86 mg of elemental iron as NaFeEDTA. One trial gave 30 mg and one trial provided 14 mg of elemental iron as microencapsulated ferrous fumarate, while one trial gave 28 mg of iron as ferrous glycine phosphate.In comparison with receiving no intervention or a placebo, children receiving iron-containing MNP for point-of-use fortification of foods had lower risk of anaemia prevalence ratio (PR) 0.66, 95% confidence interval (CI) 0.49 to 0.88, 10 trials, 2448 children; moderate-quality evidence) and iron deficiency (PR 0.35, 95% CI 0.27 to 0.47, 5 trials, 1364 children; moderate-quality evidence) and had higher haemoglobin (mean difference (MD) 3.37 g/L, 95% CI 0.94 to 5.80, 11 trials, 2746 children; low-quality evidence).Only one trial with 115 children reported on all-cause mortality (zero cases; low-quality evidence). There was no effect on diarrhoea (risk ratio (RR) 0.97, 95% CI 0.53 to 1.78, 2 trials, 366 children; low-quality evidence). AUTHORS' CONCLUSIONS: Point-of-use fortification of foods with MNPs containing iron reduces anaemia and iron deficiency in preschool- and school-age children. However, information on mortality, morbidity, developmental outcomes and adverse effects is still scarce.

Iodine supplementation for women during the preconception, pregnancy and postpartum period.

BACKGROUND: Iodine is an essential nutrient required for the biosynthesis of thyroid hormones, which are responsible for regulating growth, development and metabolism. Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, fetal and infant needs. The provision of iodine supplements may help meet the increased iodine needs during pregnancy and the postpartum period and prevent or correct iodine deficiency and its consequences. OBJECTIVES: To assess the benefits and harms of supplementation with iodine, alone or in combination with other vitamins and minerals, for women in the preconceptional, pregnancy or postpartum period on their and their children's outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 November 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (17 November 2016), contacted experts in the field and searched the reference lists of retrieved studies and other relevant papers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials with randomisation at either the individual or cluster level comparing injected or oral iodine supplementation (such as tablets, capsules, drops) during preconception, pregnancy or the postpartum period irrespective of iodine compound, dose, frequency or duration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, risk of bias, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials, and we pooled trial results using random-effects models and were cautious in our interpretation of the pooled results. MAIN RESULTS: We included 14 studies and excluded 48 studies. We identified five ongoing or unpublished studies and two studies are awaiting classification. Eleven trials involving over 2700 women contributed data for the comparisons in this review (in three trials, the primary or secondary outcomes were not reported). Maternal primary outcomesIodine supplementation decreased the likelihood of the adverse effect of postpartum hyperthyroidism by 68% (average risk ratio (RR) 0.32; 95% confidence interval (CI) 0.11 to 0.91, three trials in mild to moderate iodine deficiency settings, 543 women, no statistical heterogeneity, low-quality evidence) and increased the likelihood of the adverse effect of digestive intolerance in pregnancy by 15 times (average RR 15.33; 95% CI 2.07 to 113.70, one trial in a mild-deficiency setting, 76 women, very low-quality evidence).There were no clear differences between groups for hypothyroidism in pregnancy or postpartum (pregnancy: average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence, and postpartum: average RR 0.44; 95% CI 0.06 to 3.42, three trials, 540 women, no statistical heterogeneity, low-quality evidence), preterm birth (average RR 0.71; 95% CI 0.30 to 1.66, two trials, 376 women, statistical heterogeneity, low-quality evidence) or the maternal adverse effects of elevated thyroid peroxidase antibodies (TPO-ab) in pregnancy or postpartum (average RR 0.95; 95% CI 0.44 to 2.07, one trial, 359 women, low-quality evidence, average RR 1.01; 95% CI 0.78 to 1.30, three trials, 397 women, no statistical heterogeneity, low-quality evidence), or hyperthyroidism in pregnancy (average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence). All of the trials contributing data to these outcomes took place in settings with mild to moderate iodine deficiency. Infant/child primary outcomesCompared with those who did not receive iodine, those who received iodine supplements had a 34% lower likelihood of perinatal mortality, however this difference was not statistically significant (average RR 0.66; 95% CI 0.42 to 1.03, two trials, 457 assessments, low-quality evidence). All of the perinatal deaths occurred in one trial conducted in a severely iodine-deficient setting. There were no clear differences between groups for low birthweight (average RR 0.56; 95% CI 0.26 to 1.23, two trials, 377 infants, no statistical heterogeneity, low-quality evidence), neonatal hypothyroidism/elevated thyroid-stimulating hormone (TSH) (average RR 0.58; 95% CI 0.11 to 3.12, two trials, 260 infants, very low-quality evidence) or the adverse effect of elevated neonatal thyroid peroxidase antibodies (TPO-ab) (average RR 0.61; 95% CI 0.07 to 5.70, one trial, 108 infants, very low-quality evidence). All of the trials contributing data to these outcomes took place in areas with mild to moderate iodine deficiency. No trials reported on hypothyroidism/elevated TSH or any adverse effect beyond the neonatal period. AUTHORS' CONCLUSIONS: There were insufficient data to reach any meaningful conclusions on the benefits and harms of routine iodine supplementation in women before, during or after pregnancy. The available evidence suggested that iodine supplementation decreases the likelihood of postpartum hyperthyroidism and increases the likelihood of the adverse effect of digestive intolerance in pregnancy - both considered potential adverse effects. We considered evidence for these outcomes low or very low quality, however, because of study design limitations and wide confidence intervals. In addition, due to the small number of trials and included women in our meta-analyses, these findings must be interpreted with caution. There were no clear effects on other important maternal or child outcomes though these findings must also be interpreted cautiously due to limited data and low-quality trials. Additionally, almost all of the evidence came from settings with mild or moderate iodine deficiency and therefore may not be applicable to settings with severe deficiency.More high-quality randomised controlled trials are needed on iodine supplementation before, during and after pregnancy on maternal and infant/child outcomes. However, it may be unethical to compare iodine to placebo or no treatment in severe deficiency settings. Trials may also be unfeasible in settings where pregnant and lactating women commonly take prenatal supplements with iodine. Information is needed on optimal timing of initiation as well as supplementation regimen and dose. Future trials should consider the outcomes in this review and follow children beyond the neonatal period. Future trials should employ adequate sample sizes, assess potential adverse effects (including the nature and extent of digestive intolerance), and be reported in a way that allows assessment of risk of bias, full data extraction and analysis by the subgroups specified in this review.

Vitamin D supplementation for women during pregnancy.

BACKGROUND: Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse pregnancy outcomes. OBJECTIVES: To examine whether oral supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2015), the International Clinical Trials Registry Platform (31 January 2015), the Networked Digital Library of Theses and Dissertations (28 January 2015) and also contacted relevant organisations (31 January 2015). SELECTION CRITERIA: Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: In this updated review we included 15 trials assessing a total of 2833 women, excluded 27 trials, and 23 trials are still ongoing or unpublished. Nine trials compared the effects of vitamin D alone versus no supplementation or a placebo and six trials compared the effects of vitamin D and calcium with no supplementation. Risk of bias in the majority of trials was unclear and many studies were at high risk of bias for blinding and attrition rates. Vitamin D alone versus no supplementation or a placebo Data from seven trials involving 868 women consistently show that women who received vitamin D supplements alone, particularly on a daily basis, had higher 25-hydroxyvitamin D than those receiving no intervention or placebo, but this response was highly heterogeneous. Also, data from two trials involving 219 women suggest that women who received vitamin D supplements may have a lower risk of pre-eclampsia than those receiving no intervention or placebo (8.9% versus 15.5%; risk ratio (RR) 0.52; 95% CI 0.25 to 1.05, low quality). Data from two trials involving 219 women suggest a similar risk of gestational diabetes among those taking vitamin D supplements or no intervention/placebo (RR 0.43; 95% CI 0.05, 3.45, very low quality). There were no clear differences in adverse effects, with only one reported case of nephritic syndrome in the control group in one study (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women, low quality). Given the scarcity of data for this outcome, no firm conclusions can be drawn. No other adverse effects were reported in any of the other studies.With respect to infant outcomes, data from three trials involving 477 women suggest that vitamin D supplementation during pregnancy reduces the risk preterm birth compared to no intervention or placebo (8.9% versus 15.5%; RR 0.36; 95% CI 0.14 to 0.93, moderate quality). Data from three trials involving 493 women also suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 g than those receiving no intervention or placebo (RR 0.40; 95% CI 0.24 to 0.67, moderate quality).In terms of other outcomes, there were no clear differences in caesarean section (RR 0.95; 95% CI 0.69 to 1.31; two trials; 312 women); stillbirths (RR 0.35 95% CI 0.06, 1.99; three trials, 540 women); or neonatal deaths (RR 0.27; 95% CI 0.04, 1.67; two trials, 282 women). There was some indication that vitamin D supplementation increases infant length (mean difference (MD) 0.70, 95% CI -0.02 to 1.43; four trials, 638 infants) and head circumference at birth (MD 0.43, 95% CI 0.03 to 0.83; four trials, 638 women). Vitamin D and calcium versus no supplementation or a placeboWomen who received vitamin D with calcium had a lower risk of pre-eclampsia than those not receiving any intervention (RR 0.51; 95% CI 0.32 to 0.80; three trials; 1114 women, moderate quality), but also an increased risk of preterm birth (RR 1.57; 95% CI 1.02 to 2.43, three studies, 798 women, moderate quality). Maternal vitamin D concentration at term, gestational diabetes, adverse effects and low birthweight were not reported in any trial or reported only by one study. AUTHORS' CONCLUSIONS: New studies have provided more evidence on the effects of supplementing pregnant women with vitamin D alone or with calcium on pregnancy outcomes. Supplementing pregnant women with vitamin D in a single or continued dose increases serum 25-hydroxyvitamin D at term and may reduce the risk of pre-eclampsia, low birthweight and preterm birth. However, when vitamin D and calcium are combined, the risk of preterm birth is increased. The clinical significance of the increased serum 25-hydroxyvitamin D concentrations is still unclear. In light of this, these results need to be interpreted with caution. Data on adverse effects were lacking in all studies.The evidence on whether vitamin D supplementation should be given as a part of routine antenatal care to all women to improve maternal and infant outcomes remains unclear. While there is some indication that vitamin D supplementation could reduce the risk of pre-eclampsia and increase length and head circumference at birth, further rigorous randomised trials are required to confirm these effects.

Daily iron supplementation for improving anaemia, iron status and health in menstruating women.

BACKGROUND: Iron-deficiency anaemia is highly prevalent among non-pregnant women of reproductive age (menstruating women) worldwide, although the prevalence is highest in lower-income settings. Iron-deficiency anaemia has been associated with a range of adverse health outcomes, which restitution of iron stores using iron supplementation has been considered likely to resolve. Although there have been many trials reporting effects of iron in non-pregnant women, these trials have never been synthesised in a systematic review. OBJECTIVES: To establish the evidence for effects of daily supplementation with iron on anaemia and iron status, as well as on physical, psychological and neurocognitive health, in menstruating women. SEARCH METHODS: In November 2015 we searched CENTRAL, Ovid MEDLINE, EMBASE, and nine other databases, as well as four digital thesis repositories. In addition, we searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and reference lists of relevant reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing daily oral iron supplementation with or without a cointervention (folic acid or vitamin C), for at least five days per week at any dose, to control or placebo using either individual- or cluster-randomisation. Inclusion criteria were menstruating women (or women aged 12 to 50 years) reporting on predefined primary (anaemia, haemoglobin concentration, iron deficiency, iron-deficiency anaemia, all-cause mortality, adverse effects, and cognitive function) or secondary (iron status measured by iron indices, physical exercise performance, psychological health, adherence, anthropometric measures, serum/plasma zinc levels, vitamin A status, and red cell folate) outcomes. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures of Cochrane. MAIN RESULTS: The search strategy identified 31,767 records; after screening, 90 full-text reports were assessed for eligibility. We included 67 trials (from 76 reports), recruiting 8506 women; the number of women included in analyses varied greatly between outcomes, with endpoint haemoglobin concentration being the outcome with the largest number of participants analysed (6861 women). Only 10 studies were considered at low overall risk of bias, with most studies presenting insufficient details about trial quality.Women receiving iron were significantly less likely to be anaemic at the end of intervention compared to women receiving control (risk ratio (RR) 0.39 (95% confidence interval (CI) 0.25 to 0.60, 10 studies, 3273 women, moderate quality evidence). Women receiving iron had a higher haemoglobin concentration at the end of intervention compared to women receiving control (mean difference (MD) 5.30, 95% CI 4.14 to 6.45, 51 studies, 6861 women, high quality evidence). Women receiving iron had a reduced risk of iron deficiency compared to women receiving control (RR 0.62, 95% CI 0.50 to 0.76, 7 studies, 1088 women, moderate quality evidence). Only one study (55 women) specifically reported iron-deficiency anaemia and no studies reported mortality. Seven trials recruiting 901 women reported on 'any side effect' and did not identify an overall increased prevalence of side effects from iron supplements (RR 2.14, 95% CI 0.94 to 4.86, low quality evidence). Five studies recruiting 521 women identified an increased prevalence of gastrointestinal side effects in women taking iron (RR 1.99, 95% CI 1.26 to 3.12, low quality evidence). Six studies recruiting 604 women identified an increased prevalence of loose stools/diarrhoea (RR 2.13, 95% CI 1.10, 4.11, high quality evidence); eight studies recruiting 1036 women identified an increased prevalence of hard stools/constipation (RR 2.07, 95% CI 1.35 to 3.17, high quality evidence). Seven studies recruiting 1190 women identified evidence of an increased prevalence of abdominal pain among women randomised to iron (RR 1.55, 95% CI 0.99 to 2.41, low quality evidence). Eight studies recruiting 1214 women did not find any evidence of an increased prevalence of nausea among women randomised to iron (RR 1.19, 95% CI 0.78 to 1.82). Evidence that iron supplementation improves cognitive performance in women is uncertain, as studies could not be meta-analysed and individual studies reported conflicting results. Iron supplementation improved maximal and submaximal exercise performance, and appears to reduce symptomatic fatigue. Although adherence could not be formally meta-analysed due to differences in reporting, there was no evident difference in adherence between women randomised to iron and control. AUTHORS' CONCLUSIONS: Daily iron supplementation effectively reduces the prevalence of anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and reduces symptomatic fatigue. These benefits come at the expense of increased gastrointestinal symptomatic side effects.

Fortification of staple foods with zinc for improving zinc status and other health outcomes in the general population.

BACKGROUND: Zinc deficiency is a global nutritional problem, particularly in children and women residing in settings where diets are cereal based and monotonous. It has several negative health consequences. Fortification of staple foods with zinc may be an effective strategy for preventing zinc deficiency and improving zinc-related health outcomes. OBJECTIVES: To evaluate the beneficial and adverse effects of fortification of staple foods with zinc on health-related outcomes and biomarkers of zinc status in the general population. SEARCH METHODS: We searched the following databases in April 2015: Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3 of 12, 2015, the Cochrane Library), MEDLINE & MEDLINE In Process (OVID) (1950 to 8 April 2015), EMBASE (OVID) (1974 to 8 April 2015), CINAHL (1982 to April 2015), Web of Science (1900 to 9 April 2015), BIOSIS (1969 to 9 April 2015), POPLINE (1970 to April 2015), AGRICOLA, OpenGrey, BiblioMap, and Trials Register of Promoting Health Interventions (TRoPHI), besides regional databases (April 2015) and theses. We also searched clinical trial registries (17 March 2015) and contacted relevant organisations (May 2014) in order to identify ongoing and unpublished studies. SELECTION CRITERIA: We included randomised controlled trials, randomised either at the level of the individual or cluster. We also included non-randomised trials at the level of the individual if there was a concurrent comparison group. We included non-randomised cluster trials and controlled before-after studies only if there were at least two intervention sites and two control sites. Interventions included fortification (central/industrial) of staple foods (cereal flours, edible fats, sugar, condiments, seasonings, milk and beverages) with zinc for a minimum period of two weeks. Participants were members of the general population who were over two years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies for inclusion, extracted data from included studies, and assessed the risk of bias of the included studies. MAIN RESULTS: We included eight trials (709 participants); seven were from middle-income countries of Asia, Africa, Europe, and Latin America where zinc deficiency is likely to be a public health problem. Four trials compared the effect of zinc-fortified staple foods with unfortified foods (comparison 1), and four compared zinc-fortified staple foods in combination with other nutrients/factors with the same foods containing other nutrients or factors without zinc (comparison 2). The interventions lasted between one and nine months. We categorised most trials as having unclear or high risk of bias for randomisation, but low risk of bias for blinding and attrition. None of the studies in comparison 1 reported data on zinc deficiency.Foods fortified with zinc increased the serum or plasma zinc levels in comparison to foods without added zinc (mean difference (MD) 2.12 µmol/L, 95% confidence interval (CI) 1.25 to 3.00 µmol/L; 3 studies; 158 participants; low-quality evidence). Participants consuming foods fortified with zinc versus participants consuming the same food without zinc had similar risk of underweight (average risk ratio 3.10, 95% CI 0.52 to 18.38; 2 studies; 397 participants; low-quality evidence) and stunting (risk ratio (RR) 0.88, 95% CI 0.36 to 2.13; 2 studies; 397 participants; low-quality evidence). A single trial of addition of zinc to iron in wheat flour did not find a reduction in proportion of zinc deficiency (RR 0.17, 95% CI 0.01 to 3.94; very low-quality evidence). We did not find a difference in serum or plasma zinc levels in participants consuming foods fortified with zinc plus other micronutrients when compared with participants consuming the same foods with micronutrients but no added zinc (MD 0.03 µmol/L, 95% CI -0.67 to 0.72 µmol/L; 4 studies; 250 participants; low-quality evidence). No trial in comparison 2 provided information about underweight or stunting.There was no reported adverse effect of fortification of foods with zinc on indicators of iron or copper status. AUTHORS' CONCLUSIONS: Fortification of foods with zinc may improve the serum zinc status of populations if zinc is the only micronutrient used for fortification. If zinc is added to food in combination with other micronutrients, it may make little or no difference to the serum zinc status. Effects of fortification of foods with zinc on other outcomes including zinc deficiency, children's growth, cognition, work capacity of adults, or on haematological indicators are unknown. Given the small number of trials and participants in each trial, further investigation of these outcomes is required.

Tackling malnutrition in Latin America and the Caribbean: challenges and opportunities.

Undernutrition and micronutrient deficiencies are still a public health problem in Latin America and the Caribbean (LAC), and overweight and obesity have reached epidemic proportions. To assess the nutrition landscape in LAC countries and guide future nutrition efforts and investments, the Pan American Health Organization and the Micronutrient Initiative joined efforts to 1) identify information gaps and describe the current nutritional situation in the region; 2) map existing policies to address malnutrition in Latin America; 3) describe the impact of conditional cash transfer programs (CCTs) on nutrition and health outcomes; and 4) identify the challenges and opportunities to address malnutrition in the region. This article summarizes the methods and key findings from that research and describes the current challenges and opportunities in addressing malnutrition in the LAC region. LAC countries have advanced in reducing undernutrition and micronutrient deficiencies, but important gaps in information are a major concern. These countries have policies to address undernutrition and micronutrient deficiencies, but comprehensive and intersectoral policies to tackle obesity are lacking. CCTs in Brazil, Colombia, and Mexico have been reported to have a positive impact on child nutrition and health outcomes, providing an opportunity to integrate nutrition actions in intersectoral platforms. The current epidemiological situation and policy options offer an opportunity for countries, technical agencies, donors, and other stakeholders to jointly scale up nutrition actions. This can support the development of comprehensive and intersectoral policies to tackle the double burden of malnutrition, strengthen national nutrition surveillance systems, incorporate monitoring and evaluation as systematic components of policies and programs, document and increase investments in nutrition, and assess the effectiveness of such policies to support political commitment and guarantee sustainability.

Multiple micronutrient powders for home (point-of-use) fortification of foods in pregnant women.

BACKGROUND: It is estimated that 32 million pregnant women suffer from anaemia worldwide. Due to increased metabolic demands, pregnant women are particularly vulnerable to anaemia and vitamin and mineral deficiencies, leading to adverse health effects in both the mother and her baby. Despite the demonstrated benefits of prenatal supplementation with iron and folic acid or multiple micronutrients, poor adherence to routine supplementation has limited the effectiveness of this intervention in many settings. Micronutrient powders for point-of-use fortification are packed, single-dose sachets containing vitamins and minerals that can be added onto prepared food to improve its nutrient profile. The use of multiple micronutrient powders for point-of-use fortification of foods in pregnant women could be an alternative intervention to prenatal micronutrient supplementation. OBJECTIVES: To assess the effects of prenatal home (point-of-use) fortification of foods with multiple micronutrient powders on maternal and newborn health. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015) and the International Clinical Trials Registry Platform (ICTRP) (31 January 2015). We also contacted relevant agencies to identify ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (both individual and cluster randomisation) and quasi-randomised trials, irrespective of language or publication status.The intervention was micronutrient powders for point-of-use fortification of foods, containing at least three micronutrients with one of them being iron, provided to pregnant women of any gestational age and parity. Five comparison groups were considered: no intervention/placebo, iron and folic acid supplements, iron-only supplements, folic-acid only supplements, and multiple micronutrients in supplements. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies, extracted and checked data accuracy, and assessed the risk of bias of included studies. MAIN RESULTS: Our search identified 12 reports (relating to six studies). We included two cluster-randomised controlled trials (involving 1172 women) - these trials were considered to be at a moderate to high risk of bias due to methodological limitations. One trial is ongoing, and three studies were excluded. Micronutrient powders for point-of-use fortification of foods versus iron and folic acid supplementsOne trial (involving 478 pregnant women attending 42 antenatal care centres) compared micronutrient powders containing iron, folic acid, vitamin C and zinc with iron and folic acid tablets provided daily from 14 to 22 weeks to 32 weeks' gestation. The trial did not report on any of this review's primary outcomes: maternal anaemia at or near term, maternal iron deficiency, maternal mortality, adverse effects, low birthweight, preterm births. Nor did the trial report on the majority of this review's secondary outcomes, with the exception of maternal adherence. Adherence to micronutrient powders was lower than adherence to iron and folic acid supplements (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.66 to 0.87, one study, n = 405). Micronutrient powders for point-of-use fortification of foods versus same multiple micronutrients in supplementsOne study (involving 694 pregnant women from 18 communities), compared micronutrient powders containing iron, folic acid, vitamin C, zinc, iodine, vitamin E and vitamin B12 with tablets containing the same seven micronutrients. There was no difference in maternal anaemia at 37 weeks of gestation (RR 0.92, 95% CI 0.53 to 1.59, one study, n = 470, very low quality evidence). The trial did not report on any of this review's other primary outcomes in relation to maternal iron deficiency, maternal mortality, adverse effects, low birthweight, or preterm birth. In terms of this review's secondary outcomes, the included trial did not report on the majority of this review's prespecified secondary outcomes with one exception - there was no clear difference in maternal haemoglobin Hb or near term (mean difference (MD) 1.0 g/L, 95% CI -1.77 to 3.77, one study, n = 470). AUTHORS' CONCLUSIONS: Limited evidence suggests that micronutrient powders for point-of-use fortification of foods have no clear difference as multiple micronutrient supplements on maternal anaemia (very low quality evidence) and Hb at or near term. There is limited evidence to suggest that women were more likely to adhere to taking tablets than using micronutrient powders.The overall quality of evidence was judged very low (due to methodological limitations), and no evidence was available for the majority of primary and secondary outcomes. Therefore, more evidence is needed to assess the potential benefits or harms of the use of micronutrient powders in pregnant women on maternal and infant health outcomes. Future trials should also assess adherence to micronutrient powders and be adequately powered to evaluate the effects on birth outcomes and morbidity.