Considerations for Correction of Micronutrient Deficiencies Through Supplementation in Pregnant Women and Children Under-5 in Latin America.

BACKGROUND: Micronutrient deficiencies in Latin America are a public health concern, nonetheless, lack of information still exists in many countries, so that the true magnitude of the problem remains uncertain. OBJECTIVE: To summarise experiences that can inform the development of policies and programs to address micronutrient deficiencies throung supplementation in pregnant women and chlidren under five years of age in Latin American. METHODS: Review of the most evidence on the effects of micronutrients supplementation, focusing on pregnant women and children under five years of age. RESULTS: Certain population groups, as women of reproductive age and children under 2 years of age, are at increased risk for deficiency due to their high micronutrient requirements. This is compounded by the limited access to micronutrient-rich foods for many people living in vulnerable situations. Micronutrient supplementation is an effective intervention to prevent and treat deficiency and to mitigate its adverse effects on health, nutrition, and pregnancy outcomes in micronutrient-deficient populations. The potential benefits of supplementation programs, however, are realized only when they reach those who have the potential to benefit, that is, with inadequate intakes of micronutrients from dietary sources, and when the quality of design and delivery of the programs aresufficient to reach that population timely, regularly, and effectively to enable and motivate consumption. CONCLUSIONS: Several resources and experiences exist that can help favor the development of programs that can realize this biological and programmatic potential. There is need for continuous efforts to augment coverage and achieve results that can translate into economic benefits for individuals, families, and nations.

Plain language titleCorrecting Vitamin and Mineral Deficiencies in Pregnant Women and Children in Latin AmericaPlain language summaryPrevious articles in this supplement have highlighted the importance of micronutrient (vitamin and mineral) deficiencies in Latin America, their causes and effects in different population groups, and some alternatives for their prevention and control. At certain stages of life, particularly during the first 1000 days (from pregnancy to 2 years of age), high nutrient requirements predispose to nutritional deficiencies. This is exacerbated by the limited access to healthy foods for populations living in vulnerable situations. Dietary supplements are therefore an effective strategy for preventing and treating deficiencies and mitigating their adverse effects on the nutrition and health of the population. In this article, we review the most recent estimates on the prevalence of nutrient deficiencies, with a focus on pregnant women and children under 2 years of age; the types of supplements available, and the international recommendations for supplementation during this period of life. There is strong evidence for several benefits of short-term supplementation. In pregnant women, vitamin and mineral levels are improved and a healthy pregnancy is achieved. In children, vitamin and mineral levels are also improved, and some (such as iron and zinc) improve growth and development. In the long term, there are economic benefits for individuals, families, and nations. Several recommendations from studies and supplementation programs are also discussed. Although nutritional supplementation can be cost-effective, benefits will only be achieved if the types and formulations of supplements meet the assessed nutritional needs of the population and if a program is properly designed and implemented. Similarly, programs that include supplements need to be monitored and evaluated to ensure that supplements are taken regularly and for long enough to achieve these benefits.

Translating Evidence-Based Program Recommendations into Action: The Design, Testing, and Scaling Up of the Behavior Change Strategy EsIAN in Mexico.

BACKGROUND: The Integrated Strategy for Attention to Nutrition (EsIAN in Spanish) is a national strategy within Mexico's conditional cash transfer program (initially Progresa, then Oportunidades, then Prospera, CCT-POP) designed to strengthen the health and nutrition component, address the nutrition transition, and improve the health and nutritional status of its beneficiaries, through 3 main components: 1) procurement of functioning equipment to primary health care (PHC) units; 2) providing free micronutrient supplements to beneficiary women and children; 3) implementing a behavior change communication (BCC) strategy and a training system for PHC providers (PHCPs). OBJECTIVE: We aim to describe the iterative process and evidence-based approach used to design and roll-out the EsIAN at scale, by focusing on the BCC component. METHODS: The BCC strategy was developed by following an iterative process through the following phases: situational analysis, formative research and design of the BCC strategy (using the socioecological framework and the social marketing approach), large-scale feasibility study, redesign, and national scale-up. RESULTS: The review and formative research revealed several barriers and issues that limited program coverage, utilization, and acceptance. These included misconceptions about pregnancy and infant feeding, nonalignment of practices with international recommendations, and lack of knowledge on nutrition and related topics, among others. These results were used to identify priority behaviors and elaborate key messages for mothers/caregivers and providers to develop the BCC strategy. The feasibility study resulted in significant improvements in PHCPs' knowledge, counseling (breastfeeding, and supplement use and consumption), and caregivers' complementary feeding behaviors, and highlighted several design and delivery aspects that needed strengthening. Based on these findings, the BCC strategy was adapted prior to a national scale-up. CONCLUSIONS: The theory-based iterative approach resulted in the identification of specific actions to target, and approaches to do so, as part of the design and roll-out of the BCC strategy at scale.

Closing the Nutrition Impact Gap Using Program Impact Pathway Analyses to Inform the Need for Program Modifications in Mexico's Conditional Cash Transfer Program.

BACKGROUND: Mexico's Prospera-Oportunidades-Progresa Conditional Cash Transfer Program (CCT-POP) included the distribution of fortified food supplements (FFS) for pregnant and lactating women and young children. Rigorous evaluations showed significant impacts on nutrition outcomes but also substantial gaps in addressing nutrition problems. OBJECTIVES: To highlight the program design-related and implementation-related gaps and challenges that motivated further research and the eventual design and roll-out of a modified nutrition component for CCT-POP. METHODS: We used a program impact pathway approach to highlight the extent and quality of implementation of CCT-POP, and its impact on nutrition outcomes. We drew on previously published and new primary data, organized into 3 sources: impact evaluations, studies to inform reformulation of the FFS, and a longitudinal follow-up study using qualitative and quantitative methods to document FFS use and the dietary intake of women and children. RESULTS: Despite positive impacts, a high prevalence of malnutrition persisted in the population. Coverage and use of health services improved, but quality of care was lacking. Consumption of FFS among lactating women was irregular. Micronutrient intake improved among children who consumed FFS, but the pattern of use limited frequency and quantity consumed. Substantial diversity in the prevalence of undernutrition was documented, as was an increased risk of overweight and obesity among women. CONCLUSIONS: Three key design and implementation challenges were identified. FFS, although well accepted for children, had limited potential to substantially modify the quality of children's diets because of the pattern of use in the home. The communications strategy was ineffective and ill-suited to its objective of motivating FFS use. Finally, the program with its common design across all regions of Mexico was not well adapted to the special needs of some subgroups, particularly indigenous populations. The studies reviewed in this paper motivated additional research and the eventual redesign of the nutrition component.

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.

Effects and safety of periconceptional oral folate supplementation for preventing birth defects.

BACKGROUND: It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear. OBJECTIVES: This review aims to examine whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies (including cleft palate) without causing adverse outcomes in mothers or babies. This is an update of a previously published Cochrane review on this topic. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015). Additionally, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 August 2015) and contacted relevant organisations to identify ongoing and unpublished studies. SELECTION CRITERIA: We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. We assessed the quality of the body of evidence using the GRADE approach. MAIN RESULTS: Five trials involving 7391 women (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs) were included. Four comparisons were made: 1) supplementation with any folate versus no intervention, placebo or other micronutrients without folate (five trials); 2) supplementation with folic acid alone versus no treatment or placebo (one trial); 3) supplementation with folate plus other micronutrients versus other micronutrients without folate (four trials); and 4) supplementation with folate plus other micronutrients versus the same other micronutrients without folate (two trials). The risk of bias of the trials was variable. Only one trial was considered to be at low risk of bias. The remaining studies lacked clarity regarding the randomisation method or whether the allocation to the intervention was concealed. All the participants were blinded to the intervention, though blinding was unclear for outcome assessors in the five trials.The results of the first comparison involving 6708 births with information on NTDs and other infant outcomes, show a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58); five studies; 6708 births; high quality evidence). Only one study assessed the incidence of NTDs and showed no evidence of an effect (RR 0.07, 95% CI 0.00 to 1.32; 4862 births) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births). Subgroup analyses suggest that the positive effect of folic acid on NTD incidence and recurrence is not affected by the explored daily folic acid dosage (400 µg (0.4 mg) or higher) or whether folic acid is given alone or with other vitamins and minerals. These results are consistent across all four review comparisons.There is no evidence of any preventive or negative effects on cleft palate (RR 0.73, 95% CI 0.05 to 10.89; three studies; 5612 births; low quality evidence), cleft lip ((RR 0.79, 95% CI 0.14 to 4.36; three studies; 5612 births; low quality evidence), congenital cardiovascular defects (RR 0.57, 95% CI 0.24 to 1.33; three studies; 5612 births; low quality evidence), miscarriages (RR 1.10, 95% CI 0.94 to 1.28; five studies; 7391 pregnancies; moderate quality evidence) or any other birth defects (RR 0.94, 95% CI 0.53 to 1.66; three studies; 5612 births; low quality evidence). There were no included trials assessing the effects of this intervention on neonatal death, maternal blood folate or anaemia at term. AUTHORS' CONCLUSIONS: Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.

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

BACKGROUND: Daily iron supplementation has been traditionally a standard practice for preventing and treating anaemia but 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 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 in menstruating women, compared with no intervention, a placebo or daily supplementation. SEARCH METHODS: We searched the following databases in May 2011: CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE (1948 to May Week 3, 2011), EMBASE (1980 to 2011 Week 20), CINAHL (1937 to current), POPLINE (all available years), Science Citation Index (1970 to 27 May 2011), BIOSIS Previews (1969 to current), and CPCI-S (1990 to 27 May 2011). On 7 July 2011 we searched all available years in the following databases: SCIELO, LILACS, IBECS and IMBIOMED, the Networked Digital Library of Theses and Dissertations, metaRegister and the WHO International Clinical Trials Registry Platform (ICTRP). We also contacted relevant organisations (on 11 October 2011) to identify ongoing and unpublished studies. SELECTION CRITERIA: Randomised and quasi-randomised trials 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 no intervention, a placebo, or the use of same supplements on a daily basis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. MAIN RESULTS: We included 21 trials involving 10,258 women. Although the quality across trials was variable, the results consistently show that in comparison with no intervention or a placebo, intermittent iron supplementation (alone or with any other vitamins and minerals) reduces the risk of having anaemia (RR 0.73; 95% CI 0.56 to 0.95, 10 trials) and improves the concentration of haemoglobin (MD 4.58 g/L; 95% CI 2.56 to 6.59, 13 trials) and ferritin (MD 8.32 µg/L; 95% CI 4.97 to 11.66, six trials). However, in comparison with daily supplementation, women receiving supplements intermittently presented anaemia more frequently (RR 1.26; 95% CI 1.04 to 1.51, six trials), despite achieving similar haemoglobin concentrations on average (MD -0.15 g/L; 95% CI -2.20 to 1.91, eight trials).Information on disease outcomes, adherence, side effects, economic productivity and work performance is scarce and the evidence about the effects of intermittent supplementation on them is 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 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 is frequent, although very few trials were conducted in these settings. AUTHORS' CONCLUSIONS: Intermittent iron supplementation in menstruating women is a feasible intervention in settings where daily supplementation is likely to be unsuccessful or not possible. In comparison with daily supplementation, the provision of iron supplements intermittently is less 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.

Effects and safety of periconceptional folate supplementation for preventing birth defects.

BACKGROUND: It has been reported that neural tube defects can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear. OBJECTIVES: This review updates and expands a previous Cochrane Review assessing the effects of periconceptional supplementation with folic acid to reduce neural tube defects (NTDs). We examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010). Additionally, we searched the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies. SELECTION CRITERIA: We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity. DATA COLLECTION AND ANALYSIS: We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion, one author extracted data and a second checked for accuracy. MAIN RESULTS: Five trials involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs) were included. Overall, the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52). Only one study assessed the incidence of NTDs and the effect was not statistically significant (RR 0.08, 95% CI 0.00 to 1.33) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.32, 95% CI 0.17 to 0.60). There is no statistically significant evidence of any effects on prevention of cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects. There were no included trials assessing the effects of this intervention on maternal blood folate or anaemia at term.We found no evidence of short-term side effects. AUTHORS' CONCLUSIONS: Folic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects.