Prevalence of morbidity symptoms among pregnant and postpartum women receiving different nutrient supplements in Ghana and Malawi: A secondary outcome analysis of two randomised controlled trials.

Little is known about the impact of small-quantity lipid-based nutrient supplements (SQ-LNSs) on maternal morbidity. This secondary outcome analysis aimed to compare morbidity symptoms among women in two trials evaluating the efficacy of SQ-LNSs. From enrolment (≤20-week gestation) to 6 months postpartum, Ghanaian (n = 1320) and Malawian (n = 1391) women were assigned to consume daily: 60 mg iron and 400 µg folic acid until childbirth and placebo thereafter (iron and folic acid [IFA] group); or multiple micronutrients (MMN); or 20 g/day SQ-LNSs. Within country, we used repeated measures logistic regression and analysis of variance models to compare group differences in the period prevalence and percentage of days of monitoring when women had fever, gastrointestinal, reproductive, and respiratory symptoms during the second and third trimesters of pregnancy (n ~ 1243 in Ghana, 1200 in Malawi) and 0-3 and 3-6 months postpartum (n ~ 1212 in Ghana, 730 in Malawi). Most outcomes did not differ significantly among groups, with the following exceptions: in Ghana, overall, the prevalence of vomiting was lower in the LNS (21.5%) than MMN (25.6%) group, with the IFA group (23.2%) in-between (p = 0.046); mean ± SD percentage of days with nausea was greater in the LNS (3.5 ± 10.3) and MMN (3.3 ± 10.4) groups than the IFA (2.7 ± 8.3) group (p = 0.002). In Malawi, during 3-6 month postpartum, the prevalence of severe diarrhoea was greater in the LNS (8.1%) than the MMN (2.9%) group, with IFA (4.6%) in-between, p = 0.041). We conclude that the type of nutrient supplement received during pregnancy and lactation generally does not influence morbidity symptoms in these settings. Clinicaltrials.gov identifiers: NCT00970866; NCT01239693.

Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Small-Quantity Lipid-Based Nutrient Supplements Increase Infants' Plasma Essential Fatty Acid Levels in Ghana and Malawi: A Secondary Outcome Analysis of the iLiNS-DYAD Randomized Trials.

INTRODUCTION: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) may influence infants' plasma fatty acid (FA) profiles, which could be associated with short- and long-term outcomes. OBJECTIVES: We aimed to determine the impact of SQ-LNS consumption on infants' plasma FA profiles in Ghana and Malawi. METHODS: Ghanaian (n = 1320) and Malawian (n = 1391) women ≤20 weeks pregnant were assigned to consume 60 mg iron and 400 µg folic acid daily until delivery [iron and folic acid (IFA) group], multiple-micronutrient supplements (MMNs) until 6 months postpartum (MMN group), or SQ-LNSs (∼7.8 linoleic acid:α-linolenic acid ratio) until 6 months postpartum (LNS group). LNS group infants received SQ-LNS from 6 to 18 months of age. We compared infant plasma FAs by intervention group in subsamples (n = 379 in Ghana; n = 442 in Malawi) at 6 and 18 months using ANOVA and Poisson regression models. Main outcomes were mean percentage compositions (%Cs; percentage of FAs by weight) of α-linolenic acid (ALA), linoleic acid (LA), EPA, DHA, and arachidonic acid (AA). RESULTS: At 6 months, LNS infants had greater mean ± SD ALA %Cs in Ghana (0.23 ± 0.08; IFA, 0.21 ± 0.06; MMN, 0.21 ± 0.07; P = 0.034) and Malawi (0.42 ± 0.16; IFA, 0.38 ± 0.15; MMN, 0.38 ± 0.14; P = 0.034) and greater AA values in Ghana (6.25 ± 1.24; IFA, 6.12 ± 1.13; MMN, 5.89 ± 1.24; P = 0.049). At 18 months, LNS infants had a tendency towards greater ALA (0.32 ± 0.16; IFA, 0.24 ± 0.08; MMN, 0.24 ± 0.10; P = 0.06) and LA (27.8 ± 3.6; IFA, 26.9 ± 2.9; MMN, 27.0 ± 3.1; P = 0.06) in Ghana, and greater ALA (0.45 ± 0.18; IFA, 0.39 ± 0.18; MMN, 0.39 ± 0.18; P < 0.001) and LA (29.7 ± 3.5; IFA, 28.7 ± 3.3; MMN, 28.6 ± 3.4; P = 0.011) in Malawi. The prevalence of ALA below the population-specific 10th percentile was lower in the LNS group compared to the MMN group, but not the IFA group. Groups did not differ significantly in plasma EPA or DHA levels. CONCLUSIONS: SQ-LNS increased infants' plasma essential FA levels in Ghana and Malawi, which may have implications for health and developmental outcomes. These trials were registered at clinicaltrials.gov as NCT00970866 and NCT01239693.

Effect of multiple micronutrient supplements vs iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose.

OBJECTIVE: Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid supplements (IFA) containing 60 mg of iron. We aimed to assess the effect of MMS vs IFA on neonatal mortality stratified by iron dose in each supplement. METHODS: We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS vs. IFA on neonatal mortality in subgroups of trials (n=13) providing the same or different amounts of iron, i.e. MMS with 60 mg of iron vs IFA with 60 mg of iron; MMS with 30 mg of iron vs IFA with 30 mg of iron; MMS with 30 mg of iron vs IFA with 60 mg of iron; and MMS with 20 mg of iron vs IFA with 60 mg of iron. RESULTS: There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg vs IFA with 60 mg of iron (7 trials, 14,114 participants), yielded a nonsignificant Risk Ratio (RR) of 1.12 (95% CI 0.83 to 1.50). CONCLUSION: Neonatal mortality did not differ between MMS and IFA regardless of iron dose in either supplement.

Clinical nutrition approach in medical management of COVID-19 hospitalized patients: A narrative review.

BACKGROUND: Malnutrition in COVID-19 hospitalized patients is associated with a high-risk condition to increase disease severity and prolonging the recovery period. Therefore, nutritional therapy, including supplements plays a critical role to reduce disease-related complications and the length of hospital stay. AIM: To review the latest evidence on nutritional management options in COVID-19 hospitalized patients, as well as possibly prescribed supplements. Methods: This review was conducted by considering the latest recommendations, using the guidelines of the American Society of Enteral and Parenteral (ASPEN) and the European Society of Enteral and Parenteral (ESPEN), and searching Web of Science, PubMed/Medline, ISI, and Medline databases. The relevant articles were found using a mix of related mesh terms and keywords. We attempted to cover all elements of COVID-19 hospitalized patients' dietary management. Results: Energy demand in COVID-19 patients is a vital issue. Indirect Calorimetry (IC) is the recommended method to measure resting energy expenditure. However, in the absence of IC, predictive equations may be used. The ratio of administered diet for the macronutrients could be based on the phase and severity of Covid-19 disease. Moreover, there are recommendations for taking micronutrient supplements with known effects on improving the immune system or reducing inflammation. Conclusions: Nutritional treatment of COVID-19 patients in hospitals seems to be an important element of their medical care. Enteral nutrition would be the recommended feeding method for early nutrition support. However, data in the COVID-19 nutritional domain relating to micronutrient supplementation are still fragmentary and disputed, and further study is required.

Process of developing models of maternal nutrition interventions integrated into antenatal care services in Bangladesh, Burkina Faso, Ethiopia and India.

Integrating nutrition interventions into antenatal care (ANC) requires adapting global recommendations to fit existing health systems and local contexts, but the evidence is limited on the process of tailoring nutrition interventions for health programmes. We developed and integrated maternal nutrition interventions into ANC programmes in Bangladesh, Burkina Faso, Ethiopia and India by conducting studies and assessments, developing new tools and processes and field testing integrated programme models. This paper elucidates how we used information and data to contextualize a package of globally recommended maternal nutrition interventions (micronutrient supplementation, weight gain monitoring, dietary counselling and counselling on breastfeeding) and describes four country-specific health service delivery models. We developed a Theory of Change to illustrate common barriers and strategies for strengthening nutrition interventions during ANC. We used multiple information sources including situational assessments, formative research, piloting and pretesting results, supply assessments, stakeholder meetings, household and service provider surveys and monitoring data to design models of maternal nutrition interventions. We developed detailed protocols for implementing maternal nutrition interventions; reinforced staff capacity, nutrition counselling, monitoring systems and community engagement processes; and addressed micronutrient supplement supply bottlenecks. Community-level activities were essential for complementing facility-based services. Routine monitoring data, rapid assessments and information from intensified supervision were important during the early stages of implementation to improve the feasibility and scalability of models. The lessons from addressing maternal nutrition in ANC may serve as a guide for tackling missed opportunities for nutrition within health services in other contexts.

Supplementation with Small-Quantity Lipid-Based Nutrient Supplements Does Not Increase Child Morbidity in a Semiurban Setting in Ghana: A Secondary Outcome Noninferiority Analysis of the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD Randomized Controlled Trial.

BACKGROUND: Adequate knowledge about the safety of consumption of small-quantity lipid-based nutrient supplements (SQ-LNSs) is needed. OBJECTIVE: We aimed to test the hypothesis that SQ-LNS consumption is noninferior to control with respect to child morbidity. METHODS: Women (n = 1320) ≤20 wk pregnant were assigned to iron and folic acid until delivery with no supplementation for offspring; or multiple micronutrient supplements until 6 mo postpartum with no supplementation for offspring; or SQ-LNSs until 6 mo postpartum, and SQ-LNSs for offspring (6 mg Fe/d) from 6 to 18 mo of age [the lipid-based nutrient supplement (LNS) group]. We assessed noninferiority (margin ≤20%) between any 2 groups during 0-6 mo of age, and between the non-LNS and LNS groups during 6-18 mo of age for caregiver-reported acute respiratory infection, diarrhea, gastroenteritis, fever/suspected malaria, poor appetite, and "other illnesses." RESULTS: During 0-6 mo of age, 1197 infants contributed 190,503 infant-days. For all morbidity combined, overall mean incidence (per 100 infant-days) was 3.3 episodes, overall mean prevalence (percentage of infant-days) was 19.3%, and the 95% CIs of the incidence rate ratio (IRR) and longitudinal prevalence rate ratio (LPRR) between any 2 groups were ≤1.20. During 6-18 mo, there were 240,097 infant-days for the non-LNS group and 118,698 for the LNS group. For all morbidity combined, group mean incidences were 4.3 and 4.3, respectively (IRR: 1.0; 95% CI: 1.0, 1.1), and mean prevalences were 28.2% and 29.3%, respectively (LPRR: 1.0; 95% CI: 1.0, 1.1). Noninferiority was inconclusive for diarrhea, fever/suspected malaria, and poor appetite. CONCLUSIONS: SQ-LNS consumption does not increase reported overall child morbidity in this population compared with the 2 other treatments.This trial was registered at clinicaltrials.gov as NCT00970866.

"They Merely Prescribe and I Merely Swallow": Perceptions of Antenatal Pharmaceuticals and Nutritional Supplements Among Pregnant Women in Bamako, Mali.

OBJECTIVES: New international guidelines for antenatal care (ANC) will likely result in an increase in nutritional supplements and preventative medications for pregnant women in low and middle-income countries. Our objective was to understand how pregnant women in Mali perceive and experience multi-drug regimens in ANC in order to reveal factors that may influence uptake and adherence. METHODS: We conducted 29 semi-structured interviews and three focus groups with 21 pregnant women in two urban ANC sites in Bamako, Mali. Interviews focused on perception of purpose of ANC pharmaceuticals (particularly iron supplements, sulfadoxine-pyrimethamine as intermittent prevention of malaria and antiretroviral therapy for HIV), beliefs regarding efficacy and risk, and understanding of dosage and regimen. Transcripts were inductively coded and analyzed using the 'Framework' method. RESULTS: Participant descriptions of medication purpose, understanding of dosing, and beliefs about risks and efficacy varied widely, revealing that many pregnant women lack complete information about their medications. While some were burdened by side effects or complex regimens, women generally held favorable attitudes toward ANC medications. Responses suggest major barriers to adherence lie in the health system, namely insufficient patient-provider communication and inconsistent prescribing practices. CONCLUSIONS FOR PRACTICE: National health programs looking to improve maternal and child health with ANC pharmaceuticals need to place greater attention on patient counseling and consistent implementation of administration guidelines. Communication that positions pharmaceuticals as beneficial to mother and child, while presenting understandable information about purpose, dosing and potential side effects can promote uptake of multi-drug regimens and ANC services in general.

Multiple Micronutrient Supplements Are More Cost-effective Than Iron and Folic Acid: Modeling Results from 3 High-Burden Asian Countries.

BACKGROUND: Recent evidence has encouraged low- and middle-income countries to consider transitioning from long-standing iron and folic acid supplementation (IFA) to multiple micronutrient supplementation (MMS) during pregnancy; however, global guidance is limited. To facilitate national decision-making, a cost-effectiveness model to compare supplementation approaches was developed, and applied to Pakistan, India, and Bangladesh. OBJECTIVE: We evaluated the incremental cost-effectiveness of transitioning from IFA to MMS. METHODS: The effectiveness of IFA compared with MMS during pregnancy was compared using 8 health outcomes reported in 2 meta-analyses published in 2017 (Cochrane and The Lancet). Impacts on health outcomes were aggregated using disability-adjusted life years (DALYs). Costs included the supplements and their distribution through antenatal care. The incremental cost-effective ratio (ICER) for transitioning from IFA to MMS was calculated for each country under each meta-analysis scenario, and Monte Carlo simulations were applied to generate a measure of certainty around the results. RESULTS: The effectiveness of transitioning from IFA to MMS under the Cochrane scenario was smaller and less certain compared with The Lancet scenario. However, even under the Cochrane scenario, MMS would avert 4,391, 5,769, and 8,578 more DALYs than IFA per 100,000 pregnancies in Pakistan, India, and Bangladesh, respectively (62.6%, 76.8%, and 82.6% certainty). The ICER of transitioning from IFA to MMS was 41.54, 31.62, and 21.26 US dollars (USD 2016) per DALY averted, respectively. CONCLUSIONS: Despite discrepancies in the overall effect of MMS depending on the meta-analysis used, MMS is cost-effective and generates positive health outcomes for both infants and pregnant women. Whilst the effectiveness of MMS is sensitive to the prevalence of certain health outcomes under the conservative scenario (Cochrane), MMS nevertheless averts more DALYs than IFA with high certainty and should re-enter public health discussion in Pakistan, India, and Bangladesh.

Health service utilization, perspectives, and health-seeking behavior for maternal and child health services in the Amazon of Peru, a mixed-methods study.

BACKGROUND: Various factors influence health service utilization at the community level. Research on the barriers to uptake of local health services is essential to reduce maternal and child mortality and morbidity. The Amazon region of Peru has some of the poorest health indicators in the country. The current study set out to better understand the health-seeking behavior and perspectives of mothers in Amazonian communities, exploring individual- and contextual-level barriers for seeking care at local health facilities for common maternal and child health issues. METHODS: The study employed a mixed-methods design by conducting 50 structured interviews with mothers of children under the age of 4. The study took place in 5 communities in Loreto, Peru. The quantitative data was analyzed with descriptive statistics to identify participants' socio-demographic characteristics and reported utilization of health services. The qualitative data was analyzed in three rounds: inductive codebook development, application of the codebook, and thematic synthesis to contextualize the quantitative results and better understand the perspectives of the mothers regarding maternal and child health issues and the local health services. RESULTS: Overall, reported health service utilization among study participants was relatively high. However, the mothers identified several individual- and contextual-level factors that may affect their experiences and the health-seeking behaviors of other mothers in their communities: (i) embarrassment, fear, and trust, (ii) insufficient number and poor attitudes of health personnel, (iii) limited supply of basic medicines and materials in the health facility, and (iv) low demand for family planning services and limited awareness of adolescent-specific services. CONCLUSION: Several findings in the current study reflect the reduced conditions of health services, while others display that many mothers maintain a positive outlook on the health services available to them and are proactive in the care of their child. The study provides valuable insight into the use of local health services and the common perspectives that are hindering further uptake at the community level in the Amazon of Peru, with important implications for health policy.

Situation analysis of procurement and production of multiple micronutrient supplements in 12 lower and upper middle-income countries.

Globally, there are few vitamin and mineral ingredient manufacturers. To support local, in-country or regional procurement and production of multiple micronutrient supplements (MMS), the following production scenarios are possible: (a) straight ingredients of vitamins and minerals forms imported or locally produced that are mixed, tableted, or encapsulated and packaged by a local manufacturer; (b) import or local production of a vitamin and minerals premix that is tableted or encapsulated and packaged locally; (c) import of a bulk, finished product (tablets or capsules) that is packaged and branded; and (d) or import of a branded packaged product. This paper is a situation analysis of the market, manufacturing, and policy factors that are driving the production of MMS in 12 lower and upper middle-income countries. Key informants completed a self-administered structured questionnaire, which examined the local context of products available in the market and their cost, regulations and policies, in Brazil, Colombia, Guatemala, Mexico, Peru, Bangladesh, India, Vietnam, Ghana, Kenya, Nigeria, and South Africa. Our study found that although most countries have the capacity to produce locally MMS, the major barriers observed for sustainable and affordable production include (a) poor technical capacity and policies for ensuring quality along the value chain and (b) lack of policy coherence to incentivize local production and lower the manufacture and retail price of MMS. Also, better guidelines and government oversight will be required because not one country had an MMS formulation that matched the globally recommended formulation of the United Nations Multiple Micronutrient Preparation (UNIMMAP).

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.

Lipid-Based Nutrient Supplements During Pregnancy and Lactation Did Not Affect Human Milk Oligosaccharides and Bioactive Proteins in a Randomized Trial.

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive proteins are beneficial to infant health. Recent evidence suggests that maternal nutrition may affect the amount of HMOs and proteins in breast milk; however, the effect of nutrient supplementation on HMOs and bioactive proteins has not yet been well studied. OBJECTIVE: We aimed to determine whether lipid-based nutrient supplements (LNSs) affect milk bioactive protein and HMO concentrations at 6 mo postpartum in women in rural Malawi. These are secondary outcomes of a previously published randomized controlled trial. METHODS: Women were randomly assigned to consume either an iron and folic acid capsule (IFA) daily from ≤20 wk gestation until delivery, followed by placebo daily from delivery to 6 mo postpartum, or a multiple micronutrient (MMN) capsule or LNS daily from ≤20 wk gestation to 6 mo postpartum. Breast milk concentrations of total HMOs, sialylated HMOs, fucosylated HMOs, lactoferrin, lactalbumin, lysozymes, antitrypsin, immunoglobulin A, and osteopontin were analyzed at 6 mo postpartum (n = 647). Between-group differences in concentrations and in proportions of women classified as having low concentrations were tested. RESULTS: HMO and bioactive protein concentrations did not differ between groups (P > 0.10 for all comparisons). At 6 mo postpartum, the proportions of women with low HMOs or bioactive proteins were not different between groups except for osteopontin. A lower proportion of women in the IFA group had low osteopontin compared with the LNS group after adjusting for covariates (OR: 0.5; 95% CI: 0.3, 0.9; P = 0.016). CONCLUSION: The study findings do not support the hypothesis that supplementation with an LNS or MMN capsule during pregnancy and postpartum would increase HMO or bioactive milk proteins at 6 mo postpartum among Malawian women. This trial was registered at clinicaltrials.gov as NCT01239693.

Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity.

AIM: A previous maternal and infant nutrition intervention in rural Matlab, Bangladesh, showed that prenatal nutrient supplements improved child survival, but had no effect on size at birth. This secondary analysis examined whether prenatal multiple micronutrient supplements (MMS), on their own or combined with an early invitation to receive prenatal food supplements, affected child morbidity. METHODS: This randomised trial enrolled 4436 pregnant women from November 2001 to October 2003 and allocated them to early or standard invitations to food supplements, in the ninth and 20th weeks of pregnancy, respectively, and supplements of either the standard 60 mg iron with 400 µg folic acid, 30 mg iron with 400 µg folic acid or MMS. Quasi-Poisson regression was used to analyse morbidity. RESULTS: There were 3560 single live births and 3516 had morbidity data. The incidence rates of fever, diarrhoea and acute lower respiratory tract infection were 15.3, 3.6 and 2.3 episodes per person-year, respectively. The separate or combined interventions had no effect on morbidity up to 24 months. CONCLUSION: Early invitations to prenatal food supplements or prenatal MMS had no effect on common infections in rural Bangladesh, suggesting that earlier findings on improved child survival were not mediated by an effect on child morbidity.

Late-Pregnancy Salivary Cortisol Concentrations of Ghanaian Women Participating in a Randomized Controlled Trial of Prenatal Lipid-Based Nutrient Supplements.

BACKGROUND: High circulating cortisol is associated with miscarriage, preterm birth, and low birth weight. Research in nonpregnant individuals suggests that improved nutrition may lower cortisol concentrations. It is unknown whether nutritional supplementation during pregnancy lowers cortisol. OBJECTIVE: Our objective was to determine whether women receiving a lipid-based nutrient supplement (LNS) throughout pregnancy would have lower salivary cortisol at 36 wk gestation compared with women receiving other nutrient supplements. METHODS: We conducted a randomized controlled trial in 1320 pregnant Ghanaian women at ≤20 wk gestation who were assigned to receive daily throughout pregnancy: 1) 60 mg iron + 400 µg folic acid (IFA), 2) multiple micronutrients (MMNs), or 3) 20 g LNS (containing 118 kcal, 22 micronutrients, and protein). Morning salivary cortisol was collected from a subsample at baseline and at 28 and 36 wk gestation. RESULTS: A total of 758 women had cortisol measurements at 28 or 36 wk gestation. Salivary cortisol at 36 wk gestation did not differ between groups and was (mean ± SE) 7.97 ± 0.199 in the IFA group, 7.84 ± 0.191 in the MMN group, and 7.77 ± 0.199 nmol/L in the LNS group, when adjusted for baseline cortisol, time of waking, and time between waking and saliva collection (P = 0.67). There was an interaction between supplementation group and women's age (continuous variable, P-interaction = 0.03); and when age was dichotomized by the median, significant differences in salivary cortisol concentrations between groups were seen in women ≤26 y of age (IFA = 8.23 ± 0.284 nmol/L, MMN = 8.20 ± 0.274 nmol/L, and LNS = 7.44 ± 0.284 nmol/L; P = 0.03) but not in women >26 y old (IFA = 7.71 ± 0.281 nmol/L, MMN = 7.50 ± 0.274 nmol/L, and LNS = 8.08 ± 0.281 nmol/L; P = 0.13). CONCLUSIONS: We conclude that supplementation with LNSs or MMNs during pregnancy did not affect the cortisol concentration in the study population as a whole, in comparison with IFA, but that LNS consumption among younger women may lead to lower cortisol at 36 wk gestation. This trial was registered at clinicaltrials.gov as NCT00970866.

Expert Consensus on an Open-Access UNIMMAP MMS Product Specification: 2024 revision.

The United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) of a multiple micronutrient supplement (MMS) for pregnant women is a proven evidence-based nutrition intervention and is listed on the World Health Organization (WHO) Model List of Essential Medicines. The 2024 revision of the Expert Consensus on an Open-Access UNIMMAP MMS Product Specification provides both purchasers and manufacturers with unified guidance on the production of UNIMMAP MMS. More specifically, it outlines the minimum requirements for the manufacture of UNIMMAP MMS and provides guidance on quality and regulatory standards based on whether the product is manufactured as a medicinal product or a dietary supplement. The product specification includes ingredients, excipients/food additives, and processing aids used in manufacturing UNIMMAP MMS; stability testing for different climatic zones; packaging and labeling considerations; pharmacopeial standards, manufacturing practices, certificates of analysis, change control, and quality agreement; finished product test specifications, including tablet characterization and purity/strength assay; analytical test methods; and storage and transportation requirements.

School-based supplementation with iron-folic acid or multiple micronutrient tablets to address anemia among adolescents in Burkina Faso: a cluster-randomized trial.

BACKGROUND: Iron-deficiency anemia is a leading cause of morbidity among adolescents (aged 10-19 y), especially in low- and middle-income settings. Few policies and programs have targeted adolescent health. OBJECTIVES: This study aimed to evaluate the effectiveness of school-based supplementation with iron-folic acid (IFA) or multiple micronutrient supplements (MMSs) in addressing anemia among adolescents in Burkina Faso. METHODS: In this cluster-randomized trial, 3123 secondary school students aged 10 to 18 y in Burkina Faso were either supplemented with weekly IFA, daily MMSs, or received standard nutrition education as controls. Supplementation occurred between April 2021 and April 2022 over 2 supplementation periods (10 wk, then 16 wk) separated by a gap of 20 wk without supplementation. Hemoglobin was evaluated 4 times: at baseline prior to each supplementation period and at the end of each period. Anemia was categorized by the World Health Organization hemoglobin level cutoffs as none, mild, moderate, or severe. Associations between treatment arm and anemia or continuous hemoglobin (g/dL) were assessed using multilevel mixed effects generalized linear models with schools as a random effect, controlling for baseline hemoglobin or anemia status. RESULTS: Baseline anemia prevalence was similar across study arms, with 32.7% in IFA, 31.2% in MMS, and 29.5% in the control arm. Over the full study period, adolescents provided IFA had hemoglobin levels higher than those in the control arm (adjusted ß: 0.32; 95% CI: 0.02, 0.62). No significant associations were observed for MMS or for anemia outcomes; however, the direction and magnitude of nonsignificant associations indicate potential protective effects of IFA and MMSs on anemia. CONCLUSIONS: The results do not provide strong evidence that weekly IFA or daily MMS alone is effective, but supplementation may play a role in addressing adolescent anemia if combined with cointerventions. Additional research is required to determine the best strategy to address anemia. This trial was registered at clinicaltrials.gov as NCT04657640.

Knowledge, Attitudes and Practices of Pregnant Women and Healthcare Providers in Bangladesh regarding Multivitamin Supplements during Pregnancy.

Micronutrient deficiencies are widespread among pregnant women in low- and middle-income countries (LMIC) and lead to potentially adverse effects for mother and baby. In Bangladesh, maternal malnutrition remains a severe problem, with high rates of anemia (49.6% of pregnant women and 47.8% of lactating women are anemic) and other nutritional deficiencies. A Knowledge, Attitudes, and Practices (KAP) study was conducted to assess Bangladeshi pregnant women's perceptions and related behaviors, as well as awareness and knowledge among pharmacists and healthcare professionals concerning prenatal multivitamin supplements. This was done in both rural and urban areas across Bangladesh. A total of 732 quantitative interviews were conducted (330 with providers and 402 with pregnant women, with an equal split between urban and rural areas for both sets of audiences; 200 women were users of prenatal multivitamin supplements, while 202 women were aware non-users). The study identified a few findings that can guide further research or market-based interventions to reduce micronutrient deficiencies. These include most pregnant women not knowing the right time to start multivitamin supplements (56.0%, [n = 225], stating that a woman should start taking supplements 'after the first trimester'), not knowing their benefits, and how they help both the mother and baby-only 29.5% [n = 59] stated that they believed the supplements helped their baby to grow well). Further, barriers to taking the supplements include women believing a nutritious diet is a substitute (88.7% [n = 293]), and a perceived lack of support from other family members (21.8%, [n = 72]). This suggests that there is a need for further awareness-raising among all pregnant women, their family members, and providers.

Multiple micronutrient supplements versus iron-folic acid supplements and maternal anemia outcomes: an iron dose analysis.

Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of -0.26 g/L (95% CI: -1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92-1.07) for anemia, and 1.31 (95% CI: 0.66-2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.

Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis.

BACKGROUND AND AIMS: Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19. METHODS: We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥ 3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. RESULTS: We identified 26 studies (10 randomized controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62-1.62, P = 1.00), intubation rate (RR 1.77, 95% CI 0.56-5.56, P = 0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P = 0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49-1.17, P = 0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32-0.97, P = 0.04) and LOS (MD -1.26; 95% CI -2.27, -0.25; P = 0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60-1.03, P = 0.08). CONCLUSIONS: Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.