Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low- and middle-income countries: A scoping review.

In resource-constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient-fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low- and middle-income countries. We conducted a PubMed search using pre-defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid-based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk-based beverages [n = 2], and local food/snacks [n = 3]) that provided 118-750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost-effectiveness, and incorporation into multi-component interventions.

Prognostic value of different anthropometric indices over different measurement intervals to predict mortality in 6-59-month-old children.

OBJECTIVE: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children. DESIGN: Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations. SETTING: Community-based, prospective studies from twelve countries in Africa and Asia. PARTICIPANTS: Children aged 6-59 months living in the study areas. RESULTS: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone. CONCLUSIONS: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.

Estimating the cost and cost-effectiveness of adding zinc to, and improving the performance of, Burkina Faso's mandatory wheat flour fortification programme.

Zinc is an essential micronutrient that promotes normal growth, development and immune function. In the context of persistent dietary zinc inadequacies, large-scale food fortification can help fill the gap between intake and requirements. Burkina Faso mandates wheat flour fortification with iron and folic acid. We used activity-based cost modelling to estimate the cost of adding zinc to the country's wheat flour fortification standard assuming (1) no change in compliance with the national standard, and (2) a substantial improvement in compliance. We used household food consumption data to model effective coverage, that is, the number of women of reproductive age (WRA) predicted to achieve adequate zinc density (zinc intake/1000 kcal) with the addition of fortification to diets. Without interventions, the prevalence of inadequate dietary zinc density was ~35.5%. With no change in compliance, the annual average incremental cost of adding zinc to fortified wheat flour was $10,347, which would effectively cover <1% of WRA at an incremental cost of ~$0.54/WRA effectively covered. Improving compliance added ~$300,000/year to the cost of the fortification programme without zinc; including zinc added another ~$78,000/year but only reduced inadequate intake among WRA by 3.6% at an incremental cost of ~$0.45/WRA effectively covered. Although the incremental cost of adding zinc to wheat flour is low ($0.01/wheat flour consumer/year), given low levels of wheat flour consumption, zinc fortification of wheat flour alone contributes marginally to, but will not fully close, the dietary zinc gap. Future research should explore potential contributions of zinc to a broader set of delivery vehicles.

Anthropometric deficits and the associated risk of death by age and sex in children aged 6-59 months: A meta-analysis.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < -2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

Marginal Zinc Deficiency Alters Essential Fatty Acid Metabolism in Healthy Men.

BACKGROUND: Rice biofortification with Zinc (Zn) can improve the Zn status of rice-consuming populations. However, the metabolic impact in humans consuming Zn-biofortified rice is unknown. OBJECTIVES: To determine the effects of Zn-biofortified rice on lipid metabolism in normolipidemic men. METHODS: The men consumed a rice-based diet containing 6 mg Zn/d and 1.5 g phytate (phytate/Zn ratio = 44) for 2 wk followed by a 10-mg Zn/d diet without phytate for 4 wk. An ad libitum diet supplemented with 25 mg Zn/d was then fed for 3 wk. Fasting blood samples were taken at baseline and at the end of each metabolic period for measuring plasma zinc, glucose, insulin, triglyceride (TG), LDL and HDL cholesterol, fatty acids, oxylipins, and fatty acid desaturase activities. Statistical differences were assessed by linear mixed model. RESULTS: Fatty acid desaturase (FADS) 1 activity decreased by 29.1% (P = 0.007) when the 6-mg Zn/d diet was consumed for 2 wk. This change was associated with significant decreases in HDL and LDL cholesterol. The alterations in FADS1, HDL cholesterol, and TG remained unchanged when Zn intakes were increased to 10 mg/d for 4 wk. Supplementation with 25 mg Zn/d for 3 wk normalized these metabolic changes and significantly increased LDL cholesterol at the end of this metabolic period compared with baseline. FADS1 activity was inversely correlated with FADS2 (rmcorr = -0.52; P = 0.001) and TG (rmcorr = -0.55; P = 0.001) at all time points. CONCLUSIONS: A low-zinc, high-phytate rice-based diet reduced plasma HDL cholesterol concentrations and altered fatty acid profiles in healthy men within 2 wk. Consuming 10 mg Zn/d without phytate for 4 wk did not improve the lipid profiles, but a 25-mg Zn/d supplement corrects these alterations in lipid metabolism within 3 wk.

Endoscopic nodal staging in oligometastatic non-small cell lung cancer (NSCLC) being treated with stereotactic ablative radiotherapy (ENDO-SABR).

BACKGROUND: Research in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken. METHODS: This is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment. DISCUSSION: If a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021. PROTOCOL VERSION: 1.1 on December 9, 2021.

Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.

BACKGROUND: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences. OBJECTIVES: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children. METHODS: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA. RESULTS: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05). CONCLUSIONS: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Zinc Kinetics Correlate With Length-for-Age z Scores in Bangladeshi Infants.

OBJECTIVES: Stunting [length-for-age z score (LAZ) <-2] has multiple causes and is prevalent in areas with low dietary zinc (Zn) intake. Zinc kinetics from non-stunted infants were used in a published model for predicting linear growth; here, we directly measure zinc kinetics in stunted infants. METHODS: Zinc kinetics were determined in 9-month-old Bangladeshi infants (n = 10), who were non-wasted [weight-for-length z score (WLZ) > -2], ranging in LAZ from -2.9 to -0.43. Stable isotopes were administered 2 hours after a meal as oral ( 70 Zn) and intravenous ( 67 Zn) tracers. After isotope administration, blood was sampled within 5 hours and all urine and feces were collected for 24 hours. Urine was sampled twice-daily out to 9 days. Data were analyzed by compartmental modeling. Daily zinc intake was estimated by the model as the sum of zinc used for growth plus that lost via urine and feces. Zinc absorbed (the amount required to maintain steady state) was the sum of zinc used for growth plus urine and endogenous fecal excretions. RESULTS: The LAZ score correlated with serum zinc concentration ( R = 0.77, P = 0.001), urinary zinc excretion ( R = 0.66, P = 0.010), and fractional zinc absorption from calculated daily intake ( R = 0.58, P = 0.030). In stunted infants (n = 8), the amount of zinc absorbed did not increase with calculated zinc intake unlike published values for non-stunted infants. CONCLUSIONS: Zinc kinetics in Bangladeshi infants correlate with LAZ and show that malabsorption of supplemental sources of zinc may occur in stunted infants.

Sex differences and associations between zinc deficiency and anemia among hospitalized adolescents and young adults with eating disorders.

PURPOSE: To determine sex differences in and associations between zinc deficiency and anemia among adolescents and young adults hospitalized for medical complications of eating disorders. METHODS: We retrospectively reviewed electronic medical records of 601 patients aged 9-25 years admitted to the University of California, San Francisco Eating Disorders Program for medical instability, between May 2012 and August 2020. Descriptive statistics, crude, and adjusted logistic regression models were used to assess the association between zinc deficiency (< 55 mcg/dL) and anemia (< 13.6 g/dL in males [M] and < 11.8 g/dL in females [F]). RESULTS: A total of 87 males and 450 females met eligibility criteria (age 15.98 ± 2.81, 59.4% anorexia nervosa; admission body mass index 17.49 ± 2.82). In unadjusted comparisons, plasma zinc in males and females were not statistically different (M 64.88 ± 14.89 mcg/dL vs F 63.81 ± 13.96 mcg/dL, p = 0.517); moreover, there were no differences in the percentage of males and females with zinc deficiency (M 24.14% vs F 24.89%). However, a greater percentage of males than females were anemic (M 50.00% vs F 17.61%, p < 0.001), with similar findings in the subgroup with anorexia nervosa. In logistic regression models stratified by sex and eating disorder diagnosis, zinc deficiency was significantly associated with anemia in males (AOR 3.43, 95% CI 1.16, 10.13), but not females (AOR 1.47, 95% CI 0.86, 2.54). CONCLUSIONS: For the first time, we demonstrate that zinc deficiency is equally severe in males compared to females hospitalized with medical complications from eating disorders, with nearly a quarter of inpatients experiencing zinc deficiency. Anemia is more common in males than females hospitalized with eating disorders. LEVEL OF EVIDENCE: Level V: descriptive cross-sectional study.

Zinc-Biofortified Wheat Intake and Zinc Status Biomarkers in Men: Randomized Controlled Trial.

BACKGROUND: Biofortification is a novel method for improving the nutritional value of grains. Wheat is widely consumed worldwide. Thus, wheat zinc biofortification may improve the zinc status of populations. OBJECTIVES: We determined the effect of consuming zinc-biofortified wheat on plasma zinc concentrations and biomarkers of zinc-dependent functions in a controlled feeding study. METHODS: Thirty-six healthy adult men, aged 18 to 51 y, participated in a 10-wk zinc-controlled feeding trial. After a 2-wk run-in period [metabolic period (MP) 1] (9.3 mg zinc/d and 2.1 g total phytate/d) to standardize zinc status, the participants consumed bread made from zinc-biofortified wheat (10.9 mg zinc/d) with no additional phytate (0.6 g/d total phytate) for 6 wk (MP2). During the final 2 wk (MP3), half of the men took a 25-mg zinc supplement daily to determine if the supplement further altered zinc status biomarkers. Repeated-measures linear regression methods were used to compare plasma zinc concentrations, fatty acid desaturase (FADS) activities, glutathione (GSH) concentrations, and DNA strand breaks assessed at enrollment and the end of each metabolic period. RESULTS: Plasma zinc concentrations did not change throughout the study. From the end of MP1 to the end of MP2, the conversion of linoleic acid to γ-linolenic acid (FADS2 activity) increased from 0.020 to 0.025 (P = 0.02), and the conversion of dihomo-γ-linolenic acid to arachidonic acid (FADS1 activity) decreased from 6.37 to 5.53 (P = 0.01). GSH concentrations and DNA strand breaks did not change. Zinc supplementation (25 mg/d) in MP3 did not alter any of the endpoints. CONCLUSIONS: In healthy adult men, a 1.6-mg/d increase in dietary zinc from biofortified wheat modified FADS2 and FADS1 activities without changing DNA damage, plasma zinc, or GSH concentrations, demonstrating that FADS activities are more sensitive to small changes in zinc consumed with a meal. This trial was registered at clinicaltrials.gov as NCT03451214.