Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial.

BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point. RESULTS: At 12-wk gestation and 3-mo postpartum, no statistical differences in mean SZC were observed among arms. At 34-wk, mean SZC for arms 1 and 2 were significantly higher than for arm 3 (50.3, 50.8, 47.8 µg/dL, respectively; P = 0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-wk (<56 µg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 wk (<50 µg/dL), 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-mo postpartum (<66 µg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-wk was associated with lower birth length-for-age Z-scores (all sites P = 0.013, Pakistan P = 0.008) and weight-for-age Z-scores (all sites P = 0.017, Pakistan P = 0.022). CONCLUSIONS: Despite daily zinc supplementation for ≥7 mo, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. This trial is registered at clinicaltrials.gov as #NCT01883193.

Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial.

Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non-pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient-fortified lipid-based nutrient supplement containing 250-µg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3). Urinary I (µg/L) to creatinine (mg/dl) ratios (I/Cr) were determined at 12 weeks for Arm 1 versus Arm 2 (before supplement started) and 34 weeks for all arms. Generalized linear models were used to assess the relationship of I/Cr with arm and with newborn anthropometry. At 12 weeks gestation, adjusted mean I/Cr (µg/g) for all sites combined was significantly higher for Arm 1 versus Arm 2: (203 [95% CI: 189, 217] vs. 163 [95% CI: 152, 175], p < 0.0001). Overall adjusted prevalence of I/Cr < 150 µg/g was also lower in Arm 1 versus Arm 2: 32% (95% CI: 26%, 38%) versus 43% (95% CI: 37%, 49%) (p = 0.0052). At 34 weeks, adjusted mean I/Cr for Arm 1 (235, 95% CI: 220, 252) and Arm 2 (254, 95% CI: 238, 272) did not differ significantly but were significantly higher than Arm 3 (200, 95% CI: 184, 218) (p < 0.0001). Nominally significant positive associations were observed between I/Cr at 12 weeks and birth length and head circumference z-scores (p = 0.028 and p = 0.005, respectively). These findings support the importance of first trimester iodine status and suggest need for preconception supplementation beyond salt iodization alone.

The impact of integrated prevention and treatment on child malnutrition and health: the PROMIS project, a randomized control trial in Burkina Faso and Mali.

BACKGROUND: Evidence suggests that both preventive and curative nutrition interventions are needed to tackle child acute malnutrition (AM) in developing countries. In addition to reducing the incidence of AM, providing preventive interventions may also help increase attendance (and coverage) of AM screening, a major constraint in the community-based management of child acute malnutrition (CMAM) model. There is a paucity of evidence-based strategies to deliver integrated preventive and curative interventions effectively and affordably at scale. The aim of the Innovative Approaches for the Prevention of Childhood Malnutrition (PROMIS) study is to assess the feasibility, quality of implementation, effectiveness and cost-effectiveness of an integrated child malnutrition prevention and treatment intervention package implemented through a community-based platform in Mali and a facility-based platform in Burkina Faso. METHODS/DESIGN: The PROMIS intervention entails a comprehensive preventive package offered on a monthly basis to caregivers of children, while children are screened for acute malnutrition (AM). The package consists of behavior change communication on essential nutrition and hygiene actions, and monthly preventive doses of small quantity lipid-based nutrient supplements (SQ-LNS) for children aged 6 to 23.9 months. Positive AM cases are referred to treatment services offered by first-line health services according to the CMAM model. The PROMIS intervention will be evaluated using a mixed methods approach. The impact study encompasses two types of study design: i) repeated cross-sectional surveys conducted at baseline and at endline after 24 months of program implementation and ii) a longitudinal study with a monthly follow-up for 18 months. Primary study impact measures include the incidence and endpoint prevalence of AM, AM screening coverage and treatment compliance. A process evaluation will assess the feasibility and quality of implementation of the intervention guided by country specific program impact pathways (PIPs). Cost-effectiveness analysis will assess the economic feasibility of the intervention. DISCUSSION: The PROMIS study assesses the effectiveness of an innovative model to integrate prevention and treatment interventions for greater and more sustainable impacts on the incidence and prevalence of AM using a rigorous, theory-based randomized control trial approach. This type of programmatic research is urgently needed to help program implementers, policy makers, and investors prioritize, select and scale-up the best program models to prevent and treat AM and achieve the World Health Assembly goal of reducing childhood wasting to less than 5% globally by the year 2025. TRIAL REGISTRATION: Clinicaltrials.gov NCT02323815 (registered on December 18, 2014) and NCT02245152 (registered on September 16, 2014).

Impact of integrated preventive and curative health package on nutritional status of children under 2 years of age in the health area of Tama, Tahoua region (Niger).

Background: Niger, relevant in light of current political coup, is one of the countries with the worst human development indicators, characterized by high fertility rates and extremely high infant mortality rates. Food insecurity in the region is alarming, leading to high malnutrition rates in children. This study aimed to evaluate an integral preventive-curative health program targeting children aged under 2 years in the health area of Tama, district of Bouza, Tahoua. Methodology: Anthropometric follow-up data of 6,962 children aged under 2 years were included in this study. These children received complete vaccination and malaria chemoprevention, and those older than 6 months received nutritional supplementation with a small quantity of lipid-based nutrient supplements. Fundamental growth indicators (height-for-age, weight-for-height, weight-for-age, and middle-upper arm circumference) and the Composite Index of Anthropometric Failure were calculated at the beginning and end of the program (mean time spent in the program: 14.5 ± 6.6 months) The evolution of these indicators was compared with those of a sample from a vertical vaccination program conducted in the neighboring region of Madarounfa on similar dates. Results: The proportion of children without anthropometric failure decreased from 59.5 to 40.2% (p < 0.001), with the categories that included stunting increasing the most. When analyzing the anthropometric indicators according to the months of compliance with the program, there was a slight improvement in the indicators of acute malnutrition, whereas those of chronic malnutrition worsened significantly. However, when compared with the Madarounfa sample, the children in the present study registered a significantly lower worsening in all three indicators: height-age (-0.46 vs. -2.44; p < 0.001), weight-height (+0.31 vs. -0.55; p < 0.001) and weight-age (-0.03 vs. -1.63; p < 0.001) difference. Conclusion: The comprehensive preventive-curative health program slightly slows the worsening of cumulative malnutrition in the early years of life in complex contexts, such as southern Niger.

Evaluation of Saccharin and Resveratrol as Extrinsic Markers of Small-Quantity Lipid-Based Nutrient Supplement Consumption in Healthy Women.

BACKGROUND: Dietary supplements, like small-quantity lipid-based nutrient supplements (SQ-LNS), are used in intervention programs to prevent undernutrition among women and young children in low-income countries. An objective marker is needed to track consumption of supplements to evaluate the effectiveness of these programs. OBJECTIVE: The aim of this study was to evaluate saccharin and resveratrol as potential adherence markers for tracking recent consumption of a single serving of SQ-LNS in women. METHODS: Forty-seven healthy nonpregnant women 18-45 y of age were assigned to consume a single dose of SQ-LNS (20 g) containing either 10 mg sodium saccharin or 5 mg trans-resveratrol, under supervision. On the day before and for 2 d following SQ-LNS consumption, urine samples were collected each day for 24 h as 3 consecutive 4-h collections and one 12-h overnight collection. Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate, a resveratrol metabolite, were measured by ultra-high-performance liquid chromatography interfaced to a mass spectrometer with electrospray ionization [UHPLC-(ESI-)MS/MS]. Urinary concentrations (µmol/L urine) of saccharin and trans-resveratrol-3-O-sulfate were plotted against time, and receiver operating characteristic (ROC) curves were used to determine the discriminative capacity of each compound, at each post-consumption time point compared with baseline, to detect recent consumption of SQ-LNS. Cutoff values to differentiate supplement consumption from nonconsumption of each marker were developed using the closest-to-(0,1)-corner cut-point approach. RESULTS: Forty-five participants were included in the analysis. Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate increased within 4 h of SQ-LNS consumption. Urinary concentration cutoff values for saccharin (13.4 µmol/L) and trans-resveratrol-3-O-sulfate (0.7 µmol/L) allowed for 78% and 89% sensitivity, respectively, and 100% specificity in detecting consumption of SQ-LNS within the first 12 h after consumption. CONCLUSIONS: Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate reflect consumption of SQ-LNS containing those compounds during the first 12 h post-consumption with high sensitivity and specificity in healthy women and may be useful objective adherence markers for tracking consumption of SQ-LNS.

Process Evaluation of a Large-Scale Community-Based Nutrition Program in Malawi.

BACKGROUND: Global attention to the study of nutrition program implementation has been inadequate yet is critical for effective delivery and impact at scale. OBJECTIVES: The objective of this mixed-methods process evaluation study was to measure the recruitment, fidelity, and reach of a large-scale, community-based nutrition program in Malawi. METHODS: The nutrition program delivered a small-quantity lipid-based nutrient supplement (SQ-LNS) and social and behavior change communication (SBCC) to improve infant and young child feeding (IYCF) and water, sanitation, and hygiene (WASH) practices in households with children aged 6-23 mo. Program monitoring and evaluation data were used to measure program recruitment, reach, and fidelity. Structured direct observations and knowledge questionnaires with program volunteers measured quality aspects of program fidelity. The number of times activities were done correctly was used to tabulate proportions used to represent program functioning. RESULTS: Half (49.5%) of eligible children redeemed program benefits by 8 mo of age during the first 4 y of program implementation. Implementation of training activities for SBCC cadres exceeded program targets (100.6%), but the completion of certain modules (breastfeeding and complementary feeding) was lower (22.9% and 18.6%, respectively). Knowledge of IYCF, WASH, and SQ-LNS messages by volunteers was >85% for most messages, except ability to list the 6 food groups (35.7%). Structured direct observations of SQ-LNS distributions indicated high fidelity to program design, whereas those of household-level counseling sessions revealed lack of age-appropriate messaging. Program reach showed participation in monthly distribution sessions of 81.0%, group counseling of 93.3%, and individual-level counseling of 36.9%. CONCLUSIONS: This community-based nutrition program was implemented with high fidelity and quality, with specific interventions requiring further attention. The documentation of implementation contributes to our understanding about how program impacts were achieved.

Effect of exogenous phytase added to small-quantity lipid-based nutrient supplements (SQ-LNS) on the fractional and total absorption of zinc from a millet-based porridge consumed with SQ-LNS in young Gambian children: a randomized controlled trial.

BACKGROUND: Dietary phytate inhibits zinc absorption from composite meals in adults. OBJECTIVE: The objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children. METHODS: In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18-23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer. RESULTS: Twenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (<65 µg/dL). Total mean ± SD dietary zinc intake from the test meals was 7.3 ± 2.2 mg (phytate:zinc molar ratio = 3.1 ± 0.3, not accounting for phytase activity). Mean FAZ increased from 8.6% ± 1.3% to 16.0% ± 1.3% when exogenous phytase was added to the SQ-LNS product (P < 0.001). Mean TAZ from test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.1 ± 0.1 mg and 0.5 ± 0.1 mg, respectively; P < 0.001). CONCLUSIONS: The addition of exogenous phytase to SQ-LNS increased both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to increase zinc absorption among young children. This trial was registered at clinicaltrials.gov as NCT02668133.