Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting. OBJECTIVES: We aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3). METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation. CONCLUSIONS: Including SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Fortified Balanced Energy-Protein Supplements Increase Nutrient Adequacy without Displacing Food Intake in Pregnant Women in Rural Burkina Faso.

BACKGROUND: In many low- and middle-income countries, the prevalence of energy and nutrient deficiencies is high among pregnant women. Balanced energy-protein (BEP) supplements are a promising strategy to cover nutritional requirements during pregnancy and improve birth outcomes. However, the displacement of nutrient-dense foods by BEP might attenuate the efficacy of supplementation. OBJECTIVE: This cross-sectional study of participants in a randomized controlled trial evaluated the difference in energy and macro- and micronutrient intakes, food groups, and nutrient adequacy between a control and intervention group receiving either a daily iron-folic acid (IFA) tablet or IFA and BEP supplement during pregnancy, respectively. METHODS: We collected a single multiple-pass 24-h recall from 470 pregnant women from the MIcronutriments pour la SAnté de la Mère et de l'Enfant (MISAME) III study that investigates the efficacy of BEP supplementation on birth outcomes and infant growth. Dietary intake (median and IQR) and nutrient adequacy were assessed using individual recipes and preparation methods of mixed dishes for each participant. Linear regression models were fitted to compare energy and nutrient intakes. RESULTS: Dietary energy, and macro- and micronutrient intakes were significantly higher among women in the intervention group when including BEP [2329 kcal/d (1855, 3008 kcal/d) compared with 1942 kcal/d (1575, 2405 kcal/d) in the control group (all P < 0.001)]. The difference in median energy intake (448 kcal/d; 95% CI: 291, 605 kcal/d) was approximately equivalent to a daily dose of the BEP supplement (393 kcal). Nutrient adequacy ratios for both groups were low for all micronutrients (between 0.02 and 0.66), when excluding BEP (except iron and folic acid, due to standard supplemental doses) from analysis. However, nutrient intakes increased to the Estimated Average Requirement for pregnant women when including BEP supplements. CONCLUSIONS: BEP supplementation increases energy and macro- and micronutrient intakes among pregnant women and fills nutrient gaps without displacing food intake. This trial was registered at clinicaltrials.gov as NCT03533712 (https://clinicaltrials.gov/ct2/show/NCT03533712).

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers. RESULTS: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics. CONCLUSIONS: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

BACKGROUND: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development. OBJECTIVES: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024). RESULTS: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11). CONCLUSIONS: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. CONCLUSIONS: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Impact on child acute malnutrition of integrating small-quantity lipid-based nutrient supplements into community-level screening for acute malnutrition: A cluster-randomized controlled trial in Mali.

BACKGROUND: Community-based management of acute malnutrition (CMAM) has been widely adopted to treat childhood acute malnutrition (AM), but its effectiveness in program settings is often limited by implementation constraints, low screening coverage, and poor treatment uptake and adherence. This study addresses the problem of low screening coverage by testing the impact of distributing small-quantity lipid-based nutrient supplements (SQ-LNSs) at monthly screenings held by community health volunteers (CHVs). Screening sessions included behavior change communication (BCC) on nutrition, health, and hygiene practices (both study arms) and SQ-LNSs (one study arm). Impact was assessed on AM screening and treatment coverage and on AM incidence and prevalence. METHODS AND FINDINGS: A two-arm cluster-randomized controlled trial in 48 health center catchment areas in the Bla and San health districts in Mali was conducted from February 2015 to April 2017. In both arms, CHVs led monthly AM screenings in children 6-23 months of age and provided BCC to caregivers. The intervention arm also received a monthly supply of SQ-LNSs to stimulate caregivers' participation and supplement children's diet. We used two study designs: i) a repeated cross-sectional study (n = approximately 2,300) with baseline and endline surveys to examine impacts on AM screening and treatment coverage and prevalence (primary study outcomes) and ii) a longitudinal study of children enrolled at 6 months of age (n = 1,132) and followed monthly for 18 months to assess impact on AM screening and treatment coverage and incidence (primary study outcomes). All analyses were done by intent to treat. The intervention significantly increased AM screening coverage (cross-sectional study: +40 percentage points [pp], 95% confidence interval [CI]: 32, 49, p < 0.001; longitudinal study: +28 pp, 95% CI: 23, 33, p < 0.001). No impact on treatment coverage or AM prevalence was found. Children in the intervention arm, however, were 29% (95% CI: 8, 46; p = 0.017) less likely to develop a first AM episode (incidence) and, compared to children in comparison arm, their overall risk of AM (longitudinal prevalence) was 30% (95% CI: 12, 44; p = 0.002) lower. The intervention lowered CMAM enrollment by 10 pp (95% CI: 1.9, 18; p = 0.016), an unintended negative impact likely due to CHVs handing out preventive SQ-LNSs to caregivers of AM children instead of referring them to the CMAM program. Study limitations were i) the referral of AM cases by our research team (for ethical reasons) during monthly measurements in the longitudinal study might have interfered with usual CMAM activities and ii) the outcomes presented by child age also reflect seasonal variations because of the closed cohort design. CONCLUSIONS: Incorporating SQ-LNSs into monthly community-level AM screenings and BCC sessions was highly effective at improving screening coverage and reducing AM incidence, but it did not improve AM prevalence or treatment coverage. Future evaluation and implementation research on CMAM should carefully assess and tackle the remaining barriers that prevent AM cases from being correctly diagnosed, referred, and adequately treated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323815.

Differing growth responses to nutritional supplements in neighboring health districts of Burkina Faso are likely due to benefits of small-quantity lipid-based nutrient supplements (LNS).

BACKGROUND: Of two community-based trials among young children in neighboring health districts of Burkina Faso, one found that small-quantity lipid-based nutrient supplements (LNS) increased child growth compared with a non-intervention control group, but zinc supplementation did not in the second study. OBJECTIVES: We explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children's morbidity. METHODS: Children in the LNS study received 20g LNS daily containing different amounts of zinc (LNS). Children in the zinc supplementation study received different zinc supplementation regimens (Z-Suppl). Children in both studies were visited weekly for morbidity surveillance. Free malaria and diarrhea treatment was provided by the field worker in the LNS study, and by a village-based community-health worker in the zinc study. Anthropometric assessments were repeated every 13-16 weeks. For the present analyses, study intervals of the two studies were matched by child age and month of enrollment. The changes in length-for-age z-score (LAZ) per interval were compared between LNS and Z-Suppl groups using mixed model ANOVA or ANCOVA. Covariates were added to the model in blocks, and adjusted differences between group means were estimated. RESULTS: Mean ages at enrollment of LNS (n = 1716) and Z-Suppl (n = 1720) were 9.4±0.4 and 10.1±2.7 months, respectively. The age-adjusted change in mean LAZ per interval declined less with LNS (-0.07±0.44) versus Z-Suppl (-0.21±0.43; p<0.0001). There was a significant group by interval interaction with the greatest difference found in 9-12 month old children (p<0.0001). Adjusting for demographic characteristics and morbidity did not reduce the observed differences by type of intervention, even though the morbidity burden was greater in the LNS group. CONCLUSIONS: Greater average physical growth in children who received LNS could not be explained by known cross-trial differences in baseline characteristics or morbidity burden, implying that the observed difference in growth response was partly due to LNS.

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).

Factors Affecting the Validity of Coverage Survey Reports of Receipt of Vitamin A Supplements During Child Health Days in Southwestern Burkina Faso.

BACKGROUND: Assessment of high-dose vitamin A supplementation (VAS) coverage often relies on postevent coverage (PEC) surveys, but the validity of these methods has rarely been evaluated. OBJECTIVES: To assess reported VAS coverage and factors associated with missed coverage and to investigate the reliability of the results. METHODS: During a cross-sectional survey, 10 454 caregivers of children <27 months old were asked whether their child had received VAS in the past 6 months. During a 48-week longitudinal study of 6232 children 6 to 30 months old, caregivers were asked every 4 weeks if their child had received VAS in the past 4 weeks. RESULTS: The cross-sectional study showed that 94.4% (95% confidence interval [CI]: 93.8%, 94.9%) of eligible children 6 to 26 months of age reportedly received VAS in the previous 6 months, as did 85.8% (CI: 84.5%, 87.2%) of ineligible, 0 to 5 months old children. The longitudinal study showed that 81.6% of children surveyed within 4 weeks following a VAS campaign reportedly received VAS during the campaign and 13.4% of caregivers incorrectly reported receiving VAS when no campaign had actually occurred. False-positive reporting was more likely when oral polio vaccine (OPV) was distributed during the reporting period (20.6% vs 5.4%; P < .001). Showing a photo of OPV during the interview reduced the odds ratio (OR) of false-positive reports (OR = 0.7 [0.6-0.8]). CONCLUSIONS: The PEC surveys should include children outside the target age to assess targeting efficiency, and pictures of both VAS and oral vaccines distributed during the same period should be shown during interviews to enhance reporting accuracy.

Comparison of Preventive and Therapeutic Zinc Supplementation in Young Children in Burkina Faso: A Cluster-Randomized, Community-Based Trial.

BACKGROUND: The WHO and UNICEF recommend therapeutic zinc supplementation (TZS) for the treatment of diarrhea. In zinc-deficient populations, preventive zinc supplementation might provide greater benefits for reducing diarrhea and malaria incidence and increasing growth and plasma zinc (pZn) concentration. If effective, intermittent preventive zinc supplementation (IPZS) would cost less than daily preventive zinc supplementation (DPZS). OBJECTIVE: We assessed the effects of IPZS, DPZS, and TZS in children on the primary outcomes of diarrhea incidence, malaria incidence, growth, and pZn concentration compared with nonsupplemented control groups. METHODS: Rural Burkinabe children (n = 7641; 6-30 mo old) in 36 clusters were randomly assigned to 1 of 5 treatment groups for 16, 32, or 48 wk: 1) IPZS (10 mg Zn/d for 10 d every 16 wk); 2) DPZS (7 mg Zn/d); 3) TZS (20 mg Zn/d for 10 d for diarrhea); 4) morbidity surveillance control (MSC); or 5) nonintervention control (NIC). Supplemented groups remained masked until completion of primary analyses with mixed models. RESULTS: At baseline, stunting (28.6%) and low pZn concentration (<65 µg/dL; 43.5%) were common. After 48 wk, mean ± SE pZn increased more (P = 0.008) in the DPZS group (3.9 ± 1.3 µg/dL) than in the TZS (-0.5 ± 1.2 µg/dL) and NIC (-1.2 ± 0.9 µg/dL) groups. All supplemented groups had a moderately lower incidence of reported diarrhea (0.48-0.49 compared with 0.57 episodes/100 d, P = 0.001) and reported fever (1.1-1.2 compared with 1.5 episodes/100d, P < 0.001) and gained slightly less length (3.15-3.20 compared with 3.36 cm/16 wk, P < 0.001) than the MSC group, but did not differ from each other. Prevalence of diarrhea and incidences of confirmed fever and malaria were not different across study groups. CONCLUSIONS: The preventive and TZS groups had reduced diarrhea incidence, but it is uncertain whether this resulted from a functional response to zinc or reporting bias. The comparison should be re-examined in populations known to respond to zinc supplementation. This trial was registered at www.clinicaltrials.gov as NCT00944359.

The household food insecurity access scale and an index-member dietary diversity score contribute valid and complementary information on household food insecurity in an urban West-African setting.

The number of urban poor is increasing quickly in West Africa, yet food security early warning systems still do not include urban areas. One reason is the lack of appropriate and internationally agreed-upon indicators to measure urban household food insecurity. Our objective was to assess the performance of the household food insecurity access scale (HFIAS) and an index-member's dietary diversity score (IDDS) to approximate the adequacy of urban households' diets. A survey was performed on a random cluster sample of 1056 households in Ouagadougou, Burkina Faso. Data on HFIAS and IDDS and 2 nonconsecutive household quantitative 24-h recalls were collected twice, in June-July and in November-December 2007. Diet adequacy was assessed through the household's mean adequacy ratio (MAR) using energy and 11 micronutrients. Structural equation modeling was used to quantify the association of each candidate indicator with the MAR and receiver-operating characteristic (ROC) analyses were performed to assess their targeting performance in predicting low or high MAR. HFIAS was negatively associated with the MAR [path coefficient (P) = -7.95 × 10(-3) ± 1.45 × 10(-3); P < 0.001], whereas IDDS was positively associated with it (P = 5.19 × 10(-2) ± 1.27 × 10(-2); P < 0.001). Areas under the ROC curves ranged from 0.585 to 0.661 for HFIAS and from 0.536 to 0.629 for IDDS. In conclusion, HFIAS and IDDS performed well in approximating adequacy of urban households' diets. They are informative indicators about urban food insecurity, promising for evaluation and monitoring but not for household targeting given their insufficient predictive power.