Lipid-based Nutrient Supplements Research Articles

Implementation of a nutritional supplementation program in a population of Cambodian children and its impact on statural growth

BackgroundStunting is a major health problem in low-income countries. We aimed to describe the implementation of a lipid-based nutrient supplement (LNS) program in a rural neighborhood in Cambodia and to assess its impact on statural growth. MethodThis was a before–after comparative study. The program was promoted by the Pédiatres du Monde (PDM) organization between 2011 and 2019 in six villages in a rural area in Cambodia. The supplementation program consisted of daily administration of LNS during the third semester of pregnancy for the mothers and then between 6 and 24 months of age for the toddlers. Anthropometric data of the children were recorded during PDM visits before and after the program implementation, which allowed us to compare child growth in the two groups: control and intervention groups. Primary outcome was height-for-age between 24 and 35 months of age. ResultsOverall, 198 data were collected for children between 24 and 35 months of age in the control group. A total of 347 pregnant women were enrolled in the intervention phase. A total of 188 data were collected for children between 24 and 35 months of age in the intervention group. The mean height-for-age z-score in the population receiving LNS was higher than in the control group (−1.14 vs. −1.60, p < 0.001). There was no significant difference between the two groups regarding the weight-for-height z-score (WHZ; −1.11 vs. −1.26, p = 0.18) and children in the intervention group had a higher middle upper-arm circumference z-score (MUACZ; −0.75 vs.. −1.1, p < 0.001). ConclusionLNS supplementation significantly and increased the HAZ between 24 and 35 months of age. However, the fight against malnutrition is complex and needs intervention on multiple levels.

International Lipid-Based Nutrient Supplements (iLiNS) DYAD-Ghana Follow-Up Study: Effects on Social-Emotional Problems at Age 9–10 Years

ObjectivesWe aimed to investigate the effect of pre- and post-natal small-quantity lipid-based nutrient supplements (SQ-LNS) on child social-emotional problems at age 9–10 years in the context of children’s home environments. As previously found in the 5-year follow-up study of the same trial, we expected that SQ-LNS would reduce social-emotional problems and that greater effects of SQ-LNS would be found among children from more disadvantaged home environments. MethodsThe International Lipid-Based Nutrient Supplements (iLiNS) DYAD-Ghana trial was a randomized controlled trial conducted in 2009–2014. 1320 pregnant women ≤ 20 weeks gestation were randomly assigned to receive daily (1) iron and folic acid (IFA) during pregnancy and placebo during 6 mo postpartum, (2) multiple (18) micronutrients (MMN) during pregnancy and 6 mo postpartum, or (3) SQ-LNS (20 g/d) for pregnant women during pregnancy and 6 mo postpartum and SQ-LNS for children from 6 to 18 mo of age. In 2021, we assessed child social-emotional problems at age 9–10 years by caregiver, child, and/or teacher report using the Strengths and Difficulties Questionnaire (SDQ), Brief Problem Monitor, Early Adolescent Temperament Questionnaire, Mood and Feelings Questionnaire, Screen for Child Anxiety Related Emotional Disorders, and Children’s Emotion Management Scales. ResultsWe re-enrolled and assessed outcomes in 966 children, 79.4% of the 1217 children eligible for re-enrollment (excluding those known not survived). At age 9–10 years, a very small percentage (<2%) of children had social-emotional difficulties scores in the abnormal range on the caregiver-reported SDQ, in contrast to the high prevalence previously found at age 5 years in the same cohort (25%). No significant differences were found between SQ-LNS and control groups. Early childhood home environment score did not modify the effect of SQ-LNS on any score. ConclusionsEffects of pre- and post-natal SQ-LNS on social-emotional development previously found at age 5 y were not sustained to age 9–10 y in this cohort. This may have been due to the low prevalence of social-emotional problems at 10 y of age, such that there was little potential to benefit from early nutritional intervention at this age in this outcome domain. Funding SourcesNational Institutes of Health, Bill & Melinda Gates Foundation.

Plasma Lecithin-Cholesterol Acyltransferase Activity in Pregnant Women Enrolled in the iLiNS-DYAD Trial in Ghana

ObjectivesThe International Lipid-Based Nutrient Supplement (iLiNS) Project developed small-quantity lipid-based nutrient supplements (SQ-LNS) for mothers and their children with the goal of reducing malnutrition. The aim of this secondary outcome analysis is to investigate the effects of SQ-LNS on the activity of plasma lecithin-cholesterol acyltransferase (LCAT), a key enzyme involved in the remodeling of high-density lipoprotein (HDL) particles, which increases their cholesterol carrying capacity.MethodsPlasma samples from a subset of 197 out of 1320 women at 36-wk gestation enrolled in the iLiNS-DYAD trial in Ghana were analyzed. In the main cohort, women were enrolled during the second trimester (≤ 20 wk gestation) and randomly assigned to receive SQ-LNS, iron and folic acid (IFA), or a multiple micronutrient supplement. Women in this subset received either SQ-LNS or IFA. Plasma LCAT activity was measured using a commercial fluorometric kit and the non-transformed data was compared by Wilcoxon test (mean ± SD). LCAT activity is expressed as a ratio (390 nm/470 nm), where greater ratio indicates higher enzyme activity. We also explored whether LCAT activity differed by enrollment season (Dry, November–April; Wet, May-October) or was associated with biomarkers of inflammation.ResultsThere was no significant difference in LCAT activity between the SQ-LNS and IFA groups (1.44 ± 0.17 vs. 1.41 ± 0.14, P = 0.24). Women enrolled during the wet season had higher LCAT activity than women enrolled during the dry season (1.47 ± 0.15 vs. 1.37 ± 0.14, P < 0.001), with no differences between intervention groups stratified by season (P > 0.05). LCAT activity was negatively correlated with inflammatory biomarkers α1-acid glycoprotein (R = −0.19, P = 0.007) and C-reactive protein (R = −0.28, P < 0.001) measured at 36-wk gestation.ConclusionsPlasma LCAT activity, as a measure of HDL maturation and cholesterol carrying capacity, is more sensitive to factors mediated by seasonal variation (e.g., infection, inflammation) than by nutrient supplementation in this cohort of women in Ghana. These findings confirm a previously established link between HDL and inflammation.Funding SourcesThis project was supported by Bill & Melinda Gates Foundation grant (OPP124589) to the University of California, Davis.

Effectiveness of Nutritional Supplementation During the First 1000-Days of Life to Reduce Child Stunting: Results From a Cluster Randomised Controlled Trial in Pakistan

ObjectivesWe aimed to assess the effectiveness of nutritional supplementation during the first 1000-days on reduction in the prevalence of stunting in children at 24 months of age.MethodsIn this cluster randomised controlled trial, we enrolled women during their pregnancy from two rural districts of Sindh, Pakistan. A cluster was one union council with a population of ∼25,000 residents. Out of 29 clusters, we randomly allocated 6 clusters to intervention and 6 to control group. Pregnant women received a monthly ration of 5 kg (i.e., 165 grams/day) of wheat soya blend plus (WSB+) during pregnancy and the first six months of their lactation period, and their children received lipid-based nutrient supplement - medium-quantity (LNS-MQ) between 6–23 months of age. The primary outcome was reduction in the prevalence of stunting in children at 24 months of age. Analysis was by intention to treat. The trial is registered in ClinicalTrial.gov, number NCT02422953.Results2030 pregnant women (1017 in the intervention group and 1013 in the control group) were enrolled between August 30, 2014 and May 25, 2016. Monthly follow-ups were conducted between October 1, 2014 and October 25, 2018. At 24 months of age, data from 702 (78%) of 902 livebirths in the intervention group and 658 (76%) of 860 livebirths in the control group were available. There was a significant difference in mean length (49.4 cm vs 48.9 cm, p = 0.027), weight (3.1 kg vs 3.0 kg, p = 0.013), length for age z-scores (−1.2 vs −1.5, p = 0.004) and weight for age z-scores (−1.2 vs −1.5, p = 0.015) among infants in the intervention compared to control group. At 24 months of age, a significant difference in the prevalence of stunting (absolute difference, −10.2%, 95% CI −18.2 to −2.3, p = 0.017) and underweight (absolute difference, −13.7%, 95% CI −20.3 to −7.0, p = 0.001) were observed in the intervention as compared to the control group. The difference in the prevalence of wasting was not significant between the intervention and control groups (absolute difference, −6.9%, 95% CI −14.1 to −0.3, p = 0.057).ConclusionsProvision of WSB + and LNS-MQ during the first 1000-days of life improved child linear growth and reduced stunting in children at 24 months of age. This study can be scaled-up in the similar settings for reduction in the prevalence of stunting in children under-two years of age.Funding SourcesWorld Food Programme.

Associations of Maternal and Child Fatty Acid Status With Child Growth and Development Outcomes in Ghana

ObjectivesMaintaining adequate fatty acid intake during pregnancy and lactation is necessary to support fetal and infant growth. Low maternal intake may lead to decreased transfer of fatty acids to the fetus. Our objective was to examine associations of individual fatty acid status at three different time points with child growth and development outcomes at 18 months. MethodsA cohort of 1,320 women were enrolled in the International Lipid-Based Nutrient Supplements Dyad Ghana trial (iLiNS-DYAD-G). Fatty acids were measured in maternal plasma at 36 weeks gestation (n = 130), maternal breast milk six months postpartum (n = 303), and child plasma at 18 months (n = 369) and quantified as weight percentage of total identified fatty acids of the sample (% weight). We examined correlations between time points (maternal, breastmilk, and child) for five indicators of fatty acid status: % weight of four individual fatty acids (alpha-linolenic acid, ALA; linolenic acid, LA; docosahexaenoic acid, DHA; arachidonic acid, AA) and the n6: n3 ratio (ratio of LA & AA to ALA, DHA & EPA). We then examined whether each fatty acid indicator was associated with child growth (head circumference for age, length for age, weight for length z-scores) or developmental outcomes (motor, language, and social-emotional scores) at 18 months. Adjusted regressions included child sex, food insecurity scores, socioeconomic status, intervention group, and years of maternal education. ResultsMaternal plasma and breast milk were positively correlated for % weight AA, LA, and n6: n3 ratio. Maternal and child plasma were positively correlated for % weight DHA and n6: n3 ratio. Breast milk and child plasma fatty acids were positively correlated for % weight AA, ALA, DHA, and n6: n3 ratio. Associations of fatty acid status indicators with child growth and developmental outcomes were not significant after correcting for multiple comparisons. ConclusionsAlthough maternal fatty acid status was associated with breastmilk and child fatty acid status, maternal and child fatty acid status was not generally associated with child growth and development at 18 months of age in this sample of mother-child dyads in Ghana. Funding SourcesBill & Melinda Gates Foundation; National Institute of Child Health and Human Development & Fogarty International Center R01HD099811.

Development of a live coding method to assess infant/toddler food acceptance.

Validated measures predicting infant consumption of nutrient supplements or fortified foods are essential for the success of nutritional interventions to improve undernutrition. Behavioural coding of food acceptance is one promising approach, though the required time and resources are limiting. The overarching goal of the present study was to adapt a video coding (VC) protocol for use as a live coding (LC) method to assess infant food acceptance in naturalistic settings. Infants (n = 59; ages 7–24 months) were fed a small‐quantity lipid‐based nutrient supplement (SQ‐LNS) mixed with a familiar food by caregivers in the State of Morelos, Mexico. Trained coders used a VC scheme to rate infant acceptance of each spoon offer using a 4‐point scale. The VC scheme was subsequently adapted for use as an LC method to be used in participant homes and a video live coding (VLC) method to monitor reliability. Reliability and validity of the LC method were tested in a subsample of dyads (n = 20). Intraclass correlation coefficients (ICCs) indicated that the inter‐rater reliability between coders using the LC method was moderate or good when compared to VC methods (ICCs = 0.75 and 0.87). Live coded acceptance scores were also moderately associated with consumption of the SQ‐LNS (ρ = 0.50, p = 0.03). The LC scheme demonstrated initial reliability and validity as an assessment of infant food acceptance. Since VC is both resource and time‐intensive, the LC scheme may be useful for assessing infant food acceptance in resource‐limited settings.

Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial.

BackgroundIt is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.Methods and findingsWe conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron–folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.ConclusionsThere was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.Trial registrationClinicalTrials.gov NCT02145000.

Acceptability of 11 fortified balanced energy‐protein supplements for pregnant women in Nepal

Evidence suggests that multiple micronutrient and balanced energy protein (BEP) supplementation during pregnancy can decrease the risk of stillbirth and small‐for‐gestational‐age births and increase birth weight. We conducted a mixed‐methods formative research study to identify the most acceptable among a range of 11 candidates fortified BEP supplements for use in pregnancy and lactation in a rural district in Nepal. Forty pregnant women aged 15–40 years participated in a test meal tasting of 11 different sweet and savoury candidate BEP supplements. Each participant rated the products on organoleptic properties using a 7‐point hedonic scale (1 = Dislike it very much to 7 = Like it very much), ranked her ‘top 3’ most liked supplements, and subsequently discussed each product with peers in focus group discussions (FGDs). Five supplements (sweet lipid‐based nutrient supplement (LNS), savoury LNS, sweet vanilla biscuits, vanilla instant drinks and seasoned pillows) achieved the maximum overall median hedonic score of 7, with sweet LNS and seasoned pillows ranking as the top 2. This was consistent with the assessments in FGDs. Women in the FGDs expressed dislike of the smell and taste of the cocoa drink, savoury masala bar, sweet mango bar and savoury curry biscuit, which was consistent with the hedonic scale scores. This study provides valuable insights into our understanding of women's acceptance of different BEP supplements during pregnancy in rural Nepal and has helped identify the two most accepted BEP supplements to be used in a two‐month home trial to assess utilisation and compliance in this setting.

Serum cobalamin in children with moderate acute malnutrition in Burkina Faso: Secondary analysis of a randomized trial.

Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <-2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. ISRCTN Registry ISRCTN42569496.

Prenatal supplementation with multiple micronutrient supplements or medium-quantity lipid-based nutrient supplements has limited effects on child growth up to 24 months in rural Niger: a secondary analysis of a cluster randomized trial

ABSTRACTBackgroundPrenatal multiple micronutrient supplementation (MMS) and lipid-based nutrient supplementation (LNS) can improve birth outcomes relative to iron-folic acid supplementation (IFA); however, effects on child postnatal growth remain unclear.ObjectivesThe aim was to compare the effect of prenatal MMS, medium-quantity LNS (MQ-LNS), and IFA on child growth up to 2 y of age.MethodsWe conducted a cluster randomized controlled trial of prenatal nutritional supplementation in Madarounfa, Niger. Villages were randomly assigned for pregnant women to receive IFA (17 villages, 1105 women), MMS (18 villages, 1083 women) or MQ-LNS (18 villages, 1144 women). Pregnant women received nutritional supplements weekly until delivery, and children were followed up monthly from 6-8 wk to 24 mo of age. We assessed the effect of prenatal MMS and MQ-LNS compared with IFA and the effect of prenatal MMS compared with MQ-LNS on child length-for-age z scores (LAZ), weight-for-age z scores (WAZ), and weight-for-length z scores (WLZ) at 24 mo of age using generalized linear models. In secondary analyses, we used mixed-effects models to assess the trajectories of anthropometric z scores longitudinally from 6–8 wk to 24 mo.ResultsCompared with IFA, MMS and MQ-LNS had no effect on child LAZ, WAZ, or WLZ at 24 mo of age (P > 0.05). Children in the MQ-LNS arm had significantly higher mid-upper arm circumference at 24 mo than children in the MMS arm: mean difference 0.50 cm (95% CI 0.10, 0.91 cm). WAZ and WLZ trajectories were more negative in the MQ-LNS arm compared with IFA and MMS, with lower z scores from 14 to 20 mo of age. However, WAZ and WLZ trajectories converged after 20 mo of age, and there were no differences by 24 mo of age.ConclusionsPrenatal MMS and MQ-LNS had limited effect on anthropometric measures of child growth up to 24 mo of age as compared with IFA in rural Niger.

Provision of Small-Quantity Lipid-Based Nutrient Supplements Increases Plasma Selenium Concentration in Pregnant Women in Malawi: A Secondary Outcome of a Randomized Controlled Trial

ABSTRACTBackgroundPregnant women in Malawi are at risk of selenium deficiency, which can have adverse effects on pregnancy outcomes. Interventions for improving selenium status are needed.ObjectivesTo assess the effect of provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to Malawian women during pregnancy on their plasma selenium concentrations at 36 wk of gestation.MethodsPregnant women (≤20 wk of gestation) were randomly assigned to receive daily either: 1) iron and folic acid (IFA); 2) multiple micronutrients (MMN; 130 µg selenium per capsule); or 3) SQ-LNS (130 µg selenium/20 g). Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry at baseline and after ≥16 wk of intervention (at 36 wk of gestation) and compared by intervention group.ResultsAt 36 wk of gestation, median (quartile 1, quartile 3) plasma selenium concentrations (micromoles per liter) were 0.96 (0.73, 1.23), 0.94 (0.78, 1.18), and 1.01 (0.85, 1.28) in the IFA, MMN, and SQ-LNS groups, respectively. Geometric mean (GM) plasma selenium concentration was 5.4% (95% CI: 1.8%, 9.0%) higher in the SQ-LNS group than in the MMN group and tended to be higher than in the IFA group (+4.2%; 95% CI: 1.0%, 7.8%). The prevalence of adjusted plasma selenium concentrations <1 µmol/L was 55.1%, 57.8%, and 47.3% in the IFA, MMN, and SQ-LNS groups, respectively; it was lower in the SQ-LNS group than in the MMN group, OR = 0.44 (95% CI: 0.24, 0.83), and tended to be lower than in the IFA group, OR = 0.54 (95% CI: 0.29, 1.03). There was a significant interaction between baseline plasma selenium concentration and intervention group (P = 0.003). In the lowest tertile of baseline selenium concentrations, GM plasma selenium concentration was higher, and the prevalence of low values was lower in the SQ-LNS group compared with the MMN and IFA groups at 36 wk of gestation (P ≤ 0.007).ConclusionsProvision of SQ-LNS containing selenium to pregnant women can be an effective strategy for improving their selenium status.This trial was registered at clinicaltrials.gov (identifier: NCT01239693).

Lipid-based nutrient supplement at initiation of antiretroviral therapy does not substitute energy from habitual diet among HIV patients - a secondary analysis of data from a randomised controlled trial in Ethiopia.

IntroductionMalnutrition is common among people with HIV in sub-Saharan Africa. Nutritional supplementation at initiation of antiretroviral treatment (ART) has shown beneficial effects, but it is not known if supplementation replaces or supplements the habitual energy intake in a context of food insecurity.MethodsAs part of a randomised controlled trial among people with HIV initiating ART in Ethiopia, we assessed whether the provision of a lipid-based nutrient supplement (LNS) affected energy intake from the habitual diet. People with HIV aged ≥18 years with a body mass index (BMI) >17 were randomly allocated 2:1 to receive either early (month 1–3 after ART initiation) or delayed (month 4–6 after ART initiation) supplementation with LNS (≈4,600 kJ/day). Participants with BMI 16–17 were all allocated to early supplementation. The daily energy intake from the habitual diet (besides the energy contribution from LNS) was assessed using a 24-h food recall interview at baseline and at monthly follow-up visits. Linear mixed models were used to compare habitual energy intake in (1) early versus delayed supplementation groups and (2) supplemented versus unsupplemented time periods within groups.ResultsOf 301 participants included, 67% of the participants were women, mean (±standard deviation [SD]) age was 32.9 (±8.9) years and 68% were living in moderately or severely food insecure households. Mean (±SD) reported habitual energy intake at baseline was 5,357 kJ/day (±2,246) for women and 7,977 kJ/day(±3,557) for men. Among all participants, there were no differences in mean habitual energy intake between supplemented and unsupplemented groups in neither the first 3 (P = 0.72) nor the following 3 months (P = 0.56). Furthermore, habitual energy intake did not differ within groups when comparing periods with or without supplementation (P = 0.15 and P = 0.20). The severity of food insecurity did not modify the effect of supplementation in habitual energy intake (P = 0.55). Findings were similar when participants with BMI 16–17 were excluded.ConclusionOur findings indicate that the LNS provided after ART initiation supplement, rather than substitute, habitual energy intake among people with HIV, even among those who are food insecure. This supports the feasibility of introducing nutritional supplementation as part of HIV treatment.

Provision of small-quantity lipid-based nutrient supplements does not improve intestinal health among rural Malawian children.

Lipid‐based nutrient supplements (LNS) have been found to improve child growth and reduce child mortality. However, the mechanistic pathways for these improvements warrant exploration. One potential pathway is linked to improvement in intestinal health. Our study aimed to test a hypothesis that small‐quantity LNS (SQ‐LNS) could reduce the levels of intestinal inflammation, repair and permeability of children. As intestinal health markers we measured fecal calprotectin, regenerating 1B protein (REG1B) and alpha‐1‐antitrypsin concentrations at 18 months of age (after 12 months of supplementation) and 1 year later (12 months after cessation of supplementation). In this analysis, we included data of 735 children who participated in a randomised dietary supplementation trial in rural Malawi; 243 children who received 20 g/day SQ‐LNS from 6 to 18 months of age were in the SQ‐LNS group, while the others who received no dietary supplementation during this period were in the control group. At 18 months of age, the mean concentrations of calprotectin, REG1B and alpha‐1‐antitrypsin were 241, 105 µg/g and 7.1 mg/dl, respectively, in the SQ‐LNS group, and 224, 105 µg/g and 7.4 mg/dl, respectively, in the control group, and did not differ between the SQ‐LNS and control groups. We conclude that SQ‐LNS provision did not have an impact on children's intestinal health in rural Malawi.

Effectiveness of unconditional cash transfers combined with lipid-based nutrient supplement and/or behavior change communication to prevent stunting among children in Pakistan: a cluster randomized controlled trial

ABSTRACTBackgroundIn Pakistan, the prevalence of stunting among children younger than 5 y has remained above WHO critical thresholds (≥30%) over the past 2 decades.ObjectivesWe hypothesized that an unconditional cash transfer (UCT) combined with lipid-based nutrient supplement (LNS) and/or social and behavior change communication (SBCC) will prevent stunting among children 6–23 mo of age.MethodsThis was a 4-arm, community-based cluster randomized controlled trial conducted in the district of Rahim Yar Khan, Pakistan. A total of 1729 children (UCT, n = 434; UCT + SBCC, n = 433; UCT + LNS, n = 430; and UCT + LNS + SBCC, n = 432) were enrolled at 6 mo of age and measured monthly for 18 mo until the age of 24 mo.ResultsAt 24 mo of age, children who received UCT + LNS [rate ratio (RR): 0.85; 95% CI: 0.74, 0.97; P = 0.015) and UCT + LNS + SBCC (RR: 0.86; 95% CI: 0.77, 0.96; P = 0.007) had a significantly lower risk of being stunted compared with the UCT arm. No significant difference was noted among children who received UCT + SBCC (RR: 1.03; 95% CI: 0.91, 1.16; P = 0.675) in the risk of being stunted compared with the UCT arm. The pooled prevalence of stunting among children aged 6–23 mo was 41.7%, 44.8%, 38.5%, and 39.3% in UCT, UCT + SBCC, UCT + LNS, and UCT + LNS + SBCC, respectively. In pairwise comparisons, a significant impact on stunting among children in UCT + LNS (P = 0.029) and UCT + LNS + SBCC (P = <0.001) was noted compared with the UCT arm.ConclusionsUCT combined with LNS and UCT + LNS + SBCC were effective in reducing the prevalence of stunting among children aged 6–23 mo in marginalized populations. UCT + SBCC was not effective in reducing the child stunting prevalence. This trial was registered at clinicaltrials.gov as NCT03299218.

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

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

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

IntroductionSmall-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. ObjectivesWe aimed to determine the impact of SQ-LNS consumption on infants’ plasma FA profiles in Ghana and Malawi. MethodsGhanaian (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). ResultsAt 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. ConclusionsSQ-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.

B-Vitamins and Choline in Human Milk Are Not Impacted by a Preconception Lipid-Based Nutrient Supplement, but Differ Among Three Low-to-Middle Income Settings-Findings From the Women First Trial.

Introduction: Optimal human milk (HM) B-vitamin concentrations remain undefined, especially in areas where undernutrition is prevalent. The impact of supplementation pre-conception through pregnancy on HM B-vitamin composition remains unknown.Methods: Human milk (HM) was collected at 2-weeks postpartum from 200 women in Guatemala, India, and Pakistan (the Women First Trial). The women were randomized to start a lipid-based nutrient supplement before conception, at end of the first trimester, or not at all; intervention continued until delivery. HM concentrations of eight B-vitamins and choline were assessed via ultra-performance liquid chromatography-tandem mass spectrometry. Maternal diet was assessed in early pregnancy, and infant growth followed through 6 months post-delivery.Results: Despite supplement exposure averaging 15.7 (pre-conception arm) and 6.0 months (prenatal arm), HM B-vitamins did not differ between arms, but site differences were evident. Guatemala had higher HM concentrations of vitamin B3 than Pakistan and India. Pakistan had higher HM concentrations of thiamin and vitamin B6 than India and Guatemala. Cohort average HM vitamin B2 (162 ± 79 μg/L) and B6 (31.8 ± 24.6 μg/L) fell below values defined as deficient in 81.5 and 85.5% of samples, potentially reflecting sampling procedures and timing. Maternal dietary intakes of only vitamin B6 and choline were associated with the corresponding concentrations in HM (p < 0.005). No HM B-vitamin concentrations were associated with infant growth.Conclusion: Prenatal supplementation for at least 6 months had no impact on HM B-vitamin concentrations at 2-weeks postpartum. Results suggest that the adequacy of HM composition was generally maintained, with potential exceptions of vitamin B2 and B6.

Lipid-Based Nutrient Supplementation Increases High-Density Lipoprotein (HDL) Cholesterol Efflux Capacity and Is Associated with Changes in the HDL Glycoproteome in Children.

Prenatal plus postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) improved child growth at 18 months in the International Lipid-Based Nutrient Supplements DYAD trial in Ghana. In this secondary outcome analysis, we determined whether SQ-LNS versus prenatal iron and folic acid (IFA) supplementation improves the cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) particles and alters their lipidomic, proteomic, or glycoproteomic composition in a subset of 80 children at 18 months of age. HDL CEC was higher among children in the SQ-LNS versus IFA group (20.9 ± 4.1 vs 19.4 ± 3.3%; one-tailed p = 0.038). There were no differences in HDL lipidomic or proteomic composition between groups. Twelve glycopeptides out of the 163 analyzed were significantly altered by SQ-LNS, but none of the group differences remained significant after correction for multiple testing. Exploratory analysis showed that 6 out of the 33 HDL-associated proteins monitored differed in glycopeptide enrichment between intervention groups, and 6 out of the 163 glycopeptides were correlated with CEC. We conclude that prenatal plus postnatal SQ-LNS may modify HDL protein glycoprofiles and improve the CEC of HDL particles in children, which may have implications for subsequent child health outcomes. This trial was registered at clinicaltrials.gov as NCT00970866.

Small-quantity lipid-based nutrient supplements for the prevention of child malnutrition and promotion of healthy development: overview of individual participant data meta-analysis and programmatic implications

ABSTRACTSmall-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12–14% lower prevalence of stunting, wasting, and underweight; were 16–19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

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

ABSTRACTBackgroundSmall-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.ObjectivesWe 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.MethodsWe 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.ResultsSQ-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.ConclusionsSQ-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.