Sustained effects of small-quantity lipid-based nutrient supplements provided during the first 1000 days on child growth at 9-11 y in a randomized controlled trial in Ghana.

BACKGROUND: There is limited research on whether nutritional supplementation in the first 1000 d affects long-term child outcomes. We previously demonstrated that pre- and postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) increased birth weight and child length at 18 mo of age in Ghana. OBJECTIVES: We aimed to investigate the effect of pre- and postnatal SQ-LNS on child growth and blood pressure at 9-11 y. METHODS: In the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana trial, 1320 females ≤20 weeks of gestation were randomly assigned to receive daily: iron and folic acid (IFA) during pregnancy and placebo during 6 mo postpartum or multiple micronutrients (MMNs) during pregnancy and 6 mo postpartum, or SQ-LNS during pregnancy and 6 mo postpartum and for their children aged from 6 to 18 mo. We re-enrolled 966 children aged 9-11 y and assessed child blood pressure, height-for-age z-score (HAZ), body mass index (BMI)-for-age z-score, waist-to-height ratio, triceps skinfold, and midupper arm circumference. We compared SQ-LNS with control (IFA + MMN) groups adjusting for child's age. RESULTS: Mean (standard deviation [SD]) HAZ in SQ-LNS and control group was -0.04 (0.96) and -0.16 (0.99); P = 0.060. There were no indications of group differences in the other outcomes (P > 0.10). Effects on HAZ varied by child sex (P-interaction = 0.075) and maternal prepregnancy BMI (kg/m2; P-interaction = 0.007). Among females, HAZ was higher in the SQ-LNS [0.08 (1.04)] than in the control group [-0.16 (1.01)] (P = 0.010); among males, SQ-LNS [-0.16 (0.85)] and control groups [-0.16 (0.96)] did not differ (P = 0.974). Among children of females with BMI of <25, HAZ was higher in the SQ-LNS [-0.04 (1.00)] than in the control group [-0.29 (0.94)] (P = 0.004); among females with BMI of ≥25, SQ-LNS [-0.04 (0.91)] and control groups [0.07 (1.00)] did not differ (P = 0.281). CONCLUSIONS: There is a sustained impact of prenatal and postnatal SQ-LNS on linear growth among female children and children whose mothers were not overweight. This trial was registered at clinicaltrials.gov as NCT00970866 (https://clinicaltrials.gov/ct2/show/record/NCT00970866).

Seasonal Factors Are Associated with Activities of Enzymes Involved in High-Density Lipoprotein Metabolism among Pregnant Females in Ghana.

Background: Small-quantity lipid-based nutrient supplements (SQ-LNS) during pregnancy and postnatally were previously shown to improve high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) and length in the children of supplemented mothers at 18 mo of age in the International Lipid-Based Nutrient Supplements (iLiNS) DYAD trial in Ghana. However, the effects of SQ-LNS on maternal HDL functionality during pregnancy are unknown. Objective: The goal of this cross-sectional, secondary outcome analysis was to compare HDL function in mothers supplemented with SQ-LNS vs. iron and folic acid (IFA) during gestation. Methods: HDL CEC and the activities of 3 HDL-associated enzymes were analyzed in archived plasma samples (N = 197) from a subsample of females at 36 weeks of gestation enrolled in the iLiNS-DYAD trial in Ghana. Correlations between HDL function and birth outcomes, inflammatory markers C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP), and the effects of season were explored to determine the influence of these factors on HDL function in this cohort of pregnant females. Results: There were no statistically significant differences in HDL CEC, plasma lecithin-cholesterol acyltransferase (LCAT) activity, cholesteryl ester transfer protein (CETP) activity, or phospholipid transfer protein (PLTP) activity between mothers supplemented with SQ-LNS compared with IFA control, and no statistically significant relationships between maternal HDL function and childbirth outcomes. LCAT activity was negatively correlated with plasma AGP (R = -0.19, P = 0.007) and CRP (R = -0.28, P < 0.001), CETP and LCAT activity were higher during the dry season compared to the wet season, and PLTP activity was higher in the wet season compared to the dry season. Conclusions: Mothers in Ghana supplemented with SQ-LNS compared with IFA during gestation did not have measurable differences in HDL functionality, and maternal HDL function was not associated with childbirth outcomes. However, seasonal factors and markers of inflammation were associated with HDL function, indicating that these factors had a stronger influence on HDL functionality than SQ-LNS supplementation during pregnancy. Clinical Trial Registry number: The study was registered as NCT00970866. https://clinicaltrials.gov/study/NCT00970866.

Dietary magnesium intakes among women of reproductive age in Ghana-A comparison of two dietary analysis programs.

BACKGROUND: Despite the importance of magnesium to health and most importantly to women of reproductive age who are entering pregnancy, very few surveys have investigated the magnesium status of women of reproductive age, particularly in Africa. Additionally, the software and programs used to analyze dietary intake vary across countries in the region. OBJECTIVE: To assess the dietary magnesium intake of women of reproductive age in Ghana and to compare the estimate of magnesium intake obtained from two commonly used dietary analysis programs. METHODS: We collected magnesium intake from 63 Ghanaian women using a semiquantitative 150-item food frequency questionnaire. Dietary data was analyzed using two different dietary analysis programs, Nutrient Data Software for Research (NDSR) and the Elizabeth Stewart Hands and Associates (ESHA) Food Processor Nutrition Analysis software. We used the Wilcoxon signed rank test to compare the mean differences between the two dietary programs. RESULTS: There were significant differences between the average dietary magnesium intake calculated by the two dietary programs, with ESHA estimating higher magnesium intake than NDSR (M±SE; ESHA: 200 ± 12 mg/day; NDSR: 168 ± 11 mg/day; p<0. 05). The ESHA database included some ethnic foods and was flexible in terms of searching for food items which we found to be more accurate in assessing the magnesium intake of women in Ghana. Using the ESHA software, 84% of the study women had intake below the recommended dietary allowances (RDA) of 320mg/day. CONCLUSION: It is possible that the ESHA software provided an accurate estimate of magnesium in this population because it included specific ethnic foods. Concerted efforts such as magnesium supplementation and nutrition education should be considered to improve the magnesium intake of women of reproductive age in Ghana.

Prenatal and postnatal small-quantity lipid-based nutrient supplements and children's social-emotional difficulties at ages 9-11 y in Ghana: follow-up of a randomized controlled trial.

BACKGROUND: Provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) during early life improves growth and development. In the International Lipid-Based Nutrient Supplements DYAD-Ghana trial, prenatal and postnatal SQ-LNS reduced social-emotional difficulties at age 5 y, with greater effects among children in less-enriched home environments. OBJECTIVES: We aimed to investigate the effect of prenatal and postnatal SQ-LNS on children's social-emotional problems at age 9-11 y. METHODS: In 2009-2011, 1320 pregnant women ≤20 wk gestation were randomly assigned to receive the following daily until 6 mo postpartum: 1) iron and folic acid until delivery, then placebo, 2) multiple micronutrients (MMNs), or 3) SQ-LNS (20 g/d). Children in group 3 received SQ-LNS from 6 to 18 mo. In 2021, we evaluated children's social-emotional outcomes with 6 assessment tools that used caregiver, teacher, and/or self-report to measure socioemotional difficulties, conduct problems, temperament, mood, anxiety, and emotion management. RESULTS: We assessed outcomes in 966 children, comprising 79.4% of 1217 participants eligible for re-enrolment. No significant differences were found between the SQ-LNS and control (non-LNS groups combined) groups. Few children (<2%) experienced high parent-reported social-emotional difficulties at 9-11 y, in contrast to the high prevalence at age 5 in this cohort (25%). Among children in less-enriched early childhood home environments, the SQ-LNS group had 0.37 SD (-0.04 to 0.82) lower self-reported conduct problems than the control group (P-interaction = 0.047). CONCLUSIONS: Overall positive effects of SQ-LNS on social-emotional development previously found at age 5 y are not sustained to age 9-11 y; however, there is some evidence of positive effects among children in less-enriched environments. The lack of effects may be owing to low prevalence of social-emotional problems at preadolescence, resulting in little potential to benefit from early nutritional intervention at this age in this outcome domain. Follow-up during adolescence, when social-emotional problems more typically onset, may yield further insights. This trial was registered at clinicaltrials.gov as NCT00970866. https://clinicaltrials.gov/ct2/show/record/NCT00970866.

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

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

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.

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

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

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.

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.

Complementary Feeding Indicators in Relation to Micronutrient Status of Ghanaian Children Aged 6-23 Months: Results from a National Survey.

BACKGROUND: Optimal complementary feeding is critical for adequate growth and development in infants and young children. The associations between complementary feeding and growth have been studied well, but less is known about the relationship between complementary feeding and micronutrient status. METHODS: Using data from a national cross-sectional survey conducted in Ghana in 2017, we examined how multiple WHO-recommended complementary feeding indicators relate to anemia and the micronutrient status of children aged 6-23 months. RESULTS: In total, 42%, 38%, and 14% of the children met the criteria for minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum acceptable diet (MAD), respectively. In addition, 71% and 52% of the children consumed iron-rich foods and vitamin A-rich foods, respectively. The prevalence of anemia, iron deficiency (ID), iron deficiency anemia (IDA) and vitamin A deficiency (VAD) was 46%, 45%, 27%, and 10%, respectively. Inverse associations between MMF and socio-economic status were found, and MMF was associated with an increased risk of ID (55%; p < 0.013) and IDA (38%; p < 0.002). CONCLUSION: The pathways connecting complementary feeding and micronutrient status are complex. Findings related to MMF should be further investigated to ensure that complementary feeding programs account for the potential practice of frequent feeding with nutrient-poor foods.

Nutritional perspectives on sickle cell disease in Africa: a systematic review.

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder that predominantly affects individuals in sub-Saharan Africa. However, research that elucidates links between SCD pathophysiology and nutritional status in African patients is lacking. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa that focused on nutritional aspects of SCD, and highlights gaps in knowledge that could inform priority-setting for future research. METHODS: The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised original, peer-reviewed research published between January 1995 and November 2020 involving individuals in Africa with any phenotypic variant of SCD and at least one nutritional status outcome. Nutritional status outcomes were defined as those that assessed dietary intakes, growth/anthropometry, or nutritional biomarkers. Databases used were Ovid Embase, Medline, Biosis and Web of Science. RESULTS: The search returned 526 articles, of which 76 were included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient status (41%), and interventional studies (11%). Findings consistently included growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food (RUSF), and oral arginine on health outcomes. CONCLUSIONS: The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark dearth of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings from the investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutrition-related interventions for patients with SCD in sub-Saharan Africa to promote optimal growth and improve health outcomes.

Maternal Blood Pressure in Relation to Prenatal Lipid-Based Nutrient Supplementation and Adverse Birth Outcomes in a Ghanaian Cohort: A Randomized Controlled Trial and Cohort Analysis.

BACKGROUND: It is unknown whether prenatal lipid-based nutrient supplements (LNSs) affect blood pressure (BP). Associations between hypertension and birth outcomes using recently updated BP cutoffs are undetermined. OBJECTIVES: We aimed to assess the impact of LNSs on maternal hypertension and associations between hypertension and birth outcomes. METHODS: Pregnant Ghanaian women at ≤20 weeks of gestation (n = 1320) were randomly assigned to receive daily 1) iron and folic acid (IFA), 2) multiple micronutrients (MMN), or 3) LNSs until delivery. BP was measured at enrollment and 36 weeks of gestation. We analyzed the effect of LNSs on BP using ANOVA and associations between hypertension [systolic BP (SBP) ≥130 mm Hg or diastolic BP (DBP) ≥80 mm Hg] and birth outcomes by linear and logistic regressions. RESULTS: Mean ± SD SBP and DBP were 110 ± 11 and 63 ± 8 mm Hg at 36 weeks of gestation and did not differ by supplementation group (SBP, P > 0.05; DBP, P > 0.05). At enrollment, higher DBP was associated with lower birth weight and shorter gestation; women with high DBP had greater risk of low birth weight (LBW) [risk ratio (RR): 2.58; 95% CI: 1.09, 6.08] and preterm birth (PTB) (RR: 3.30; 95% CI: 1.47, 7.40). At 36 weeks of gestation, higher SBP was associated with lower birth weight, length, and head circumference and shorter gestation; higher DBP was associated with lower birth weight and length; and women with high DBP had greater risk of LBW (RR: 3.39; 95% CI: 1.32, 8.69). Neither high SBP nor hypertension were associated with birth outcomes at either time point. CONCLUSIONS: Daily provision of LNSs does not affect maternal hypertension, compared with IFA and MMN. Higher SBP and DBP are associated with a shorter gestation and smaller birth size; however, only high DBP is associated with LBW and PTB. The new BP cutoffs may help identify pregnancies at risk of adverse birth outcomes.This trial was registered at clinicaltrials.gov as NCT00970866.

Consumption of multiple micronutrients or small-quantity lipid-based nutrient supplements containing iodine at the recommended dose during pregnancy, compared with iron and folic acid, does not affect women's urinary iodine concentration in rural Malawi: a secondary outcome analysis of the iLiNS DYAD trial.

OBJECTIVES: Inadequate iodine intake during pregnancy increases the risk of neonatal morbidity and mortality. We aimed to evaluate whether prenatal supplements containing iodine affect urinary iodine concentrations (UIC) of pregnant women in Malawi. DESIGN: A randomised controlled trial. Pregnant women (n 1391) were assigned to consume 60 mg/d Fe and 400 µg/d folic acid (IFA) or 18 vitamins and minerals including 250 µg/d iodine (MMN) or 20 g/d small-quantity lipid-based nutrient supplements (SQ-LNS) with similar nutrient contents as MMN group, plus macronutrients (LNS) until childbirth. In a sub-study (n 317), we evaluated group geometric mean urinary iodine concentration (UIC) (µg/L) at 36 weeks of gestation controlling for baseline UIC and compared median (baseline) and geometric mean (36 weeks) UIC with WHO cut-offs: UIC < 150, 150-249, 250-499 and ≥500 reflecting insufficient, adequate, above requirements and excessive iodine intakes, respectively. SETTING: Mangochi District, Malawi. PARTICIPANTS: Women ≤20 weeks pregnant. RESULTS: Groups had comparable background characteristics. At baseline, overall median (Q1, Q3) UIC (319 (167, 559)) suggested iodine intakes above requirements. At 36 weeks, the geometric mean (95 % CI) UIC of the IFA (197 (171, 226)), MMN (212 (185, 243)) and LNS (220 (192, 253)) groups did not differ (P = 0·53) and reflected adequate intakes. CONCLUSIONS: In this setting, provision of supplements containing iodine at the recommended dose to pregnant women with relatively high iodine intakes at baseline, presumably from iodised salt, has no impact on the women's UIC. Regular monitoring of the iodine status of pregnant women in such settings is advisable. Clinicaltrials.gov identifier: NCT01239693.

Impact of nutrient supplementation on maternal nutrition and child growth and development in Sub-Saharan Africa: the case of small-quantity lipid-based nutrient supplements.

Micronutrient deficiencies remain common among women and children in Sub-Saharan Africa (SSA); in pregnant/lactating women, the intakes of essential fatty acids may also be low. Enriching home-prepared foods with small-quantity lipid-based nutrient supplements (SQ-LNSs) is a promising new strategy of delivering additional micronutrients, essential fatty acids and good quality protein to women and children. This narrative review aimed to examine the impact of SQ-LNSs supplementation among women and infants and young children in SSA, and to discuss the differential impact of SQ-LNS consumption across different settings. Papers reporting randomized trials conducted in SSA in which apparently healthy women and/or ≥6-mo-old children received SQ-LNSs were identified through electronic and manual searches. Prenatal SQ-LNS consumption reduced the prevalence of low gestational weight gain in Ghana when compared with multiple micronutrients supplementation, and was associated with poorer iron/hemoglobin status when compared with iron-plus-folic acid supplementation. SQ-LNSs received alone or as intervention package improved infant/child growth in two trials in Ghana and one trial each in Burkina Faso, Kenya, Zimbabwe and South Africa, but had no impact on growth in two trials in Malawi. SQ-LNSs supplementation improved motor development in Ghana, Burkina Faso, Malawi, Kenya, and South Africa, but had no impact on language, socio-emotional, and executive functions in Ghana and Malawi and on Griffiths' developmental scores in Malawi. SQ-LNSs may contribute to improving child growth in SSA. More research is needed to determine the iron level in SQ-LNSs effective for improving both maternal hemoglobin/iron status and birth outcomes.

Lessons learned from implementing the pilot Micronutrient Powder Initiative in four districts in Ghana.

BACKGROUND: Micronutrient deficiencies affect many children in low-income settings due primarily to over-reliance on complementary foods low in nutrients. Home-fortification (HF) could improve children's diet quality in these settings. The Ghana Health Service, supported by UNICEF, integrated the pilot Micronutrient Powder Initiative (MPI) into Child Welfare Clinic (CWC) services in four districts (Tain, Tolon, Talensi, and Ho West), whereby micronutrient powder (MNP) is supplied for HF for children aged 6-23 months attending CWCs. This study's main aim was to identify the facilitators, barriers and "lessons learned" after 2 years of program implementation. METHODS: This was a qualitative cross-sectional study. MNP distributed and children enrolled were obtained from program records. Primary data were collected from November to December 2019 and included, by district: interviews with senior program staff; key informant interviews and focus group discussion with caregivers in each of 6 sub-districts; and discussions workshop with frontline staff from at least 10 health facilities. Besides field notes, all interactions were audio-recorded and transcribed verbatim. Qualitative data were analyzed using NVivo10. RESULTS: The MPI remains on-going, with about 2.5 million MNP sachets distributed to nearly 30,000 children within 90 district-months. Caregivers generally accept the MNP; reported positive responses in children include: "increased appetite", "less frequent illnesses, "increased energy/strength", "increased weight", and "walking independently relatively early". Main facilitators are: generally regular MNP availability; increased patronage of CWC services; various contact points for supplying MNPs; fairly strong social mobilization strategy; good integration of MPI with CWC services; "one-on-one" counselling for caregivers reporting side effects; and tracing caregivers to address concerns and monitor adherence. Main barriers are: lack of counselling materials; caregivers' suspicions towards the program; absence of refresher training for frontline workers; and perceived MNP side-effects. Key lessons learned are: incorporating MNPs into CWC services is feasible, acceptable, and could reduce child micronutrient deficiencies in program districts; and MPI's success requires stronger community sensitization, equipping frontline workers to advise caregivers and manage side-effects, and consciously identifying and managing logistical challenges. CONCLUSION: Further research is needed to evaluate the effectiveness of the MPI in reducing micronutrient deficiencies among 6-23-months-olds in Ghana.

Impact of a nutritional supplement during gestation and early childhood on child salivary cortisol, hair cortisol, and telomere length at 4-6 years of age: a follow-up of a randomized controlled trial.

Dysregulation of the stress response can occur early in life and may be affected by nutrition. Our objective was to evaluate the long-term effect of nutritional supplementation during gestation and early childhood on child cortisol and buccal telomere length (a marker of cellular aging) at 4-6 years of age. We conducted a follow-up study of children born to women who participated in a nutritional supplementation trial in Ghana. In one group, a lipid-based nutrient supplement (LNS) was provided to women during gestation and the first 6 months postpartum and to their infants from age 6 to 18 months. The control groups received either iron and folic acid (IFA) during gestation or multiple micronutrients during gestation and the first 6 months postpartum, with no infant supplementation. At age 4-6 years, we measured hair cortisol, buccal telomere length, and salivary cortisol before and after a stressor. Salivary cortisol was available for 364 children across all three trial arms and hair cortisol and telomere length were available for a subset of children (n = 275 and 278, respectively) from the LNS and IFA groups. Telomere length, salivary cortisol, and hair cortisol did not differ by supplementation group. Overall, these findings suggest that nutritional supplementation given during gestation and early childhood does not have an effect on child stress response or chronic stress in children at 4-6 years. Trial registration: ClinicalTrials.gov Identifier NCT00970866.Lay SummaryThis study addressed a research gap about whether improved nutrition during pregnancy and early childhood impacts telomere length and cortisol in preschool children. There was no difference in child telomere length or cortisol between two trial arms of a nutritional supplementation trial that began during pregnancy. The research outcomes indicate lipid-based nutrient supplements, a relatively new form of supplementation, do not have an effect on markers of stress or cellular aging measured in later childhood.

The impact of maternal supplementation during pregnancy and the first 6 months postpartum on the growth status of the next child born after the intervention period: Follow-up results from Bangladesh and Ghana.

Pregnancy and breastfeeding make demands on maternal nutrient stores. The extent of depletion and the degree to which nutrient stores are replenished between pregnancies has implications for a mother's nutritional status at conception of the subsequent child and therefore that child's birth outcomes and growth. Using follow-up data collected several years after a randomized effectiveness trial conducted in rural Bangladesh and a randomized efficacy trial conducted in semiurban Ghana, we evaluated the impact of maternal supplementation with small-quantity lipid-based nutrient supplements (LNS) or multiple micronutrients (MMN) through pregnancy (the index pregnancy) and 6 months postpartum on the growth status of the next living younger sibling conceived and born after the index pregnancy. In both Bangladesh (n = 472 younger siblings) and Ghana (n = 327 younger siblings), there were no overall differences in the growth status or the prevalence of undernutrition among younger siblings whose mothers had received LNS (or MMN, Ghana only) during and after the index pregnancy compared with the younger siblings of mothers who had received iron plus folic acid (IFA) during the index pregnancy (Ghana) or during and for 3 months after the index pregnancy (Bangladesh). These findings do not indicate that preconception nutrition interventions do not improve child growth. Rather, they suggest that any benefits of maternal LNS or MMN supplementation during one pregnancy and for 6 months postpartum are unlikely to extend to the growth of her next child beyond any effects due to IFA alone.

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

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