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.

Lipid-based nutrient supplements for prevention of child undernutrition: when less may be more.

BACKGROUND: Both small-quantity and medium-quantity lipid-based nutrient supplements (LNS) have been used for the prevention of child undernutrition. A meta-analysis of 14 trials of small-quantity lipid-based nutrient supplements (SQ-LNS) - no LNS showed effects on length-for-age z-score {LAZ, +0.14 [95% confidence interval (CI): 0.11, 0.16]} and weight-for-length z-score [WLZ, +0.08 (0.06, 0.10)] z-scores, as well as prevalence ratios (95% CI) for stunting [LAZ < -2, 0.88 (0.85, 0.91)] and wasting [WLZ < -2, 0.86 (0.80, 0.93)]. However, little is known about the effects of medium-quantity lipid-based nutrient supplements (MQ-LNS) on growth. OBJECTIVES: We aimed to examine the effects of preventive MQ-LNS (∼250-499 kcal/d) provided at ∼6-23 mo of age on growth outcomes - no LNS or provision of SQ-LNS. METHODS: We conducted a systematic review of studies of MQ-LNS for prevention, and categorized them as providing <6 mo - ≥6 mo of supplementation; for the latter category, we conducted a meta-analysis, with the main outcomes being change in WLZ and LAZ, and prevalence of wasting and stunting. RESULTS: Three studies provided MQ-LNS for 3-5 mo (seasonal) for children 6-36 mo of age, and did not show consistent effects on growth outcomes. Eight studies provided MQ-LNS for 6-18 mo, generally starting at 6 mo of age; in the meta-analysis (max total n = 13,954), MQ-LNS increased WLZ [+0.09 (95% CI: 0.05, 0.13)] and reduced wasting [0.89 (0.81, 0.97)], but had no effect on LAZ [+0.04 (-0.02, 0.11)] or stunting [0.97 (0.92, 1.02)] - no LNS. Two studies directly compared SQ-LNS and MQ-LNS and showed no significant differences in growth outcomes. CONCLUSIONS: The current evidence suggests that MQ-LNS offer no added benefits over SQ-LNS, although further studies directly comparing MQ-LNS with SQ-LNS would be useful. One possible explanation is incomplete consumption of the MQ-LNS ration and thus lower than desirable intake of certain nutrients. TRIAL REGISTRATION NUMBER: Registry and registry number for systematic reviews or meta-analyses: Registered with PROSPERO as CRD42022382448 on December 18, 2022: =https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382448.

The cost-effectiveness of small-quantity lipid-based nutrient supplements for prevention of child death and malnutrition and promotion of healthy development: modelling results for Uganda.

OBJECTIVE: Recent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anaemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modelling framework to estimate the cost and cost-effectiveness of SQ-LNS and applied the framework in the context of rural Uganda. DESIGN: We adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anaemia and developmental disability. SETTING: Rural Uganda. PARTICIPANTS: Not applicable. RESULTS: Providing SQ-LNS daily to all children in rural Uganda (> 1 million) for 12 months (from 6 to 18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars) or ∼$58·7 million annually. SQ-LNS could avert an average of > 242 000 disability-adjusted life years (DALYs) annually as a result of preventing 3689 deaths, > 160 000 cases of moderate or severe anaemia and ∼6000 cases of developmental disability. The estimated cost per DALY averted is $242. CONCLUSIONS: In this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a programme including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.

What more can be done? Prioritizing the most promising antenatal interventions to improve birth weight.

BACKGROUND: Low birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. OBJECTIVE: We sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. METHODS: We utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. RESULTS: In addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. CONCLUSION: These promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.

Biological and pathological mechanisms leading to the birth of a small vulnerable newborn.

The pathway to a thriving newborn begins before conception and continues in utero with a healthy placenta and the right balance of nutrients and growth factors that are timed and sequenced alongside hormonal suppression of labour until a mature infant is ready for birth. Optimal nutrition that includes adequate quantities of quality protein, energy, essential fats, and an extensive range of vitamins and minerals not only supports fetal growth but could also prevent preterm birth by supporting the immune system and alleviating oxidative stress. Infection, illness, undernourishment, and harmful environmental exposures can alter this trajectory leading to an infant who is too small due to either poor growth during pregnancy or preterm birth. Systemic inflammation suppresses fetal growth by interfering with growth hormone and its regulation of insulin-like growth factors. Evidence supports the prevention and treatment of several maternal infections during pregnancy to improve newborn health. However, microbes, such as Ureaplasma species, which are able to ascend the cervix and cause membrane rupture and chorioamnionitis, require new strategies for detection and treatment. The surge in fetal cortisol late in pregnancy is essential to parturition at the right time, but acute or chronically high maternal cortisol levels caused by psychological or physical stress could also trigger labour onset prematurely. In every pathway to the small vulnerable newborn, there is a possibility to modify the course of pregnancy by supporting improved nutrition, protection against infection, holistic maternal wellness, and healthy environments.

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.

Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Effects of prenatal nutritional supplements on gestational weight gain in low- and middle-income countries: a meta-analysis of individual participant data.

BACKGROUND: Gestational weight gain (GWG) below or above the Institute of Medicine (IOM) recommendations has been associated with adverse perinatal outcomes. Few studies have examined the effect of prenatal nutrient supplementations on GWG in low- and middle-income countries (LMICs). OBJECTIVES: We aimed to investigate the effects of multiple micronutrient supplements (MMSs) and small-quantity lipid-based nutrient supplements (LNSs) on GWG in LMICs. METHODS: A 2-stage meta-analysis of individual participant data was conducted to examine the effects of MMSs (45,507 women from 14 trials) and small-quantity LNSs (6237 women from 4 trials) on GWG compared with iron and folic acid supplements only. Percentage adequacy of GWG and total weight gain at delivery were calculated according to the IOM 2009 guidelines. Binary outcomes included severely inadequate (percentage adequacy <70%), inadequate (<90%), and excessive (>125%) GWG. Results from individual trials were pooled using fixed-effects inverse-variance models. Heterogeneity was examined using I2, stratified analysis, and meta-regression. RESULTS: MMSs resulted in a greater percentage adequacy of GWG [weighted mean difference (WMD): 0.86%; 95% CI: 0.28%, 1.44%; P < 0.01] and higher GWG at delivery (WMD: 209 g; 95% CI: 139, 280 g; P < 0.01) than among those in the control arm. Women who received MMSs had a 2.9% reduced risk of severely inadequate GWG (RR: 0.971; 95% CI: 0.956, 0.987; P < 0.01). No association was found between small-quantity LNSs and GWG percentage adequacy (WMD: 1.51%; 95% CI: -0.38%, 3.40%; P = 0.21). Neither MMSs nor small-quantity LNSs were associated with excessive GWG. CONCLUSIONS: Maternal MMSs were associated with greater GWG percentage adequacy and total GWG at delivery than was iron and folic acid only. This finding is consistent with previous results on birth outcomes and will inform policy development and local recommendations of switching routine prenatal iron and folic acid supplements to MMSs.

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.

Association between prenatal provision of lipid-based nutrient supplements and caesarean delivery: Findings from a randomised controlled trial in Malawi.

In populations with a high prevalence of childhood and adolescent undernutrition, supplementation during pregnancy aiming at improving maternal nutritional status and preventing fetal growth restriction might theoretically lead to cephalopelvic disproportion and delivery complications. We investigated whether the prenatal provision of small-quantity lipid-based nutrient supplements (SQ-LNS) was associated with an increased risk of caesarean section (CS) or other delivery complications. Pregnant Malawian women were randomised to receive daily i) iron-folic acid (IFA) capsule (control), ii) multiple micronutrient (MMN) capsule of 18 micronutrients (second control), or iii) SQ-LNS with similar micronutrients as MMN, plus four minerals and macronutrients contributing 118 kcal. We analysed the associations of SQ-LNS, CS, and other delivery complications using log-binomial regressions. Among 1391 women enrolled, 1255 had delivery information available. The incidence of CS and delivery complications was 6.3% and 8.2%, respectively. The incidence of CS was 4.0%, 6.0%, and 8.9% (p = 0.017) in the IFA, MMN, and LNS groups, respectively. Compared to the IFA group, the relative risk (95% confidence interval) of CS was 2.2 (1.3-3.8) (p = 0.006) in the LNS group and 1.5 (0.8-2.7) (p = 0.200) in the MMN group. We found no significant differences for other delivery complications. Provision of SQ-LNS to pregnant women may have increased the incidence of CS. The baseline rate was, however, lower than recommended. It is unclear if the higher CS incidence in the SQ-LNS group resulted from increased obstetric needs or more active health seeking and a better supply of services. Trial registered at clinicaltrials.gov, NCT01239693.

Effect of multiple micronutrient supplements vs iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose.

OBJECTIVE: Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid supplements (IFA) containing 60 mg of iron. We aimed to assess the effect of MMS vs IFA on neonatal mortality stratified by iron dose in each supplement. METHODS: We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS vs. IFA on neonatal mortality in subgroups of trials (n=13) providing the same or different amounts of iron, i.e. MMS with 60 mg of iron vs IFA with 60 mg of iron; MMS with 30 mg of iron vs IFA with 30 mg of iron; MMS with 30 mg of iron vs IFA with 60 mg of iron; and MMS with 20 mg of iron vs IFA with 60 mg of iron. RESULTS: There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg vs IFA with 60 mg of iron (7 trials, 14,114 participants), yielded a nonsignificant Risk Ratio (RR) of 1.12 (95% CI 0.83 to 1.50). CONCLUSION: Neonatal mortality did not differ between MMS and IFA regardless of iron dose in either supplement.

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.

Background: Pregnant women in Malawi are at risk of selenium deficiency, which can have adverse effects on pregnancy outcomes. Interventions for improving selenium status are needed. Objectives: To 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. Methods: Pregnant 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. Results: At 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). Conclusions: Provision 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).

Multiple micronutrient supplements versus iron-folic acid supplements and maternal anemia outcomes: an iron dose analysis.

Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of -0.26 g/L (95% CI: -1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92-1.07) for anemia, and 1.31 (95% CI: 0.66-2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.

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.

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.

Dietary and Complementary Feeding Practices of US Infants, 6 to 12 Months: A Narrative Review of the Federal Nutrition Monitoring Data.

Complementary foods and beverages (CFBs) are key components of an infant's diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing of introduction and types of CFBs reported. FMF infants (42%) are more likely to be introduced to CFBs before 4 months compared with HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed, including fruit, grains, dairy, proteins, and solid fats. Compared with HMF infants of the same age, FMF infants consume more total energy (845 vs 631 kcal) and protein (22 vs 12 g) from all sources, and more energy (345 vs 204 kcal) and protein (11 vs 6 g) from CFBs alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs 7%), zinc (54% vs <3%), and protein (27% vs <3%). FMF infants are more likely to have an early introduction (<12 months) to fruit juice (45% vs 20%) and cow's milk (36% vs 24%). Registered dietitian nutritionists and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could refine findings from this analysis.

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.