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.

Factors associated with diarrhea and acute respiratory infection in children under two years of age in rural Bangladesh.

BACKGROUND: Diarrhea and acute respiratory infection (ARI) are major causes of child mortality. We aimed to identify risk factors associated with diarrhea and ARI among children under 2 years of age in rural northern Bangladesh. METHOD: We collected information on diarrhea and ARI in the previous 14 days and the previous 6 months at 6, 12, 18 and 24 months of age as part of a longitudinal, cluster randomized effectiveness trial, the Rang-Din Nutrition Study which enrolled 4011 pregnant women at ≤20 gestational weeks. Women and their children were followed up until 2 years postpartum. Information on household socioeconomic status, type of toilet, garbage disposal system, food insecurity, number of under-five children in the household, type of family, maternal characteristics and child characteristics was collected at baseline and/or at 6, 12, 18 and 24 months postpartum. Data on newborn health and feeding behaviors were collected within 72 h of delivery. Associations between potential risk factors and morbidity prevalence outcomes were assessed using logistic regression controlling for potential confounders. RESULTS: Out of 3664 live born children, we collected information from ~ 3350 children at 6, 12, 18 and 24 months of age. Diarrhea in the previous 14 days, and in the previous 6 months, was associated with maternal depression score and food insecurity; diarrhea in the previous 6 months was also associated with family type (nuclear vs. joint). ARI in the previous 14 days was associated with maternal depression score, type of toilet and garbage disposal, household food insecurity and sex. Cough or nasal discharge in the past 6 months was associated with maternal depression score, type of toilet and garbage disposal, household food insecurity, sex and perceived overall physical condition of the infant after birth. CONCLUSION: Maternal depression and food insecurity appear to be important risk factors for diarrhea and respiratory infection among children under 2 years of age in this setting. These findings suggest that policies and programs that include strategies to address maternal mental health and household food insecurity may contribute to improved child health. TRIAL REGISTRATION: The trial was registered with the US National Institutes of Health at ClinicalTrials.gov, # NCT01715038 , with registration completed October 26, 2012.

Provision of Pre- and Postnatal Nutritional Supplements Generally Did Not Increase or Decrease Common Childhood Illnesses in Bangladesh: A Cluster-Randomized Effectiveness Trial.

BACKGROUND: Nutritional interventions may affect child morbidity. OBJECTIVE: The aim of this study was to examine whether providing lipid-based nutrient supplements (LNSs) to pregnant and lactating women or LNS or micronutrient powder (MNP) to their infants influences child morbidity. METHODS: In a 4-arm cluster-randomized effectiveness trial, participants enrolled at ≤20 weeks of gestation (n = 4011) received: 1) maternal LNSs until 6 mo postpartum and child LNSs from 6-24 mo of age (LNS-LNS); 2) iron and folic acid (IFA) until 3 mo postpartum and child LNSs at 6-24 mo (IFA-LNS); 3) IFA (as above) and child MNP at 6-24 mo (IFA-MNP); or 4) IFA and no child supplement (IFA-Control). At 6, 12, 18, and 24 mo of age, we collected information on acute lower and upper respiratory infection (ALRI/AURI), diarrhea, and fever in the previous 14 d, and on episodes of illness in the previous 6 mo. RESULTS: At 6 mo, prevalence of ALRI, fever, or diarrhea in the previous 14 d (17.6%, 18.9% and 6.8%, respectively) did not differ between infants of women who received LNS and infants of women who received IFA, but prevalence of AURI was lower in the LNS-LNS group than in all other groups combined (27.7% compared with 31.7%; OR: 0.83; 95% CI: 0.70, 0.99). At 12, 18, and 24 mo, the 4 arms did not differ in prevalence of fever (∼18.3%) or ALRI (≤15%) in the previous 14 d, but prevalence of AURI at 12 mo was lower in IFA-LNS than in IFA-Control infants (27.6% compared with 33.9%, OR: 0.74; 95% CI: 0.56, 0.99). The mean ± SD number of diarrhea episodes in the previous 6 mo was significantly higher among IFA-LNS than among IFA-Control infants at 6-12 (0.46 ± 0.04 compared with 0.33 ± 0.03) and 12-18 (0.45 ± 0.03 compared with 0.33 ± 0.02) mo. No other pairwise group differences were significant. CONCLUSION: Providing LNSs to women or LNSs or MNP to children generally did not increase or decrease childhood illnesses. This trial was registered at clinicaltrials.gov as NCT01715038.

Newborn physical condition and breastfeeding behaviours: Secondary outcomes of a cluster-randomized trial of prenatal lipid-based nutrient supplements in Bangladesh.

Prenatal nutritional supplements may improve birth outcomes. This study aims to examine the effect of prenatal lipid-based nutrient supplements (LNS), compared with iron and folic acid (IFA), on general newborn physical condition and feeding behaviours. We conducted a cluster-randomized effectiveness trial that enrolled 4,011 pregnant women at ≤20 gestational weeks. LNS and IFA were provided to women in 48 and 16 clusters, respectively, for daily consumption until delivery. We collected data on household socio-economic, food insecurity, and maternal characteristics during early pregnancy and on newborn condition and feeding within 72 hr of delivery. We analysed intervention effects on these secondary outcomes using mixed models with analysis of covariance for continuous outcomes and logistic regression for dichotomous outcomes. Among 3,664 live births, intervention groups did not differ in newborn response, mother's rating of the general condition of her newborn, early initiation of breastfeeding (EIBF), suckling ability, or frequency and exclusivity of breastfeeding in the first 24 hr. If the mother perceived her infant to be healthy, EIBF was more likely (OR [95% CI]: 2.08 [1.46, 2.97]) and frequency of breastfeeding in the first 24 hr was greater (mean difference [95% CI]: 3.0 [1.91, 4.01]), but there was no difference in exclusive breastfeeding in the first 24 hr. Newborn condition and early breastfeeding practices were not affected by giving mothers prenatal LNS versus IFA. However, early breastfeeding practices were related to maternal perception of her newborn's condition. Thus, interventions to improve breastfeeding practices for newborns with poorer perceived health status may be useful.

Prenatal and Postnatal Supplementation with Lipid-Based Nutrient Supplements Reduces Anemia and Iron Deficiency in 18-Month-Old Bangladeshi Children: A Cluster-Randomized Effectiveness Trial.

Background: Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) among young children are public health concerns in developing countries. Objective: We evaluated the effects of small-quantity lipid-based nutrient supplements (LNSs) and micronutrient powder (MNP) on anemia, ID, and IDA in 18-mo-old Bangladeshi children. Methods: We enrolled 4011 pregnant women in a cluster-randomized effectiveness trial with 4 arms-1) LNS-LNS: LNSs (including 20 mg Fe) for women daily during pregnancy and 6 mo postpartum and LNSs (including 9 mg Fe) for children daily from 6 to 24 mo of age (LNS-C); 2) IFA-LNS: iron (60 mg) and folic acid (IFA) for women daily during pregnancy and every other day for 3 mo postpartum and LNS-C for children; 3) IFA-MNP: IFA for women, and MNP (including 10 mg Fe) for children daily from 6 to 24 mo; and 4) IFA-Control: IFA for women and no child supplement. Hemoglobin, serum ferritin, and soluble transferrin receptor (sTfR) were assessed in a subsample of children (n = 1121) at 18 mo to identify anemia (hemoglobin <110g/L), ID (ferritin <12 µg/L or sTfR >8.3 mg/L), and IDA. Data were analyzed with the use of mixed-effects modeling. Results: Compared with the IFA-Control arm, hemoglobin was higher in the LNS-LNS and IFA-LNS arms and ferritin was higher and sTfR was lower in the LNS-LNS, IFA-LNS, and IFA-MNP arms; LNS-LNS children had reduced odds of anemia (OR: 0.46; 95% CI: 0.25, 0.84), high sTfR (OR: 0.47; 95% CI: 0.29, 0.73), and ID (OR: 0.45; 95% CI: 0.28, 0.71); and all 3 groups had lower odds of low ferritin [corrected for inflammation; OR (95% CI)-LNS-LNS: 0.29 (0.13, 0.63); IFA-LNS: 0.25 (0.11, 0.59); and IFA-MNP: 0.37 (0.18, 0.76)] and IDA [LNS-LNS: 0.35 (0.18, 0.67); IFA-LNS: 0.45 (0.24,0.85); and IFA-MNP: 0.47 (0.26, 0.87)]. Conclusions: Home fortification using LNSs or MNP reduced IDA in 18-mo-old Bangladeshi children. The provision of LNSs in both pregnancy and childhood also reduced child anemia and ID. These findings are relevant to programs targeting similar populations. This trial was registered at www.clinicaltrials.gov as NCT01715038.

Daily Consumption of Lipid-Based Nutrient Supplements Containing 250 µg Iodine Does Not Increase Urinary Iodine Concentrations in Pregnant and Postpartum Women in Bangladesh.

Background: Maternal iodine deficiency during pregnancy and lactation is common in Bangladesh.Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on urinary iodine concentration (UIC).Methods: We conducted a cluster-randomized controlled effectiveness trial in which we enrolled 4011 pregnant women at ≤20 gestational weeks. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe/d + 400 µg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing 22 vitamins and minerals (including 250 µg I). We randomly selected a subsample of 1159 women for repeated urine sample collection, i.e., at enrollment, at 36 wk of gestation, and at 6 mo postpartum, for UIC analysis, a secondary outcome of the trial.Results: The geometric mean UIC at 36 wk of gestation and at 6 mo postpartum did not differ significantly between the IFA and LNS-PL groups. The median (quartile 1, quartile 3) UIC at 36 wk was 27.4 µg/L (16.9, 52.7 µg/L) in the IFA group and 30.2 µg/L (17.7, 56.6 µg/L) in the LNS-PL group; at 6 mo, these were 23.0 µg/L (10.0, 45.9 µg/L) in the IFA group and 22.2 µg/L (9.1, 50.4 µg/L) in the LNS-PL group.Conclusion: Daily consumption of LNS-PL containing 250 µg I did not increase the UICs of pregnant and lactating women in Bangladesh. Iodine from lipid-based nutrient supplements may have been stored in the thyroid gland or secreted in breast milk instead of being excreted in urine. Additional research that uses other biomarkers of iodine status is needed to determine how to meet the iodine requirements of pregnant and lactating women in Bangladesh and similar settings. This trial was registered at clinicaltrials.gov as NCT01715038.

Lipid-based nutrient supplementation in the first 1000 d improves child growth in Bangladesh: a cluster-randomized effectiveness trial.

Background: Stunting in linear growth occurs mainly during the first 1000 d, from conception through 24 mo of age. Despite the recognition of this critical period, there have been few evaluations of the growth impact of interventions that cover most of this window.Objective: We evaluated home fortification approaches for preventing maternal and child undernutrition within a community-based health program. We hypothesized that small-quantity lipid-based nutrient supplements (LNSs) provided to women during pregnancy and the first 6 mo postpartum, LNSs provided to their offspring from 6 to 24 mo of age, or both would result in greater child length-for-age z score (LAZ) at 24 mo than iron and folic acid (IFA) provided to women during pregnancy and postpartum plus micronutrient powder (MNP) or no supplementation for their offspring from 6 to 24 mo.Design: We conducted a cluster-randomized effectiveness trial with 4 arms: 1) women and children both received LNSs (LNS-LNS group), 2) women received IFA and children received LNSs (IFA-LNS group), 3) women received IFA and children received MNP (IFA-MNP group), and 4) women received IFA and children received no supplements (IFA-Control group). We enrolled 4011 women at ≤20 wk of gestation within 64 clusters, each comprising the supervision area of a community health worker. Analyses were primarily performed by using ANCOVA F tests and Tukey-Kramer-corrected pairwise comparisons.Results: At 24 mo, the LNS-LNS group had significantly higher LAZ (+0.13 compared with the IFA-MNP group) and head circumference (+0.15 z score compared with the IFA-Control group); these outcomes did not differ between the other groups. Stunting prevalence (LAZ <-2) was lower in the LNS-LNS group at 18 mo than in the IFA-MNP group (OR: 0.70; 95% CI: 0.53, 0.92), but the difference diminished by 24 mo (OR: 0.81; 95% CI: 0.63, 1.04).Conclusion: Home fortification with small-quantity LNSs, but not MNP, during the first 1000 d improved child linear growth and head size in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038.

Home fortification during the first 1000 d improves child development in Bangladesh: a cluster-randomized effectiveness trial.

Background: Nutrition during the first 1000 d is critical for brain development.Objective: We evaluated the effects on child development of home fortification with lipid-based nutrient supplements (LNSs) for mothers and/or children or micronutrient powder (MNP) for children.Design: We conducted a cluster-randomized effectiveness trial with 4 arms: 1) LNSs during pregnancy and the first 6 mo postpartum and LNSs for the offspring from 6 to 24 mo (LNS-LNS), 2) iron and folic acid (IFA) during pregnancy and the first 3 mo postpartum and LNSs for the children from 6 to 24 mo (IFA-LNS), 3) IFA (as above) and MNP for the offspring from 6 to 24 mo (IFA-MNP), and 4) IFA (as above) and no child supplement (IFA-Control). Women were enrolled at ≤20 wk of gestation; children were assessed at 12 (n = 3331), 18 (n = 3364), and 24 (n = 3379) mo.Results: Compared with the IFA-Control group, motor development scores were higher in the LNS-LNS (P = 0.016) and IFA-LNS groups (P = 0.006) at 18 mo and in the IFA-MNP group (P = 0.048) at 24 mo. Receptive language scores were higher for the LNS-LNS group (P = 0.028) at 18 mo and for all 3 groups at 24 mo (P = 0.008 for LNS-LNS, P = 0.022 for IFA-LNS, and P = 0.009 for IFA-MNP compared with IFA-Control). Expressive language scores did not differ at 18 mo (P = 0.236) but were higher in the LNS-LNS (P = 0.035) and IFA-MNP (P = 0.002) groups than in the IFA-Control group at 24 mo. Groups did not differ in personal-social scores at 18 (P = 0.233) or 24 (P = 0.146) mo or in executive function score at 24 mo (P = 0.467).Conclusion: Prenatal LNSs, postnatal LNSs, or both, or postnatal MNP had a positive effect on motor and language development in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT01715038.