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Author(s): Priliani, Lidwina; Prado, Elizabeth L; Restuadi, Restuadi; Waturangi, Diana E; Shankar, Anuraj H; Malik, Safarina G | Abstract: BackgroundThe Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood.ObjectiveThe aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN).MethodsWe used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models.ResultsIn both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P l 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (β = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (β = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (β = -7.39, P = 0.017).ConclusionMaternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

Background Anemia is a global public health problem that undermines childhood development. India provides government-sponsored integrated nutrition/child development preschools. Objectives This double-masked, cluster-randomized controlled trial examines whether point-of-use multiple micronutrient powder (MNP) compared with placebo fortification of preschool meals impacts child development and whether effects vary by preschool quality (primary outcome) and biomarkers of anemia and micronutrients (secondary outcomes). We also measured growth and morbidity. Methods We randomly assigned 22 preschools in rural India to receive MNP/placebo fortification. We administered baseline and endline blood sampling and measures of childhood development (Mullen Scales of Early Learning, inhibitory control, social–emotional), anthropometry, and morbidity to preschoolers (aged 29–49 mo). Preschools added MNP/placebo to meals 6 d/wk for 8 mo. We conducted linear mixed-effects regression models accounting for preschool clustering and repeated measures. We evaluated child development, examining effects in high- compared with low-quality preschools using the Early Childhood Environment Rating Scale–Revised and the Home Observation for the Measurement of the Environment Inventory, modified for preschools. Results At baseline, mean age ± SD was 36.6 ± 5.7 mo, with 47.8% anemic, 41.9% stunted, and 20.0% wasted. Baseline expressive/receptive language scores were higher in high-quality compared with low-quality preschools (P = 0.02 and P = 0.03, respectively). At endline (91% retention, n = 293/321), we found MNP compared with placebo effects in expressive language (Cohen's standardized effect d = 0.4), inhibitory control (d = 0.2), and social–emotional (d = 0.3) in low-quality, not high-quality, preschools. MNP had significantly greater reduction of anemia and iron deficiency compared with placebo (37% compared with 13.5% and 41% compared with 1.2%, respectively). There were no effects on growth or morbidity. Conclusions Providing multiple micronutrient-fortified meals in government-sponsored preschools is feasible; reduced anemia and iron deficiency; and, in low-quality preschools, increased preschoolers’ expressive language and inhibitory control and reduced developmental disparities. Improving overall preschool quality by incorporating multiple components of nurturing care (responsive care, learning, and nutrition) may be necessary to enhance preschoolers’ development. This trial was registered at clinicaltrials.gov as NCT01660958.

BackgroundEggs are a rich source of choline, an essential nutrient important for child growth and development. In a randomized trial of 1 egg/d in young children in Ecuador, an egg intervention led to significant improvements in growth, which were partially mediated by increased plasma choline concentration. A similar trial in Malawi (clinicaltrials.gov: NCT03385252) found little improvement in child growth or development.ObjectivesWe aimed to evaluate the effect of 1 egg/d for 6 mo on plasma choline concentrations in Malawian children enrolled in a randomized trial.MethodsInfants aged 6-9 mo in rural Malawi were randomly assigned to receive 1 egg/d (n=331) or serve as a nonintervention control (n=329) for 6 mo. Anthropometric, developmental, and dietary data were collected at baseline and 6-mo follow-up, along with a blood draw. Plasma choline, betaine, dimethylglycine, trimethylamine N-oxide (TMAO), and DHA were measured at both time points using ultrahigh performance liquid chromatography-tandem MS (n=200 per group). Linear regression analysis was used to determine the difference in plasma choline and related metabolites between groups after 6 mo of intervention.ResultsPlasma choline, betaine, dimethylglycine, and DHA concentrations did not differ between groups at 6-mo follow-up. Plasma TMAO was significantly (26%; 95% CI: 7%, 48%) higher in the egg intervention group in a fully adjusted model.ConclusionsProvision of 1 egg/d for 6 mo did not result in increases in plasma choline or related metabolites, except TMAO. This could partially explain the lack of effect on growth and development. Additional interventions are needed to improve choline status, growth, and development in this population.

Background Maternal and infant undernutrition is negatively associated with infant development. Aims We tested the hypothesis that provision of small-quantity lipid-based nutrient supplements (SQ-LNS) to pregnant women and infants positively affects infant development. Study design In a partially double-blind randomized controlled trial, we compared the following daily maternal supplements during pregnancy and until 6 months post-partum: iron/folic acid capsule (IFA), capsule containing 18 micronutrients (MMN), or 20 g SQ-LNS. Children in the SQ-LNS group also received SQ-LNS from age 6 to 18 months. The study is registered as NCT00970866 . Subjects 1320 pregnant women in Ghana enrolled in the trial; 1173 of their children participated in developmental assessment. Outcome measures We monitored the acquisition of 10 developmental milestones monthly by parental report, observed the attainment of 6 motor milestones at 6, 12, and 18 months, and conducted detailed assessment of motor, language, socio-emotional, and executive function at 18 months. Results By researcher observation, a greater percentage of children in the SQ-LNS group (53%) was able to walk alone at 12 months than in the IFA group (43%; RR = 1.23, 95% CI = 1.02–1.49; p = 0.025). We found no significant differences between groups in milestone acquisition by parent report or in any scores at 18 months. The difference in mean z-scores between groups ranged from 0.03–0.13 for motor (p = 0.84), 0.01–0.08 for language (p = 0.46), 0.01–0.02 for socio-emotional (p = 0.75), and 0.00–0.02 for executive function (p = 0.95). Conclusion While provision of maternal and child SQ-LNS in Ghana may affect walking at 12 months, it did not affect infant development at 18 months.

Background: Adequate nutrition is necessary for the rapid brain development that occurs during infancy. Objectives: We tested the hypothesis that the provision of small-quantity, lipid-based nutrient supplements (SQ-LNSs) plus malaria and diarrhea treatment positively affects infant development. We also tested the effect of various doses of zinc provided in SQ-LNSs or in a tablet. Methods: In a partially masked, cluster-randomized controlled trial, communities in rural Burkina Faso were stratified by selected characteristics and then randomly assigned within strata to the intervention (IC; 25 communities, 2435 children) or the nonintervention (NIC; 9 communities, 785 children) cohorts. IC children were randomly assigned to 4 groups. As secondary outcomes, a subsample of 3 of these 4 groups (n = 747) and of the NIC (n = 376) were assessed for motor, language, and personal-social development at age 18 mo by using the Developmental Milestones Checklist II. The 3 IC groups received 20 g SQ-LNSs/d containing 0 or 10 mg added zinc with a placebo tablet or 20 g SQ-LNSs/d containing 0 mg added zinc with a tablet containing 5 mg Zn. All IC groups received treatment of malaria and diarrhea from age 9 to 18 mo. Data collectors and participants were aware of allocation to the IC or NIC but did not know the particular IC subgroup. Results: Children in the IC scored 0.34 (95% CI: 0.21, 0.46), 0.30 (95% CI: 0.15, 0.44), and 0.32 (95% CI: 0.16, 0.48) SDs higher in motor, language, and personal-social development, respectively, than did children in the NIC (All P < 0.001). Children who received different amounts of zinc did not differ significantly in any of the scores. No effect on caregiver-child interaction was found. Conclusion: In rural Burkina Faso, the provision of SQ-LNSs to infants from age 9 to 18 mo, regardless of added zinc content, plus malaria and diarrhea treatment positively affected motor, language, and personal-social development at age 18 mo. This trial was registered at clinicaltrials.gov as NCT00944281.

BACKGROUND: Maternal and infant undernutrition is associated with poor infant development; however few studies have examined the impact of combined pre- and postnatal dietary supplementation on infant development. OBJECTIVE: Our objective was to determine whether provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to mothers during pregnancy and the first 6 mo postpartum and to children aged 6-18 mo improves infant development in Malawi. DESIGN: We randomly assigned 869 pregnant women to receive one of the following daily: an iron and folic acid (IFA) capsule a multiple micronutrient (MMN) capsule containing 18 micronutrients or a 20-g sachet of SQ-LNSs containing 22 vitamins and minerals protein carbohydrates essential fatty acids and 118 kcal. Children in the lipid-based nutrient supplement (LNS) group only received SQ-LNSs from 6 to 18 mo of age. We monitored the acquisition of 11 developmental milestones monthly by maternal report; observed the attainment of 7 motor milestones at 6 12 and 18 mo of age; and conducted a comprehensive assessment of motor language and socioemotional development and executive function at 18 mo of age. The primary analysis was by intention-to-treat. RESULTS: By maternal report children in the LNS group achieved walking alone (B = 0.53; 95% CI: 0.11 0.94; P = 0.034) and waving goodbye (B = 0.60; 95% CI: 0.12 1.08; P = 0.040) earlier than the IFA group and standing with assistance earlier than the MMN group (B = 0.51; 95% CI: 0.12 0.89; P = 0.029). By researcher observation there was a trend (P = 0.052) for a greater percentage of children in the LNS group (58%) to walk alone at age 12 mo than in the IFA (49%) and MMN (49%) groups. At age 18 mo there were no significant differences between groups in any scores. CONCLUSION: Although provision of SQ-LNSs to pregnant women and infants in Malawi may affect the age of acquisition of certain developmental milestones it did not affect our assessments of motor language socioemotional or executive function skills at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT01239693. (c) 2016 American Society for Nutrition.

OBJECTIVES: Complementary feeding diets in low- and middle-income countries are usually inadequate to meet requirements for healthy growth and development. Food-based interventions may prevent nutrient inadequacies provided they do not replace other nutrient-rich foods. They may also be more sustainable than manufactured food supplements. We describe the contribution of daily egg supplementation to usual energy intake, usual energy intake by food group, and minimum dietary diversity of rural Malawian infants and young children. METHODS: We conducted a randomized controlled trial in rural Malawi in which 660 children aged 6 to 9 months were randomly allocated to receive an egg a day for 6 months or to a control group. Dietary intake of foods and drinks was assessed at baseline, 3-month midline, and 6-month endline visits using a tablet-based mulitpass 24-hour recall. Up to two repeat recalls were collected at each timepoint in a subsample of 100 children per intervention group. RESULTS: The intervention resulted in an increased usual energy intake in the intervention group of 30 kcal at midline (P = 0.128) and 36 kcal at endline (P = 0.087). It also resulted in a 7 kcal displacement of legumes and nuts in children at endline (P = 0.059). At midline and endline, usual energy intake from eggs was about 30 kcal higher in the egg group compared to controls (P

OBJECTIVES: To examine the association of maternal functional health literacy (FHL), a mother's ability to understand health information written in words and pictures, with child health, growth, and development in rural Malawi. METHODS: Maternal FHL was measured at six months postpartum among 671 participants in the International Lipid-Based Nutrient Supplements (iLiNS) DYAD-M trial in Malawi. Field staff asked comprehension questions about written health materials that were common in Malawi, such as medication instructions, breastfeeding information, and growth charts. Outcomes were child length-for-age (LAZ) and weight-for-length (WLZ) z scores at age 6 and 18 mo, change in LAZ and WLZ from 6 to 18 mo, motor and language development at 18 mo, and illness monitored weekly from birth to 18 mo (highest quartile prevalence of diarrhea, highest quartile prevalence of malaria or undefined fever, and incidence of acute respiratory infection). In Model 1, we examined the unadjusted association between maternal FHL and each outcome. In Model 2, we adjusted for household and parental background characteristics collected at baseline, child age and sex, and trial group. In Model 3, we added maternal cognition, depression, and caregiving characteristics collected after baseline. RESULTS: Over 90% of participants understood the growth charts, immunization record, and breastfeeding information in the health passport. Understanding of medication instructions was lower, with 72% understanding malaria, 81% Panadol, and 63% erythromycin instructions (Figure 1). Maternal FHL z score significantly predicted motor (β ± SE = 0.087 ± 0.040, P = 0.029) and language z scores (β ± SE = 0.093 ± 0.040, P = 0.020) at 18 mo in unadjusted models. However, after adjusting for covariates, these associations were not significant. Maternal FHL was not significantly associated with any other outcomes. CONCLUSIONS: Revision of written medication instructions in Malawi may be needed to increase mothers’ understanding of how to deliver medication to their children. However, in this sample, maternal FHL was not associated with indicators of child growth, development, or illness after adjusting for parental, household, and caregiving characteristics. FUNDING SOURCES: This publication is based on research funded by a grant to the University of California, Davis from the Bill & Melinda Gates Foundation. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

OBJECTIVES: Multiple studies have found associations between hemoglobin concentration (Hb) and cognitive development in children under age 2 y, including development of language and motor skills; however, its association with early memory development is less well studied. Our objective was to assess whether hemoglobin concentration was associated with scores on a memory task in a sample of children aged 12–15 months in Malawi. METHODS: This analysis includes a subset of children (n = 450) from an ongoing trial evaluating eggs during complementary feeding in 660 Malawian children. Hb was measured using the HemoCue 201 Analyser at baseline, when children were 6–9 months old, and at endline 6 months later. The elicited imitation test, a nonverbal measure of memory, was administered at endline. In the test, children were shown eight novel objects. After a period of spontaneous interaction, children were shown a two-action sequence for each object and asked to imitate it, either immediately or after a delay of 10 minutes. Children were scored on their ability to perform the actions in any order (total actions score, 0–16) and to complete the sequences correctly (total sequences score, 0–8). The association of Hb at each time point with total actions was examined using multiple linear regression and with total sequences, categorized (