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The first 1000 days of life is marked by intense metabolic activity and tissue deposition. The increased nutritional needs during this period, and the challenges to meeting them, are often not understood or appreciated. Here, we describe the nutritional needs during the first 1000 days, highlight the challenges to meeting these needs in developing countries, outline intervention strategies, and examine the consumption of small-quantity lipid-based nutrient supplements (SQ-LNS) as a promising strategy. In low-income settings, the challenge to meeting nutritional needs during the first 1000 days is worsened by overreliance on cereal-based diets of low nutrient density and high prevalence of infections and infestations. Dietary diversification is the ideal long-term solution to nutritional deficiencies, but difficulties with obtaining adequate amounts of iron, zinc, and certain vitamins may still remain. Several other interventions are available, but applying them is often fraught with challenges, including cost and contextual factors limiting efficacy. Evidence suggests that SQ-LNS supplementation may help reduce inadequate gestational weight gain and promote fetal and child growth and development in some populations. More research is needed to evaluate the effectiveness of SQ-LNS and other fortified products in different contexts and within integrated programs that address other determinants of maternal and child undernutrition.

We report a short channel high performance Ge PMOS integrated with Si NMOS in sequential monolithic 3D stacking. A layer transfer Ge PMOS with record I ON = 497 μA/μm at I OFF = 8nA/μm and I ON = 630 μA/μm at I OFF = 100nA/μm and V DS = -0.5V is achieved for the first time. Optimized design of metal gate and contact on bottom Si NMOS device layer, along with a low process thermal budget developed for Ge layer transfer and top Ge PMOS device fabrication, allow for sequential stacking with no degradation on each MOS device characteristics. Heterogeneous 3D stacked Ge-Si CMOS inverter is also successfully demonstrated with drive performance maintained on Ge PMOS and Si NMOS.

Low gestational weight gain (GWG) is a known predictor of fetal growth restriction in higher income countries, but there is little information on this association in lower income countries. Our objective is to describe the association between GWG and birth outcomes among pregnant women in rural Bangladesh. Pregnant women were identified in a community-based programme and enrolled into the study at an average of 13weeks' gestation (n=4,011). Maternal weight and height were measured at enrolment, maternal weight was measured at 36weeks' gestation, and newborns were measured after birth. Rate of GWG (g/weeks) was calculated, and women were categorized as having adequate or inadequate GWG (Institute of Medicine recommendations). Newborn anthropometric outcomes included weight-for-age z score (WAZ), length-for-age z score (LAZ), head-circumference-for-age z score (HCZ), body mass index (BMI)-for-age z score (BMIZ), low birthweight (LBW&nbsp

Evidence on whether nutritional supplementation affects physical activity (PA) during early childhood is limited. We examined the long-term effects of lipid-based nutrient supplements (LNS) on total PA, moderate-to-vigorous PA (MVPA) and sedentary behaviour (SB) of children at 4–6 years using an accelerometer for 1 week. Their mothers were enrolled in the International Lipid-based Nutrient Supplement-DYAD randomised controlled trial in Ghana, assigned to daily LNS or multiple micronutrients (MMN) during pregnancy through 6 months postpartum or Fe and folic acid (IFA) during pregnancy and placebo for 6 months postpartum. From 6 to 18 months, children in the LNS group received LNS; the other two groups received no supplements. Analysis was done with intention to treat comparing two groups: LNSv. non-LNS (MMN+ IFA). Of the sub-sample of 375 children fitted with accelerometers, 353 provided sufficient data. Median vector magnitude (VM) count was 1374 (interquartile range (IQR) 309), and percentages of time in MVPA and SB were 4·8 (IQR 2) and 31 (IQR 8) %, respectively. The LNS group (n129) had lower VM (difference in mean −73 (95 % CI −20, −126),P= 0·007) and spent more time in SB (LNSv. non-LNS: 32·3v. 30·5 %,P= 0·020) than the non-LNS group (n224) but did not differ in MVPA (4·4v. 4·7 %,P= 0·198). Contrary to expectations, provision of LNS in early life slightly reduced the total PA and increased the time in SB but did not affect time in MVPA. Given reduced social-emotional difficulties in the LNS group previously reported, including hyperactivity, one possible explanation is less restless movement in the LNS group.

Objectives The determinants of gut microbiota composition and its effects on common childhood illnesses are only partly understood, especially in low-income settings. The aim of the present study was to investigate whether morbidity predicts gut microbiota composition in Malawian children and whether microbiota predicts subsequent morbidity. We tested the hypothesis that common infectious disease symptoms would be predictive of lower microbiota maturity and diversity. Methods We used data from 631 participants in a randomized-controlled nutrition intervention trial, in which a small-quantity lipid-based nutrient supplement was provided to pregnant and lactating mothers and their children at 6 to 18 months of age. Fecal samples were collected from the children at 6, 12, 18, and 30 months of age and analyzed using 16S rRNA sequencing. Microbiota variables consisted of measures of microbiota diversity (Shannon Index), microbiota maturity (microbiota-for-age z score), and the relative abundances of taxa. Morbidity variables included gastrointestinal and respiratory symptoms and fever. Results Diarrhea and respiratory symptoms from 11 to 12 months were predictive of lower microbiota-for-age z score and higher Shannon Index, respectively (P = 0.035 and P = 0.023). Morbidity preceding sample collection was predictive of the relative abundances of several bacterial taxa at all time points. Higher microbiota maturity and diversity at 6 months were predictive of a lower incidence rate of fever in the subsequent 6 months (P = 0.007 and P = 0.031). Conclusions Our findings generally do not support the hypothesis that morbidity prevalence predicts a subsequent decrease in gut microbiota maturity or diversity in rural Malawian children. Certain morbidity symptoms may be predictive of microbiota maturity and diversity and relative abundances of several bacterial taxa. Furthermore, microbiota diversity and maturity may be associated with the subsequent incidence of fever.

Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection for mother and child. We conducted a systematic review and meta-analysis to examine the associations of maternal Hb concentrations with a range of maternal and infant health outcomes, accounting for the timing of measurement (preconception, and first, second, and third trimesters), etiology of anemia, and cutoff category. The systematic review included 272 studies and the meta-analysis included 95 studies. Low maternal Hb (130g/L) was associated with increased odds of SGA, stillbirth, preeclampsia, and gestational diabetes. Relationships varied by the timing of measurement and cutoff category (stronger associations with lower cutoffs); limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long-term child health outcomes. Current data are insufficient for determining if revisions to current Hb cutoffs are required. Pooled high-quality individual-level data analyses, as well as prospective cohort studies, would be valuable to inform the reevaluation of Hb cutoffs.

Approaches to deplete persistent HIV infection are needed. We investigated the combined impact of the latency reversing agent vorinostat (VOR) and AGS-004, an autologous dendritic cell immunotherapeutic, on the HIV reservoir. HIV+, stably treated participants in whom resting CD4+ T cell-associated HIV RNA (rca-RNA) increased after VOR exposure ex vivo and in vivo received 4 doses of AGS-004 every 3 weeks, followed by VOR every 72 hours for 30 days, and then the cycle repeated. Change in VOR-responsive host gene expression, HIV-specific T cell responses, low-level HIV viremia, rca-RNA, and the frequency of resting CD4+ T-cell infection (RCI) was measured at baseline and after each cycle. No serious treatment-related adverse events were observed among five participants. As predicted, VOR-responsive host genes responded uniformly to VOR dosing. Following cycles of AGS-004 and VOR, rca-RNA decreased significantly in only two participants, with a significant decrease in SCA observed in one of these participants. However, unlike other cohorts dosed with AGS-004, no uniform increase in HIV-specific immune responses following vaccination was observed. Finally, no reproducible decline of RCI, defined as a decrease of >50%, was observed. AGS-004 and VOR were safe and well-tolerated, but no substantial impact on RCI was measured. In contrast to previous clinical data, AGS-004 did not induce HIV-specific immune responses greater than those measured at baseline. More efficacious antiviral immune interventions, perhaps paired with more effective latency reversal, must be developed to clear persistent HIV infection.

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.

WHO recommendations for hemoglobin (Hb) cutoffs to define anemia are based on a handful of studies conducted in the 1960s that did not include participants from all life stages. To evaluate whether there is a need to update Hb cutoffs, we conducted a narrative review of the literature to identify more recent studies that have reported Hb cutoffs in males and females in various life stages. We compiled information from 60 studies conducted around the globe between 1975 and 2018. Many studies reported cutoffs that were similar to WHO recommendations, but cutoffs identified in studies of infants, young children, premenopausal women, and the elderly tended to be lower than WHO recommendations, while cutoffs identified in studies of men tended to be higher than WHO cutoffs. Few studies excluded individuals with iron deficiency or inflammation, which limits the conclusions that can be drawn regarding normal reference ranges. Further research using more stringent exclusion criteria is needed to develop revised recommendations for Hb cutoffs to define anemia.

Author(s): Nkhoma, Minyanga; Ashorn, Per; Ashorn, Ulla; Dewey, Kathryn G; Gondwe, Austrida; Maleta, Kenneth | Abstract: ObjectivesBoth maternal HIV infection and antiretroviral therapy are associated with adverse birth outcomes. The role of antenatal nutrient supplements with regard to adverse birth outcomes in HIV infected women exposed to antiretroviral therapy is not well known. We assessed the association between HIV and birth outcomes and explored whether antenatal lipid-based nutrient supplements (LNS) modulated this association.MethodsWe analysed a nested cohort of pregnant Malawian women who received daily LNS, multiple micronutrients (MMN) or iron and folic acid (IFA). Birth weight, length-for-age z-score (LAZ) and weight-for-age z-score (WAZ) were analysed as continuous outcomes and proportion of stunting and small-for-gestational age (SGA) as dichotomous outcomes.Results134 HIV infected (46 LNS, 39 MMN, 49 IFA) and 833 HIV uninfected (271 LNS, 287 MMN, 275 IFA) women were included. Maternal HIV infection was associated with a lower mean birth weight (-129g (-209, -48), P = 0.002); LAZ (-0.34 (-0.54, -0.13), P = 0.002) and WAZ (-0.21 (-0.40, -0.02), P = 0.041) and a higher risk of stunting (RR (95% confidence interval), 1.87 (1.24, 2.83), P = 0.003) and SGA (1.66 (1.21, 2.26), P = 0.001) in the newborn. If the women received LNS, HIV was not associated with LAZ (mean difference (95%); -0.02 (-0.35, 0.31), P = 0.918) or newborn stunting (RR (95% CI), 0.84 (0.34, 2.03), P = 0.691). However HIV tended to be associated with LAZ if the women received MMN (-0.42 (-0.80, -0.03), P = 0.053); and was significantly associated with LAZ if the women received IFA (-0.52 (-0.89, -0.14), P = 0.021) and with newborn stunting if they received MMN (2.40 (1.15, 4.98), P = 0.029) or IFA (2.40 (1.26, 4.59), P = 0.024).ConclusionsFurther research to investigate the impact of LNS on various aspects of foetal growth in HIV infected women is warranted.

It is important to identify the periods during childhood when exposure to environmental risk factors results in long-term neurodevelopmental deficits. Stunting and anaemia may be sensitive indicators of exposure to such risks. In a prospective cohort enrolled before birth, we investigated the association of developmental scores at 4-6years with (a) birth length and linear growth during three postnatal periods and (2) haemoglobin (Hb) concentration at three time points. Children were participants in a follow-up study of a randomized controlled trial of nutritional supplementation in Ghana. At 4-6years, cognitive, motor, and social-emotional developments were assessed using standard tests adapted for this population. We estimated the associations of length-for-age z-score (LAZ) at birth and postnatal linear growth (n=710) and Hb (n=617) with developmental scores in regression models, using multistage least squares analysis to calculate uncorrelated residuals for postnatal growth. Cognitive development at 4-6years was significantly associated with LAZ at birth (β=0.12, 95% CI=0.05, 0.19), ΔLAZ from 6 to 18months (β=0.16, 95% CI=0.04, 0.28), and Hb at 18months (β=0.13, 95% CI=0.06, 0.20), but not with ΔLAZ during 0-6months, ΔLAZ from 18months to 4-6years, Hb at 6months, or Hb at 4-6years. No evidence of associations with motor or social-emotional development were found. These results suggest that in similar contexts, the earlier periods prior to birth and up to 18months are more sensitive to risk factors for long-term cognitive development associated with LAZ and Hb compared with later childhood. This may inform the optimal timing of interventions targeting improved cognitive development.

Background Systematic reviews were conducted as part of the USDA and the US Department of Health and Human Services Pregnancy and Birth to 24 Months Project to examine the relation between complementary feeding and developmental milestones. Objectives The aim of this study was to describe systematic reviews examining the relationship between timing of introduction of complementary foods and beverages (CFB), and the types and amounts of CFB consumed, and developmental milestones. Methods The literature was searched using 4 databases (PubMed, Cochrane, Embase, and CINAHL) to identify articles that met predetermined criteria for inclusion. Data extraction and risk of bias assessment were conducted for each included study. The body of evidence for each systematic review was qualitatively synthesized to develop a conclusion statement, and the strength of evidence was graded. Results Three included articles (1 randomized controlled trial; 2 observational studies) examined timing of introduction of CFB. Eight included articles (3 randomized controlled trials; 5 observational studies) examined types and amounts of CFB. There was insufficient evidence to draw conclusions about the relation between either timing of CFB introduction or types and amounts of CFB, and developmental milestones. Conclusions The ability to draw conclusions about the relationship between complementary feeding and developmental milestones was restricted by an inadequate amount of evidence with potential for issues with reverse causality and wide variation in design, type/age of outcome assessment, exposure assessment, and reported results. Additional research to address these gaps and limitations would be useful.

Background The systematic review described in this article was conducted as part of the USDA and Department of Health and Human Services Pregnancy and Birth to 24 Months Project. Objectives The aim was to describe the relationship between timing of introduction of complementary foods and beverages (CFBs) and growth, size, and body-composition outcomes across the life span. Methods The literature was searched and selected using predetermined criteria. Data were extracted and risk of bias assessed for each included study. Evidence was qualitatively synthesized, conclusion statements were developed, and the strength of the evidence was graded. Results Eighty-one articles were included in this systematic review that addressed timing of CFB introduction relative to growth, size, and body-composition outcomes from infancy through adulthood. Moderate evidence suggests that introduction of CFBs between the ages of 4 and 5 mo compared with ∼6 mo is not associated with weight status, body composition, body circumferences, weight, or length among generally healthy, full-term infants. Limited evidence suggests that introduction of CFBs before age 4 mo may be associated with higher odds of overweight/obesity. Insufficient evidence exists regarding introduction at age ≥7 mo. Conclusions Although several conclusions were drawn in this systematic review, additional research is needed to address gaps and limitations in the evidence on timing of introduction of CFBs and growth, size, and body composition, such as randomized controlled trials that examine multiple outcomes and/or CFB introduction between the ages of 4 and 6 mo, and research that accounts for potential confounders such as feeding practices and baseline growth status and considers issues of reverse causality.

Inadequate micronutrient intakes are relatively common in low‐ and middle‐income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost‐effectiveness of MMS compared with IFA. Recent meta‐analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual‐participant data meta‐analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost‐effective method to reduce the risk of adverse birth outcomes., This review presents the conclusions of a task force that set out to provide guidance to countries considering using multiple micronutrient supplements in pregnant women by assessing the available evidence.

OBJECTIVES: To inform the 2020–2025 Dietary Guidelines for Americans, USDA and HHS identified important public health questions to be examined by the 2020 Dietary Guidelines Advisory Committee. The Committee conducted 2 systematic reviews with support from USDA's Nutrition Evidence Systematic Review (NESR) team to answer the following questions: What is the relationship between dietary patterns (DP) consumed during 1) pregnancy and gestational weight gain (GWG)?, and 2) lactation and postpartum weight loss (PPWL)? METHODS: The Committee developed protocols that described how they would use NESR's systematic review methodology to examine the systematic review questions. NESR conducted a literature search and dual-screened the results using pre-defined inclusion and exclusion criteria to identify articles published between Jan 2000 and Nov 2019. NESR extracted data and assessed risk of bias of included studies. The Committee synthesized the evidence, developed conclusion statements, and graded the strength of the evidence underlying the conclusion statements. RESULTS: Twenty-six articles were included in the GWG review and 1 article in the PPWL review. The GWG review included 5 RCTs and 21 prospective cohort studies. Two RCTs showed that a “beneficial” DP was associated with lower GWG. Thirteen of the 20 observational studies showed an association between DP and GWG. Although the DPs examined were characterized by different combinations of foods and beverages, the patterns consistently associated with lower GWG were higher in vegetables, fruits, nuts, legumes, and fish and lower in added sugars and red and processed meats. The PPWL review included only one RCT, which was limited by high attrition, issues with implementing the intervention, and lack of blinding. CONCLUSIONS: Limited evidence suggests that certain DPs during pregnancy are associated with a lower risk of excessive GWG. These patterns are higher in vegetables, fruits, nuts, legumes, and fish, and lower in added sugar, and red and processed meat (Grade: Limited). Insufficient evidence is available to determine the relationship between DPs during lactation and PPWL (Grade: Grade Not Assignable). FUNDING SOURCES: USDA, Food and Nutrition Service, Center for Nutrition Policy and Promotion.

11569 Background: Kaposi sarcoma (KS) is the leading cancer in Malawi (34% of cancers). Outside of clinical trials, prospective KS studies from sub-Saharan Africa (SSA) are few and limited by loss to follow up. We conducted a prospective KS cohort study of standard of care bleomycin/vincristine (BV) at Lighthouse HIV clinic, in Lilongwe, Malawi. Methods: We enrolled pathologically confirmed, newly diagnosed, HIV+ KS patients from Feb 2017 to Jun 2019. We collected clinical and treatment characteristics, toxicity, and outcomes of KS with follow-up censored Jun 2020. Patients were treated with bleomycin (25 mg/m2) and vincristine (0.4 mg/m2) every 14 days for a planned maximum of 16 cycles. STATA v13.0 was used to calculate descriptive statistics and Kaplan Meier survival analysis. Toxicity was graded using NCI CTCAE v5.0. Results: We enrolled 138 participants, median age 36 (IQR 32-44) and 110 (80%) male. By ACTG staging, 107 (78%) were T1 (tumour severity), 46 (33%) were S1 (illness severity) and 46 (33%) had Karnofsky performance status ≤70. Presenting symptoms included edema in 69 (53%), visceral disease in 9 (7%), and oral involvement in 43 (33%). Prior to KS diagnosis, 70 (51%) participants were aware of being HIV+ for median 17 months (IQR 6-60) and had been on ART for median 16 months (IQR 6-60). Median CD4 count was 197 (IQR 99-339), median HIV-viral load was 2.6 log copies/mL (IQR 1.6 – 4.8) and 57% were HIV-suppressed ( < 1000 HIV copies/ml). The median number of cycles was 16 (IQR 7-16). 62 (45%) participants missed at least one dose due to stock out. Amongst patients with missed doses, the median number was 3 (IQR 2-4) for bleomycin and 2 (IQR 1-3) for vincristine. 14 (10%) participants experienced at least one reduced dose due to toxicity. 5 (4%) participants suffered grade ≥3 anaemia, 13 (9%) grade ≥3 neutropenia, and one participant had grade 4 bleomycin-induced dermatitis. There was no reported grade ≥3 bleomycin lung toxicity or vincristine-induced neuropathy. Of 115 evaluable participants, responses at the end of therapy were: complete response in 52 (45%), partial response in 27 (23%) stable disease in 5 (4%), and progressive disease in 31 (28%). Median duration of follow-up was 20 months. At censoring, 69 (50%) were alive, 36 (26%) dead, and 33 (24%) lost to follow-up. Overall survival is shown Table as crude and worst-case scenario; worst-case assumes all participants lost to follow up died. Conclusions: Here, we present one of the most complete characterizations of KS presentation and treatment from SSA. As in other studies from the region, the majority of patients presented with advanced disease, chemotherapy stock-outs and loss to follow up were common, and mortality was high. Studies are planned to understand the virologic characteristics, improve therapies, and better implement existing therapies.[Table: see text]

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.

Objectives Undernutrition during early life contributes to more than 200 million children globally not fulfilling their developmental potential. Our objective was to determine whether dietary supplementation with several formulations of lipid-based nutrient supplements (LNS), which differed in dose per day and milk content, positively affect infant development in Malawi. Methods We randomly assigned 1932 infants age 6 months to receive one of the following for 12 months: 10, 20 g, or 40 g/day milk-containing LNS, 20 g or 40 g/day milk-free LNS, or no supplement until 18 months of age (control group). We assessed motor, language, socio-emotional, and executive function at age 18 months. Primary analysis was by intention-to-treat and we also examined 13 potential effect modifiers, including the child's initial nutritional status and level of developmental stimulation. The study is registered as clinical trial NCT00945698. Results We found no significant differences between intervention groups in any scores. The difference in mean z-scores between children in the control group and children in the intervention groups ranged from -0.08 to 0.04 for motor development (p = 0.76), -0.05 to 0.01 for language development (p = 0.97), -0.15 to 0.11 for socio-emotional development (p = 0.22), and -0.02 to 0.20 for executive function (p = 0.24). We did not find that initial nutritional status, developmental stimulation, or other factors modified the effect LNS versus control group. Conclusions for Practice Our results suggest that in a population such as this one, provision of LNS from age 6 to 18 months would not affect motor, language, socio-emotional, or executive function skills at age 18 months.

Meeting the high nutrient needs of pregnant and lactating women and their young children in regions such as South Asia is challenging because diets are dominated by staple foods with low nutrient density and poor mineral bioavailability. Gaps in nutritional adequacy in such populations probably date back to the agricultural revolution ~10 000 years ago. Options for improving diets during the first 1000 days include dietary diversification and increased intake of nutrient-rich foods, improved complementary feeding practices, micronutrient supplements and fortified foods or products specifically designed for these target groups. Evidence from intervention trials indicates that several of these strategies, both prenatal and post-natal, can have a positive impact on child growth, but results are mixed and a growth response is not always observed. Nutrition interventions, by themselves, may not result in the desired impact if the target population suffers from frequent infection, both clinical and subclinical. Further research is needed to understand the mechanisms underlying both prenatal and post-natal growth restriction. In the meantime, implementation and rigorous evaluation of integrated interventions that address the multiple causes of stunting is a high priority. These intervention packages should ideally include improved nutrition during both pregnancy and the post-natal period, prevention and control of prenatal and post-natal infection and subclinical conditions that restrict growth, care for women and children and stimulation of early child development. In regions such as South Asia, such strategies hold great promise for reducing stunting and enhancing human capital formation.

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.

ObjectiveSafety of home fortificants in children is uncertain in areas where infections are common. We tested the hypothesis that provision of lipid-based nutrient supplements (LNS) containing Fe does not increase infectious morbidity in children.DesignRandomized controlled trial. Infants were randomised to receive 10, 20 or 40 g LNS/d; or no supplement until age 18 months. All LNS contained 6 mg Fe/d. Morbidity outcomes (serious adverse events, non-scheduled visits and guardian-reported morbidity episodes) were compared between control and intervention groups using a non-inferiority margin of 20 %.SettingNamwera and Mangochi catchment areas in rural Malawi.SubjectsInfants aged 6 months (n1932).ResultsThe enrolled 1932 infants contributed 1306 child-years of follow-up. Baseline characteristics were similar across groups. Compared with the control group, the relative risk (95 % CI) of serious adverse events was 0·71 (0·48, 1·07), 0·67 (0·48, 0·95) and 0·91 (0·66, 1·25) in 10, 20 and 40 g LNS/d groups, respectively. The incidence rate ratio (95 % CI) of non-scheduled visits due to malaria was 1·10 (0·88, 1·37), 1·08 (0·89, 1·31) and 1·21 (1·00, 1·46), and of guardian-reported morbidity episodes was 1·04 (0·96, 1·11), 1·03 (0·97, 1·10) and 1·04 (0·97, 1·10), in the respective LNS groups.ConclusionsProvision of 10 and 20 g LNS/d containing 6 mg Fe/d did not increase morbidity in the children. Provision of 40 g LNS/d did not affect guardian-reported illness episodes but may have increased malaria-related non-scheduled visits.

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: To identify key changes in child diets during the transition to agriculture by synthesizing evidence on 1) infant and child hunter-fisher-gatherer diets to identify common elements of an evolutionary child diet and 2) early agricultural groups. METHODS: We searched five databases (Academic Search Complete via EBSCO, Anthropology Plus via EBSCO, Medline via PubMed, Scopus, and SocIndex with Full Text via EBSCO). Childhood was defined as children 10 years or younger. Early agriculture was defined as cultivation activities during the Neolithic or regional Neolithic equivalent era (e.g., Woodland Period), to account for the variation in the transition to agriculture. Studies examining hominins from the following species were eligible: Homo erectus/Homo ergaster, Homo neanderthalensis, Homo heidelbergensis, and Homo sapiens. We included peer-reviewed papers of qualitative, quantitative, and mixed methods on infant and childhood diets for groups whose primary subsistence method was hunting, fishing, or gathering or groups who were transitioning to early agriculture. Title and abstract reviews were conducted in Rayyan QCRI by two blinded authors. Discrepancies were reviewed by a third author. Full text review was also blinded. We scored studies with the Mixed Methods Appraisal Tool (2018), and we synthesized evidence using a narrative synthesis with sub-group analysis as appropriate. RESULTS: The publications covered a range of subsistence groups and study types (e.g., ethnography, isotopic analysis). Groups from Africa, Asia, Europe, North America and South America were represented, and time periods ranged from the Mesolithic Era to present. Our analysis indicated a significant shift in child diet accompanying the shift to agriculture. Hunter-gatherer-fisher children had more varied diets with a larger proportion of animal-source foods during and after the complementary feeding period compared to early agricultural groups. CONCLUSIONS: Early agricultural diets, similar to current child dietary patterns, have diverged from the diets of hunter-fisher-gatherer children in important ways. These differences could offer insight into child feeding guidelines today. FUNDING SOURCES: This project was internally funded by the E3 Nutrition Lab at Washington University in St. Louis.

Author(s): Adu-Afarwuah, Seth; Young, Rebecca R; Lartey, Anna; Okronipa, Harriet; Ashorn, Per; Ashorn, Ulla; Oaks, Brietta M; Dewey, Kathryn G | Abstract: BackgroundAdequate knowledge about the safety of consumption of small-quantity lipid-based nutrient supplements (SQ-LNSs) is needed.ObjectiveWe aimed to test the hypothesis that SQ-LNS consumption is noninferior to control with respect to child morbidity.MethodsWomen (nn=n1320)n≤20 wk pregnant were assigned to iron and folic acid until delivery with no supplementation for offspring; or multiple micronutrient supplements until 6nmo postpartum with no supplementation for offspring; or SQ-LNSs until 6nmo postpartum, and SQ-LNSs for offspring (6nmg Fe/d) from 6 to 18nmo of age [the lipid-based nutrient supplement (LNS) group]. We assessed noninferiority (marginn≤20%) between any 2 groups during 0-6nmo of age, and between the non-LNS and LNS groups during 6-18nmo of age for caregiver-reported acute respiratory infection, diarrhea, gastroenteritis, fever/suspected malaria, poor appetite, and "other illnesses."ResultsDuring 0-6nmo 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 weren≤1.20. During 6-18nmo, 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.ConclusionsSQ-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.

Studies from several low- and middle-income countries have shown that antenatal depression may be a risk factor for poor neonatal outcomes. However, those studies conducted in sub-Saharan Africa have not consistently demonstrated this association. We set out to investigate whether antenatal depression is associated with shorter duration of pregnancy and reduced newborn size in rural Malawi. Pregnant women recruited from four antenatal clinics to the International Lipid-Based Nutrient Supplements Project-DYAD-Malawi (iLiNS-DYAD-M) randomised controlled trial of nutrient supplementation were screened for antenatal depression in the second or third trimester using a locally validated version of the Self Reporting Questionnaire (SRQ). Outcomes were duration of pregnancy, birthweight, newborn length for age z-score (LAZ), head circumference z-score, and mid-upper arm circumference (MUAC). Other potential confounding factors and predictors of birth outcome were measured and adjusted for in the analysis. 1,391 women were enrolled to the trial. 1,006/1,391 (72.3%) of these women completed an SRQ and gave birth to a singleton infant whose weight was measured within 2weeks of birth. 143/1,006 (14.2%) scored SRQ≥8, indicating likely depression. Antenatal depression was not associated with birth weight, duration of pregnancy, newborn LAZ, or head-circumference Z-score. There was an inverse association with newborn MUAC (adjusted mean difference-0.2cm (95% CI -0.4 to 0, p=0.021) the significance of which is unclear. The study was conducted within a randomised controlled trial of nutritional supplementation and there was a high proportion of missing data in some enrolment sites; this may have affected the validity of our findings.

Background: Food aid is a valuable tool for meeting global nutrition goals, particularly for vulnerable populations of children and reproductive-aged women. On October 21, 2017, the Food Aid Quality Review Project hosted a scientific symposium at the 21st International Congress on Nutrition in Buenos Aires, Argentina, to take stock of what the global community has learned about selected topics in the research literature on food aid used to address malnutrition. Objective: This article presents the discussion that took place during the symposium, which was guided by presentations by 6 experts from the field of nutrition, food aid, and humanitarian response. Conclusion: The recent upsurge in research on food aid has advanced the collective knowledge of what food aid products and programs work for addressing nutrition, but there is much more to learn. Presentations in this symposium called for further inquiry on (1) different and novel food aid formulations, (2) the cost-effectiveness of products and programs, and (3) market-based approaches to food assistance. Continuing to expand the evidence base on these topics is critical to improving global nutrition programs.

Although poor complementary feeding is associated with poor child growth, nutrition interventions only have modest impact on child growth, due to high burden of infections. We aimed to assess the association of malaria with linear growth, hemoglobin, iron status, and development in children aged 6–18 months in a setting of high malaria and undernutrition prevalence. Prospective cohort study, conducted in Mangochi district, Malawi. We enrolled six-months-old infants and collected weekly data for ‘presumed’ malaria, diarrhea, and acute respiratory infections (ARI) until age 18 months. Change in length-for-age z-scores (LAZ), stunting, hemoglobin, iron status, and development were assessed at age 18 months. We used ordinary least squares regression for continuous outcomes and modified Poisson regression for categorical outcomes. Of the 2723 children enrolled, 2016 (74.0%) had complete measurements. The mean (standard deviation) incidences of ‘presumed’ malaria, diarrhea, and ARI, respectively were: 1.4 (2.0), 4.6 (10.1), and 8.3 (5.0) episodes/child year. Prevalence of stunting increased from 27.4 to 41.5% from 6 to 18 months. ‘Presumed’ malaria incidence was associated with higher risk of stunting (risk ratio [RR] = 1.04, 95% confidence interval [CI] = 1.01 to 1.07, p = 0.023), anemia (RR = 1.02, 95%CI = 1.00 to 1.04, p = 0.014) and better socio-emotional scores (B = − 0.21, 95%CI = − 0.39 to − 0.03, p = 0.041), but not with change in LAZ, haemoglobin, iron status or other developmental outcomes. Diarrhea incidence was associated with change in LAZ (B = − 0.02; 95% CI = − 0.03 to − 0.01; p = 0.009), stunting (RR = 1.02; 95% CI = 1.01 to 1.03; p = 0.005), and slower motor development. ARI incidence was not associated with any outcome except for poorer socio-emotional scores. In this population of young children living in a malaria-endemic setting, with active surveillance and treatment, ‘presumed’ malaria is not associated with change in LAZ, hemoglobin, or iron status, but could be associated with stunting and anemia. Diarrhea was more consistently associated with growth than was malaria or ARI. The findings may be different in contexts where active malaria surveillance and treatment is not provided. NCT00945698 (July 24, 2009) and NCT01239693 (November 11, 2010).

A child’s endowment is a reflection of his/her genetic makeup and the conditions faced in early life. Parents build on their child’s endowment by investing resources in their child, and together, a child’s endowment and subsequent investments act as input into important later-life outcomes. A positive or negative shock to a child’s endowment can have a direct biological effect on a child’s long-term outcomes but may also affect parents’ decisions about investments in the health and human capital of their children. Using follow-up data collected several years after a randomized trial in Ghana, we explored whether maternal and child supplementation with small-quantity lipid-based nutrient supplements (SQ-LNS) throughout much of the first 1,000 days influenced parental investments in the health and human capital of their children. Across the domains of family planning, breastfeeding, health, education, and paternal financial support, we found that, in general, the intervention did not affect investments in the treated child nor his/her untreated siblings. These results suggest that given production technologies, constraints, and preferences, the intervention either did not change parents’ optimal investment strategies or that the effects of the intervention, namely increased birth size and attained length at 18 months of age, were too small for parents to perceive or to have any meaningful impact on parents’ expectations about the returns to investments in their children.

Poor infant and young child feeding (IYCF) practices are associated with linear growth faltering. Our objective was to evaluate the impact of a nutrition and water and sanitation for health intervention on three IYCF indicators—minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum acceptable diet (MAD) in Kenyan children. Households were randomized into one of eight groups: (a) active control; (b) passive control; (c) water quality (W); (d) sanitation (S); (e) handwashing (H); (f) combined Water, Sanitation, and Handwashing; (g) nutrition (N); and (h) combined WSH + N. In the N and WSH + N arms, community-based promoters counselled households on optimal IYCF practices, and small-quantity lipid-based nutrient supplements (SQ-LNS) were provided to children 6–24 months of age. Twelve months (Year 1) and 24 months (Year 2) after interventions began, enumerators surveyed mothers to ascertain IYCF practices. We made pairwise comparisons of each intervention arm versus the active control arm using log binomial models. In total, 3,652 caretakers were surveyed at Year 1 and 4,987 caretakers at Year 2. Compared with the active control, there were no differences in any of the arms in MDD, MMF, or MAD, aside from an increase in MDD at Year 1 in the nutrition only arm but not in the combined WSH + N arm (N: 68%; WSH + N: 61%; C: 61%; N arm prevalence ratio: 1.13 95% CI [1.01, 1.25]). In this setting, a nutrition behaviour change communication intervention had little impact on IYCF indicators. The provision of SQ-LNS was not detrimental to current IYCF indicators in the community.

Author(s): Adu-Afarwuah, Seth; Young, Rebecca T; Lartey, Anna; Okronipa, Harriet; Ashorn, Per; Ashorn, Ulla; Oaks, Brietta M; Arimond, Mary; Dewey, Kathryn G | Abstract: BackgroundInterventions are needed to address iron deficiency in low-income settings.ObjectiveThis secondary outcome analysis aimed to compare the hemoglobin (Hb) and iron status [zinc protoporphyrin (ZPP)] of children born to women enrolled in the iLiNS-DYAD trial in Ghana.MethodsWomen ≤20 wk pregnant (nn=n1320) were assigned to receive 60 mg Fe/d and 400 µg folic acid/d until delivery and placebo thereafter, and no supplementation for infants (IFA group); or multiple micronutrients containing 20 mg Fe/d until 6 mo postpartum and no supplementation for infants (MMN); or small-quantity lipid-based nutrient supplements (SQ-LNSs) containing 20 mg Fe/d until 6 mo postpartum, and SQ-LNSs for infants from 6 to 18 mo of age (LNS). We compared infants' Hb (g/L) and ZPP (µmol/mol heme) at 6 and 18 mo of age.ResultsAt 6 mo of age, groups did not differ in meann±nSD Hb (overall: 113n±n9.9 g/L) or geometric mean (95% CI) ZPP [overall: 62.6 (60.6, 64.7)]. At 18 mo of age, meann±nSD Hb (overall: 112n±n10.4 g/L) did not differ significantly between groups, whereas geometric mean (95% CI) ZPP was lower (Pn=n0.031) in the LNS group [53.9 (50.7, 57.3)] than the IFA [60.4 (56.7, 64.3)] but not the MMN [58.8 (55.6, 62.2)] group. Further, the LNS group, compared with the IFA and MMN groups combined, had a lower prevalence of elevated (g70) ZPP (27.5% compared with 35%; Pn=n0.02) and a marginally lower prevalence of anemia (38.7% compared with 44.9%; Pn=n0.06). These results generally remained unchanged when controlling for prespecified covariates or correcting for inflammation.ConclusionsIn this setting, providing SQ-LNSs or multiple micronutrients with 20 mg Fe/d, compared with iron (60 mg/d) and folic acid, to pregnant women does not affect their infants' Hb or iron status at 6 mo of age, but maternal and infant supplementation with SQ-LNSs increases infants' iron status at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT00970866.

Background The impact of feeding a slightly sweet nutrient supplement early in life on later sweet taste preference is unknown. Objective We tested the hypothesis that the level of sucrose most preferred by 4–6-y-old children exposed to a slightly sweet lipid-based nutrient supplement (LNS) early in life would not be higher than that of children never exposed to LNS. Design We followed up children born to women (n = 1,320) who participated in a randomized trial in Ghana. In one group, LNS was provided to women on a daily basis during pregnancy and the first 6 mo postpartum and to their infants from age 6 to 18 mo (LNS group). The control groups received daily iron and folic acid or multiple micronutrients during pregnancy and the first 6 mo postpartum, with no infant supplementation (non-LNS group). At age 4–6 y, we randomly selected a subsample of children (n = 775) to assess the concentration of sucrose most preferred using the Monell 2-series, forced-choice, paired-comparison tracking procedure. We compared LNS with non-LNS group differences using a noninferiority margin of 5% weight/volume (wt/vol). Results Of the 624 children tested, most (61%) provided reliable responses. Among all children, the mean ± SD sucrose solution most preferred (% wt/vol) was 14.6 ± 8.6 (LNS group 14.9 ± 8.7; non-LNS group 14.2 ± 8.4). However, among children with reliable responses, it was 17.0 ± 10.2 (LNS group 17.5 ± 10.4; non-LNS group 16.5 ± 10.0). The upper level of the 95% CI of the difference between groups did not exceed the noninferiority margin in either the full sample or those with reliable responses, indicating that the LNS group did not have a higher sweet preference than the non-LNS group. Conclusion Exposure to a slightly sweet nutrient supplement early in life did not increase the level of sweet taste most preferred during childhood. This trial was registered at clinicaltrials.gov as NCT00970866.

Author(s): Ocansey, Maku E; Adu-Afarwuah, Seth; Kumordzie, Sika M; Okronipa, Harriet; Young, Rebecca R; Tamakloe, Solace M; Oaks, Brietta M; Dewey, Kathryn G; Prado, Elizabeth L | Abstract: Background:Adequate nutrition is necessary for brain development during pregnancy and infancy. Few randomized controlled trials of supplementation during these periods have measured later developmental outcomes. Objective:Our objective was to investigate the effects of provision of prenatal and postnatal lipid-based nutrient supplements (LNS) on child development at preschool age. Methods:We conducted a follow-up study of 966 children aged 4-6 y in 2016, born to women who participated in the International Lipid-Based Nutrient Supplements-DYAD trial conducted in Ghana in 2009-2014, representing 79% of eligible children. Women ≤20 weeks of gestation were randomized to daily LNS or multiple micronutrient (MMN) capsules during pregnancy through 6 mo postpartum or iron and folic acid (IFA) capsules during pregnancy and calcium placebo capsules during 6 mo postpartum. Children in the LNS group received LNS from 6 to 18 mo. Primary outcomes of this follow-up study were (1) a cognitive factor score based on a test battery adapted from several standard tests, 2) fine motor score (9-hole pegboard test), and (3) social-emotional difficulties (Strengths and Difficulties Questionnaire; SDQ). Eight secondary outcomes were calculated in specific domains (e.g., language, SDQ prosocial). Analysis was by a complete case intention to treat in a 2-group comparison: LNS compared with non-LNS (MMNn+nIFA). Results:Children in the LNS group had significantly lower social-emotional difficulties z-scores than children in the non-LNS group (adjusted for child age βn=n-0.12, 95% CI: -0.25, 0.02, Pn=n0.087; fully adjusted βn=n-0.16, 95% CI: -0.29, -0.03, Pn=n0.013). The effect of LNS on social-emotional difficulties score was larger among children living in households with lower home environment scores (P-interactionn=n0.081). No other outcomes differed between the 2 intervention groups. Conclusions:Provision of LNS during the first 1000 d of development improved behavioral function, particularly for children from low nurturing and stimulation households, but did not affect cognition at preschool age in this setting. Trial Registration: clinicaltrials.gov, Identifier NCT00970866.

Summary: Background: Poor nutrition and exposure to faecal contamination are associated with diarrhoea and growth faltering, both of which have long-term consequences for child health. We aimed to assess whether water, sanitation, handwashing, and nutrition interventions reduced diarrhoea or growth faltering. Methods: The WASH Benefits cluster-randomised trial enrolled pregnant women from villages in rural Kenya and evaluated outcomes at 1 year and 2 years of follow-up. Geographically-adjacent clusters were block-randomised to active control (household visits to measure mid-upper-arm circumference), passive control (data collection only), or compound-level interventions including household visits to promote target behaviours: drinking chlorinated water (water); safe sanitation consisting of disposing faeces in an improved latrine (sanitation); handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate maternal, infant, and young child feeding plus small-quantity lipid-based nutrient supplements from 6–24 months (nutrition); and combined water, sanitation, handwashing, and nutrition. Primary outcomes were caregiver-reported diarrhoea in the past 7 days and length-for-age Z score at year 2 in index children born to the enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105. Findings: Between Nov 27, 2012, and May 21, 2014, 8246 women in 702 clusters were enrolled and randomly assigned an intervention or control group. 1919 women were assigned to the active control group; 938 to passive control; 904 to water; 892 to sanitation; 917 to handwashing; 912 to combined water, sanitation, and handwashing; 843 to nutrition; and 921 to combined water, sanitation, handwashing, and nutrition. Data on diarrhoea at year 1 or year 2 were available for 6494 children and data on length-for-age Z score in year 2 were available for 6583 children (86% of living children were measured at year 2). Adherence indicators for sanitation, handwashing, and nutrition were more than 70% at year 1, handwashing fell to less than 25% at year 2, and for water was less than 45% at year 1 and less than 25% at year 2; combined groups were comparable to single groups. None of the interventions reduced diarrhoea prevalence compared with the active control. Compared with active control (length-for-age Z score −1·54) children in nutrition and combined water, sanitation, handwashing, and nutrition were taller by year 2 (mean difference 0·13 [95% CI 0·01–0·25] in the nutrition group; 0·16 [0·05–0·27] in the combined water, sanitation, handwashing, and nutrition group). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth. Interpretation: Behaviour change messaging combined with technologically simple interventions such as water treatment, household sanitation upgrades from unimproved to improved latrines, and handwashing stations did not reduce childhood diarrhoea or improve growth, even when adherence was at least as high as has been achieved by other programmes. Counselling and supplementation in the nutrition group and combined water, sanitation, handwashing, and nutrition interventions led to small growth benefits, but there was no advantage to integrating water, sanitation, and handwashing with nutrition. The interventions might have been more efficacious with higher adherence or in an environment with lower baseline sanitation coverage, especially in this context of high diarrhoea prevalence. Funding: Bill & Melinda Gates Foundation, United States Agency for International Development.

Background There is evidence that suggests that undernutrition has a detrimental effect on malarial immunity in children. The aim of the study was to discover whether nutrient supplementation improved development of malarial antibody immunity in children up to 18 months of age. Methods The study was conducted with a subset of 432 Malawian children from a randomized controlled trial of nutritional supplements. The arms included pre- and postnatal small-quantity lipid-based nutrient supplements for both mother and child; prenatal supplementation with iron and folic acid; and pre- and postnatal supplementation with multiple micronutrients. Paired plasma samples were collected at 6 and 18 months of age. The levels of antibodies against merozoite surface protein 1 (MSP1 19kD) and MSP2, erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2A (Rh2A9), schizont extract and variant antigens expressed on the surface of infected erythrocytes were measured. Results At 18 months of age, 5.4% of children were parasitaemic by microscopy and 49.1% were anaemic. Antibodies to the tested merozoite antigens and schizont extract increased between 6 and 18 months and this increase was statistically significant for MSP1, MSP2 and EBA175 (p Conclusions Pre- and postnatal lipid-based nutrient supplementation did not alter malaria antibody acquisition during infancy, compared to prenatal supplementation with iron and folic acid or pre- and postnatal supplementation with multiple micronutrients. Trail registeration Clinicaltrials.gov registration number NCT01239693

Background Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain. Objective To evaluate lactation and the 2-year incidence of DM after GDM pregnancy. Design Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030). Setting Integrated health care system. Participants 1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011. Measurements Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders. Results Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios. Limitation Randomized design is not feasible or desirable for clinical studies of lactation. Conclusion Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery. Primary funding source National Institute of Child Health and Human Development.

Low nutritional value of complementary foods is associated with high incidence of childhood growth stunting in low-income countries. This study was done to test a hypothesis that dietary complementation with lipid-based nutrient supplements (LNS) promotes linear growth and reduces the incidence of severe stunting among at-risk infants. A total of 840 6-month-old healthy infants in rural Malawi were enrolled to a randomised assessor- blinded trial. The participants received 12-month supplementation with nothing, milk-LNS, soy-LNS, or corn- soy blend (CSB). Supplements provided micronutrients and approximately 280 kcal energy per day. Outcomes were incidence of severe and very severe stunting (length-for-age z-score, (LAZ) < -3.00 and

The International Lipid-Based Nutrient Supplements (iLiNS) Project began in 2009 with the goal of contributing to the evidence base regarding the potential of lipid-based nutrient supplements (LNS) to prevent undernutrition in vulnerable populations. The first project objective was the development of acceptable LNS products for infants 6–24 months and for pregnant and lactating women, for use in studies in three countries (Burkina Faso, Ghana and Malawi). This paper shares the rationale for a series of decisions in supplement formulation and design, including those related to ration size, ingredients, nutrient content, safety and quality, and packaging. Most iLiNS supplements have a daily ration size of 20 g and are intended for home fortification of local diets. For infants, this ration size is designed to avoid displacement of breast milk and to allow for dietary diversity including any locally available and accessible nutrient-dense foods. Selection of ingredients depends on acceptability of flavour, micronutrient, anti-nutrient and essential fatty acid contents. The nutrient content of LNS designed to prevent undernutrition reflects the likelihood that in many resource-poor settings, diets of the most nutritionally vulnerable individuals (infants, young children, and pregnant and lactating women) are likely to be deficient in multiple micronutrients and, possibly, in essential fatty acids. During ingredient procurement and LNS production, safety and quality control procedures are required to prevent contamination with toxins or pathogens and to ensure that the product remains stable and palatable over time. Packaging design decisions must include consideration of product protection, stability, convenience and portion control.

Background: Linear growth faltering in the first 2 y contributes greatly to a high stunting burden, and prevention is hampered by the limited capacity in primary health care for timely screening and intervention. Objective: This study aimed to determine an approach to predicting long-term stunting from consecutive 1-mo weight increments in the first year of life. Methods: By using the reference sample of the WHO velocity standards, the analysis explored patterns of consecutive monthly weight increments among healthy infants. Four candidate screening thresholds of successive increments that could predict stunting were considered, and one was selected for further testing. The selected threshold was applied in a cohort of Bangladeshi infants to assess its predictive value for stunting at ages 12 and 24 mo. Results: Between birth and age 12 mo, 72.6% of infants in the WHO sample tracked within 1 SD of their weight and length. The selected screening criterion ("event") was 2 consecutive monthly increments below the 15th percentile. Bangladeshi infants were born relatively small and, on average, tracked downward from approximately age 6 to

Exclusive breastfeeding is recommended during the first 6 months of life; thereafter, continued breastfeeding along with nutritious complementary foods is recommended. Continued breastfeeding contributes a substantial proportion of nutrient needs and promotes healthy growth and development, but the quantity of breast milk consumed may be highly variable and little is known about the factors associated with breast milk intake after 6 months of age. The present study was conducted to assess factors associated with breast milk intake of Malawian infants at 9-10 months of age. Breast milk intake was measured using the dose-to-mother deuterium oxide dilution method in a subsample of 358 Malawian infants who were participating in a randomized controlled trial of lipid-based nutrient supplements. Regression analysis was used to assess associations between breast milk intake and several maternal and infant variables. Mean (standard deviation) breast milk intake was 752 (244) g day(-1) . In multiple regression, breast milk intake was positively associated with infant weight (+62 g per kg body weight, P

Nutritional supplementation during pregnancy is increasingly recommended especially in low-resource settings, but its oral health impacts have not been studied. Our aim was to examine whether supplementation with multiple micronutrients (MMN) or small-quantity lipid-based nutrient supplements affects dental caries development or periodontal health in a rural Malawian population. The study was embedded in a controlled iLiNS-DYAD trial that enrolled 1391 pregnant women

Background: Intrauterine growth restriction may be reduced by supplementing maternal diets during pregnancy, but few studies have assessed the impact of combined prenatal and postnatal interventions on child growth. Objective: We tested a hypothesis that provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to mothers in pregnancy and 6 mo postpartum and to their infants from 6 to 18 mo of age would promote infant and child growth in the study area in rural Malawi. Methods: We enrolled 869 pregnant women in a randomized trial in Malawi. During pregnancy and 6 mo thereafter, the women received daily 1 capsule of iron-folic acid (IFA), 1 capsule containing 18 micronutrients (MMN), or one 20-g sachet of SQ-LNS [lipid-based nutrient supplements (LNS), containing 21 MMN, protein, carbohydrates, essential fatty acids, and 118 kcal]. Children in the IFA and MMN groups received no supplementation; children in the LNS group received SQ-LNSs from 6 to 18 mo. Primary outcome was child length at 18 mo. Results: At 18 mo, the mean length in the IFA, MMN, and LNS groups was 77.0, 76.9, and 76.8 cm (P = 0.90), respectively, and the prevalence of stunting was 32.7%, 35.6%, and 37.9% (P = 0.54), respectively. No intergroup differenceswere found in the mean weight, head circumference, or midupper arm circumference or the proportions with low z scores for these variables (P > 0.05). Covariate adjustment did not change the analysis results, and the associations between the intervention and child length were not modified by maternal parity, age, or nutritional status (P > 0.10). Conclusions: The findings do not support a hypothesis that provision of SQ-LNSs to women in pregnancy and postpartum and to children from 6 to 18 mo of age would promote child growth in this Malawian study area. This trial was registered at clinicaltrials.gov as NCT01239693. JN utr2015;145:1345‐53.

BACKGROUND The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women. OBJECTIVE We evaluated the effects of prenatal LNS supplementation on fetal growth. DESIGN In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length. RESULTS This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women. CONCLUSION Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866.

Adequate long-chain polyunsaturated fatty acid (LCPUFA) intake is critical during the fetal and infant periods. We quantified fatty acid content of breast milk (n=718) and plasma from six month old infants (n=412) in southern Malawi, and in usipa (n=3), a small dried fish from Lake Malawi. Compared to global norms, Malawian breast milk fatty acid content (% of total fatty acids) was well above average levels of arachidonic acid [ARA] (0.69% vs. 0.47%) and docosahexaenoic acid [DHA] (0.73% vs. 0.32%). Average Malawian infant plasma ARA (7.5%) and DHA (3.8%) levels were comparable to those reported in infants consuming breast milk with similar fatty acid content. The amounts (mg) of DHA, EPA and ARA provided by a 3 oz (85 g) portion of dried usipa (1439, 659 and 360, respectively) are considerably higher than those for dried salmon. Usipa may be an important source of LCPUFA for populations in this region.

World Health Organization recommends exclusive breastfeeding for infants for the first 6 months of life, followed by introduction of nutritious complementary foods alongside breastfeeding. Breast milk remains a significant source of nourishment in the second half of infancy and beyond; however, it is not clear whether more breast milk is always better. The present study was designed to determine the association between amount of breast milk intake at 9-10 months of age and infant growth and development by 12-18 months of age. The study was nested in a randomized controlled trial conducted in Malawi. Regression analysis was used to determine associations between breast milk intake and growth and development. Mean (SD) breast milk intake at 9-10 months of age was 752 (244) g/day. Mean (SD) length-for-age z-score at 12 months and change in length-for-age z-score between 12 and 18 months were -1.69 (1.0) and -0.17 (0.6), respectively. At 18 months, mean (SD) expressive vocabulary score was 32 (24) words and median (interquartile range) skills successfully performed for fine, gross, and overall motor skills were 21 (19-22), 18 (16-19), and 38 (26-40), respectively. Breast milk intake (g/day) was not associated with either growth or development. Proportion of total energy intake from breast milk was negatively associated with fine motor (β = -0.18, p = .015) but not other developmental scores in models adjusted for potential confounders. Among Malawian infants, neither breast milk intake nor percent of total energy intake from breast milk at 9-10 months was positively associated with subsequent growth between 12 and 18 months, or development at 18 months.

Women of reproductive age are at nutritional risk due to their need for nutrient-dense diets. Risk is further elevated in resource-poor environments. In one such environment, we evaluated feasibility of meeting micronutrient needs of women of reproductive age using local foods alone or using local foods and supplements, while minimizing cost. Based on dietary recall data from Ouagadougou, we used linear programming to identify the lowest cost options for meeting 10 micronutrient intake recommendations, while also meeting energy needs and following an acceptable macronutrient intake pattern. We modeled scenarios with maximum intake per food item constrained at the 75th percentile of reported intake and also with more liberal maxima based on recommended portions per day, with and without the addition of supplements. Some scenarios allowed only commonly consumed foods (reported on at least 10% of recall days). We modeled separately for pregnant, lactating, and nonpregnant, nonlactating women. With maxima constrained to the 75th percentile, all micronutrient needs could be met with local foods but only when several nutrient-dense but rarely consumed items were included in daily diets. When only commonly consumed foods were allowed, micronutrient needs could not be met without supplements. When larger amounts of common animal-source foods were allowed, all needs could be met for nonpregnant, nonlactating women but not for pregnant or lactating women, without supplements. We conclude that locally available foods could meet micronutrient needs but that to achieve this, strategies would be needed to increase consistent availability in markets, consistent economic access, and demand.

Both iron deficiency (ID) and excess can lead to impaired health status. There is substantial evidence of a U-shaped curve between the risk of adverse birth outcomes and maternal hemoglobin concentrations during pregnancy; however, it is unclear whether those relations are attributable to conditions of low and high iron status or to other mechanisms. We summarized current evidence from human studies regarding the association between birth outcomes and maternal hemoglobin concentrations or iron status. We also reviewed effects of iron supplementation on birth outcomes among women at low risk of ID and the potential mechanisms for adverse effects of high iron status during pregnancy. Overall, we confirmed a U-shaped curve for the risk of adverse birth outcomes with maternal hemoglobin concentrations, but the relations differ by trimester. For low hemoglobin concentrations, the link with adverse outcomes is more evident when hemoglobin concentrations are measured in early pregnancy. These relations generally became weaker or nonexistent when hemoglobin concentrations are measured in the second or third trimesters. Associations between high hemoglobin concentration and adverse birth outcomes are evident in all 3 trimesters but evidence is mixed. There is less evidence for the associations between maternal iron status and adverse birth outcomes. Most studies used serum ferritin (SF) concentrations as the indicator of iron status, which makes the interpretation of results challenging because SF concentrations increase in response to inflammation or infection. The effect of iron supplementation during pregnancy may depend on initial iron status. There are several mechanisms through which high iron status during pregnancy may have adverse effects on birth outcomes, including oxidative stress, increased blood viscosity, and impaired systemic response to inflammation and infection. Research is needed to understand the biological processes that underlie the U-shaped curves seen in observational studies. Reevaluation of cutoffs for hemoglobin concentrations and indicators of iron status during pregnancy is also needed.

Small‐quantity lipid‐based nutrient supplements (SQ‐LNS) have been studied in efficacy and effectiveness trials, but little is known about how parents perceive the products and their effects. In a randomised trial in Ghana, efficacy of SQ‐LNS provided to women during pregnancy and the first 6 months postpartum and to their children from 6 to 18 months of age was assessed by comparison with iron‐folic acid (IFA) capsules and multiple micronutrient (MMN) capsules provided to women. In a follow‐up study conducted when the index children from the original trial were between 4 and 6 years of age, we used survey‐based methods to assess retrospective and current parental perceptions of nutrient supplements generally and of SQ‐LNS and their effects compared with perceptions IFA and MMN capsules. Most parents perceived that the assigned supplements (SQ‐LNS, IFA, or MMN) positively impacted the mother during pregnancy (approximately 89% of both mothers and fathers) and during lactation (84% of mothers and 86% of fathers). Almost all (≥90%) of mothers and fathers perceived that the assigned supplement positively impacted the index child and expected continued positive impacts on the child's health and human capital into the future. A smaller percentage of parents perceived negative impacts of the supplements (7%–17% of mothers and 4%–12% of fathers). Perceptions of positive impacts and of negative impacts did not differ by intervention group. The results suggest that similar populations would likely be receptive to programs to deliver SQ‐LNS or micronutrient capsules.