Early life nutritional exposures, combined with changes in lifestyle in adult life, can result in increased risk of chronic diseases. Although much of the focus on the developmental origins of ...disease has been on birth size and growth in postnatal life and the availability of energy and protein during these critical developmental periods, micronutrient deficiencies may also play an important role in fetal growth and development. Micronutrient status in fetal and early life may alter metabolism, vasculature, and organ growth and function, leading to increased risk of cardiometabolic disorders, adiposity, altered kidney function, and, ultimately, to type 2 diabetes and cardiovascular diseases. This review elucidates pathways through which micronutrient deficiencies lead to developmental impairment and describes the research to date on the evidence that micronutrient deficiencies in utero influence the development of chronic disease risk. Animal studies, observational human studies examining maternal diet or micronutrient status, and limited data from intervention studies are reviewed. Where data are lacking, plausible mechanisms and pathways of action have been derived from the existing animal and in vitro models. This review fills a critical gap in the literature related to the seminal role of micronutrients in early life and extends the discussion on the developmental origins of health and disease beyond birth size and energy and protein deficiency.
Micronutrients, vitamins and minerals accessible from the diet, are essential for biologic activity. Micronutrient status varies widely throughout pregnancy and across populations. Women in ...low-income countries often enter pregnancy malnourished, and the demands of gestation can exacerbate micronutrient deficiencies with health consequences for the fetus. Examples of efficacious single micronutrient interventions include folic acid to prevent neural tube defects, iodine to prevent cretinism, zinc to reduce risk of preterm birth, and iron to reduce the risk of low birth weight. Folic acid and vitamin D might also increase birth weight. While extensive mechanistic and association research links multiple antenatal micronutrients with plausible materno-fetal health advantages, hypothesized benefits have often been absent, minimal or unexpected in trials. These findings suggest a role for population context in determining health responses and filling extensive gaps in knowledge. Multiple micronutrient supplements reduce the risks of being born with low birth weight, small for gestational age or stillborn in undernourished settings, and justify micronutrient interventions with antenatal care. Measurable health effects of gestational micronutrient exposure might persist into childhood but few data exists on potential long-term benefits. In this Review, we discuss micronutrient intake recommendations, risks and consequences of deficiencies, and the effects of interventions with a particular emphasis on offspring.
Eggs are a good source of nutrients for growth and development. We hypothesized that introducing eggs early during complementary feeding would improve child nutrition.
A randomized controlled trial ...was conducted in Cotopaxi Province, Ecuador, from March to December 2015. Children ages 6 to 9 months were randomly assigned to treatment (1 egg per day for 6 months
= 83) and control (no intervention
= 80) groups. Both arms received social marketing messages to encourage participation in the Lulun Project (
meaning "egg" in Kichwa). All households were visited once per week to monitor morbidity symptoms, distribute eggs, and monitor egg intakes (for egg group only). Baseline and end point outcome measures included anthropometry, dietary intake frequencies, and morbidity symptoms.
Mothers or other caregivers reported no allergic reactions to the eggs. Generalized linear regression modeling showed the egg intervention increased length-for-age
score by 0.63 (95% confidence interval CI, 0.38-0.88) and weight-for-age
score by 0.61 (95% CI, 0.45-0.77). Log-binomial models with robust Poisson indicated a reduced prevalence of stunting by 47% (prevalence ratio PR, 0.53; 95% CI, 0.37-0.77) and underweight by 74% (PR, 0.26; 95% CI, 0.10-0.70). Children in the treatment group had higher dietary intakes of eggs (PR, 1.57; 95% CI, 1.28-1.92) and reduced intake of sugar-sweetened foods (PR, 0.71; 95% CI, 0.51-0.97) compared with control.
The findings supported our hypothesis that early introduction of eggs significantly improved growth in young children. Generally accessible to vulnerable groups, eggs have the potential to contribute to global targets to reduce stunting.
Eggs have been consumed throughout human history, though the full potential of this nutritionally complete food has yet to be realized in many resource‐poor settings around the world. Eggs provide ...essential fatty acids, proteins, choline, vitamins A and B₁₂, selenium, and other critical nutrients at levels above or comparable to those found in other animal‐source foods, but they are relatively more affordable. Cultural beliefs about the digestibility and cleanliness of eggs, as well as environmental concerns arising from hygiene practices and toxin exposures, remain as barriers to widespread egg consumption. There is also regional variability in egg intake levels. In Latin American countries, on average, greater proportions of young children consume eggs than in Asian or African countries. In China and Indonesia, nutrition education and social marketing have been associated with greater amounts of eggs in the diets of young children, though generally, evidence from interventions is minimal. Homestead chicken‐and‐egg production with appropriate vaccination, extension service, and other supports can simultaneously address poverty and nutrition in very poor rural households. With undernutrition remaining a significant problem in many parts of the world, eggs may be an uncracked part of the solution.
Child stunting is a global problem and is only modestly responsive to dietary interventions. Numerous observational studies have shown that water quality, sanitation, and handwashing (WASH) in a ...household are strongly associated with linear growth of children living in the same household. We have completed three randomised efficacy trials testing improved household-level WASH with and without improved infant and young child feeding (IYCF) on stunting and diarrhoea in Bangladesh, Kenya, and Zimbabwe. In all trials, improved IYCF had a statistically significant benefit, but WASH had no effect on linear growth. In observational analyses of data from the control groups of the three trials, baseline sanitation was a strong risk factor for stunting in the study populations, suggesting this frequently reported association might be confounded by unmeasured factors of household wellbeing. WASH interventions reduced diarrhoea in Bangladesh, but not in Kenya or Zimbabwe. Intervention promoters visited participants six times per month in Bangladesh compared with monthly in Kenya and Zimbabwe; a review of the literature shows that virtually all published studies that have reported an effect on diarrhoea through home-based water treatment and handwashing promotion achieved high adherence by visiting participants at daily to fortnightly intervals. Despite achieving substantial behavioural change and significant reduction in infection prevalence for some enteric pathogens, detection of enteropathogens among children in the WASH groups of the trials was typically at ten times higher prevalence compared with high-income countries. Considering these results, we recommend that future research in the WASH sector focus on developing and evaluating interventions that are radically more effective in reducing faecal contamination in the domestic environment than the interventions implemented in these trials.
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.
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.
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.
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.
Bill & Melinda Gates Foundation, United States Agency for International Development.
Stunted growth is a significant public health problem in many low-income countries.
The aim of this study was to evaluate the impact of 1 egg per day on child growth in rural Malawi.
We conducted an ...individually randomized controlled trial in which 660 children aged 6–9 mo were equally allocated into an intervention (1 egg/d) or control group. Eggs were provided during twice-weekly home visits for 6 mo. Control households were visited at the same frequency. Assessors blinded to intervention group measured length, weight, head circumference, and midupper arm circumference at baseline and the 6-mo follow-up visit. To assess adherence, multipass 24-h dietary recalls were administered at baseline, 3-mo, and 6-mo visits.
Between February and July 2018, 660 children were randomly assigned into the intervention (n = 331) and control (n = 329) groups. Losses to follow-up totaled 10%. In the intervention group, egg consumption increased from 3.9% at baseline to 84.5% and 70.3% at the 3-mo and 6-mo visits, whereas in the control group, it remained below 8% at all study visits. The baseline prevalence of stunting was 14%, underweight was 8%, and wasting was 1% and did not differ by group. There was no intervention effect on length-for-age, weight-for-age, or weight-for-length z scores. There was a significantly higher head circumference for age z score of 0.18 (95% CI: 0.01, 0.34) in the egg group compared with the control group. There was a significant interaction with maternal education (P = 0.024), with an effect on length-for-age z score only among children whose mothers had higher education.
The provision of 1 egg per day to children in rural Malawi had no overall effect on linear growth. A background diet rich in animal source foods and low prevalence of stunting at baseline may have limited the potential impact. This trial was registered at clinicaltrials.gov as NCT03385252.
An estimated 165 million children are stunted due to the combined effects of poor nutrition, repeated infection and inadequate psychosocial stimulation. The complementary feeding period, generally ...corresponding to age 6–24 months, represents an important period of sensitivity to stunting with lifelong, possibly irrevocable consequences. Interventions to improve complementary feeding practices or the nutritional quality of complementary foods must take into consideration the contextual as well as proximal determinants of stunting. This review presents a conceptual framework that highlights the role of complementary feeding within the layers of contextual and causal factors that lead to stunted growth and development and the resulting short‐ and long‐term consequences. Contextual factors are organized into the following groups: political economy; health and health care systems; education; society and culture; agriculture and food systems; and water, sanitation and environment. We argue that these community and societal conditions underlie infant and young child feeding practices, which are a central pillar to healthy growth and development, and can serve to either impede or enable progress. Effectiveness studies with a strong process evaluation component are needed to identify transdisciplinary solutions. Programme and policy interventions aimed at preventing stunting should be informed by careful assessment of these factors at all levels.
Cluster randomized trials are often used to study large-scale public health interventions. In large trials, even small improvements in statistical efficiency can have profound impacts on the required ...sample size and cost. Location integrates many socio-demographic and environmental characteristics into a single, readily available feature. Here we show that pair matching by geographic location leads to substantial gains in statistical efficiency for 14 child health outcomes that span growth, development, and infectious disease through a re-analysis of two large-scale trials of nutritional and environmental interventions in Bangladesh and Kenya. Relative efficiencies from pair matching are ≥1.1 for all outcomes and regularly exceed 2.0, meaning an unmatched trial would need to enroll at least twice as many clusters to achieve the same level of precision as the geographically pair matched design. We also show that geographically pair matched designs enable estimation of fine-scale, spatially varying effect heterogeneity under minimal assumptions. Our results demonstrate broad, substantial benefits of geographic pair matching in large-scale, cluster randomized trials.
Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted ...towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12–14% lower prevalence of stunting, wasting, and underweight; were 16–19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.
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