Malnutrition and Catch-Up Growth during Childhood and Puberty

Introduction

In 2020, approximately 149.2 million children, or 22%, of all children under 5 years of age across the globe were estimated to be affected by stunting, and 45.4 million children under 5 by wasting, of whom 13.6 million were severely wasted [1]. Although the rates of both stunting and wasting have been significantly reduced over the past couple of decades, these numbers are still staggering. According to the WHO, the number of people affected by hunger globally have increased by 150 million since the outbreak of COVID-19 [2]. Amidst climate changes, economic instability, and growing inequalities, achieving the global targets of reducing the number of children with stunting to 104 million by 2025 and to 87 million by 2030 seems more challenging than ever. This chapter reviews the most recent data on childhood malnutrition and catch-up growth, published between July 1, 2021, and June 30, 2022, and addresses several topics: (a) etiology and mechanisms of malnutrition in children, (b) adolescent nutrition (Lancet Series), (c) interventions, and (d) late outcomes of malnutrition.

Etiology and Mechanisms of Malnutrition in Children

Determinants of malnutrition among children: a systematic review

Comments: Despite considerable progress in reducing undernutrition and related stunting and wasting in the past 2 decades, as of 2020 there are still 149 million children under the age of 5 years affected with stunting worldwide. Numerous factors are related to childhood malnutrition, having a direct or indirect effect on child nutrition in developing countries. This systematic review and meta-analysis aim to determine the most consistent factors related to childhood stunting in the past decade by reviewing relevant studies published between 2012 and 2021. The review included 37 studies (each including a population of between 100 and 798,961 children) from various countries worldwide. The study found that the most significant determinants of childhood malnutrition were maternal education, household income, maternal nutritional status, age of the child, availability of sanitation facilities at home, size of family, birth order in the family, and the child’s birth weight. Interestingly, older children were found to be at higher risk for malnutrition and stunting than younger children. Although this meta-analysis did not exclude studies with suboptimal design, the large numbers and the diversity of social, geographic, and ethnic backgrounds in the studies included validate its findings.

Greater male vulnerability to stunting? Evaluating sex differences in growth, pathways and biocultural mechanisms

Comments: Sex and gender have implications on health outcomes throughout the course of life, and across the globe. Sex can affect disease susceptibility, progression, and prognosis via genetic, immune, and hormonal pathways. Moreover, gender roles, norms and perceptions, gender-based differences in access to resources and health services, and differences in health behaviors also strongly influence health outcomes. This review presents evidence regarding the differences in susceptibility to stunting between boys and girls, and discusses the many ways in which both sex and gender influence stunting in children. The review addresses sex-based differences in sensitivity to infectious diseases, differences in requirements for growth, in environmental exposures, and in care practices, and aims to integrate the biological and social pathways influencing growth, from the prenatal period throughout childhood. It highlights the need to tailor interventions aimed at stunting prevention according to the child’s specific environmental and social surroundings.

Adolescent Nutrition, Lancet Series

Strategies and interventions for healthy adolescent growth, nutrition, and development

Comments: Adolescents are not simply younger adults or older children; they are unique, with specific needs, risks, attitudes, and opportunities related to dietary intake and food choices. Like other age groups, adolescents face various nutritional problems, including micronutrient deficiencies and food insecurity, low weight, short stature, as well as obesity and metabolic disorders. However, adolescence is a unique phase of life, in several ways. First, the linear growth rate during adolescence is greater than in any other stage of life, excluding the first year of life. Hence, adolescence is a nutritionsensitive phase of growth, in which the benefits of good nutrition extend to many other physiological systems. Second, adolescence is the time of transition from primary dependence on caregivers to an increasing number of roles and responsibilities related to food purchase, preparation, and consumption, presenting an opportunity to establish healthy eating habits. Furthermore, adolescents differ from younger children in exercising greater choice over their nutrition, as they have strong opinions regarding their eating choices, and the factors that may motivate them to change. Adolescents in the current generation, more than any before, have concerns about the harmful impacts of the food industry on the environment. A new Lancet Series provides a comprehensive overview on the existing data on adolescent nutrition and sets out the challenges and opportunities for addressing healthy adolescent nutrition and development. This series highlights the neglect in policy, programming, and research means regarding this age group compared with other age groups. The series mentions several research gaps in this field and highlights the need of further research and data collection. It also recommends that adolescent nutrition promotion and interventions should occur in partnership with young people and be framed within broader commercial, cultural, and ecological contexts. The series includes an introduction (Patton et al.) followed by 3 parts: 
1. “Nutrition in adolescent growth and development,” by Norris et al., which synthesizes the understanding of adolescent biological development and its relationship with nutrition.
2. “Food choice in transition: adolescent autonomy, agency, and the food environment,” by Neufeld et al. This paper describes patterns of dietary intake among adolescents, maps how food choices can be influenced by unique features of adolescent development, and ends with a series of key considerations for policies, programs, and further research.
3. “Strategies and interventions for healthy adolescent growth, nutrition, and development,” by Hargreaves et al. This paper discusses how a nutrition-focused strategy based on adolescent interventions offers new options for coping with the global burden of obesity, undernutrition, and climate change.

Intervention

Small-quantity lipid-based nutrient supplements for the prevention of child malnutrition and promotion of healthy development: overview of individual participant data meta-analysis and programmatic implications

Comments:  The first ready-to-use therapeutic food (RUTF) for treating severe malnutrition, based on fat-based matrix and micronutrients, was developed in the late 1990s. This technology allows the product to have a low water content, which inhibits the growth of bacteria without refrigeration. Small-quantity lipid-based nutrient supplements (SQLNSs) for preventing malnutrition in vulnerable populations were later developed, based on the same type of food-based matrix as RUTF, but using a much smaller quantity of food, typically about 4 teaspoons (about 100 kcal) per day. SQ-LNSs provide energy, protein, essential fatty acids, and multiple micronutrients. 
This meta-analysis by Dewey et al., which included 14 randomized controlled trials (RCTs), and more than 37,000 participants, aimed to study the effects of SQ-LNSs provided to children 6–24  months of age on various outcomes. This meta-analysis showed that intervention with SQ-LNSs had significant benefits in reducing the prevalence of stunting, wasting, and underweight; improved cognitive and motor development outcomes; and prevented iron deficiency and anemia. Beneficial effects of SQ-LNSs were shown in heterogenous study designs and settings (various geographical regions, levels of stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, and compliance with SQ-LNSs). The benefits of SQ-LNSs were greater in populations with a higher stunting burden, higher anemia prevalence, and lower socioeconomic status, and among acutely malnourished children. According to the results of this meta-analysis, the authors suggest intervention with SQ-LNSs in more vulnerable populations who have greater potential to benefit by it (populations with lower socioeconomic status who are at greater risk of malnutrition and anemia). The authors also suggest that a greater impact of SQ-LNSs may be obtained by combination with other interventions such as prevention and control of infections and inflammation, improving access to health care, and promoting early child development.

Effectiveness of community nutrition-specific interventions on improving malnutrition of children under 5 years of age in the Eastern Mediterranean region: a systematic review and meta-analysis

Comments: The Eastern Mediterranean Region (EMR) comprises 22 countries extending from Pakistan in Southern Asia to Morocco in North Africa. These countries are very heterogenous in their ecology, economy, and healthcare services. Many of these regions are inflicted by war and conflicts, therefore resulting in poverty and poor nutrition. Several reviews, which included children from the EMR, have reported different rates of wasting, stunting, and underweight across these countries, and show that the 2 opposing nutrition-related diseases, malnutrition and obesity, paradoxically coexist. Numerous efforts have been made to reduce child malnutrition in the region. However, published information is scarce. This systematic review and meta-analysis by Ghodsi et al. aimed to evaluate the effectiveness and the cost-effectiveness of community based nutrition-specific interventions on the nutritional status of children under 5 years of age in the EMR. 
The systematic review yielded only 8 RCTs that met the inclusion criteria, 7 from Pakistan and 1 from Iran. Only one study reported the cost-effectiveness of nutrition specific interventions. The most common strategies used for management of child malnutrition in the EMR countries were nutrition education (including counseling on child complementary feeding) and cash-based interventions. Only 4 studies were included in the meta-analysis and showed that the different interventions had resulted in a significant improvement in weight-for-height z-score. No improvement was seen in height-for-age z-score.
The authors conclude that the scarcity of available studies in the region and their heterogeneity make it difficult to conclude which type of intervention is the most effective. The authors further note that although the results of the meta-analysis indicate that nutritional education and supplementary food distribution may have favorable effects on the weight and height status of children, these strategies obviously cannot eliminate poverty and poor sanitation, which are the underlying causes of child malnutrition. Poverty and poor sanitation should be addressed through appropriate policies and interventions.

Ready-to-use therapeutic food (RUTF) containing low or no dairy compared to standard RUTF for children with severe acute malnutrition: a systematic review and meta-analysis

Comments: Ready-to-use therapeutic food (RUTF) was developed for nutritional rehabilitation of children with severe acute malnutrition (SAM). Current guidelines, as specified by WHO, state that at least 50% of protein in RUTF should come from milk products, due to their higher protein quality as compared to other protein sources. However, milk proteins are more costly ingredients than nonmilk proteins. Hence, RUTF containing less dairy may be an attractive lower-cost treatment alternative for SAM. 
The aim of this systematic review and meta-analysis by Potani et al. was to compare the effectiveness of RUTF containing nondairy sources of protein, or less than 50% of protein from dairy products, with standard RUTF in children aged 6 months or older with SAM.
The meta-analysis included 6 RCTs which met the inclusion criteria, with a total sample of 6,356 children, examining the effect of 7 different intervention RUTF recipes. The results of the meta-analysis showed that nondairy or lower-dairy RUTF resulted in less weight gain, lower recovery, and lower weight-for-age z-scores near program discharge. Other anthropometric measures (height-for-age z-scores, weight-forheight z-score, and mid-upper-arm circumference), mortality, time to recovery, and adherence to the program did not differ between groups.
This systematic review has several important limitations. First, all the studies included in this review were of short term and followed participants only until discharge or shortly thereafter. Studies with longer follow-up durations are also needed to fully understand the effects of alternative versions of RUTF on different outcomes, like anthropometry, body composition, the gut microbiota, child development, and overall health. A second limitation is the heterogeneity of the low- or no-dairy RUTF formulations that were included in the meta-analysis. The differences in the nutritional composition, and in protein source and quality, make it difficult to interpret the results and define the ideal nutritional composition of alternative RUTF. A third limitation is that this systematic review does not include a cost-effectiveness evaluation. Although low- or no-dairy RUTF formulations could possibly lower SAM treatment costs, if these alternative RUTF result in worse outcomes or longer treatment duration, the total costs may be similar or even higher. The authors emphasize the need in continuing the research aimed to optimize more cost-effective versions of RUTF. They further suggest whey protein, which is a lower-cost dairy alternative to skimmed-milk powder, as a future direction of research.

Worldwide evidence about infant stunting from a public health perspective: a systematic review

Comments: Linear growth rate is a strong indicator of overall child development during the first years of life and of inequalities in child development. The aim of this systematic review by Rueda-Guevara et al. was to identify and describe worldwide evidence on prevention, nutritional interventions, and intersectoral collaboration efforts against stunting in infants under 2 years of age.
This extensive systematic review included 231 studies, most of which were interventional studies and cross-sectional studies. Most of the studies were conducted in low and middle-income countries (Africa, Southeast Asia, and the Americas WHO regions). The most frequent topics were stunting prevention, intersectoral collaboration, and nutritional interventions, which were targeted at 3 main populations: pregnant women, babies from birth to 6 months, and infants from 6 months to 2 years. The most frequent interventions were prebirth care (i.e., promotion and assessment of adequate gestational weight-gain), nutritional counseling for the mother and the child (i.e., counseling on breastfeeding and complementary feeding), and counseling on micronutrient supplementation.
This systematic review may be useful for informing public health policy decision-makers and researchers, as it summarizes, interprets, and highlights knowledge gaps of the existing literature regarding stunting prevention in infants.

Effect of oral nutritional supplementation on growth in children with undernutrition: a systematic review and meta-analysis

Comments: Many children worldwide experience undernutrition and growth faltering. Poor growth due to undernutrition is more commonly the result of multiple nutrient deficiencies and not a single-nutrient deficiency. Oral nutritional supplements (ONS) are liquid, semisolid, or powder formulas containing proteins and at least one nonprotein source of energy (carbohydrate and/or fat) in balanced amounts, as well as a wide range of micronutrients. Hence, ONS may be an effective nutrition intervention approach to tackle growth faltering in at-risk or undernourished children.
The systematic review and meta-analysis by Zhang et al. summarizes the evidence of the effects of ONS on growth in undernourished, or those at nutritional risk, healthy children aged 9 months to 12 years.
This systematic review included 11 RCTs (2,287 children) that met the inclusion criteria. The results of the meta-analysis showed that the provision of ONS had significant positive effects on weight and height gain compared to the control groups who received usual diet, placebo, or dietary counseling. Longitudinal analyses of up to 90 days of follow-up showed that the gains in weight were seen earlier than the gains in height: while greater gains in weight indices were reported from 30 days onward, a trend toward greater height gains were reported at 90 days. This suggests that nutritional supplementation in undernourished children should be given for at least 3 months to promote height catch-up.
The meta-analysis highlights several limitations and research gaps in the existing literature. First, no RCTs were available for children above 12 years of age, although catch-up growth occurs not only in early childhood but also during puberty. Second, most of the studies were of short duration (up to 90 days). Third, there was a big heterogeneity in the age ranges of the children, the ONS nutritional composition, the duration of the intervention, dosing, and compliance. This heterogeneity makes it difficult to conclude what is the ideal nutritional composition of ONS and the most effective setting for the intervention.
Further studies are needed to evaluate the effect of ONS on promoting catch-up growth, with longer follow-up duration (90 days or more), and including children above 12 years of age, particularly those going through puberty.

Effective interventions to address maternal and child malnutrition: an update of the evidence

Comments: This is an update of the evidence base of interventions to address global maternal and child nutrition challenges since the last such review in 2013 [3]. The review focused on emerging and new evidence on interventions such as antenatal multiple micronutrient supplements with benefits of reducing the risk of low birth weight and babies born small-for-gestational-age, with consequent impacts on stunting and human development. The evidence strengthened the benefits of supplementary foods in food-insecure settings and community-based approaches with the use of locally produced supplementary and therapeutic food to manage children with acute malnutrition. While relatively few strategies had looked at affordable and effective complementary feeding options, the evidence related to preventive small-quantity lipidbased nutrient supplements for child growth among children aged 6–23 months was strong and positive. For the prevention and management of childhood obesity, integrated interventions (e.g. diet, exercise, and behavioral therapy) were effective, but few had been evaluated in low- and middle-income country settings. The review also assessed evidence-based indirect nutrition strategies, such as malaria prevention, preconception care, family planning, water, sanitation, and hygiene promotion, delivered inside and outside the healthcare sector, which also provide important nutritional benefits. A lot more work is needed around scaling up and delivery platforms for nutrition interventions, especially in neglected areas like school-age and young adolescents [4].

Birth length is the strongest predictor of linear growth status and stunting in the first 2 years of life after a preconception maternal nutrition intervention: the children of the Women First trial

Comments: These are important data from the multicountry Women First trial showing that nutritional supplementation initiated prior to conception or early in pregnancy and continued until delivery was associated with significantly greater length at birth and 6 months of age compared with control infants. The Women First trial was conducted in several low-income population settings in the Democratic Republic of Congo, Guatemala, India, and Pakistan. Longitudinal models evaluated intervention effects on infants’ growth trajectory from birth to 24 months of age, with additional modeling used to identify adjusted predictors for growth trajectories and outcomes at 24 months. A large proportion (95% of original live births) of infants were evaluated at 24 months of age. While stunting rates were still high at 24 months of age (>62%), the length-forage z-score (LAZ) trajectory was better with both preconception and pregnancy supplementation (with adjusted mean differences of 0.19 SD [95% CI: 0.08, 0.30; p < 0.001] and 0.17 SD [95% CI: 0.07, 0.27; p < 0.001]) compared with the control group, respectively. The strongest predictors of LAZ at 24 months were birth LAZ < -2 and < -1 to ≥ -2, with adjusted mean differences of -0.76 SD (95% CI: -0.93, -0.58; p < 0.001) and -0.47 SD (95% CI: -0.56, -0.38; p < 0.001), respectively. This study underscores the importance of maternal nutrition in pregnancy for improving fetal and infant health and nutrition (in addition to substantial benefits for the mother herself). Similar findings are notable from studies of exemplars of reduction in stunting across countries with investments in indirect interventions in poverty reduction, maternal education, health and nutrition programs [5], and in malaria endemic areas, investments in reducing malaria burden in pregnancy [6].

Late Outcomes of Childhood Malnutrition

Liver fat in adult survivors of severe acute malnutrition

Comments: Acute malnutrition is a major public health problem in low- and middle-income countries and a leading cause of death in children aged under 5 years in these regions. Over the past decades, early intervention and treatment with RUTFs has lowered immediate mortality from acute malnutrition and increased the number of malnutrition survivors. These survivors may experience late adverse effects such as stunted growth and mental and physical disability, and have a higher risk of developing cardiometabolic diseases in adulthood. Both of the above studies focus on the late outcomes of acute malnutrition in adults, in an attempt to clarify the metabolic mechanisms leading to increased risk for noncommunicable diseases. The first study (Mwene-Batu et al.) examined body composition (BC) in adults who were exposed to acute malnutrition compared to the BC of age-, sex- and BMI-matched controls from the same communities, who had not been exposed to malnutrition. The authors found similarly normal BC in both groups, except for lower fat-free mass in men previously exposed to malnutrition, and attributed this finding to the shorter stature in this group. The second study (Thompson et al.) investigated differences in liver fat in survivors of severe wasting, versus survivors of edematous malnutrition and community controls. The authors found that after adjusting for birth weight, survivors of severe wasting had more liver fat than survivors of edematous malnutrition. No differences in liver fat were found between both group of survivors and controls. These results are in line with previous studies showing a greater susceptibility for cardiovascular disease in survivors of severe wasting than in survivors of kwashiorkor. These studies highlight the need to continue monitoring adults who were exposed to malnutrition in childhood and further study the sources of the double burden of malnutrition

References:

1. World Health Organization. World Health Statistics 2022: Monitoring health for the SDGs, sustainable development goals. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO.  
2. FAO, IFAD, UNICEF, WFP, WHO. The state of food security and nutrition in the world 2022. Repurposing food and agricultural policies to make healthy diets more affordable. Rome: FAO; 2022.
3. Bhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S, et al. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet. 2013;382(9890):452–7.
4. Vaivada T, Lassi ZS, Irfan O, Salam RA, Das JK, Oh C, et al. What can work and how? An overview of evidencebased interventions and delivery strategies to support health and human development from before conception to 20 years. Lancet. 2022;399(10337):1810–29.
5. Bhutta ZA, Akseer N, Keats EC, Vaivada T, Baker S, Horton SE, et al. How countries can reduce child stunting at scale: lessons from exemplar countries. Am J Clin Nutr. 2020;112(Suppl. 2):894S–904S.
6. Keats EC, Kajjura RB, Ataullahjan A, Islam M, Cheng B, Somaskandan A, et al. Malaria reduction drives childhood stunting decline in Uganda: a mixed-methods country case study. Am J Clin Nutr. 2022;115:1559–68