Malnutrition and Catch-Up Growth during Childhood and Puberty

Introduction

Stunting and wasting are the result of poor nutrient intake and/or disease. Children suffering from stunting may never attain their full genetic height. Children suffering from stunting and/or wasting also suffer from weakened immunity, increased risk of mortality and death, and are susceptible to long-term developmental delays [1]. According to the 2021 edition of the UNICEF, WHO, and World Bank report [1], the rates of children with malnutrition remain alarmingly high, and this condition is still far from being eliminated. According to this report, in 2020, about 149.2 million children aged under 5 years suffered from stunting, and 45.4 million children under 5 years were affected by wasting, of whom 13.6 million were severely wasted. These numbers may increase due to limitations in accessing nutritious diets and nutrition services during the COVID-19 pandemic [1]. Malnutrition can be prevented by various strategies, including adequate maternal nutrition before and during pregnancy and while breastfeeding; optimal breastfeeding during the first 2 years of life; nutritious, diverse, and safe foods in early childhood; and a healthy environment [1]. Many of these strategies are under threat, including due to the COVID-19 pandemic, and have the potential to attenuate the progress towards reaching the global targets of reducing the global rate of malnutrition in all its forms. More intensive efforts will be required to achieve global targets of reducing the number of children with stunting to 104 million by 2025 and to 87 million by 2030 [1].

This chapter reviews the most recent data on childhood malnutrition and catch-up growth, published between July 1, 2020 and June 30, 2021, and addresses several topics:

a. The changing face of global stunting (Vaivada et al. and NCD-RisC collaboration)

b. New suggested biomarkers for malnutrition in children (Scheffer et al.)

c. Association between nutritional components and growth indices: vitamin D (Song et al.)

d. COVID-19 and malnutrition (Akseer et al.)

e. Outcomes of malnutrition (Villar et al., Martínez-Oca et al.)

f. Outcome of malnutrition in unique populations: children adopted internationally (Ivey et al.), female adolescents with anorexia nervosa (Modan-Moses et al.)

g. Outcomes of different intervention strategies to treat malnutrition and under nutrition (Keats et al., Huey et al., Bhutta et al.)

Stunting in childhood: an overview of global burden, trends, determinants, and drivers of decline

Comments: Although global rates of stunting in children have decreased in past decades, not all regions of the world have witnessed the same rates of decline. The authors of this paper aimed to review and analyze the available data on predictors of reduced stunting rates worldwide, in order to determine which factors were most strongly associated with a decline in childhood stunting. Factors which were found to have a particular impact on stunting reduction include improvements in maternal and paternal education, household socioeconomic status, sanitation conditions, maternal health services access, and family planning. This study, although observational, is helpful in that it synthesizes data on various socio-economic and health-related factors and estimates their relative effect on stunting decline. This approach is warranted, as stunting appears to have a complex, multifactorial etiology, and does not always respond to the elimination of factors suspected as causative. Unfortunately, not enough data on dietary intake and diversity were available to assess the impact of these determinants on change in stunting rates, an important knowledge gap highlighted by this study.

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2,181 population-based studies with 65 million participants.

Comments: The majority of global health and nutrition studies and policies are focused on the beginning of life, from conception to age 5 years. However, evaluation of childhood growth and weight gain beyond the age of 5 years is crucial for identifying disparities and nutritional imbalances that may have a large impact on future health in adulthood. Apparently, this is the first comparison of the current height and BMI of children aged 5–19 years in all countries in the world, and includes age trajectories of mean height and BMI, intended to identify the age of diversion from healthy height and BMI in each country and region, and to enable intervention where possible. This is a very impressive global pooled analysis of over 2,100 population-based studies across the world. The scope of this study is staggering, covering some 65 million children and adolescents, over a period of 34 years (between 1985 and 2019). Importantly, height and BMI are presented alongside each other, showing their interactions during childhood, both genders are addressed separately, and comparisons between regions are performed. This is an important study for all professionals working in the field of pediatric growth and development.

Catch-up growth is a better indicator of undernutrition than thresholds for stunting

Comments: Stunting is usually interpreted as a marker of chronic undernutrition. Scheffler et al. argue that stunting per se is not a synonym of undernutrition. For example, many stunted children of modern Indonesia and Guatemala, countries with a high prevalence of stunting, appear well nourished, some are even obese, and thus lack convincing evidence of undernutrition. The authors want to discover how many of the world’s stunted children are indeed undernourished, and what surrogate measures can answer this question. To try and answer these questions, the authors conducted a cross-sectional study to investigate the association between height and indicators of energetic undernutrition: BMI SDS <−2; mid-upper arm circumference divided by height (MUAC [mm] × 10/height [cm] <1.36) and mean skinfold thickness (SF) <7 mm; using breakpoint regression analysis. The study included 4- to 18-year-old Indonesian and Guatemalan children (n = 5,554) with up to 50% stunted children. The results showed no relation between BMI, MUAC, and skinfold thickness as indicators of the nutritional status, and height in this population with a high prevalence of stunting. The authors conclude that the results failed to detect relevant associations between BMI, MUAC, or SF and stunting. They propose using the presence of a catch-up growth spurt during early re-feeding (4–6 weeks) instead, as an immediate and sensitive indicator of pre-existing malnutrition. The authors claim that the absence of catch-up growth following re-feeding indicates that malnutrition was not the cause of stunting. They further suggest that nutrition alone is not the leading cause of stunting in developing countries, but rather education and social-economic-political-emotional factors.

However, it is important to note that undernutrition can result from micronutrient deficiencies, even when energy intake and weight status are adequate. This may explain the lack of association between BMI and body composition parameters and stunting in this cross-sectional study. Furthermore, some ethnic populations in low income countries are indeed short-statured due to genetic causes. More prospective
cohort studies in different populations are needed to evaluate the rate of malnutrition among stunted children. These studies should also explore other potential indicators for malnutrition, such as dietary evaluation.

Association between vitamin D status and undernutrition indices in children: a systematic review and meta-analysis of observational studies

Comments: Micronutrients have an essential role in children’s growth. A recent meta-analysis by Roberts and Stein [2] found that zinc, vitamin A, and multiple micronutrients have significant positive effects on linear growth. Vitamin D is essential for bone metabolism and bone health; however, the effects of vitamin D deficiency on undernutrition indices are controversial. This meta-analysis of observational studies by Song et al. aimed to evaluate the association between vitamin D status and undernutrition indices. Seven observational
studies fulfilled the meta-analysis inclusion criteria (4 cohorts and 3 cross-sectional, in total 8,295 participants). The results showed that children with the lowest serum vitamin D concentration had a greater risk of wasting than children with the highest serum vitamin D level category. However, no relationships were found between vitamin status and stunting or underweight. It is important to note that most of the studies included in the meta-analysis were conducted in low socioeconomic status populations, with high risk for other growth related
macro- and micronutrient deficiencies. Thus, the impact of vitamin D on growth outcomes may be trivial in light of other growth-related nutrient deficiencies in children. The results of this meta-analysis have important public health implications and suggest that strategies to improve vitamin D status in children may decrease undernutrition, especially wasting. More prospective large and long-term cohort
studies and interventional studies with vitamin D supplementation are needed to confirm the effect of vitamin D on undernutrition indices in children.

COVID-19 pandemic and mitigation strategies: implications for maternal and child health and nutrition

Comments: This review describes and explains the many ways in which the COVID-19 pandemic and the responses to it have negatively influenced child health and nutrition in LMICs. The authors suggest various possible interventions to overcome the new challenges,
such as food insecurity interventions, social protection programs for at-risk populations, improving access to health care, and more.

Fetal cranial growth trajectories are associated with growth and neurodevelopment at 2 years of age: INTERBIO-21st Fetal Study

Comments: This important study is one of the series of analyses from the InterBIO fetal growth study exploring the relationship between fetal growth patterns in standardized cohorts and birth outcomes as well as growth and development in early childhood. The study was based on a cohort of 3,598 pregnant women from six global sites (the UK, Nigeria, Pakistan, Thailand, Kenya, and the USA) who were followed-up between 2012 and 2019. They evaluated the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks’ gestation, against international standards and growth and neurodevelopment up to 2 years of age. The authors identified five fetal cranial growth trajectories, mainly between 20 and 25 weeks’ gestation, which were associated with specific neurodevelopmental, behavoral, visual, and growth outcomes, independent of fetal abdominal growth, postnatal morbidity, and growth measures at birth and age 2 years. These growth patterns correlated with the maturation of cognitive, language, and visual skills. The study underscores the potential importance of critical periods of fetal growth which are associated with important neurodevelopmental outcomes in children and could be amenable to preventive measures as well as potential early diagnostic strategies.

Gut DYSBIOSIS and altered barrier function precedes the appearance of metabolic syndrome in a rat model of nutrient-induced catch-up growth

Comments: Children exposed to restricted nutrition prenatally and in early life are more prone to develop metabolic syndrome in adulthood – hence the double burden of childhood malnutrition. The authors of this study investigate a possible mechanism of this phenomenon
in an animal model, by comparing offspring of dams fed ad libitum during pregnancy and suckling (controls), with offspring of undernourished dams after weaning both groups to either normal chow or high-fat diet (HFD). The previously undernourished pups fed on HFD developed glucose tolerance, insulin resistance, and white adipose inflammation as expected, compared to the control group fed on
the same diet. The authors found alterations in gut microbial composition, intestinal permeability, and endotoxemia evident in the previously underfed rats, even before catch-up growth occurred. There is a known association between dysbiosis and the development of insulin resistance, obesity, and type 2 diabetes in humans. The observations in this study may help to explain the increased susceptibility for an adverse metabolic profile in the specific set-up of exposure to early life malnutrition.

The nutritional status of individuals adopted internationally as children: a systematic review

Comments: Adopted children, particularly those who are adopted internationally, often experience growth faltering and developmental delay. These medical issues are related to their suboptimal pre-adoption quality of care, including low birth weight, infectious diseases, inadequate nutrition, and psychological deprivation. Children adopted internationally (CAI) typically relocate from low-income countries with traditional diets and low food availability to high-income countries with obesogenic environments. The traditional treatment strategies in this population of CAI have so far focused on preventing short-term malnutrition-associated mortality. However, there is increasing
awareness of possible adverse long-term consequences, including a higher risk of chronic diseases in adulthood. This systemic review of observational and cross-sectional studies by Ivey et al. aimed to describe the nutritional status of individuals adopted internationally and their long-term nutritional and health outcomes. The review included 24 papers published between 1997 and 2019. The main findings
of the review showed that CAI were commonly malnourished when they arrived in their adoptive families, regardless of their country of origin and sex. Furthermore, children adopted at an older age were more undernourished than younger children, regardless of their prior living situation. Very few studies described the nutritional status of CAI post-adoption, but these suggest that substantial catch-up growth is possible for all CAI in weight, height, and head circumference. The authors identified several existing knowledge gaps, mainly the need to describe the long-term health effects of international adoption. The authors conclude that although CAI are at high risk of malnutrition at the time of adoption, remarkable catch-up growth is possible, including for those older than 2 years of age on arrival. Further studies examining the long-term outcomes on weight status and health of CAI are needed to clarify factors and mechanisms which are also
relevant to the wider population of children recovering from any type of early life malnutrition.

Prospective longitudinal assessment of linear growth and adult height in female adolescents with anorexia nervosa

Comments: It is well established that undernutrition during infancy and early childhood is associated with growth retardation. However, relatively little is known regarding the effect of undernutrition during adolescence on linear growth and adult height (AH). Anorexia nervosa (AN) is a severe psychiatric disorder that occurs mainly in adolescence. In AN patients, malnutrition occurs in the absence of physical illnesses, and weight rehabilitation is a primary treatment. Hence, AN may serve as a good model for studying the effect of malnutrition and following weight rehabilitation during adolescence on linear growth. This prospective observational study by Modan-Moses et al. is one of the largest studies to evaluate linear growth from admission until achievement of AH, as well as premorbid and parental height data. The study included 255 female adolescent AN patients hospitalized in the pediatric psychosomatic department at Chaim Sheba Medical Center, Israel, between 2000 and 2015. The results showed that malnutrition has a significant effect on linear growth of adolescent females with AN. Height-SDS at the time of admission (–0.36 ± 0.99) and after weight rehabilitation at discharge (–0.34 ± 0.96) were significantly lower as compared to their premorbid height-SDS (0.005 ± 0.96), which was not significantly different from expected in normal adolescents. In most patients, weight rehabilitation did not result in an improvement in linear growth, and AH-SDS (–0.29 ± 0.95) was lower than expected compared both to the normal population and to the mid-parental target height. Older age and younger skeletal age at admission, as well as linear growth during hospitalization, were predictors of improvement in height-SDS between admission and AH. The results of this study emphasize the importance of early detection and initiation of treatment of AN in adolescents. It also emphasizes the need to develop and evaluate new nutritional treatment strategies that may improve linear catchup growth and final height in these patients.

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

Comments: This was the long-awaited update of the nutrition interventions evidence since the last compilation of interventions in the 2013 Lancet series on maternal and child nutrition [3]. Since then, the evidence on the ten recommended interventions has increased, along with evidence of newer interventions, such as from preventive small quantity lipid-based nutrient supplements for children aged 6–23 months, interventions for the prevention and management of childhood obesity, integrated interventions (e.g., diet, exercise, and behavioral therapy) and the newer evidence on the effectiveness of antenatal multiple micronutrient supplementation. The updated evidence also supports the provision of supplementary food in food-insecure settings and community-based approaches with the use of locally produced supplementary and therapeutic foods to manage children with acute malnutrition. A major challenge, however, remains the implementation of such interventions in scale, especially in settings such as conflict settings and those in fragile health systems.

Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age

Comments: This systematic review explored the role of Vitamin D, a secosteroid hormone, on linear growth and other health outcomes among infants and children under 5 years of age. The authors reviewed a large body of evidence, mostly representing randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of oral vitamin D supplementation, with or without other micronutrients, compared to no intervention, placebo, a lower dose of vitamin D, or the same micronutrients alone (and not vitamin D) among infants and children under 5 years of age without any geographic restriction. They synthesized 75 studies summarized in 187 reports with12,122 participants of which 64 studies (169 reports; 10,854 participants) were included in the meta-analysis. In comparing vitamin D supplementation versus placebo or no intervention (31 studies) vitamin D supplementation (at doses of 200–2,000 IU daily, or up to 300,000 IU bolus at enrolment) made little to no difference in linear growth (measured length/ height in cm) among children under 5 years of age (mean difference [MD] 0.66, 95% CI –0.37 to 1.68; 3 studies, 240 participants; low-certainty evidence), probably improved length/height-for-age z-score (L/HAZ) (MD 0.11, 95% CI 0.001 to 0.22; 1 study, 1,258 participants; moderate-certainty evidence), and probably made little to no difference in stunting (risk ratio 0.90, 95% CI 0.80 to 1.01; 1 study, 1,247 participants; moderate-certainty evidence). Comparison of high versus low dose vitamin D supplementation did not make any difference. Overall assessment of the evidence suggests that oral vitamin D supplementation resulted in little to no difference in linear growth, stunting, hypercalciuria, or hypercalcemia compared to placebo or no intervention, but could lead to a slight increase in L/HAZ. The authors recommend larger, well designed studies of longer duration among children, especially those under 24–36 months of age.

How countries can reduce child stunting at scale: lessons from exemplar countries

Comments: This paper reports the synthesis of the Exemplars in Stunting project supported by Gates Ventures in partnership with the SickKids Centre for Global Child Health. The paper is a qualitative and quantitative synthesis of findings from existing literature and 5 exemplar country studies (Nepal, Ethiopia, Peru, Kyrgyz Republic, Senegal) and focuses on the outcomes from the Oxaca-Blinder decomposition analysis of drivers of stunting also guided by a robust policy and implementation analysis and in-country qualitative studies. The exemplars analysis across these five countries showed that a rapid and significant reduction in stunting was possible, often but not always with reduction in the population of geographic inequities. Countries reduced stunting through a variety of interventions including direct and indirect health and nutrition interventions, as well as indirect interventions from outside these sectors. Despite significant heterogeneity and differences in context, contributions were comparable from health and nutrition sectors (40% of change) and other sectors (50%), previously called nutrition-specific and nutrition-sensitive strategies. Improvements in maternal education, maternal nutrition, maternal and newborn care, and reductions in fertility/reduced interpregnancy intervals were strong contributors to change. The paper also presents a roadmap to reducing child stunting at scale; a ten-step process that includes robust situational analysis, stakeholder consultations, and implementing direct and indirect nutrition interventions related to the health sector and non-health sectors, especially in gap areas.

References
1 World Health Organization. Levels and trends in child malnutrition: UNICEF/WHO/The World Bank Group joint child malnutrition estimates: key findings of the 2021 edition. https://www.who.int/publications/i/ item/9789240025257 (accessed November 29, 2021).
2 Roberts JL, Stein AD. The impact of nutritional interventions beyond the first 2 years of life on linear growth: a systematic review and meta-analysis. Adv Nutr. 2017;8:323–33.
3 Series from the Lancet Journals. Maternal and child nutrition. https://www.thelancet.com/series/maternaland- child-nutrition (accessed November 29, 2021)