Field Notes

Malnutrition Early in Life Sets Stage for Poor Growth and Early Death

In a trio of studies appearing in Nature, researchers offer the most comprehensive look yet at how malnutrition affects growth in the first two years of life, underscoring a devastating reality for millions of children in the Global South, particularly Asia.

In 2022, more than one in five children around the world—nearly 150 million—didn’t get enough calories to grow normally, and more than 45 million showed signs of wasting or weighing too little for their height. More than a million children die each year as a consequence of wasting, and more than 250,000 die from stunting. People who experience stunting and wasting in childhood also may experience worse cognitive development, which translates into worse economic outcomes as adults.

Stunting, or being too short for their age, indicates chronic malnutrition while wasting measures acute malnutrition. The global health community uses both indications to monitor progress toward ending malnutrition.

"Children whose growth begins to falter before they’re six months old are much more likely to die and much more likely to have severe forms of growth faltering by the time they're 18 to 24 months old," says the studies' senior author, Benjamin Arnold, PhD, MPH, an associate professor at University of California, San Francisco's Francis I. Proctor Foundation. "This suggests there’s a very narrow period in which we can intervene, ideally in the prenatal period. It also suggests broader interventions are needed to improve nutrition among women of childbearing age."

Arnold, an infectious disease epidemiologist and biostatistician, helped lead the research while at UC Berkeley in conjunction with the Center for Targeted Machine Learning (CTML).

Season of Birth Makes a Difference
The analysis involved an international team of more than 100 researchers led by UC Berkeley that examined data on nearly 84,000 children under age 2 from 33 major studies that began between 1987 and 2014. The cohorts came from 15 countries in South Asia, Sub-Saharan Africa, Latin America, and Eastern Europe.

The effects of malnutrition are seen throughout lower resource settings, but the burden is starkest in South Asia, where 20% of children were stunted at birth, and more than 52% had experienced wasting by their second birthday, according to new estimates provided by the study.

The researchers observed large seasonal changes in wasting that coincided with rainfall, likely reflecting seasonal food insecurity in places where people rely on crops as their main source of nutrition.

In the South Asian cohorts, a child born in May was far more likely to experience wasting than a child born in January, primarily due to seasonal food availability and the nutrition status of the mother during pregnancy.

"By virtue of when a child happens to be born, they could be set off on a completely different trajectory in terms of growth," Arnold says. But he notes that no known health interventions have been able to correct the levels of seasonal deficits uncovered in this analysis.

Earlier Intervention Is Key
While some children can catch up with improvements to their health and nutrition, the earlier onset of growth faltering revealed in this research suggests that public health interventions should expand their focus to include children under 6 months old and pregnant mothers.

Currently, most childhood nutrition interventions begin after about six months of age because they often include nutritional supplementation, and public health programs don't want to interfere with breast-feeding.

"Our findings suggest that if health interventions aren’t delivered before age six months, it’s too late to prevent stunted growth for about a third of children in the populations represented in this study and as many as half of children in South Asia," says Jade Benjamin-Chung, PhD, MPH, first author of a study in the series and an assistant professor at Stanford University. Benjamin-Chung helped lead the research as part of the division of epidemiology and biostatistics while she was at UC Berkeley.

The studies also highlight the need to provide nutrition and health support to women before conception and continue that support during and after pregnancy. In the studies, the researchers observed that a malnourished mother is likely to give birth to a child who will repeat that cycle of malnutrition into the next generation.

"Early life malnutrition sets a concerning course that can span generations," says Andrew Mertens, PhD, a research data analyst at CTML and lecturer at UC Berkeley and one of the study’s first authors. "Immediate interventions are essential, but we also need sustained investments in development and in public health and nutrition programs to break this cycle. Support during the first 1,000 days of life matters immensely for the individual and for society as a whole."

— Source: University of California, San Francisco

Earlier Detection of Cardiometabolic Risk Factors for Kids May Be Possible

The next generation of cardiometabolic biomarkers should pave the way for earlier detection of risk factors for conditions such as obesity, diabetes, and heart disease in children, according to a new scientific statement from the American Heart Association published in the journal Circulation.

“The rising number of children with major risk factors for cardiometabolic conditions represents a potential tsunami of preventable disease for our health care system,” says the statement’s lead author Michele Mietus-Snyder, MD, a preventive cardiologist and clinical research scientist at Children’s National Hospital. “But by the time a child is identified based on today’s clinical biomarkers, it’s often too late to reverse the disease trajectory.”

The Big Picture
The scientific statement included biomarkers that met the following three criteria:

early and precise clinical detection of metabolic abnormalities before a child begins to show the current clinical signs such as high BMI, blood pressure, or cholesterol;
mechanistic intervention targets providing immediate risk measures and giving clinicians new targets to personalize and optimize interventions; and
modifiable biomarkers that are capable of tracking progression toward or away from cardiometabolic health.

The statement’s identified biomarkers included measures of the following:

epigenetic, or environmental, factors;
gut microbiome health;
small particle metabolites in the body;
different types of lipids and their impacts on cell membranes; and
inflammation and inflammatory mediators.

The authors proposed these biomarkers with the goal of “expanding awareness to include a whole new realm of biomarkers that precede the traditional risk factors we currently rely upon, such as BMI, blood pressure, cholesterol, and blood sugar,” Mietus-Snyder says. “Ideally, these new biomarkers will be added to the array of measures used in clinical research to better assess their value for earlier identification and prevention of global patterns of cardiometabolic health and risk.”

Why It Matters
The next generation cardiometabolic biomarkers the authors outlined are all currently used in research studies and would need to be validated for clinical use. However, Mietus-Snyder notes that the data already collected from these biomarkers in research can make a difference in clinical practice by enhancing our understanding of the deep metabolic roots for children at risk.

Evidence reviewed in the statement shows the risk factors children are exposed to, even before birth, can set the stage for cardiovascular and metabolic health across the lifespan.

Interestingly, all the different factors reviewed have been found to alter the functioning of the mitochondria—the complex organelles responsible for producing the energy for the body that every cell and organ system, in turn, needs to function. Every class of biomarkers reviewed also is favorably influenced by heart-healthy nutrition, a simple but powerful tool known to improve mitochondrial function.

What’s Next
Even as the new so-called “omic” biomarkers reviewed in this statement are developed for clinical applications, there are steps clinicians can take to optimize them and improve mitochondrial function, according to Mietus-Snyder.

Most important is to strengthen the collective dedication of care providers to removing the barriers that prevent people, especially expecting mothers and children, from living heart-healthy lifestyles.

We have long known that lifestyle factors influence health. Even as complicated metabolic reasons for this are worked out, families can reset their metabolism by decreasing sedentary time and increasing activity, getting better and screen-free sleep, and eating more real foods, especially vegetables, fruits, and whole grains, rich in fiber and nutrients, with fewer added sugars, chemicals, preservatives, and trans fats. Clinicians can work with their patients to set goals in these areas.

“We know diet and lifestyle are effective to some degree for everyone but terribly underutilized. As clinicians, we have compelling reasons to rededicate ourselves to advocating for healthful lifestyle interventions with the families we serve and finding ways to help them implement them as early as possible. The evidence shows the sooner we can intervene for cardiometabolic health, the better.”

— Source: Children’s National Hospital