Wasting, occurring predominately in the developing world, results from inadequate intake of a wide range of nutrients, and is often exacerbated by inflammation from infectious causes. 

While the consequences of wasting have long been recognized by anthropometry, and treated with therapeutic foods, the effect of wasting on the brain has not been appreciated or measured.

To truly heal the malnourished child, nutritional considerations of brain need to be elucidated and integrated into the standard of care.

Our team has utilized 3 methods of measuring cognition; problem solving assessment, saccadic reaction time and more traditional global neurodevelopment assessments.

Because we work in sub-Saharan Africa we use the Malawi Developmental Assessment Tool (MDAT) for the neurodevelopmental assessments.

We have investigated the effect of the provision of more dietary omega-3 polyunsaturated fatty acids (PUFA) and less omega-6 PUFA in severely malnourished children and found significant improvement in longterm cognition.

This has now been codified as a requirement in ready-to-use therapeutic food (RUTF), the most widely used food aid product in severely wasted children. Additional nutrients that might further augment neurocognitive recovery will be discussed as well.

This talk will briefly introduce some of the various forms of malnutrition across the life cycle as a means of setting the stage for the more detailed talks to follow during the course of the symposium.

In Lao PDR, 34% of children under the five years of age are stunted and 27% are underweight.  To address malnutrition, the government of Lao PDR, the US government and OHSU partnered to establish the National Institute of Nutrition (NIN).  Educational priorities for the NIN were collaboratively established and a Clinical Nutrition and Dietetics Curriculum was implemented.  

The curriculum includes nutrition assessment, diagnosis, Nutrition Focused Physical Exam techniques, counseling, intervention, and follow-up.   Pre-tests and final exams were administered to each cohort and resulted in a 94% increase in malnutrition related content.  

To date, 38 clinicians have successfully completed the “Clinical Nutrition Specialist” program and are working in 7 provinces in district, provincial and national hospitals in Lao PDR.  

Nutrient-poor diets during pregnancy are associated with abnormal baby growth patterns in the womb, which can lead to long-term childhood and adult health risks. Consuming nutrient-dense food choices as part of healthy eating patterns prior to pregnancy and continuing throughout gestation can help reduce pregnancy complications and support healthy offspring development.

Westernized countries are heavily dependent on diets enriched in saturated fatty acids (SFAs); however, most research models of inflammation and infection are carried out in mice fed a low-SFA diet, creating a scenario that overlooks SFA-dependent control of disease outcome.  Here we identify a previously unrecognized role of dietary SFAs, specifically palmitic acid (PA), in inducing a broad and long-lived innate immune memory response which is harmful during an acute septic response, but beneficial for pathogen clearance during systemic infection. 

Moderator: Diane Stadler, PhD, RDN, LD

Panelists: Cummings, Napier, Trehan, Valent

Once thought to be sterile, human milk has its own unique microbes that are likely important in helping establish the infant's gastrointestinal microbiome during early life.

The neonatal intestine forms early during development, but continues to mature right up to and even after birth. The single layer of epithelial cells that lines the surface of the intestine is the most rapidly renewing tissue in the human body. These cells are responsible for an incredible array of functions: 1) nutrient digestion and absorption, 2) secretion of factors important for growth and metabolism, 3) maintenance of the microbial community within the gut, 4) establishing and preserving a selectively permeable barrier to prevent potentially harmful intestinal contents from entering the body cavity, and 5) regulating the intestinal immune system.

This talk will incorporate the latest research findings in the field to describe the elegant sophistication of the neonatal intestinal epithelium; discuss the role of environmental factors, such as nutrients and microbes, in shaping the infant gut; and reveal a role for the intestinal epithelium in conditions such as malnutrition or diseases like necrotizing enterocolitis.

Background: Milk proteins have evolved to benefit the suckling neonate. The extent to which most human milk proteins survive within the infant remains mostly unknown, and thus their bioactive potential is unclear. For many milk proteins, partial digestion releases fragments—peptides—with known antimicrobial, prebiotic, immune-modulating, calcium-delivery, antihypertensive, and pain-modulating activities. The extent to which these peptides survive within the digestive tract need to be further examined to determine their biological relevance. Our objective is to determine the survival of milk proteins and release of bioactive peptides in the intestine of human infants.  

Methods: Milk and infant digestive samples were analyzed using mass spectrometry-based peptidomics, glycopeptidomics, protease assays, ELISA and bioactive peptide database searching to determine how proteins are degraded within the digestive system and which potential bioactive peptides are released. Peptides were tested for function with antimicrobial and macrophage assays.   

Results: In the stomach and intestine of human infants, both infant-produced and milk-derived proteases actively degrade milk proteins, releasing thousands of new peptides while allowing the survival of some milk proteins. Fractions of intestinal peptides had antimicrobial and immunomodulatory actions. 

Conclusion: We have identified an array of peptides released during digestion with antimicrobial and immunomodulatory actions.   

The evolutionary origin of lactation and the composition, structures and functions of milk’s biopolymers highlight the Darwinian pressure on lactation as a complete, nourishing and protective diet. For example, milk contains free oligosaccharides; polymers of sugars whose stereospecific linkages are not matched by glycosidic enzymes within the infant. Hence, these glycan polymers travel to the lower intestine undigested.

In this microbe-rich environment, bacteria compete for the sugars via different hydrolytic strategies. One specific strain of bacteria, Bifidobacteria longum subspecies infantis, is uniquely equipped with a repertoire of enzymes capable of taking up, hydrolyzing and metabolizing the complex glycans of human milk. The intestinal microbiome dominated by B. infantis, protects the infant from gram negative enteropathogens and their endotoxins.

Another example, milk contains proteins synthesized by the mammary gland as food for the infant. Milk also guides the digestion of its proteins with a group of proteases that activate within the infant and cleave the proteins into specific peptides.

These peptides display discrete functions including explicitly inhibiting the growth of intestinal pathogens. Scientists are struggling to understand how to guide the future of agriculture and food in response to 21^st century challenges. 

Lactation provides an inspiring model of what that future could be.

Moderator: Brian Scottoline, MD, PhD

Panelists: Andres, Dallas, German McGuire

In recent decades, the prevalence of pediatric neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism spectrum disorder have risen dramatically.

Mounting evidence indicates an association between developmental exposure to maternal obesity and poor nutrition and increased risk of neurodevelopmental disorders; however, the mechanisms for this association remain unknown.

Our work, using non-human primate models, demonstrates causal effects of maternal obesity and poor nutrition on offspring brain development and behavior, specifically increased anxious behaviors and impairments in social behavior. We hypothesize that developmental exposure to maternal obesity and/or poor maternal nutrition alters child behavior and increases risk for neurodevelopmental disorders. We examine this hypothesis in a longitudinal, prospective human study.

Our data support unique effects of maternal adiposity and diet on infant temperament and emotional regulation. Specifically, we find that maternal obesity increases child negative emotions (sadness and fear) and omega-3 fatty acids are protective. We provide evidence that maternal inflammation during pregnancy is a mechanistic link between poor nutrition and obesity to child behavioral impairments and risk for psychopathology.

We also find evidence that maternal prenatal inflammation may be one common pathway by which prenatal risk factors including obesity, poor nutrition and depression influence offspring mental health outcomes.

This talk will focus on recent and upcoming efforts to advance understanding of the effects of prenatal conditions on brain development.

Stress sensitive aspects of the biology of a pregnant person and fetus create pathways through which the prenatal environment can impact the developing fetal brain. It is therefore not surprising that adverse conditions during pregnancy have repeatedly been associated with heightened risk for offspring development of psychiatric disorders.

The COVID-19 pandemic represents a unique stressor involving social isolation, instability in life circumstances, and threat of illness. Initial results from our ongoing longitudinal study of the effects of pandemic related stress on mental health during pregnancy and infant development will be presented with an emphasis on the importance of considering individual differences, variability in mental health symptoms over time, and specific factors that may mitigate or exacerbate effects of pandemic related stress on parents and infants.

The upcoming HEALthy Brain and Child Development Study, a national effort involving 25 sites around the country, will then be presented as a unique opportunity to further investigate how conditions during pregnancy and in the postnatal environment influence the developing brain.

This study is designed to address major limitations of prior work and provide a more nuanced understanding of how a wide variety of environmental influences and individual differences can lead to risk or resilience.

Women who must rely on mostly rice-based diets can have inadequate thiamine intake, placing their breastfed infants at risk of thiamine deficiency and, in turn, a range of physical and neurocognitive impairments.

We investigated the impact of maternal thiamine supplementation on different aspects of infants’ neurocognitive development across the first year of life. In this double-blind, four-parallel-arm, randomized controlled trial, healthy mothers of exclusively breastfed newborn infants were recruited in Cambodia.

At 2 weeks postnatal, women (n = 335) were randomized to one of four treatment groups to consume one capsule/day with varying amounts of thiamine for 22 weeks: 0, 1.2, 2.4, and 10 mg. At 2, 12, 24, and 52 weeks of age, infants’ development was assessed with a variety of neurological and cognitive measures.

Maternal thiamine supplementation displayed a dose-response relationship to the magnitude of infants’ improved neurocognitive development. However, only infants whose mothers received 10mg daily thiamine showed robust enhancements.

The RAPID-EC surveys have been gathering information from national samples of households with young children and child care providers since the start of the pandemic. One of the predominant findings of the survey is the difficulties around paying for basic needs that both families and providers have been experiencing. A particular area of concern is food insecurity, or hunger.

Data from our household survey show that 18% of families with young children reported experiencing hunger prior to the pandemic. By October 2020, 30% of families reported hunger. The experience of hunger decreased gradually throughout 2021, yet remained above pre-pandemic levels. Since September 2021, the trend has again been on the rise; 23% of families with young children experienced hunger in February 2022.

Child care providers have also reported concerning rates of hunger. In February 2022, one in three child care providers reported experiences of hunger. This is the highest rate we have observed since we began collecting these data from the workforce in 2021. This rate is even higher than the rate of hunger reported by families with young children during the same period.

In this presentation we will describe these results and related data from the RAPID-EC surveys, and consider how these experiences are affecting child well-being currently—as well as how they may affect the development of children who have lived through the pandemic across their lifespans.

Moderator: Dan Marks, MD, PhD

Panelists: Fisher, Graham, Measelle, Sullivan