In neonates to pediatric surgical patients to adults undergoing gastric bypass procedures, micronutrient deficiencies can cause macro problems, speakers said during an ASPEN 2023 Nutrition Science & Practice Conference webinar.
“Micronutrients are needed in minuscule amounts, but they are essential for body function—for hormones, homeostasis, tissue growth and repair,” said Lingtak-Neander Chan, PharmD, BCNSP, a professor of pharmacy and nutrition sciences at the University of Washington, in Seattle. “A deficiency can lead to very, very serious health threats,” Dr. Chan noted.
The causes of micronutrient malnutrition vary widely, from cystic fibrosis–induced pancreatic insufficiency in neonatal ICU patients to chronic inflammation and late-onset celiac disease in adults. But the common end point of treatment for patients of all ages is the restoration of normal levels of vitamins and minerals.
To help achieve that end, Dr. Chan recommended the European Society for Clinical Nutrition and Metabolism (ESPEN) micronutrient guideline published in 2022. “It’s one of the best references we have in terms of assessing micronutrients, the type of laboratory tests to consider and the approach toward it,” he stressed (Clin Nutr 2022;41[6]:1357-1424).
For infants in the NICU, the restoration of micronutrient sufficiency often entails a prolonged “journey to freedom” from IV catheters to full enteral nutrition, said Julia Muzzy, PharmD, BCPPS, BCNSP, an associate professor of pharmacy practice at North Dakota State University and a pediatric clinical pharmacist at Sanford Medical Center, both in Fargo.
“In the NICU, in the world of malabsorption, my mind instantly goes to patients who have short bowel syndrome, either of congenital etiology or acquired through surgical intervention,” Dr. Muzzy said.
Although other factors can precipitate neonatal micronutrient deficiencies, including medications that risk compromising patients’ nutritional status, such as cholestyramine, laxatives and diuretics, Dr. Muzzy noted there is a “much higher occurrence of malnutrition in short bowel syndrome patients.” These are secondary, she added, to conditions such as necrotizing enterocolitis (NEC), intestinal atresia and gastroschisis.
Guiding these very complex patients to full enteral nutrition can be challenging, she said. They may have less than 25% of bowel left after NEC surgery, and they frequently have hyperbilirubinemia. “They have a higher likelihood of staying in our ‘hotel’ NICU,” Dr. Muzzy said.
The first step to patients’ full enteral nutrition status, she noted, is to make sure their electrolytes are managed. “We’re good at that. We know how to manipulate TPN [total parenteral nutrition] to give us the numbers we want. Over time, the bowel has to adapt. We have to give them that time and give them trophic feeds. That way the bowel can grow, and eventually we can do a lengthening procedure, allowing enteral nutrition to become our final and main nutritional source.”
Still, Dr. Muzzy said, “there is so much we don’t know about how to optimize nutrition for these babies because we don’t even know what normal levels are, or ultimately the consequences of too much or too little. We also struggle with appropriate dosage forms, especially for babies that weigh less than [1 kg]. On top of that, she added, “we have to put out fires throughout this journey.”
Micronutrient Malabsorption In Adults
In his presentation, Dr. Chan highlighted deficiencies of two micronutrients—copper and folic acid—which he suggested were not always top of mind as a threat for adults. “It can take weeks or even years to develop full-blown copper deficiency,” he said. “This is really a gradual process,” he noted, “most prominent in patients with duodenal and proximal jejunum complications, such as Roux-en-Y gastric bypass surgery, resection of the stomach or proximal small intestine, or chronic inflammation of the small intestine such as Crohn’s disease.” He mentioned the ESPEN micronutrient guideline referenced above as a key source for assessing and managing copper deficiency.
Dr. Chan recommended patients on home parenteral nutrition should have their copper levels monitored every six to 12 months “to prevent toxicity as well as deficiency, especially in a time of shortage. The goal is to normalize lab values and prevent/resolve hematological and neurological symptoms, including blindness.”
For adults, he said, the established oral copper regimen in treating deficiency is from 2 to 8 mg per day. “Two mg per dose is probably optimal in most patients based on established evidence. Oral doses greater than 2 mg should be given as separate doses. For intravenous infusion, it should be 2 mg per dose diluted in at least 100 mL of saline. Undiluted copper can cause phlebitis, infusion-related pain.”
As for folic acid deficiency, Dr. Chan said, “it is not something we think about in the United States because of folate supplementation and fortification in food.” But celiac disease and other states of chronic malabsorption can alter the clinical picture, “especially for women of child-bearing age,” he noted.
Dr. Chan pointed to two recent population studies, in Canada and the United Kingdom, showing that the risk for birth defects is higher in women with undiagnosed or untreated celiac disease before pregnancy. But neural tube defects, such as spina bifida and cleft palate, were not observed in women with documented celiac disease who received at least 5 mg of folic acid supplementation daily before conception or in the first trimester of pregnancy (Gut 2021;70[6]:1198-1199; Br J Obstet Gynecol 2015;122[13]:1833-1841).
“A few studies showed that the average folic acid intake in patients with celiac disease is about 130 mcg per day due to gluten-free diet and food avoidance and sometimes chronic enteropathy,” Dr. Chan said. This is well below the recommended daily allowance of 400 mcg. This suggests that “women with celiac disease of child-bearing age are often in a chronic state of folate deficiency and at increased risk for birth defects,” he added. “The U.K. study shows that patients with celiac disease diagnosed during pregnancy or after were four times more likely to have babies with neural tube defects, which is preventable with adequate folic acid supplementation.”
“This is very, very significant from the public health standpoint because the adverse outcomes are preventable with folic acid supplementation,” Dr. Chan stressed. “It raises the question of when to start routinely screening folate status, even in patients with no risk of developing enteropathy because now we have a new category of patients who do not have celiac disease but go on a gluten-free diet for other reasons.”
Micronutrient Deficiencies In Pediatric Surgical Patients
For pediatric patients undergoing surgery, micronutrient malabsorption poses another set of clinical challenges. That’s why it’s important “to have time for preoperative assessment and to think about what we need to watch out for in these children before and after surgery,” said Catherine Larson-Nath, MD, CNSC, an associate professor at the University of Minnesota, in Minneapolis. “Why do we worry about the presurgical patient or the surgical patient in general? They are at such high risk for many reasons.” If they’re on parenteral nutrition, she explained, iron and iodine deficiencies can be a problem. “And if there is feeding intolerance, there may be competing needs with their fluid status and medication compatibilities.”
In addition, she said, “Patients may have increased nutrition losses from vomiting or diarrhea due to malabsorption as well as increased nutritional needs due to wound healing and inflammation.” Moreover, surgeries involving gastrointestinal tract alterations are going to decrease overall absorption.
Nutrition data focusing on pediatric surgical patients were limited, Dr. Larson-Nath noted. But she cited one study that looked at children undergoing cardiac surgery and found that those who underwent a two-week “nutritional prehabilitation,” compared with one week for others, had higher preoperative weight, higher postoperative weight gain and better outcomes overall, including shorter ICU and hospital stays and shorter durations on mechanical ventilation (Nutrition 2021;84:111027. doi:10.1016/j.nut.2020.111027).
Along with macronutrients such as protein and amino acids, micronutrients also play a key role in wound healing, Dr. Larson-Nath said. “Wound healing is a complex process that builds on itself and increases metabolic needs for both macro- and micronutrients,” she noted. “We know that many micronutrients, including vitamins A and C as well as zinc and copper, are used in the healing process.” These compounds are crucial to healing processes, including angiogenesis, collagen synthesis, epithelialization and fibroblast maturation.
“It’s also important to remember that you can give too much of a good thing,” Dr. Larson-Nath added. For example, she said, over-supplementation of zinc can impede copper absorption, and too much vitamin C can increase the risk for kidney stones.
—Bruce Buckley
The sources reported no relevant financial disclosures.
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