LETTERS
TO THE
Fat-Soluble Vitamin Deficiency in Children With Intestinal Failure Receiving Home Parenteral Nutrition
T
o the Editor: Ubesie et al (1) reported a high prevalence of vitamin D deficiency (39.8%) in children with intestinal failure (IF). We routinely monitored vitamin A, E, and D levels every 6 months for children who were receiving home parenteral nutrition for IF, following European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines (2). In 2013, we completed a cross-sectional assessment of 32 home parenteral nutrition patients who had fat-soluble vitamin levels measured for 1 year. Twenty children with nonsurgical IF (dysmotility and malabsorption) (group A) and 12 with surgical IF (short bowel syndrome) (group B) were included in the study. All of the patients received daily parenteral nutrition with a standard pediatric multivitamin formulation containing vitamin A, 3500 IU; vitamin D, 250 IU; and vitamin E, 11.20 IU. Vitamin levels were low in groups A and B, respectively, as follows: vitamin A in 5 (25%) and 4 (30%), vitamin D in 9 (45%) and 4 (30%), and vitamin E in 2 (10%) and 0. Overall, 15 patients in group A (75%) and 6 patients in group B (50%) showed low levels of fat-soluble vitamins. The likelihood of low fat-soluble vitamin levels was significantly greater in nonsurgical IF than in patients with short bowel syndrome (odds ratio 6, 95% confidence interval 1.5–24.5). Thus, we agree that routine surveillance of fat-soluble vitamins and consideration of enteral or parenteral supplementation, including periodic intramuscular injection, may be useful in children with IF. Antonella Diamanti, Teresa Capriati, Sabrina Cardile, Sabina Benedetti, yPaola Francalanci, and Domenica Elia Surgical Department y Laboratory Department, Pediatric Hospital ‘‘Bambino Gesu`,’’ IRCCS, Rome, Italy y
REFERENCES 1. Ubesie AC, Heubi JE, Kocoshis SA, et al. Vitamin D deficiency and low bone mineral density in pediatric and young adult intestinal failure. J Pediatr Gastroenterol Nutr 2013;57:372–6. 2. Koletzko B, Goulet O, Hunt J, et al. Guidelines on pediatric parenteral nutrition of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41:S70–5.
Authors’ Response
T
o the Editor: Diamanti et al referred to our earlier work, wherein we reported a high prevalence of vitamin D deficiency (39.8%) in children with intestinal failure (IF) (1). In their letter, they found that fat-soluble vitamin (A, D, and E) deficiencies were common among patients with IF receiving home parenteral nutrition (PN), especially those with nonsurgical IF. This is extremely interesting and revealing. Our group has also published our evaluation comparing micronutrient deficiencies among
EDITOR
patients with IF during and after transition to full enteral nutrition (EN) (2). In that study we reported that deficiencies of the fatsoluble vitamins were more common than those of the water-soluble vitamins, both during and after transition to EN. The proportion of patients with vitamin A and E deficiencies after transition to EN improved, whereas the incidence of vitamin D deficiency remained relatively stable. Finally, primary gastrointestinal diagnosis of Hirschsprung disease, dysmotility, and complex gastroschisis were significantly associated with micronutrient deficiencies (P ¼ 0.003) during but not after successful transition to EN. The high rate of fatsoluble vitamin deficiencies reported in these studies and the letter by Diamanti et al (1,2) may be explained by the following observations: impaired absorption, particularly in patients with resected terminal ileum owing to interrupted enterohepatic circulation; dysmotility secondary to a generalized malabsorption state, related to bacterial overgrowth, which may lead to deconjugation of bile salts and increased inflammation with further small intestinal injury; and PN-associated cholestasis from prolonged PN, even after successful transition to full EN, as shown by our group. In conclusion, we agree with Diamanti et al that closer monitoring (as recommended by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (3)) for at-risk patients such as those with dysmotility, cholestasis, and extensive ileal resection is necessary while they are receiving long-term PN. Encouraging intestinal adaptation and ultimately weaning patients with IF off PN could ameliorate deficiencies. Issues of compliance, however, must be addressed, especially among patients weaned to full oral or enteral feeds only. Agozie Ubesie and yConrad R. Cole Department of Pediatrics, University of Nigeria, Enugu, Nigeria y Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
REFERENCES 1. Ubesie AC, Heubi JE, Kocoshis SA, et al. Vitamin D deficiency and low bone mineral density in pediatric and young adult intestinal failure. J Pediatr Gastroenterol Nutr 2013;57:372–6. 2. Ubesie AC, Kocoshis SA, Mezoff AG, et al. Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition. J Pediatr 2013;163:1692–6. 3. Koletzko B, Goulet O, Hunt J, et al. Guidelines on pediatric parenteral nutrition of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41:S70–5.
Growth Faltering in VLBW Infants Fed Breast Milk Fortified With New Sterile Liquid Fortifier
T
o the Editor: Adequate protein intake in the enterally fed very-low-birth-weight (VLBW) infant is essential to meet both growth and deficit requirements during the stay in the neonatal intensive care unit (NICU). Recent guidelines have stressed the importance of increasing the protein content of breast milk fed to VLBW infants (1).
e46 JPGN Volume 59, Number 5, November 2014 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
JPGN
Volume 59, Number 5, November 2014
Letters to the Editor
REFERENCES
TABLE 1. Growth z scores and intake data
Birth z score: W/FOC/L Discharge z score: W/FOC/L Kilocalorie per kilogram intake on day 21/28 Protein intake (g/kg) on day 21/28 BUN (mg/dL) on day 21/28
Liquid fortifiers, N ¼ 82
Powder fortifier, N ¼ 99
0.20/0.30/0.13 1.02 /0.94/1.29
0.19/0.09/0.28 0.77 /0.70/0.99
120 /124 4.1 /4.3 14 /11
112 /120 3.8 /4.0 17 /16
z score: 2010 Fenton growth curves. Standard deviation for each variable omitted for clarity (available from author). BUN ¼ blood urea nitrogen; FOC ¼ fronto-occipital circumference; L ¼ length; W ¼ weight. P < 0.05; P < 0.01. Student t test used.
We have used the new sterile concentrated liquid human milk fortifier (HMF) released in 2013 and also the new liquid protein concentrate (Abbott, Lake Forest, IL) in all breast milk (donor and mother) fed to VLBW babies admitted to our NICU. This change to ready-to-feed sterile liquid fortifiers was done to reduce risk of bacterial contamination, especially with Cronobacter sakazakii. We compared these infants’ growth with that of a similar cohort from the previous year (2012) who had breast milk fortified in an identical fashion with powder HMF (Abbott) and modular protein powder (Beneprotein, Nestle Health Science, Florham Park, NJ). The constituents of the powder and liquid HMF were similar (2). Expressed breast milk was fortified to 24 kcal/oz with HMF when feeds reached 100 mL/kg in both time periods. When 150 mL kg1 day1 feeds were attained, additional protein was added (one-fourth tablespoon Beneprotein per 50 mL or 2.4 mL liquid protein per 60 mL; both calculated to provide an additional 1 g kg1 day1 of protein intake). When we used liquid HMF, we noted frequent sedimentation that required agitation of the feed by the bedside nurse. This phenomenon had not been seen with the powdered HMF. In addition, to maintain growth velocity from week to week, we noted a more frequent need to fortify feeds to 26 kcal/oz. Birth anthropometrics were similar in the 2 cohorts, but by the time of discharge, the weight z score was significantly lower when liquid fortifier and liquid protein were used (Table 1). This decreased z score occurred despite similar calculated protein intakes in both time periods. Not only was calorie intake increased significantly in the liquid fortified cohort but also, most strikingly, the blood urea nitrogen values were significantly lower. We speculate that the sedimentation we observed with the new liquid HMF has resulted in poorer protein delivery and/or absorption, resulting in poorer growth. We are evaluating our options for breast milk fortification but believe that this new liquid ready-to-feed fortifier does not meet the protein needs of the VLBW infant in our NICU. Shelley Blakeney, Jennifer Seale, Heather Hendrikson, and Jonathan Whitfield Department of Pediatrics, Division of Neonatology and Nutrition, Baylor University Medical Center, Dallas, Texas
www.jpgn.org
1. Agostini C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from European Society of Pediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatric Gastroenterol Nutr 2010;50:85–91. 2. Whitfield J, Blakeney S, Hendrikson H, et al. Fortification of breast milk in VLBW infants: ready to feed liquid or ‘‘should not feed’’ powder? Abstract 3555.3. Human Milk Monday; Vancouver, Canada; May 5, 2014.
Inflammatory Bowel Disease in Sickle Cell Disease: Diagnostic and Treatment Challenges
T
o the Editor: We would like to alert our colleagues to the diagnostic challenge that is faced when symptoms of an underlying condition, in this case sickle cell disease (SCD), mask new-onset inflammatory bowel disease. A 13-year-old African American boy with homozygous SCD presented to the emergency department with abdominal pain and occasional blood-streaked stools. He was treated for vasoocclusive pain crisis. Two weeks later he returned with worsened abdominal pain, emesis, hematochezia, 13-lb weight loss, and elevated inflammatory markers. Endoscopy and colonoscopy with biopsies revealed patchy chronic active pancolitis and normal terminal ileum, and magnetic resonance enterography revealed wall thickening of the mid and distal small bowel, ascending and left colon, all consistent with Crohn disease. Owing to the concern for increased SCD morbidity from systemic corticosteroids (1), mesalamine monotherapy was initially used with symptomatic control; however, he subsequently required systemic corticosteroids for Crohn disease exacerbation, which he tolerated well, possibly because of high (23%) fetal hemoglobin. Prednisone was tapered, and for the past year his condition has been controlled effectively with weekly subcutaneous methotrexate. Providers need to maintain a high index of suspicion because signs and symptoms can be similar in both conditions. Interdisciplinary management is crucial for optimal outcome. Corticosteroids can cause increased morbidity in SCD, but tolerance can be improved with disease-modifying therapies such as chronic red blood cell transfusion or hydroxyurea. Justin M. Azar, Deepika S. Darbari, Emily R. Meier, Laurie S. Conklin, and Anil Darbari Children’s National Health System, Washington, DC
REFERENCE 1. Darbari DS, Castro O, Taylor JG 6th, et al. Severe vaso-occlusive episodes associated with use of systemic corticosteroids in patients with sickle cell disease. J Natl Med Assoc 2008;100:948–51.
e47
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
TO THE
Fat-Soluble Vitamin Deficiency in Children With Intestinal Failure Receiving Home Parenteral Nutrition
T
o the Editor: Ubesie et al (1) reported a high prevalence of vitamin D deficiency (39.8%) in children with intestinal failure (IF). We routinely monitored vitamin A, E, and D levels every 6 months for children who were receiving home parenteral nutrition for IF, following European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines (2). In 2013, we completed a cross-sectional assessment of 32 home parenteral nutrition patients who had fat-soluble vitamin levels measured for 1 year. Twenty children with nonsurgical IF (dysmotility and malabsorption) (group A) and 12 with surgical IF (short bowel syndrome) (group B) were included in the study. All of the patients received daily parenteral nutrition with a standard pediatric multivitamin formulation containing vitamin A, 3500 IU; vitamin D, 250 IU; and vitamin E, 11.20 IU. Vitamin levels were low in groups A and B, respectively, as follows: vitamin A in 5 (25%) and 4 (30%), vitamin D in 9 (45%) and 4 (30%), and vitamin E in 2 (10%) and 0. Overall, 15 patients in group A (75%) and 6 patients in group B (50%) showed low levels of fat-soluble vitamins. The likelihood of low fat-soluble vitamin levels was significantly greater in nonsurgical IF than in patients with short bowel syndrome (odds ratio 6, 95% confidence interval 1.5–24.5). Thus, we agree that routine surveillance of fat-soluble vitamins and consideration of enteral or parenteral supplementation, including periodic intramuscular injection, may be useful in children with IF. Antonella Diamanti, Teresa Capriati, Sabrina Cardile, Sabina Benedetti, yPaola Francalanci, and Domenica Elia Surgical Department y Laboratory Department, Pediatric Hospital ‘‘Bambino Gesu`,’’ IRCCS, Rome, Italy y
REFERENCES 1. Ubesie AC, Heubi JE, Kocoshis SA, et al. Vitamin D deficiency and low bone mineral density in pediatric and young adult intestinal failure. J Pediatr Gastroenterol Nutr 2013;57:372–6. 2. Koletzko B, Goulet O, Hunt J, et al. Guidelines on pediatric parenteral nutrition of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41:S70–5.
Authors’ Response
T
o the Editor: Diamanti et al referred to our earlier work, wherein we reported a high prevalence of vitamin D deficiency (39.8%) in children with intestinal failure (IF) (1). In their letter, they found that fat-soluble vitamin (A, D, and E) deficiencies were common among patients with IF receiving home parenteral nutrition (PN), especially those with nonsurgical IF. This is extremely interesting and revealing. Our group has also published our evaluation comparing micronutrient deficiencies among
EDITOR
patients with IF during and after transition to full enteral nutrition (EN) (2). In that study we reported that deficiencies of the fatsoluble vitamins were more common than those of the water-soluble vitamins, both during and after transition to EN. The proportion of patients with vitamin A and E deficiencies after transition to EN improved, whereas the incidence of vitamin D deficiency remained relatively stable. Finally, primary gastrointestinal diagnosis of Hirschsprung disease, dysmotility, and complex gastroschisis were significantly associated with micronutrient deficiencies (P ¼ 0.003) during but not after successful transition to EN. The high rate of fatsoluble vitamin deficiencies reported in these studies and the letter by Diamanti et al (1,2) may be explained by the following observations: impaired absorption, particularly in patients with resected terminal ileum owing to interrupted enterohepatic circulation; dysmotility secondary to a generalized malabsorption state, related to bacterial overgrowth, which may lead to deconjugation of bile salts and increased inflammation with further small intestinal injury; and PN-associated cholestasis from prolonged PN, even after successful transition to full EN, as shown by our group. In conclusion, we agree with Diamanti et al that closer monitoring (as recommended by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (3)) for at-risk patients such as those with dysmotility, cholestasis, and extensive ileal resection is necessary while they are receiving long-term PN. Encouraging intestinal adaptation and ultimately weaning patients with IF off PN could ameliorate deficiencies. Issues of compliance, however, must be addressed, especially among patients weaned to full oral or enteral feeds only. Agozie Ubesie and yConrad R. Cole Department of Pediatrics, University of Nigeria, Enugu, Nigeria y Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
REFERENCES 1. Ubesie AC, Heubi JE, Kocoshis SA, et al. Vitamin D deficiency and low bone mineral density in pediatric and young adult intestinal failure. J Pediatr Gastroenterol Nutr 2013;57:372–6. 2. Ubesie AC, Kocoshis SA, Mezoff AG, et al. Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition. J Pediatr 2013;163:1692–6. 3. Koletzko B, Goulet O, Hunt J, et al. Guidelines on pediatric parenteral nutrition of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41:S70–5.
Growth Faltering in VLBW Infants Fed Breast Milk Fortified With New Sterile Liquid Fortifier
T
o the Editor: Adequate protein intake in the enterally fed very-low-birth-weight (VLBW) infant is essential to meet both growth and deficit requirements during the stay in the neonatal intensive care unit (NICU). Recent guidelines have stressed the importance of increasing the protein content of breast milk fed to VLBW infants (1).
e46 JPGN Volume 59, Number 5, November 2014 Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
JPGN
Volume 59, Number 5, November 2014
Letters to the Editor
REFERENCES
TABLE 1. Growth z scores and intake data
Birth z score: W/FOC/L Discharge z score: W/FOC/L Kilocalorie per kilogram intake on day 21/28 Protein intake (g/kg) on day 21/28 BUN (mg/dL) on day 21/28
Liquid fortifiers, N ¼ 82
Powder fortifier, N ¼ 99
0.20/0.30/0.13 1.02 /0.94/1.29
0.19/0.09/0.28 0.77 /0.70/0.99
120 /124 4.1 /4.3 14 /11
112 /120 3.8 /4.0 17 /16
z score: 2010 Fenton growth curves. Standard deviation for each variable omitted for clarity (available from author). BUN ¼ blood urea nitrogen; FOC ¼ fronto-occipital circumference; L ¼ length; W ¼ weight. P < 0.05; P < 0.01. Student t test used.
We have used the new sterile concentrated liquid human milk fortifier (HMF) released in 2013 and also the new liquid protein concentrate (Abbott, Lake Forest, IL) in all breast milk (donor and mother) fed to VLBW babies admitted to our NICU. This change to ready-to-feed sterile liquid fortifiers was done to reduce risk of bacterial contamination, especially with Cronobacter sakazakii. We compared these infants’ growth with that of a similar cohort from the previous year (2012) who had breast milk fortified in an identical fashion with powder HMF (Abbott) and modular protein powder (Beneprotein, Nestle Health Science, Florham Park, NJ). The constituents of the powder and liquid HMF were similar (2). Expressed breast milk was fortified to 24 kcal/oz with HMF when feeds reached 100 mL/kg in both time periods. When 150 mL kg1 day1 feeds were attained, additional protein was added (one-fourth tablespoon Beneprotein per 50 mL or 2.4 mL liquid protein per 60 mL; both calculated to provide an additional 1 g kg1 day1 of protein intake). When we used liquid HMF, we noted frequent sedimentation that required agitation of the feed by the bedside nurse. This phenomenon had not been seen with the powdered HMF. In addition, to maintain growth velocity from week to week, we noted a more frequent need to fortify feeds to 26 kcal/oz. Birth anthropometrics were similar in the 2 cohorts, but by the time of discharge, the weight z score was significantly lower when liquid fortifier and liquid protein were used (Table 1). This decreased z score occurred despite similar calculated protein intakes in both time periods. Not only was calorie intake increased significantly in the liquid fortified cohort but also, most strikingly, the blood urea nitrogen values were significantly lower. We speculate that the sedimentation we observed with the new liquid HMF has resulted in poorer protein delivery and/or absorption, resulting in poorer growth. We are evaluating our options for breast milk fortification but believe that this new liquid ready-to-feed fortifier does not meet the protein needs of the VLBW infant in our NICU. Shelley Blakeney, Jennifer Seale, Heather Hendrikson, and Jonathan Whitfield Department of Pediatrics, Division of Neonatology and Nutrition, Baylor University Medical Center, Dallas, Texas
www.jpgn.org
1. Agostini C, Buonocore G, Carnielli VP, et al. Enteral nutrient supply for preterm infants: commentary from European Society of Pediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatric Gastroenterol Nutr 2010;50:85–91. 2. Whitfield J, Blakeney S, Hendrikson H, et al. Fortification of breast milk in VLBW infants: ready to feed liquid or ‘‘should not feed’’ powder? Abstract 3555.3. Human Milk Monday; Vancouver, Canada; May 5, 2014.
Inflammatory Bowel Disease in Sickle Cell Disease: Diagnostic and Treatment Challenges
T
o the Editor: We would like to alert our colleagues to the diagnostic challenge that is faced when symptoms of an underlying condition, in this case sickle cell disease (SCD), mask new-onset inflammatory bowel disease. A 13-year-old African American boy with homozygous SCD presented to the emergency department with abdominal pain and occasional blood-streaked stools. He was treated for vasoocclusive pain crisis. Two weeks later he returned with worsened abdominal pain, emesis, hematochezia, 13-lb weight loss, and elevated inflammatory markers. Endoscopy and colonoscopy with biopsies revealed patchy chronic active pancolitis and normal terminal ileum, and magnetic resonance enterography revealed wall thickening of the mid and distal small bowel, ascending and left colon, all consistent with Crohn disease. Owing to the concern for increased SCD morbidity from systemic corticosteroids (1), mesalamine monotherapy was initially used with symptomatic control; however, he subsequently required systemic corticosteroids for Crohn disease exacerbation, which he tolerated well, possibly because of high (23%) fetal hemoglobin. Prednisone was tapered, and for the past year his condition has been controlled effectively with weekly subcutaneous methotrexate. Providers need to maintain a high index of suspicion because signs and symptoms can be similar in both conditions. Interdisciplinary management is crucial for optimal outcome. Corticosteroids can cause increased morbidity in SCD, but tolerance can be improved with disease-modifying therapies such as chronic red blood cell transfusion or hydroxyurea. Justin M. Azar, Deepika S. Darbari, Emily R. Meier, Laurie S. Conklin, and Anil Darbari Children’s National Health System, Washington, DC
REFERENCE 1. Darbari DS, Castro O, Taylor JG 6th, et al. Severe vaso-occlusive episodes associated with use of systemic corticosteroids in patients with sickle cell disease. J Natl Med Assoc 2008;100:948–51.
e47
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
