Iodine Deficiency in Extremely Low Gestational Age Newborns Receiving Parenteral Nutrition

Briefly noted: N Kanike et al. Nutrients 202012(6), 1636; https://doi.org/10.3390/nu12061636 (from Kipp Ellsworth Twitter feed)

Full text: Risk of Iodine Deficiency in Extremely Low Gestational Age Newborns on Parenteral Nutrition

Background/Methods: Extremely Low Gestational Age Newborns (ELGAN) do not receive Iodine supplementation while on parenteral nutrition (PN)….We measured urine iodine levels and thyroid function tests in 50 mother–infant dyads at birth, at 1 week, 1, 2, 3 months and near discharge. In our study, 64% of mothers were iodine deficient at the time of delivery.

Key findings:

  • At 1 month of age, ELGAN on PN developed iodine deficiency (p = 0.017) and had high thyroglobulin levels of 187 (156–271) ng/mL
  • Iodine levels improved with enteral feeds by 2 months of age (p = 0.01).

My take: The authors note that “Iodine supplementation during pregnancy and postnatally should be considered to avoid iodine deficiency.”  In addition, in those at risk, there needs to be monitoring and treatment of hypothyroidism.

Related blog posts:

Don’t Forget the Kidneys in Children with Intestinal Failure

Increasingly, kidney problems are recognized in children with intestinal failure/short bowel syndrome who receive long-term parenteral nutrition.  A recent study (H Billing et al JPGN 2018; 66: 751-54) highlights the experience with this issue at a pediatric intestinal rehabilitation center in Germany.

Key findings:

  • Among 50 patients with a median age of 4.2 years, 76% had proteinuria
  • 30% had chronic kidney disease –indicated by reduced creatinine clearance of <90 min (1.73 squared)/min
  • Hypercalciuria was identified in 30 patients (60%)
  • Nephrocalcinosis was identified in 9 patients (18%)

The authors note that end-stage renal failure has not been reported in association with intestinal failure, though proteinuria is associated as a risk factor.

My take: This observational study shows a high frequency of kidney issues in children with intestinal failure. With improvements in survival, chronic kidney disease could become a more significant clinical issue.

 

Tweet below indicates need for careful nutrition input when children are placed on unusual diets, including the ketogenic diet.

Severe Hypothyroidism due to Iodine Deficiency Associated with Parenteral Nutrition

From Kipp Ellsworth Twitter Feed:

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J Parenter Enteral Nutr November 2016 vol. 40 no. 8 1191-1193

Abstract:

Parenteral nutrition is crucial for supply of nutrients in children who cannot tolerate a full enteral diet. In the United States, it is not standard of care to give iodine to children dependent on parenteral nutrition, hence iodine is not routinely included in the micronutrient package. Herein, we present a case of a boy with hypothyroidism secondary to iodine deficiency after prolonged exclusive use of parenteral nutrition. Our case highlights the importance of screening for iodine deficiency and administering timely iodine supplementation in these at-risk children to prevent iatrogenic hypothyroidism.

Related blog posts:

Case Report: Management after Accidental Bolus of Parenteral Nutrition

Fortunately, most mistakes do not result in long-lasting consequences.  The authors’ of a recent report  (JPEN J Parenter Enteral Nutr August 2016 vol. 40 no. 6 883-885note a severe setback for a patient after accidental bolus of parenteral nutrition:

Here’s the abstract:

There is a paucity of data that exists regarding acute toxicity and management in the setting of parental nutrition (PN) overdose. We describe a case of a patient who received an accidental rapid bolus of PN and fat emulsion. She developed a seizure, metabolic acidosis, arrhythmias, myocardial ischemia, altered mental status, hypotension, and hypoxemia likely caused by elevated triglycerides, leading to a hyperviscosity syndrome. After failing standard therapy, she was successfully treated with a single-volume plasma exchange with resolution of symptoms. Fat emulsion or intravenous lipid emulsion and much of its safety have been recently described in its use as a rescue therapy in resuscitation from drug-related toxicity. Elevated serum triglyceride levels can result in a picture similar to a hyperviscosity syndrome. Plasma exchange is a known therapeutic modality for the management of hyperviscosity syndrome and a novel therapy in the treatment of hyperviscosity syndrome due to fat emulsion therapy. In a patient receiving PN with development of rapid deterioration of clinical status, without an obvious etiology, there should be consideration of PN overdose. A rapid assessment and treatment of severe electrolyte abnormalities should be undertaken immediately to prevent life-threatening cardiovascular and central nervous system collapse. If fat emulsion was rapidly coadministered and there are signs and symptoms of hyperviscosity syndrome, then consideration should be given to plasma exchange as an effective therapeutic treatment option.

Detrimental Effect of Early Parenteral Nutrition in Critically-ill Children

Ahead of publication: T Fizez et al. Early versus Late Parenteral Nutrition in Critically Ill Children. DOI: 10.1056/NEJMoa1514762

Link to quick take video summary (<2 minutes) : NEJM Quick Take on Parenteral Nutrition in Children

Abstract:

BACKGROUND

Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear.

METHODS

We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided.

RESULTS

Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006).

CONCLUSIONS

In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.)

More details:

Methods:

  • “In both study groups, enteral nutrition was initiated early and was increased in accordance with local guidelines. Both study groups also received intravenous micronutrients (trace elements, minerals, and vitamins) starting from day 2 and continuing until the enteral nutrition provided reached 80% of the caloric targets. Starting from the morning of day 8 in the pediatric ICU, supplementary parenteral nutrition was provided for patients in both groups who were not yet receiving 80% of the caloric target enterally.”
  • 45% of patients were less than 1 year of age

Discussion:

“Late parenteral nutrition resulted in fewer new infections, a shorter duration of dependency on intensive care, and a shorter hospital stay. The clinical superiority of late parenteral nutrition was shown irrespective of diagnosis, severity of illness, risk of malnutrition, or age of the child.”

My take:  The concept of providing early aggressive nutrition is NOT supported by this study; this study shows that early parenteral nutrition may be detrimental in critically-ill children.  This study echoes the results of a similar study in adults: Early versus late parenteral nutrition in critically ill adults

Springtime in my neighborhood

Springtime in my neighborhood

Enteral Autonomy in Pediatric Intestinal Failure

A recent study (FA Khan et al. J Pediatr 2015; 167: 29-34 -thanks to Mike Hart for forwarding this reference) provides data from a multicenter retrospective cohort of 272 infants.  These infants had of IF were defined by requiring >60 days of PN; they were enrolled in the Pediatric Intestinal Failure Consortium.  The median followup was 33.5 months.  The most common etiologies of IF were necrotizing enterocolitis (NEC), gastroschisis, small bowel atresia, and volvulus. Key findings:

  • 43% achieved enteral autonomy (EA), defined as freedom from PN for >3 months, 13% remained dependent on PN, and 43% had died, undergone intestinal transplantation, or both.
  • Infants with EA were more likely to have had NEC, preserved ileocecal valve, longer preserved small bowel length, and care at a non-transplant center (with retrospective study, high likelihood of a selection bias).

The associated editorial by Valeria Cohran (pages 6-8) notes that pediatric intestinal transplants peaked in frequency in 2007, but in 2014 there only 56 performed.  She also notes that the care of these children with short bowel syndrome in the first year of life is approximately $500,000 ± $250,000!  The improved survival is attributed to minimizing cholestasis with new lipid strategies, minimizing blood stream infections with better care and ethanol locks, and the use of autologous bowel reconstruction surgery. Bottomline: This study and several others show that meticulous care and advances in the treatment of intestinal failure improve the likelihood of survival without the need for intestinal transplantation. FULL CITATION: Khan FA et al. Predictors of enteral autonomy in children with intestinal failure: A multicenter cohort study. J Pediatr 2015 Jul; 167:29-34. [Free full-text J Pediatr article PDF | PubMed® abstract] Related blog posts:

These windows were huge -Grand Tetons in background

These windows were huge -Grand Tetons in background

 

 

Iron Deficiency Common in Patients Requiring Long-Term Parenteral Nutrition

A recent study (JPEN J Parenter Enteral Nutr May 13, 2015 0148607115587329) demonstates a high rate of iron deficiency anemia in patients requiring home parenteral nutrition (Thanks to Kipp Ellsworth for reference).

From Abstract:

Methods: Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated.

Results: Of 185 patients (122 women), 60 (32.4%) were iron deficient…Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2–149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P < .0001); mean hemoglobin increased from 11.0 to 12.5 g/dL (P = .0001); and mean MCV increased from 84.5 to 89.0 fL (P = .007).

Conclusions: Patients receiving HPN are susceptible to IDA. Iron supplementation should be addressed for patients who rely on PN.

Zoo Atlanta

Zoo Atlanta

 

One More Way to Prevent CVL Infections

While a recent study (JPGN 2014; 59: 177-81) discusses the results of several strategies for limiting CVL infections, I found one approach in particular of interest.

This single center study (2009-2013, n=48 children) from Birmingham, UK examined a multidisciplinary enhanced care pathway regarding CVL care.  Implementation of this pathway lowered the risk of all-cause line infections from 1.98 per 1000 parenteral nutrition days to 0.45.  The pathway included training care providers, careful discharge planning, having those with skin conditions see dermatologists, and monitoring compliance.

One important observation was that methicillin-sensitive Staphylococcus aureus (MSSA) infections were often preceded by local signs of infection for a short period prior to systemic infection.  “We devised a pathway for exit site infections in which a swab is taken and empiric topical mupirocin commenced immediately. A decision on any further management is made after 24 to 48 hours.”

Take-home message: Implementing a CVL care pathway lowers CVL infections.  Implementing topical therapy at the first signs of a localized infection can be an important part of this effort.

Related blog posts:

Nutrition Module

More notes from this year’s postgraduate course:

Clinical issues in parenteral nutritionPraveen S. Goday, MBBS, CNSC (page 105)

  • Fish‐oil vs minimizing soybean oil‐based lipid emulsions
  • Catheter‐related bloodstream infections (CRBSI): Ethanol locks “Humans like ethanol and bacterial don’t.”  Meta‐analysis:  In comparison with heparin locks, ETOH locks (various regimens) reduced the following: a) CRBSI‐rate per 1000 catheter days by 7.67 events (81% ↓)  b) catheter replacements by 5.07 (72% ↓), c) 108‐150 catheter days of ETOH lock exposure were necessary to prevent 1 CRBSI, d) Adverse events – rare and included thrombotic events.  Reference: Oliveira et al. Pediatrics 2012;129:318–329

Parenteral Drug Shortages: All PN products except dextrose and water have been in short supply at some point since spring 2010

Imported components from Europe (higher cost)

• Peditrace™ – zinc, copper, manganese, selenium, fluoride, and iodine

• Addamel N™ – zinc, copper, manganese, selenium, fluoride, and iodine, molybdenum, iron, and chromium

Summary / Take‐home points

  • Reduction in soybean oil emulsion or provision of fish oil emulsion results in improvement in cholestasis
  • Ethanol lock therapy decreases CRBSI in children on home PN
  • Significant PN shortages have affected our ability to care for our PN patients; thus need vigilance and good communication between physician, dietitian and pharmacist

Severe Obesity in Your Clinic: The disconnect between the epidemic and the intervention Sarah E. Barlow, MD, MPH (page 125)

What to do for obesity?

  • Behavior modification
  • Pharmacotherapy (and behavior modification)
  1. Orlistat (Xenical, Alli) -Enteric lipase inhibitor, FDA approved starting at age 12 years (OTC $200 per month)
  2. Approved for adults Lorcaserin (Belviq): 5-HT2C agonist
  3. Approved for adults: phentermine and topirimate (Qsymia)
  • Surgery (and behavior modification)
  • Meal replacement (and behavior modification)

Orlistat trial for adolescent obesity:

  • 54 week double-blind RCT
  • 539 subjects: 12 to 16 years of age, BMI 36 ±  4 kg/m2
  • BMI change kg/m2 (mean):  – .55  vs. + 0.31 for control
  • Fecal urgency (%) 20.7 (11.0 in controls)
  • Flatulence (%) 9.1 (4.4 in controls)
  • Fecal incontinence (%) 8.8 (0.6 in controls)
  • Reference: Chanoine et al. JAMA 2005;293:2873

Orlistat meta-analysis among adults :

  • -2.87 kg [95CI -3.21, -2.53] = placebo-subtracted change at 1 year
  • Reference  Rucker D. BMJ 2007;225:1194

Multiple potential medications are being studied

Selection criteria for adolescent bariatric surgery

  • Tanner stage IV or V
  • BMI ≥ 35 kg/m2 with severe
  • Comorbidity or BMI ≥ 40 kg/m2 with comorbidity
  • “Have failed” 6 month of organized attempts at weight loss
  • Committed to pre and post medical and psychological care
  • Supportive family
  • Able to give informed assent
  • Frequent barriers: Distance from center, Insurance, Age, Reluctance
  • Reference: Pratt Obesity 2009;17:901

Complications from Surgery

  • For all procedures: nutritional deficiencies, especially iron, vitamins B12, D, and thiamine
  • For gastric bypass: postprandial hypoglycemia in adults
  • For lap band: need for re-operation for slippage or erosion in adults and small adolescent study.
  • Also pouch dilatation
  • For sleeve gastrectomy: leak or bleeding along suture site

Summary

  1. 4% of children 6 to 19 are severely obese
  2. Severe obesity leads to high levels of cardiovascular disease risk factors, NAFLD, OSA, and pre-diabetes
  3. Behavior modification has modest efficacy, is a partner in all other intensive interventions, but is not readily available behavior modification is underutilized because it is time-intensive and resource-intensive.  It it is necessary even though it is not sufficient.
  4. Orlistat is the only medication currently available for adolescents.

 5 2 1 0

  • 5 servings of fruits and vegetables a day
  • 2 hours or less of screen time
  • 1 hour (60 minutes) or more of physical activity
  • 0 sugar-sweetened beverages

Postgraduate Course Syllabus (posted with permission): PG Syllabus

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

NASPGHAN Preview

I had a few free minutes so I decided to take a look at a bunch of upcoming lectures from the 2013 NASPGHAN upcoming meeting.  With electronic media, it is easy to take a quick glance.  Here’s the master link to all of the following talks:

Annual Meeting page.

Some of the power point lectures that I’ve seen so far:

  • Is my PPI dangerous for me? Eric Hassall MBChB, University of British Columbia One point in his slides that I had not seen much about was a hypothesis that PPI use may predispose to the development of eosinophilic esophagitis by allowing food proteins to be more intact ( attributed to Merwat, Spechler. Am J Gastro ’09).  He explains that “acid reflux” is a clever marketing term and has a slide with Madmen actors.  If there is “acid,” one must need acid suppression.
  • My child doesn’t go to school Lynne Walker MD, Vanderbilt University.  Lynne shows an interesting fax from a parent that asks if the problem is physical, how will she help? And, if it is psychological, how can this be remedied?  She outlines a lot of pain theory and indicates that parents need to become health coaches, avoid catastrophizing (?spelling), and encourages mental health evaluation.  Use the parents words ‘I’m going to refer xxx for relaxation and stress management.’
  • My child’s H. pylori will not go away – (the resistant bug) Benjamin Gold MD, Children’s Center for Digestive Healthcare. Ben manages to stuff so much information into his talk.  His talk is like one of those clown cars where more and more people keep coming out.  He has slides with worldwide resistance maps, slides with treatment regimens and algorithms, and the reasons for treatment failure. Perhaps I can convince him to give a live preview.
  • Administrative/executive functioning Richard Colletti MD, Fletcher Allen Healthcare. Offers personal and pragmatic advice for career advancement.  His slides indicate that he started his GI fellowship at age 40.  One of his quotes, “80% of success is showing up” (Woody Allen) is definitely true.  It’s pretty much akin to what I learned about success in medical school.  You need the three As: availability, affability, and ability.  My mentor said the first was what people needed most.
  • The changing face of intestinal transplantation
    Simon Horslen MD, Seattle Children’s Hospital.  Lecture notes that number of intestinal transplants have decreased dramatically, particularly in children. In 2012, only about 100 intestinal transplants were performed whereas it had peaked at nearly 200.  Much of the credit is due to intestinal rehabilitation work and adjustments in parenteral nutrition (eg. lipid minimization, line care).  Two most common reasons for intestinal transplantation at this time are gastroschisis and volvulus.
  •  Gluten sensitivity: Fact or fiction Alessio Fasano MD, MassGeneral Hospital for Children. This blog has covered a lot of the same material, but Alessio’s slides are pretty impressive.  Also, I was not aware that Lady Gaga consumes a gluten-free diet
  • Controversies in parenteral nutrition Christopher Duggan MD, Boston Children’s Hospital.  This lecture provides a timely update on nutrient deficiencies due to component shortages and discusses lipid minimization compared with fish oil-based lipid emulsions.
  • Vitamin D and immunity James Heubi MD, Cincinnati Children’s Hospital and Medical Center.  In the beginning of the slides, Jim provides a very user-friendly definition of an expert and a suitable picture.  He indicates that in 2011 there were 3746 vitamin D publications but inexplicably only chooses to review a tiny fraction.

At the time of this posting, I haven’t had a chance to look through these talks: