A cross-sectional study (LN Anderson et al. J Pediatr 2017; 180: 47-52) of 2713 children extends prior observations that there is little evidence supporting the need for fasting prior to measurement of lipids.
Prior blog on this topic: Is Fasting Needed Before Checking Lipids
This study showed that fasting duration (0-5 hrs) was not significantly associated with total cholesterol, LDL, HDL, or triglycerides. This is most evident on the graphs on their Figure.
In the discussion, the authors note that the NHANES study 1999-2008 had similar results for the younger children. Overall, there were 12,744 children aged 3-17 years; 80% fasted at least 8 hrs. In this study, fasting did have a small effect on lipids, but among children 3-5 yrs, only LDL was statistically affected by fasting status.
My take: Based on this study and others, fasting seems to have only a small effect on lipid measurement and for routine screening, it is probably not needed.
Yosemite Natl Park
There has been controversy regarding the American Academy of Pediatric recommendations on lipid screening and treatment, mainly because the guidelines propose earlier screening and more aggressive treatment than other guidelines, including guidelines from the American College of Cardiology and the American Heart Association. However, according to a recent article (N Joyce et al. J Pediatr 2015; 167: 113-9), it does not appear that many children (8-20 years) are actually being treated.
The authors used commercial health plan data between 2004-2010 and collected data from more than 13 million children. Only 665 were initiated on lipid lowering therapy which equates to an incidence rate of 2.6/100,000 person-years.
Rates of lipid lowering therapy were higher in those ≥15 years with odds ratio of 2.9 and much higher in those with a familial hypercholesterolemia (OR 165.2).
Take home message from authors: “our findings suggest lipid lowering therapy is underutilized in this population.” It is likely that many who have undergone testing and who have abnormal lipids are not being treated. If so, why bother testing?
A recent publication in JPGN indicates that resuming low dose soy-based parenteral lipid can be effective in patients (n=7) whose cholestasis had resolved on a fish oil-based parenteral lipid. It does not resolve the larger question of whether fish oil-based parenteral lipids are truly more effective than soy-based parenteral lipids (see previous blog links below).
Here’s the abstract:
Objectives: Intestinal failure associated liver disease (IFALD) contributes to significant morbidity in pediatric intestinal failure (IF) patients. However, the use of parenteral nutrition (PN) with a fish oil-based IV emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: as it can only be administered under FDA compassionate use protocols requiring special monitoring, is not available as a 3-in-1 solution and is more expensive than comparable soy-based lipid formulation (SO). Due to these pragmatic constraints a series of patient families were switched to low-dose (1 g/kg/day) SO following biochemical resolution of cholestasis. This study examines if reversal of cholestasis and somatic growth are maintained following this transition.
Methods: Chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons performed using Wilcoxon signed-rank test.
Results: 7 patients aged 25.9 (16.2,43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow up 13.9 (4.3,50.1) months there were no significant differences between pre- and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z-scores. Due to recurrence of cholestasis, one patient was restarted on FO after four months on SO.
Conclusions: Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6/7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select home PN patients.
Related blog posts:
Intravenous lipids may cause parenteral nutrition associated cholestasis (PNAC), parenteral nutrition associated liver disease (PNALD), or intestinal failure associated cholestasis (IFAC) (J Pediatr 2012; 160: 421-7 & editorial 361-2). PNAC refers to cholestasis due to parenteral nutrition and PNALD refers to PNAC that has progressed to liver dysfunction or permanent liver injury.
In a previous blog (Four advances for intestinal failure), one of the advances for intestinal failure that was noted was the reduction of lipid infusions with parenteral nutrition which reduces IFAC. This study adds additional information to this area. In this prospective study, 31 patients were enrolled in a reduced IV fat emulsion group and compared with a matched historical control group. The reduced fat group received 1gm/kg of a standard soybean-based lipid emulsion (liposyn 20%) twice weekly. Patients were eligible if they received PN for >2 weeks and had a direct bilirubin >2.5 mg/dL.
- Total bilirubins dropped 0.73 mg/dL each week in the reduced fat group; in the control group, the bilirubin increased 0.29 mg/dL each week
- Growth was similar in both groups
- Essential fatty acid deficiency (biochemical not clinical features) was identified in 13 of 31 infants among the restricted IV fat emulsion group.
Essential fatty acid deficiency was defined as having a triene: tetraene ratio >0.05 (mild), >0.2 (moderate) or >0.4 (severe).
- Historical control group & small study population
- Fat-restricted group received enteral antibiotics which may have helped reduce cholestasis
- Majority of patients with relatively short duration of TPN: 18 of 31 for less than one month
The reasons why lipids may contribute to PNAC/PNALD/IFAC include the presence of phytosterols. This in turn may damage hepatocytes via the farnesoid X receptor. One other aspect of the study was that the fat-restricted cohort had a higher mortality. This was thought to be related to the cohort being sicker rather than to any nutritional effect. Specific causes of death included respiratory failure in a patient with an abdominal wall defect, chylothorax/sepsis in a patient with a congenital diaphragmatic hernia, and cardiopulmonary failure in a patient with pulmonary hypoplasia.
The article does throw into question whether the use of a fish oil lipid preparation is needed to improve cholestasis. In studies supporting fish oil preparations, a confounder was that the total lipid administered was reduced to 1 gm/kg/day in comparison to soybean lipids which were administered at 2-3 gm/kg/day. This study suggests that reducing the total amount of lipid infusion is the more important factor.
The accompanying editorial makes a couple of useful points:
- Increasing enteral feeds (>50%) is as effective as using less intravenous lipids
- Use of standard lipids at 1gm/kg/day decreased IFAC from 15% to 4% in their intestinal failure patient population
- Drastic reductions in lipids lead to essential fatty acid deficiency and should be avoided.
- Use of Omegaven has not been shown to prevent liver fibrosis even with resolution of cholestasis; similarly, these studies do not inform fully on the long-term liver effects of reducing standard lipids
- Neurologic followup will be important
- Explains “Morton’s fork.” John Morton was a 16th century Archbishop who wanted to increase taxes on people who were living lavishly. In addition, he wanted to increase taxes on those living modestly (must be hiding wealth).
- -NEJM 2010; 362: 181. Letter to editor describes use of fish oil in (n=125) Boston pediatric patients.
- -JPGN 2009; 48: 209. n=12. SBS. 9/12 improved with Omegaven. 3 had transplant (L-ITx). No controls.
- -Pediatrics 2008; 121: e678-86. n=18. Use of fish oil improved cholestasis compared to historical controls.
- -Pediatrics 2006; 118: e197-e201. Reversal of TPN-AC c IV omega-3 fatty acids (fish oil-derived) instead of intralipids