Tag Archives: arachidonic acid

New lipid emulsions — lacking data to support usage

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According to a systematic review of the literature regarding ω-3 (n-3FA) fatty acid lipid emulsions, there is a “lack of sufficient high-quality data to support the use of parenteral n-3FA lipid emulsions in children” (JPEN 2013; 37: 44-55). Thanks to Kipp Ellsworth for this reference.

The authors of this study researched 4 databases up to March 2011 and extracted relevant studies.  Five randomized controlled trials and 3 high-quality prospective cohort studies were included.  The strength of evidence was “consistently low or very low across all lipid emulsion comparisons and outcomes.”

Specific criticisms:

  • Few studies examined important outcomes like length of hospital stay or intensive care stay.
  • There was lack of data on growth, cognitive development or potential long-term effects/harms.
  • All of the studies in children varied considerably with regard to the dosing regimens, duration of administration, and duration of followup.
  • The studies were small with sample sizes ranging from 28-91 patients.
  • The 5 RCTs had unclear risk of bias due to inadequate blinding of participants and study personnel.
  • All of the RCTs were funded by the manufacturer.
  • While some biochemical outcomes improved, no difference in mortality has been identified.  A biochemical response is a poor measure of effectiveness.  In fact, several studies have shown deterioration in liver histology and fibrosis despite improved biochemical measures in infants on Omegaven.
  • For Omegaven (fish oil) treatment, all studies used a historical control group.  In these studies, typically the Omegaven dose was half the dose of Intralipid used in the control group.

This article (in its Table 1) identifies the constituents in the commercial available lipid products which include Intralipid, Clinoleic, Liposyn II, Omegaven, SMOFLipid, and Lipoplus.  Intralipid which is widely used is devoid of substantial arachidonic acid (ARA) and docosahexaenoic adic (DHA).  This is particularly important in premature infants as noted in recent blogs:

Omegaven, in particular, and SMOFLipid, to a lesser degree, have much more AA and DHA.  As such, both of these emulsions have the potential improve vision and cognitive outcome in premature infants.

Related blog posts:

Visual Acuity and LCPUFA

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Long-chain polyunsaturated fatty acids (LCPUFA) have been examined due to their potential to affect infant cognition (Long–chain polyunsaturated fatty acids, breastmilk … – gutsandgro).  A recent meta-analysis has reviewed 19 studies with regard to LCPUFA supplementation and infant visual acuity (Pediatrics 2013; 131: e262-72 -thanks to Mike Hart for sharing this reference).

Since 75% of U.S. infants are formula fed by 1 year of age and there is widespread dependence on formula for nutritional completeness, these formulas have been designed to mimic breast milk composition.  Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are the two main LCPUFAs and are integral to  the structural membranes of cells in the central nervous system and retina.  DHA comprises >50% of the phospholipid content of the retinal membrane bilayer.

These 16 studies (in the abstract it erroneously states 19 studies), identified by a literature search, involved 1949 infants.  Overall, a significant benefit of LCPUFA supplementation on infants’ visual acuity was noted at 2, 4, and 12 months of age when assessed by visual evoked potential.  A benefit was also seen at 2 months of age by using behavioral methods.  Studies were included if they were randomized control trials comparing LCPUFA supplementation to unsupplemented formula.  Initially, 286 citations were identified but most did not meet inclusion criteria.

This study findings differ from two recent Cochrane reviews on the effect of LCPUFA on visual acuity.  The Cochrane reviews failed to combine trials that  measured “visual acuity in logMAR and cycles/degree and assessed preterm and term infants separately.”  The authors state that this reduced the Cochrane reviews power to detect potential benefits of LCPUFA supplementation.

While this study demonstrates improvement during the first year of life, there is a scarcity of data beyond this time point.  Limitations of this review included heterogeneity in the study results, varying doses of LCPUFA supplementation, variable DHA/AA ratio supplied, and variability in maternal diets.

Related blog post:

Low levels of LCPUFA in Premature Infants … – gutsandgrowth

Low levels of LCPUFA in Premature Infants Associated with Intravenous Lipids

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Low levels of the long-chain polyunsaturated fatty acids (LCPUFA) docosahexanenoic acid (DHA) and arachidonic acid (ARA) in premature infants are correlated with an increased risk of developmental, respiratory, and infectious morbidities in premature infants.  A new report suggests that prolonged exposure to intravenous lipids exacerbates these low levels and could contribute to poor neurodevelopmental outcomes (J Pediatr 2013; 162: 56-61).

This study followed 26 extremely low birth weight premature infants with serial blood draws during the first two months of life using a prospective cohort design.  Infants who received more than 28 days of intravenous lipid emulsion had significantly decreased DHA levels compared to infants with shorter duration of parenteral lipid exposure; at 8 weeks, the DHA levels were 2.7 ± 0.6 compared with 4.2 ± 1.9 (all levels reported as g/100 g).  DHA levels at birth were 5.5 ± 1.4.

ARA levels decreased in a similar fashion in both groups, though values were mildly lower in the prolonged lipid group.  At 8 weeks, the ARA values were 9.4 ± 1.6 and 11.5 ± 2.5 respectively.  Thus, with a larger study group, this could be a significant finding as well.

These lower LCPUFA (especially DHA) levels may reflect a suboptimal intravenous lipid emulsion.  Alternatively, the underlying reason for the prolonged lipids, like sepsis and NEC , could result in these lower levels.  Perhaps attention to LCPUFA in parenteral formulations can improve neurodevelopmental outcomes in this vulnerable population.

Related blog entry:

Long-chain polyunsaturated fatty acids, breastmilk, and infant cognition

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A lot has been written about improving infant cognition and breastfeeding, even on this blog (More evidence that breastfeeding improves cognitive development).  Formula companies in their efforts to duplicate the nutritional value of breast milk have supplemented with a number of agents, including long-chain polyunsaturated fatty acids (LCPUFA).  But, does this work?

A meta-analysis of LCPUFA supplementation failed to show any significant effect on early infant cognition (Pediatrics 2012; 129: 1141-49).  Twelve trials with 1802 infants met inclusion criteria.  Included trials were randomized clinical studies that measured cognition with Bayley Scales of Infant Development.

LCPUFAs have been hypothesized to be a potential reason for improved cognition.  LCPUFAs are vital for cell membranes and play a critical role in development and growth.  The two main LCPUFAs are docosahexaenoic acid (DHA) and arachidonic acid (AHA). “An estimated 30-fold increase in the amount of DHA and AA in the infant forebrain occurs between the last trimester of pregnancy and the first 2 years of life.”

The authors note that while breastfed babies tend to have higher intelligence, confounding factors have made it difficult to determine whether actual nutritional differences in breast milk are the reason for this difference.  On average, breastfeeding mothers have higher intelligence, larger incomes, and spend more time with their infants.  Thus, bonding/social interactions as well as other breast milk properties (eg antimicrobial, antiinflammatory, and immunomodulatory) may be important factors.

On the same subject, a second article in the same issue (Pediatrics 2012; 129: 1134-40) also showed that breastfed infants had slightly improved cognitive development compared with formula-fed babies (both cow’s milk and soy formula).  This conclusion was based on Bayley Scales of Infant Development and the Preschool Language Scale-3.  In total, this study examined 391 infants at ages 3, 6, 9, and 12 months.  The authors state that “models were used while adjusting for socioeconomic status, mother’s age and IQ, gestational age, gender, birth weight, head circumference, race, age, and diet history”  –that’s a lot of variables to adjust!

More on breast milk from previous blog entries:

Breastfed babies less likely to develop fatty liver

Breastfeeding: protection from asthma