REVIEW URRENT C OPINION

Long-chain polyunsaturated fatty acids supplementation in preterm infants Ricardo Uauy and Patricia Mena

Purpose of review Extremely low birth weight and very low birth weight infants are born immature and are commonly sick and are, therefore, not able to receive appropriate enteral or sufficient parenteral nutrition to meet the needs for optimal brain, lung and gut growth and development. Recent findings We provide an updated view of essential fatty acid metabolism and discuss the potential protective effect of fatty acids that serve as precursors for eicosanoids and docosanoids. The balance of n-3 or n-6 longchain polyunsaturated fatty acids (LCPUFAs) supplied may enhance or ameliorate the effects of hypoxia, inflammation, infection, thrombosis and oxidative damage of key organs (lung, brain and retina). In addition, n-3 and n-6 LCPUFAs are necessary for normal structure and function of the central nervous system and sensory organ development. These lipids generate eicosanoids that are mediators of oxidative damage, as well as potential protectors of retina, brain cortex, lung and vascular endothelium. Summary n-3 and n-6 LCPUFAs may condition in part the long-term consequences of preterm birth. Early n-3 and n-6 LCPUFA supply may moderate the impact of hypoxia and oxidative damage, thus affecting the recovery from injury, later organ (brain, retina, lung, gut, liver and skin) growth and neurodevelopmental outcomes. Keywords essential fatty acids, low birth weight nutrition, visual and cognitive development

INTRODUCTION The functional consequences of dietary long chain polyunsaturated fatty acids (LCPUFAs) on nervous system development during the perinatal period and early infancy have been better defined over the past decade [1]. Studies of metabolic pathways in very low birth weight (VLBW) and low birth weight (LBW) infants using stable isotopes to mark metabolic conversions and final disposition have served to establish the essentiality of both linoleic acid (the parent omega-6) and of linolenic acid (LNA, the parent omega-3) fatty acids in early life. The impact of docosahexaenoic acid (DHA) supply during the neonatal period and the first years of life has been better defined using neurophysiological assessments of retinal, visual cortical, auditory and cognitive functions. The need for preformed DHA for normal retinal and brain development is clear [2 ]. However, characterizing the potential long-term benefits of n-3 supply, especially on cognitive function beyond 2– 4 years of age has remained elusive. The most recent data regarding prenatal DHA supplementation demonstrated no significant effect on neurodevelopment at 4-year follow-up [3 ].

Essential fatty acids (EFAs) belong to the omega6 (also termed n-6) and omega-3 (also n-3) series of derived compounds. The parent n-6 EFA is linoleic acid (linoleic acid 18 : 2 n-6), it has 18 carbons and two double bonds one in position (n-6). The parent EFA of the n-3 family is a–linolenic acid (18 : 3n–3). Figure 1 illustrates the metabolism of n-6 and n-3 EFAs, which can include up to six unsaturated chemical bonds. The shared pathways for n-3 and n-6 elongation and desaturation provide opportunities for interaction such that in the absence of a balanced supply of n-6 to n-3 precursors, biological membranes change their composition based on dietary intake Fig. 2 [1]. A diet rich in n-6 linoleic acid will lead to more arachidonic acid derived prostanoids, whereas a diet rich in n-3 LNA or

&&

&&

Department of Pediatrics and Neonatology, Catholic University Medical School, Santiago, Chile Correspondence to Ricardo Uauy, MD, PhD, Facultad de Medicina Pediatria, Lira 85 5 piso Santiago-Chile, Chile. Tel: +56 22 978 1490; e-mail: [email protected] Curr Opin Pediatr 2015, 27:165–171 DOI:10.1097/MOP.0000000000000203

1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.

www.co-pediatrics.com

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Neonatology and perinatology

KEY POINTS  Omega-3 (n-3) and omega-6 (n-6) fatty acids of greater than 18 carbon chain length are essential for normal organ growth and mental development throughout fetal life, infancy and childhood.

aggregation, tissue responses and recovery from hypoxia, reperfusion injury, immune response and other eicosanoid or docosanoid related phenomena. EPA and DHA derived prostanoids may ameliorate tissue damage and promote repair. The various interactions between the n-6 and n-3 derived compounds are summarized in Fig. 3 [4,5 ]. These control major functions that affect neonatal health and disease, recovery from hypoxic or inflammatory injury and potential long-term outcomes. We are just beginning to unravel the effects of modifying eicosanoid production to prevent inflammation or enhance tissue recovery after hypoxia. The parenteral administration of LCPUFAs that provide a more balanced n-6 : n-3 supply, or, in specific cases, the exclusive administration of n-3 long chain polyunsaturated fatty acids (LCPs), may prevent tissue damage and promote recovery. These interventions have yet to be designed and tested in critically ill preterm infants. However, novel information relative to DHA and EPA derived docosanoids offers great promise for potential benefits in preventing or ameliorating damage due to hypoxia, oxidative injury, excess inflammation or other cytokine mediated responses leading to tissue damage (Fig. 3). DHA and EPA derived resolvins, protectins and other docosanoids may offer new preventive or &&

 Preterm and VLBW infants require n-6 and n-3 fatty acids for normal growth and mental development. The balance between n-3 and n-6 is also important to prevent early morbidity, as it affects inflammatory responses, lipid peroxidation, membrane function and thus affects maturation of brain, retina, lung and other organs.  The beneficial effect of human milk on sensory and central nervous system development in preterm infants is explained in part by the presence and balance of n-6 and n-3 LCPs.  LCPs from parenteral lipids or breast milk can modify the risk and severity of multiple neonatal disease by modulating inflammatory responses, clotting, damage/ recovery and cell repair after hypoxia and may contribute to improved outcomes after perinatal injury.

containing eicosapentaenoic acid (EPA) and DHA will lead to increase in n-3 derived eicosanoid and docosanoids [4,5 ]. The n-6 to n-3 balance affects tissue responses to inflammation, platelet &&

ωCOOH Stearic acid (C18:0)

CH3

nOleic acid (C18:1 n-9)

CH3

COOH

COOH

Linoleic acid (18:2 n-6)

COOH

α - Linolenic acid (C18:3 n-3)

COOH COOH

Arachidonic acid AA (C20:4 n-6)

Docosahexaenoic acid DHA (C22:6 n-3)

FIGURE 1. Top panel; chemical nomenclature to describe fatty acids based on number of carbon atoms and number of double, thus stearic, a nonessential fatty acid with 18 carbons and no double bonds, is summarized as 18 : 0; if one double bond is placed in position 9 we have oleic acid 18 : 1 n-9 (predominant fatty acid in olive oil and also in human milk). The bottom panel presents the structure of parent n-6 and n-3 EFAs, and the corresponding long chain derived fatty acids AA precursor of EPA. EPA can undergo further elongation to form DHA, if n-3 precursors are insufficient 22 : 5 n-6 DPA is formed. DHA and EPA give rise to n-3 eicosanoids and docosanoids, which antagonize the action of the n-6 eicosanoids affecting thrombosis and thrombolysis, recovery from hypoxic injury, inflammation, oxidative damage and cell survival. AA, arachidonic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EFA, essential fatty acids; EPA, eicosapentaenoic acid. 166

www.co-pediatrics.com

Volume 27  Number 2  April 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Long-chain polyunsaturated fatty acids supplementation Uauy and Mena

Metabolism of n-6 and n-3LCPs 18:3 n-3

18:2 n-6

α: Linoleni acid

Linoleic acid Arachidonic AA (20:4 n-6) 22:4 n-6

Eicosapentaenoic EPA Elongase Elongase

22:4 n-6

(20:5 n-3) 22:5 n-3 DPA 24:5 n-3

6 Desaturase

PEROXISOMAL STEP

24:5 n-6

(22:5 n-6) Docosapentaenoic

Partialβ oxidation

24:6 n-3

(22:6 n-3) Docosahexaenoic DHA

FIGURE 2. Metabolism of parent n-6 and n-3 EFAs yields AA and EPA. EPA can undergo further elongation to form DHA, if n-3 precursors are insufficient 22 : 5 n-6 DPA is formed. DHA comprises 40% of the polyunsaturated fatty acids in the brain and 60% of the PUFAs in the retina, 50% of the weight of a neuron’s plasma membrane is composed of DHA, levels in breast milk are generally high despite low intakes; maternal dietary DHA supplementation enhances fetal DHA levels at birth and breast milk DHA content in the postnatal period. DHA and EPA give rise to n-3 eicosanoids and docosanoids antagonize the action of the n-6 eicosanoids affecting thrombosis and thrombolysis, recovery from hypoxic injury, inflammation, oxidative damage and cell survival. AA, arachidonic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EFA, essential fatty acids; EPA, eicosapentaenoic acid; PUFA, polyunsaturated fatty acids.

therapeutic modalities that will help lessen functional losses associated with ischemic/hypoxic encephalopathy, intraventricular hemorrhage and bronchopulmonary dysplasia. Changes in cell and organelle membrane fatty acid composition may in fact prevent apoptosis (programmed cell death) and protect cells and tissues from hypoxic and oxidative damage [6 ]. &

FETAL AND NEONATAL ACCRETION OF LONG CHAIN POLYUNSATURATED FATTY ACIDS The maternal circulation remains the major source of LCPs for the fetus. Dietary fatty acids and adipose tissue are important during pregnancy and lactation, however, this is dependent on the mother’s dietary intake of n-3 and n-6 LCPs. The placenta plays a unique role in the selective uptake and accumulation of LCPs for transfer to the fetal compartment: this process has been termed as bio-magnification [9]. The DHA content of fetal and placental tissues during pregnancy, especially in the cell membrane of the amnion, plays an

important role in allowing for a full gestation. Thus, populations consuming fatty fish rich in DHA (such as the inhabitants of the Faroe Islands) have the longest gestation with less premature labor, lower rates of premature rupture of membranes and less preterm birth [10–12]. Epidemiologic data support the hypothesis that DHA supplementation helps prevent preterm labor and promotes normal fetal growth. Controlled prospective studies of DHA supplementation during early pregnancy suggest improved birth weight and less preterm labor [13]. Placental function is also enhanced by DHA supplementation. DHA transfer to the fetus plays an important role in central nervous system (CNS) development and may enhance cognition in preterm infants [1,2 ,3 ]. However, the potential long-term benefits in later life have not been demonstrated. Studies assessing the need for DHA supplementation during pregnancy have revealed a gradual loss of n-3 fatty acids in western diets. Decreased DHA content in breast milk, placental tissues and maternal plasma levels has been noted. Observational studies document an association between neonatal cord, plasma and red blood cell DHA content with maternal dietary DHA intake. The associations of plasma and tissue DHA content with infant’s early neurodevelopment and cognitive outcomes have also been established [14,15]. The different capacity of mothers to produce n-3 and n-6 LCPs DHA and arachidonic acid, respectively, depends in part on a genetic trait coding for desaturase activity [Fatty acid desaturases 1 (FADS1), 2 and 3] [16]. Fatty acid desaturases are enzymes that introduce double bonds into fatty acyl chains. FADS2 is localized in chromosome 11q12.2, codifies for delta 6 desaturase, and is the rate-limiting enzyme to form long chain omega-6 y omega-3 fatty acids [17]. Thus, changes in the activity of the enzyme will modify dietary effects. For example, in the Avon cohort in the UK, children with IQ’s in the lowest quartile predominantly exhibited the specific FADS polymorphism associated with lower formation of DHA from LNA [18]. A randomized controlled trial investigating DHA supplementation during pregnancy revealed no differences in attention, working memory and inhibitory control in term children born to women supplemented during pregnancy compared with controls [19]. However, it is important to note that the DHA content of cord blood phospholipids did not differ between study groups [19]. In addition, this study did not assess FADS polymorphisms. Similarly, Makrides et al. [3 ] found that prenatal DHA supplementation did not influence objective assessments of cognition, language and executive function at preschool age.

1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.

&&

&&

&&

www.co-pediatrics.com

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

167

Neonatology and perinatology

n - 6/n - 3 LCPUFA ratio and eicosanoids mediated effects Linoleate

Arachidonic ac

α-linolenic acid ac

Eicosapentaenoic ac

n-6 PUFA

n-3 PUFA Membrane phospholipids

Docosahexaenoic ac

Arachidonic ac Eicosapentaenoic ac Docosahexaenoic ac

Prostaglandins Inflammation cytokines

Prostacyclins

Thromboxanes

Leukotrienes

Bronchoconstriction Thrombosis bronchoconstriction Chemotaxis inflammation

Inmune response vascular reactivity

Docosanoids Neuroprotectin ameliorates reperfusion injury

FIGURE 3. Docosahexaenoic ac (C22 : 6 n-3) DHA is the most abundant omega-3 fatty acid in the brain and retina. DHA and EPA give rise to n-3 eicosanoids and docosanoids, which antagonize the action of the n-6 eicosanoids, affecting thrombosis and thrombolysis, recovery from hypoxic injury, inflammation, oxidative damage and cell survival. DHA comprises 40% of the polyunsaturated fatty acids in the brain and 60% of the PUFAs in the retina, 50% percentage of the weight of a neuron’s plasma membrane is composed of DHA, levels in breast milk are generally high despite low intakes; maternal dietary DHA supplementation enhances fetal DHA levels at birth and breast milk DHA content in the postnatal period [7,8 ]. DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; PUFA, polyunsaturated fatty acids. &&

It is likely that the effects of DHA supplementation during the perinatal period on early childhood neurodevelopment, may be confined to children who perform on the lower end of the normal distribution and that DHA supplementation during the perinatal period will not enhance cognitive development scores of infants who are already normal [20 ]. Present knowledge suggests that fetal and LBW tissue desaturase and elongase activities are insufficient to convert precursor linoleic acid (n-6 LCPs) and LNA (n-3 LCPs) to form arachidonic acid and DHA at a rate that meets the infant’s LCP needs. Human milk fatty acid content is in part determined by the maternal dietary supply of both linoleic acid and LNA and by the mother’s ability to elongate and further desaturate these fatty acids. Additionally, the maternal diet may provide preformed LCPUFAs from marine foods or specific dietary supplements. The most recent Cochrane systematic review concluded that there is no consistent benefit of LCPUFA supplementation of infant formulas for preterm infants in terms of visual development [21]. The authors acknowledge, however, that the major differences in assessment methods utilized does not allow for an adequate meta-analysis of data [21]. &

168

www.co-pediatrics.com

Plasma and membrane arachidonic acid and DHA content decrease after birth. This observed decrease is related to the sufficiency of the neonatal n-6 and n-3 LCPs supply. Levels are also affected by early neonatal morbidity; lower DHA levels are seen in infants with late-onset sepsis and bronchopulmonary dysplasia (BPD) [22]. A systematic review of the effect of DHA supplementation in early life also demonstrated lower plasma levels in infants with these same comorbidities. In 2014, a systematic review of the literature indicated a trend toward a reduction in the risk of BPD and necrotizing enterocolitis (NEC) in children less than 32 weeks gestation supplemented with LCPUFA [23]. Human milk is the natural way to deliver EFAs and LCPUFAs in early life. However, the content of LCPs in human milk will vary depending on the maternal diet. Mothers in western countries consuming high n-6 fats (corn, sunflower and safflower oils) will have high n-6 fats (linoleic acid) in their milk, but very low n-3 fats (LNA), as western diets are low in soy, rapeseed or canola oils. Traditionally, parent EFAs from soy and corn oils were added to infant formula as a source of fat energy; in the late 1990s the addition of soy or canola oils provided Volume 27  Number 2  April 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Long-chain polyunsaturated fatty acids supplementation Uauy and Mena

LNA as a source of n-3 EFAs. More recently fish oil, algal oils and other oils from marine foods rich in preformed LCPs such as EPA and DHA have been added. These are key structural components of neural membranes such as retinal photoreceptors and play a role in synapsis formation and neurotransmitter mediated signal transduction. Human milk fatty acid composition reflects in part maternal dietary intake, so the amount of n-6, n-3 fatty acids and DHA in human milk will increase with maternal diets rich in soy, canola, oily fish or other n-3 rich marine foods, whereas it will decrease with the typical western diet particularly high in corn or sunflower oil [2 ,24]. &&

RECENT ADVANCES IN THE USE OF PARENTERAL LIPIDS (N-3 & N-6 LCPS) The use of parenteral nutrition including the early administration of intravenous lipids serves to supply not only fatty acids as energy sources but also provides the parent EFAs (LA, and LNA present in corn and soy oil emulsions). More recently the supply of elongated, n-3 LCPUFAs products such as EPA and DHA from fish oil have been incorporated in Europe, Australia, Asia and Latin America [25]. This serves not only to secure the supply of these nutrients needed for optimal brain growth and nervous system development, but additionally provide a more balanced provision of n-3 to n-6 LCPUFAs. The recognition of the potential adverse effects of excess n-6 relative to n-3 LCPs supplied by parenteral lipids was on the basis of the use of corn and sunflower oil in the preparation of lipid emulsions. More recently, the addition of soy oils has improved the relative balance n-6 and n-3 EFAs. At present, the use of a mix of olive oil with soy in addition to the n-6 sources provide n-6/n-3 of > 2. Furthermore, the addition of DHA from algal or fish oil provides a more balanced emulsion with greater amounts of DHA and EPA, lower phytosterols and appropriate amounts of tocopherols. The information from adult studies documenting the adverse effects of excess n-6 LCPs has led to a lowering of the n-6 concentration and an increase in n-3 LCPs [26,27 ]. Adults in an ICU setting exhibited a reduction in the duration of hospitalization and fewer days on the ventilator when the n-6/n-3 was approximately 5– 7 : 1. These studies cannot isolate the factor or the specific mechanism that is most critical to induce these benefits, but it may be due to a decrease in pro-inflammatory n-6 arachidonic acid dependent cytokines. The differential effect of these two classes of lipid mediators is well characterized for some conditions, such as for patent ductus arteriosus (PDA), wherein &

pharmacologic means are used to inhibit COX 2 (cyclooxygenase 2) to facilitate ductal closure. However, prostaglandin synthetase has two catalytic activities, which are complementary: a cyclooxygenase and a peroxidase. The cyclooxygenase activity catalyzes arachidonic acid to form PGG2, which is then catalyzed by the peroxidase into PGH2. Indomethacin and Ibuprofen are both effective COX inhibitors and act by competing with arachidonic acid, the normal substrate for the cyclooxygenase site. Therefore, the effectiveness of these drugs will be influenced by endogenous arachidonic acid concentrations. Conversely, paracetamol acts to inhibit the enzymatic activity at the peroxidase segment of prostaglandin synthetase and thus is less affected by available arachidonic acid. This supports the concept that paracetamol is a better alternative, as its action is not fully mediated by COX 2. The peroxidase enzyme is activated at 10-fold lower peroxide concentrations than that needed by COX. Paracetamol, therefore, will work well under low local peroxide concentrations, such as those observed in hypoxia [28]. This example serves to illustrate the potential effects of changing membrane lipid composition in early life. Today this can be achieved by providing parenteral lipids soon after birth. In the future, we may use specific fatty acid substrates that will modify membrane composition in terms of n-3 and n-6 balance, thus, affecting enzyme functions, or the corresponding biological responses such as tissue repair or biological responses, as illustrated by the example of PDA closure. The initial n-3 parenteral lipids were based on soy. More recently, n-3 LCPs with EPA and DHA from marine oils have been used. Initial trials demonstrated dramatic benefits lowering cholestasis and obstructive liver disease by administering both LNA and n-3 LCPs [29 ]. Trials to assess the effect of these new formulations on the incidence of BPD, retinopathy of prematurity and NEC are underway. The clear benefit on bile flow, prevention of cholestasis and extrauterine growth have been well documented [30–33,34 ]. Large multicenter trials are needed to fully assess the benefits and examine possible adverse effects. A systematic review combining the data in a meta-analysis demonstrated a trend toward decreased serum bilirubin, but no difference in serum triglycerides or the risk of sepsis [30]. &&

&

CONCLUSION Linoleic and LNAs, n-3 and n-6 LCPs (DHA and arachidonic acid) provided by the mother are essential for normal embryonic and fetal development. Postnatally, these nutrients are provided by human

1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.

www.co-pediatrics.com

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

169

Neonatology and perinatology

milk or by formula supplemented with these components. The advent of parenteral lipids that provide essential LCPs is of potential interest, not only to support growth and development of nervous and vascular tissues, but also to modulate multiple organ functions related to eicosanoid metabolism (e.g., clotting, inflammation, recovery and damage from hypoxia, transport systems, lung, vascular responses and integrity and oxidative damage), which are affected by the balance between n-3 and n-6 LCPs. These considerations are of special relevance to immature and growth restricted neonates born too early and often malnourished pre and postnatally. The advent of new methods to explore CNS and sensory organ functional and tissue integrity may help define new approaches to prevent or ameliorate neurodevelopmental injury in preterm infants. Furthermore, they will help determine the optimal dose, timing and duration of supplementation for DHA and other LCPs Future studies should serve to define the optimal timing and doses of DHA and other LCPs for preterm and VLBW infants. These studies should consider the differential needs across sexes, weights and gestational age, but also consider genetic variance in the capacity to form the active LCP derived eicosanoids and docosanoids. Additionally, we should consider the pathologic conditions that are all too frequent in VLBWs. Doses may need to be individually adjusted based on genetic polymorphisms that regulate metabolism and on the specific pathological condition affecting our patients. Only then we will be able to define what are the key factors for optimal benefits. Acknowledgements P.M. and R.U. prepared this manuscript; they would like to acknowledge the contribution of Dr Norman Salem as a partner in the study of n-3 and n-6 metabolism using stable isotope tracers to advance or knowledge on the role of EFAs in neonatal nutrition and to Professor Joseph Warshaw Chairman Department of Pediatrics at Yale Medical School for providing guidance early in our careers leading us to explore and challenge the science base of nutritional practices in early life. Financial support and sponsorship The research work leading to this paper was supported mainly by grants from public agencies [US National Institute of Child Health and Development (NICHD/ NIH), Chilean Science and Technology Fund (Fondecyt) and a Presidential Award in Science to RU)]. Conflicts of interest None. 170

www.co-pediatrics.com

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Uauy R, Mena P, Rojas C. Essential fatty acids in early life: structural and functional role. Proc Nutr Soc 2000; 59:3–15. 2. Makrides M, Uauy R. LCPUFAs as conditionally essential nutrients for very low && birth weight and low birth weight infants metabolic, functional, and clinical outcomes — how much is enough? Clin Perinatol 2014; 41:451–546. Recent recommendations for LCPs in early life. 3. Makrides M, Gould JF, Gawlik NR, et al. Four year follow up of children born to && women in a randomized trial of prenatal DHA supplementation. JAMA Pediatr 2014; 311:1802–1804. Effects of n-3 LCPs on growth and development of VLBW 4 year follow-up. 4. Bazan NG, Molina MF, Gordon WC. Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuro-inflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases. Annu Rev Nutr 2011; 31:321–351. 5. Jenssen C, Kilian A. Long-chain polyunsaturated fatty acids [LCPUFA] from && genesis to senescence: the influence of LCPUFA on neural development, aging, and neuro-degeneration. Progr Lip Res 2014; 53:1–17. Excellent review of the impact of n-6/n-3 LCPs on neurodevelopment in early life and throughout the life course. 6. Williams JJ, Mayurasakorn K, Vannucci SJ, et al. N-3 fatty acid rich triglyceride & emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice. PLoS One 2013; 8:e56233. Role of n-3 LCPs in protection from CNS hypoxic-ischemic injury. 7. Zhang M, Spite M. Resolvins: anti-inflammatory and proresolving mediators derived from omega PUFAs. Annual Rev Nutr 2012; 32:203–227. 8. Dean J, Bennet L, Back SA, et al. What brakes the preterm brain? An arresting && story. Pediatr Res 2014; 75:225–233. Excellent review of a novel interpretation of cognitive damage in preterm considering analyses of white matter diffusion tensor imaging and volumetric imaging. 9. Hagarty P. Fatty acid supply to the human fetus. Annu Rev Nutr 2010; 30:237–255. 10. Larque´ E, Gil-Sa´nchez A, Prieto-Sa´nchez MT, Koletzko B. Omega 3 fatty acids, gestation and pregnancy outcomes. Br J Nutr 2012; 107 (Suppl 2):S77–S84. 11. Rogers LK, Valentine CJ, Keim SA. DHA supplementation: current implications in pregnancy and childhood. Pharmacol Res 2013; 70:13–19. 12. Carlson SE, Colombo J, Gajewski BJ, et al. DHA supplementation and pregnancy outcomes. AJCN 2013; 97:808–815. 13. Carvajal JA. Docosahexaenoic acid supplementation early in pregnancy may prevent deep placentation disorders. Biomed Res Int 2014; 2014: 526895. 14. Qawasmi A, Landeros-Weisenberger A, Leckman J, Bloch M. Meta-analysis of long-chain polyunsaturated fatty acid supplementation of formula and infant cognition. Pediatr 2012; 129:1141–1149. 15. Montgomery P, Burton JR, Sewell RP, et al. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. Plos One 2013; 8:e66697. 16. Marquardt A, Stohr H, White K, et al. cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics 2000; 66:175–183. 17. Glaser C, Lattka E, Rzehak P, et al. Genetic variation in polyunsaturated fatty acid metabolism and its potential relevance for human development and health. Matern Child Nutr 2011; 7 (Suppl 2):27–40. 18. Steer CD, Lattka E, Koletzko B, et al. Maternal fatty acids in pregnancy, FADS polymorphisms, and child intelligence quotient at 8 y of age. Am J Clin Nutr 2013; 98:1575–1582. 19. Gould J, Makrides M, Colombo J, Smithers LG. Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control. Am J Clin Nutr 2014; 99:851–859. 20. Makrides M. DHA supplementation during the perinatal period and neurode& velopment: do some babies benefit more than others? Prostaglandins Leukot Essent Fatty Acids 2013; 88:87–90. Provides a framework to better understand variance in results after provision of LCPs. 21. Schulzke SM, Patole SK, Simmer K. Long-chain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev 2011; (2): CD000375. 22. Martin CR, Dasilva DA, Cluette-Brown JE, et al. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr 2011; 159:743–749; e2. 23. Zhang P, Lavoie PM, Lacaze-Masmonteil T, et al. Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a systematic review. Pediatrics 2014; 134:120–134.

Volume 27  Number 2  April 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Long-chain polyunsaturated fatty acids supplementation Uauy and Mena 24. Lauritzen L, Carlson SE. Maternal fatty acid status during pregnancy and lactation and relation to newborn and infant status. Matern Child Nutr 2011; 7 (Suppl 2):41–58. 25. Deshpande G, Simmer K. Lipids for parenteral nutrition in neonates. Curr Opin Clin Nutr Metab Care 2011; 14:145–150. 26. Manzanares W, Dhaliwal R, Jurewitsch B, et al. Alternative lipid emulsions in the critically ill: a systematic review of the evidence. Intensive Care Med 2013; 39:1683–1694. 27. Edmunds CE, Brody RA, Parrott JS, et al. the effects of different IV fat & emulsions on clinical outcomes in critically ill patients. Crit Care Med 2014; 42:1168–1177. Interesting analysis of adult intensive care unit clinical data in relation to IV fat emulsion. 28. Dang D, Wang D, Zhang C, et al. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLoS One ; 8:e77888. doi: 10.1371/journal.pone.0077888. 29. Burrin D, Ng K, Stoll B, Sa´enz De Pipao´n M. Impact of new-generation lipid && emulsions on cellular mechanisms of parenteral nutrition-associated liver disease. Adv Nutr 2014; 5:82–91. Good review of the effects of omega 6 and omega 3 on cellular function and pathological mechanism of liver damage.

30. Finn KL, Chung M, Rothpletz-Puglia P, Byham-Gray L. Impact of providing a combination lipid emulsion compared with a standard soybean oil lipid emulsion in children receiving parenteral nutrition: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr 2014. [Epub ahead of print] 31. Nandivada P, Carlson SJ, Cowan E, et al. Role of parenteral lipid emulsions in the preterm infant. Early Hum Dev 2013; 89:S45–S49. 32. Pawlik D, Lauterbach R, Walczak M, et al. Fish-oil fat emulsion supplementation reduces the risk of retinopathy in very low birth weight infants: a prospective, randomized study. J Parenter Enteral Nutr 2013; 38:711– 716. 33. Beken S, Dilli D, Fettah ND, et al. The influence of fish-oil lipid emulsions on retinopathy of prematurity in very low birth weight infants: a randomized controlled trial. Early Hum Develop 2014; 90:27–31. 34. Vlaardingerbroek H, Vermeulen MJ, Carnielli VP, et al. Growth and fatty acid & profiles of VLBW infants receiving a multicomponent lipid emulsion from birth. JPGN 2014; 58:417–427. Randomized study of premature infants given total parenteral nutrition (TPN) until enteral feeds are sufficient. Results show better growth with no difference in morbidity. Random allocation to TPN until full enteral feeds are reached. Significantly better growth, no changes in morbidity, higher EPA and DHA levels, lower plasma phytosterol relative to parenteral lipids based on soybean oil.

1040-8703 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.

www.co-pediatrics.com

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

171

Long-chain polyunsaturated fatty acids supplementation in preterm infants.

Extremely low birth weight and very low birth weight infants are born immature and are commonly sick and are, therefore, not able to receive appropria...
406KB Sizes 0 Downloads 15 Views