Abstract
The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-α-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, μg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/precursor enrichment versus gas chromatography for the n-6 series had an r of −0.5, p = 0.001, and for the n-3 series had an r of −0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- AA:
-
arachidonic acid
- d:
-
deuterated
- DHA:
-
docosahexaenoic acid
- GA:
-
gestational age
- AGA:
-
adequate for gestational age
- GC:
-
gas chromatography
- IUGR:
-
intrauterine growth retardation
- LCP:
-
long chain polyunsaturated fatty acid(s)
- LA:
-
linoleic acid
- LNA:
-
α-linolenic acid
References
Sprecher H, Luthria DL, Mohammed BS, Baykousheva SP 1995 Reevaluation of the pathways of the biosynthesis of polyunsaturated fatty acids. J Lipid Res 36: 2471–2477.
Hamosh M, Salem N 1998 Long chain polyunsaturated fatty acids. Biol Neonate 74: 106–120.
Gibson RA, Makrides M 1998 The role of long chain polyunsaturated fatty acids in neonatal nutrition. Acta Paediatr 87: 1017–1022.
Uauy R, Birch DG, Birch EE, Tyson JE, Hoffman DR 1990 Effect of dietary omega-3 fatty acids on retinal function of very low birth weight neonates. Pediatr Res 28: 485–492.
Carlson SE, Werkman SH, Rhodes PG, Tolley EA 1993 Visual acuity development in healthy preterm infants effect of marine oil supplementation. Am J Clin Nutr 58: 35–42.
Makrides M, Neumann M, Simmer K, Pater J, Gibson R 1995 Are long-chain polyunsaturated fatty acids essential nutrients in infancy?. Lancet 345: 1463–1468.
Salem N, Wegher B, Mena P, Uauy R 1996 Arachidonic and docosahexaenoic acids are biosynthesized from the 18-carbon precursors in human infants. Proc Natl Acad Sci USA 93: 49–54.
Demmelmair H, Schenck UV, Behrendt E, Sauerwald T, Koletzko B 1995 Estimation of arachidonic acid synthesis in full term neonates using natural variation of 13C content. J Pediatr Gastroenterol Nutr 21: 31–36.
Carnielli VP, Wattimena DJL, Luijendijk I, Boerlage A, Degenhart HJ, Sauer PJJ 1996 The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids. Pediatr Res 40: 169–174.
Sauerwald T, Hachey D, Jensen CL, Chen H, Anderson RE, Heird W 1997 Intermediates in endogenous synthesis of C22: n-3 and C20:n-6 by term and preterm infants. Pediatr Res 441: 183–187.
ESPGAN. European Society of Paediatric Gastroenterology and Nutrition 1991 Committee on Nutrition: comment on the content and composition of lipids in infant formulas. Acta Paediatr Scand 80: 887–896.
FAO/WHO Report of Expert Consultation 1995 The role of dietary fats and oils in human nutrition. FAO Food Nutr Pap 57: 49–55.
ISSFAL 1994 Recommendations for the essential fatty acid requirements of infant formula. ISSFAL Newsletter 1: 4
American Society of Nutritional Sciences 1998 LSRO report: assessment of nutrient requirements for infant formulas. J Nutr 128: 2059S–2078S.
Willats P, Forsyth JS, DiModugno S, Varma S, Colvin M 1998 Effect of long chain polyunsaturated fatty acids in infant formula on problem solving at months of age. Lancet 352: 688–691.
Birch EE, Hoffman DR, Uauy R, Birch DG, Prestidge C 1998 Visual acuity and the essentiality of docosahexaenoic and arachidonic acid in the diet of term infants. Pediatr Res 44: 201–209.
Lubchenco LO, Hansman C, Boyd E 1963 Intrauterine growth as estimated from liveborn birth weight data at 24 to 42 wk of gestation. Pediatrics 32: 793–800.
Metcoff J 1994 Clinical assessment of nutritional status at birth. Pediatr Clin North Am 41: 875–891.
Ballard JL, Khoury JC, Wang L, Eilers-Wasman BL, Lipp R 1991 New Ballard score, expanded to include extremely premature infants. J Pediatr 119: 417–423.
Folch J, Lees M, Sloane Stanley GH 1957 A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509.
Morrison WR, Smith LM 1964 Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J Lipids Res 5: 600–608.
Yeh KC, Kwan KC 1979 A comparison of numerical integrating algorithms by trapezoidal, Lagrange and spline approximation. J Pharmacokin Biopharm 6: 79–98.
Greiner RCS, Winter J, Nathaniels PW, Brenna JT 1997 Brain docosahexaenoate accretion in fetal baboons: bioequivalence of dietary alpha linolenic and docosahexaenoic acids. Pediatr Res 42: 826–834.
Su HM, Bernardo L, Mirmiran M, Ma XH, Corso TN, Nathaniels PW, Brenna JT 1999 Bioequivalence of dietary alpha linolenic and docosahexaenoic acids as source of docosahexaenoate accretion in brain and associated organs of neonatal baboons. Pediatr Res 45: 87–93.
Martinez M 1992 Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr 120: S129–S138.
Cogo PE, Giordano G, Badon T, Orzali A, Zimmermann L, Zacchello F, Sauer P, Carnielli VP 1997 Simultaneous measurement of the rates of appearance of palmitic and linoleic acid in critically ill infants. Pediatr Res 41: 178–182.
Uauy R, Mena P, Rojas C 2000 Essential fatty acid metabolism in the micropremie. Clin Perinatol (in press).
Uauy R, Mena P, Hoffman D 1998 Nutrition, diet, and infant development: long-chain polyunsaturated fatty acids in infant neurodevelopment. In: Perman JA, Rey J (eds) Clinical Trials in Infant Nutrition. Lippincott-Raven, New York, 153–180.
Demmelmair H, Sauerwald T, Koletzko B, Richter T 1997 New insights into lipid and fatty acid metabolism via stable isotopes. Eur J Pediatr 156: S70–S74.
Cunnane SC, Moine G, Likhodii SS, Vogt J, Corso TN, Brenna JT, Demmelmair H, Koletzko B, Tovar KH, Kohn G, Sawatzki G, Muggli R 1997 [3–13C]gamma-linolenic acid: a new probe for 13C nuclear magnetic resonance studies of arachidonic acid synthesis in the suckling rat. Lipids 32: 211–217.
Thomas EL, Hanrahan JD, Ala-Korpela M, Jenkinson G, Azzopardi D, Iles RA, Bell JD, Steiner R 1997 Noninvasive characterization of neonatal adipose tissue by 13C magnetic resonance spectroscopy. Lipids 32: 645–651.
Szitanyi P, Koletzko B, Mydlilova A, Demmelmair H 1999 Metabolism of 13C-labeled linoleic acid in newborn infants during the first week of life. Pediatr Res 45: 669–673.
Acknowledgements
The authors thank Gloria Icaza, Ph.D., who provided data management and statistical support for this work.
Author information
Authors and Affiliations
Additional information
This work was supported by Fondo Nacional de Ciencia y Tecnología (Fondecyt) Chile grant 1960001. R.U. is the recipient of a Presidential Award in Science given by the Chilean Government.
Rights and permissions
About this article
Cite this article
Uauy, R., Mena, P., Wegher, B. et al. Long Chain Polyunsaturated Fatty Acid Formation in Neonates: Effect of Gestational Age and Intrauterine Growth. Pediatr Res 47, 127 (2000). https://doi.org/10.1203/00006450-200001000-00022
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-200001000-00022
This article is cited by
-
Fatty acid concentrations in preterm infants fed the exclusive human milk diet: a prospective cohort study
Journal of Perinatology (2023)
-
Factors associated with plasma n-3 and n-6 polyunsaturated fatty acid levels in Tanzanian infants
European Journal of Clinical Nutrition (2020)
-
An infant formula containing dairy lipids increased red blood cell membrane Omega 3 fatty acids in 4 month-old healthy newborns: a randomized controlled trial
BMC Pediatrics (2018)
-
No effect of adding dairy lipids or long chain polyunsaturated fatty acids on formula tolerance and growth in full term infants: a randomized controlled trial
BMC Pediatrics (2018)
-
Low omega-3 index values and monounsaturated fatty acid levels in early pregnancy: an analysis of maternal erythrocytes fatty acids
Lipids in Health and Disease (2018)


