Infants with Intrauterine Growth Restriction Have Impaired Formation of Docosahexaenoic Acid in Early Neonatal Life: A Stable Isotope Study

Abstract

This study evaluated the arachidonic acid (AA) and docosahexaenoic acid (DHA) formation from d5-labeled linoleic acid (d5-LA) and ␣-linolenic acid (d5-LNA) precursors in infants with intrauterine growth restriction (IUGR) compared with control groups matched by gestational age (GA) or birth weight. We compared DHA and AA formation from deuterated precursors d5-LA and d5-LNA in 11 infants with IUGR with 13 and 25 control subjects who were appropriate for GA and matched by GA and by birth weight, respectively. After an enteral administration of d5-LA and d5-LNA, we determined unlabeled and d5-labeled fatty acids at 24, 48, and 96 h in plasma. Absolute concentrations and area under the curve (AUC) over the 96-h study were used for analysis. Absolute concentration of d5-DHA and the product/precursor ratio of the d5-labeled AUCs indicated a less active DHA formation from LNA in infants with IUGR compared with their GAmatched (2-fold) and birth weight-matched (3-fold) control subjects. The ratios of eicosapentaenoic and n-3 docosapentaenoic acid to DHA were also affected. Similar evaluation for the n-6 series was not significant. DHA metabolism is affected in infants with IUGR; the restricted DPA to DHA conversion step seems to be principally responsible for this finding. Abbreviations AA, arachidonic acid AGA, appropriate for gestational age AUC, area under the curve DHA, docosahexaenoic acid d5-LA, deuterated linoleic acid d5-LNA, deuterated ␣-linolenic acid DPA, docosapentaenoic acid EFA, essential fatty acids EPA, eicosapentaenoic acid GA, gestational age IUGR, intrauterine growth restriction LA, linoleic acid LCP, long-chain polyunsaturated fatty acids LNA, ␣-linolenic acid PGC-1, peroxisome proliferator-activated receptor-␥ coactivator-1 PPAR, peroxisome proliferator-activated receptor SGA, small for gestational age Intrauterine growth restriction (IUGR) is the result of the failure of the placenta to provide the necessary nutrients required by the fetus to maintain adequate growth (1). During the last trimester of gestation, there is a significant accumulation of long-chain polyunsaturated fatty acids (LCPs) in the fetus and an increase in the relative content of both n-6 and n-3 LCPs in the human brain and retina. Fetal tissue content of LCPs is dependent on maternal intake and on an adequate placental transfer. Thus, a greater risk for restricted in utero LCPs supply may occur in pregnancies that are complicated with abnormal placental function affecting nutrient transfer. Data derived from IUGR animal models indicate that placental insufficiency is associated with abnormalities in fetal lipid metabolism of skeletal muscle and liver (2,3). Cetin et al. (4) reported that fetuses with IUGR have a lower proportion of long-chain n-6 and n-3 fatty acids, arachidonic acid (AA), and docosahexae-

Whole Blood Fatty Acid Composition Differs in Term Versus Mildly Preterm Infants: Small Versus Matched Appropriate for Gestational Age

“…Our data are consistent with findings from the studies with stable isotopes in IUGR infants showing specific impairments in the final biosynthetic pathways leading to the synthesis of LCPUFA, particularly DHA (8,9). Compared with these studies, the new information from our study includes the lack of associations with major differences in PUFA maternal dietary intakes, the high EPA-low monounsaturated FA levels in term SGA, and that even mild prematurity (that is, an average gestational age of around 35 wks) is associated with lower LCPUFA levels, particularly DHA, compared with term infants.…”

“…Studies with stable isotopes have shown that growth retardation slows down or reduces LCPUFA formation (8), the synthesis of n-3 compounds being more extensively affected (9). The evaluation of the LCPUFA status is therefore relevant to appreciate physiologic processes and establish dietary needs of preterm and SGA infants, respectively.…”

Investigating the Role of Polyunsaturated Fatty Acids in Bone Development Using Animal Models

“…Thus, increasing n-3 PUFA in the diet, particularly long chain n-3 PUFA, may reduce production of AA derived PGE 2 and subsequent osteoclastogenesis. In tandem, EPA is a substrate for PGE 3 , and while PGE 3 also promotes osteoclastogenesis, the conversion of EPA to PGE 3 is much less efficient, resulting in lower levels of PGE 3 [49]. In addition, osteoblasts produce osteoprotegerin (OPG), a decoy receptor for RANKL.…”

“…Although many of these products are marketed to and consumed by children, the majority of research investigating the effects of n-3 PUFA on growth has focused on visual acuity and neurodevelopment [2][3][4]. In contrast, the potential benefits of these fatty acids on bone outcomes from the early stages of the life cycle through infancy and adulthood is poorly understood.…”

Dietary lipids and the brain during development and ageing

“…These data indicate that the usual dietary provision of LA from formula or breast milk is sufficient to support tissue needs. LCP formation of in utero growth-restricted infants has also been explored, and a limited capacity for microsomal b-oxidation was identified in such infants; these infants accumulate docosapentaenoic acid (22:5 n-3 DPA) owing to impaired function of peroxisomes (12).…”