Long Chain Polyunsaturated Fatty Acid Formation in Neonates: Effect of Gestational Age and Intrauterine Growth

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-alpha-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, microg/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.

Relationship between plasma fatty acid profile and antioxidant vitamins during normal pregnancy

“…These findings suggest that although the fatty acid mix delivered to the fetus is largely determined by the fatty acid composition of the maternal blood, the placenta is able to preferentially transfer AA and DHA to the fetus by a combination of several mechanisms, as has recently been reviewed (Haggarty, 2002). Furthermore, although LC-PUFA synthesis from EFA precursors has been demonstrated to occur in preterm infants as early as 26-week gestation (Uauy et al, 2000), other reports have estimated that the contribution of endogenous synthesis to the total plasma LC-PUFA pool in term neonates is small (Demmelmair et al, 1995;Szitanyi et al, 1999).…”

“…The synthesis of these fatty acids from EFA precursors by the fetus cannot be ruled out as contributing to the high proportion of AA and DHA in fetal circulation. The capacity for the metabolic elongation and desaturation of LA and ALA to form AA and DHA, respectively, has been consistently demonstrated to occur during the first days of life in humans, including very premature preterm neonates (Demmelmair et al, 1995;Carnielli et al, 1996;Salem Jr et al, 1996;Sauerwald et al, 1997;Szitanyi et al, 1999;Uauy et al, 2000), and it has also been shown to take place in fetal baboons (Su et al, 1999(Su et al, , 2001. Placental transfer of EPA (20:5(n-3)) has not been reported despite its growth inhibitor action (Sellmayer et al, 1996), its inhibitory effect on human placental membrane binding of EFA (Dutta-Roy, 2000) and its effect in reducing the availability of AA and its metabolites by a competition effect on pathways of EFA metabolism (Dutta-Roy, 1994), all of this denoting an important and active functional activity.…”

Role of long-chain polyunsaturated fatty acids in infant nutrition

“…Moreover, the level of DHA in the brain cortex and liver of preterm infants who died suddenly and that had been fed with artificial formulas was lower than of those fed with human milk (Farquharson et al, 1995). Nonetheless, recent in vivo studies using LA and LNA labelled with stable isotopes in at-term newborns, preterm infants and small for date infants have demonstrated that all infants are able to synthesise LC-PUFA (Demmelmair et al, 1995;Uauy et al, 2000). However, whether the amounts of AA and DHA synthesised are able to meet the daily requirements of infants, particularly in small for date infants, who exhibit the lowest rate of synthesis, is currently unknown.…”

Whole blood fatty acid composition at birth: From the maternal compartment to the infant

“…The biomechanisms at the basis of these differences are actually under active investigation. In spite of the documented LC-PUFA biosynthesis in both preterm and term newborns, 9 the two major LC-PUFA (AA and DHA) in whole blood are already decreased at four days of life compared to cord levels Consumption and/or utilization rates higher than synthetic capacities of infants might explain these observations. Of interest, maternal n-3 LC-PUFA levels (including both EPA and DHA) are related to the n-3 LC-PUFA levels of cord but not of infants.…”