Is intravenous fish oil associated with the neurodevelopment of extremely low birth weight preterm infants on parenteral nutrition?

BACKGROUND & AIMS: Preterm infants are at increased risk of long-term neurodevelopmental disabilities (NDD). Long chain n-3 fatty acids play a key role during the development of the central nervous system and some studies in preterm infants showed benefits of docosahexaenoic acid and arachidonic acid supplementation for visual and cognitive development. In recent years fish oil has been added to the fat blend of intravenous (IV) lipid emulsions (LE) but to date scanty data are available on neurodevelopmental outcome of preterm infants that received fish oil containing LE. We studied the effect of fish oil containing IV LE vs standard IV LE on neurodevelopment in a large cohort of preterm infants who received routine parenteral nutrition (PN) from birth. METHODS: We retrospectively reviewed the neurodevelopmental outcome of 477 preterm infants (birth weight (BW): 400-1249 g and gestational age (GA) at birth: 24+0 - 35+6 weeks (W)) admitted to our NICU between Oct-2008 and June-2017, who received routine PN with different LE, with and without fish oil (IV-FO vs CNTR). We compared neurodevelopment at 2 years corrected age by the Bayley III development scale and the incidence of NDD. RESULTS: Demographics, birth data and the incidence of the main clinical short-term outcomes of prematurity were similar in the two groups (IV-FO: n = 178, GA 197 ± 14 days, BW 931 ± 182 g; CNTR: n = 192, GA 198 ± 15 days, BW 944 ± 194 g). No differences were found in maternal demographics nor in parental education between the two groups. Cognitive score was not significantly different between IV-FO and CNTR (92 ± 15 vs 93 ± 13, p = 0.5). No differences were found in motor and language scores, and in the incidence of NDD in the two groups. CONCLUSIONS: Contrary to our hypothesis, the use of fish oil containing LE in a large cohort of preterm infants on routine PN did not result in better neurodevelopment. Large randomized controlled trials powered for neurodevelopment are needed to clarify the impact of the widely used fish oil containing LE on neurodevelopment of preterm infants.

Does intravenous fish oil affect the growth of extremely low birth weight preterm infants on parenteral nutrition?

BACKGROUND & AIMS: Long chain n-3 fatty acids (n-3 LCPUFA) play a pivotal role during central nervous system development and the provision of docosahexaenoic acid (DHA) is recommended for the preterm infant. However, there are concerns that oral fish oil, which is a good source of DHA, may adversely affect growth of preterm infants, as it decreases arachidonic acid (ARA). It has been about ten years since fish oil was added to the fat blend of intravenous (IV) lipid emulsions (LE) but information on growth and other clinical outcomes of preterm infants is still scarce. We studied the effect of fish oil containing IV LE vs standard IV LE on growth in a large cohort of preterm infants who received routine parenteral nutrition (PN). METHODS: We retrospectively reviewed growth data of 546 preterm infants with a birth weight (BW) < 1250 g consecutively admitted to our NICU between Oct-2008 and Jun-2017 who received PN starting from the first day of life. Individual patients received only one of 5 commercially available IV LE. For the purpose of this study we grouped the patients who received the fish oil containing LE (IV-FO) and those who received conventional LE (CNTR). We compared PN and enteral nutrition (EN) intakes, and growth from birth to 36+0 weeks post-menstrual age (W PMA). RESULTS: Demographics, birth data and the incidence of the main complications of prematurity were similar between the two groups (IV-FO: n = 240, Gestational age (GA) 197 ± 16 d, BW 942 ± 181 g; CNTR: n = 237, GA 199 ± 17 d, BW 960 ± 197 g). No difference was found in PN and EN energy and macronutrient intakes from birth to 36+0W PMA, as well as in the proportion of human milk to infant milk formula. Weight gain from the regained BW to 36+0W PMA was slightly but significantly higher in IV-FO group: 17.3 ± 2.8 and 16.8 ± 2.7 g∙kg-1∙d-1, IV-FO and CNTR respectively (p = 0.03). There was no difference in length gain and head growth nor in body size at 36+0W PMA between the two groups. CONCLUSIONS: The use of IV fish oil did not negatively affect weight gain in a cohort of preterm infants. Large randomized controlled trials are needed to assess the effect of IV fish oil on the complication of prematurity and on selected domains of infant development.

Double blind exploratory study on de novo lipogenesis in preterm infants on parenteral nutrition with a lipid emulsion containing 10% fish oil.

BACKGROUND & AIMS: Provision of long chain polyunsaturated fatty acids (LCP) both of the omega-3 and omega-6 families is recommended for preterm infants (PI). Fish oil (FO) contains omega-3 and omega-6 LCP and it is incorporated in the fat blend of the new generation lipid emulsions (LE). Omega-3 LCP have been shown to reduce the expression of genes involved in lipogenesis, which could be important for several organs development. The aim of this study was to ascertain if the use of intravenous FO has an effect on lipogenesis in PI. METHODS: Forty PI were randomized to receive two LE: MSF (50:40:10 Medium Chain Triglycerides (MCT): Soybean oil (SO): FO) or MS (50:50 MCT:SO). We measured plasma lipids on day 7 and the fractional and absolute synthesis rates (FSR and ASR) of cholesterol and of selected fatty acids (FA) after (2)H2O body water labeling. RESULTS: Plasma phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) concentrations were all lower in MSF than in MS. In spite of lower plasma FC and CE concentrations, cholesterol biosynthesis was similar between the two study groups (FC: FSR 16.0 ± 1.4 vs 14.1  ± 1.1%/d, p = 0.74; ASR 6.8 ± 0.6 vs 7.1 ± 0.6 mg kg(-1) d(-1), p = 0.93; CE: FSR 3.6 ± 0.5 vs 4.2 ± 0.4%/d, p = 0.38; ASR: 3.3 ± 0.4 vs 4.4 ± 0.5 mg kg(-1) d(-1), p = 0.13, in MSF and MS respectively). FSR and ASR of selected FA were, or tended to be, lower in MSF than in MS. ASR of PL palmitate (4.0 ± 0.3 vs 4.8 ± 0.4 mg kg(-1) d(-1), p = 0.045), PL oleate (0.2 ± 0.04 vs 0.4 ± 0.05 mg kg(-1) d(-1), p = 0.02) and CE oleate (0.5 ± 0.1 vs 0.9 ± 0.1 mg kg(-1) d(-1), p = 0.03) were significantly lower in MSF than in MS. There were no differences in plasma TG FA biosynthesis. CONCLUSIONS: Cholesterol biosynthesis was not affected by 10% FO during neonatal parenteral nutrition. Ten percent FO caused a statistically significant reduction in the lipogenesis of selected FA and an overall tendency towards a reduced lipogenesis. The magnitude seems to be limited and the biological significance is unknown. Our data warrant follow-up studies in PI who receive intravenous FO, especially in those infants who receive larger doses than in the present study. Since this trial started in 2007, trial registration was not required.

Higher docosahexaenoic acid, lower arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: a randomized clinical trial.

BACKGROUND & AIMS: Lipid emulsions containing fish oil, as source of long chain omega 3 fatty acids, have recently became available for parenteral nutrition in infants, but scanty data exist in extremely low birth weight preterms. The objective of this study was to compare plasma fatty acids and lipid tolerance in preterm infants receiving different doses of a 15% fish oil vs. a soybean oil based lipid emulsion. METHODS: Preterm infants (birth weight 500-1249 g) were randomized to receive parenteral nutrition with MOSF (30% Medium-chain triglycerides, 25% Olive oil, 30% Soybean oil, 15% Fish oil) or S (S, 100% Soybean oil) both at two levels of fat intake: 2.5 or 3.5 g kg(-1) d(-1), named 2.5Fat and 3.5Fat respectively. Plasma lipid classes and their fatty acid composition were determined on postnatal day 7 and 14 by gas chromatography together with routine biochemistry. RESULTS: We studied 80 infants. MOSF infants had significantly higher plasma phospholipid Docosahexaenoic acid and Eicosapentaenoic and lower Arachidonic acid. Plasma phospholipids, triglycerides and free cholesterol were all significantly higher in the MOSF-3.5Fat group, while cholesterol esters were lower with MOSF than with S. The area under the curve of total bilirubin was significantly lower with MOSF than with S. CONCLUSIONS: The use of a lipid emulsion with 15% FO resulted in marked changes of plasma long-chain fatty acids. Whether the benefits of increasing Docosahexaenoic acid outweigh the potential negative effect of reduced Arachidonic acid should be further studied. MOSF patients exhibited reduced lipid tolerance at 3.5 g kg(-1) d(-1) fat intake. The trial was conducted between January 2008 and December 2012 so we had not registered it in a public trials registry as it is now required for trials that started after July 2008.

The effect of 5 intravenous lipid emulsions on plasma phytosterols in preterm infants receiving parenteral nutrition: a randomized clinical trial.

BACKGROUND: Elevated plasma phytosterol concentrations are an untoward effect of parenteral nutrition (PN) with vegetable oil-based lipid emulsions (LEs). Phytosterols are elevated in neonatal cholestasis, but the relation remains controversial. OBJECTIVE: The objective was to study the effect of 5 LEs on plasma phytosterols in preterm infants. DESIGN: One hundred forty-four consecutive admitted preterm infants (birth weight: 500-1249 g) were studied. Patients were randomly assigned to receive 1 of 5 different LEs: S [100% soybean oil (SO)], MS [50% medium-chain triglycerides (MCTs) and 50% SO], MSF (50% MCTs, 40% SO, and 10% fish oil (FO)], OS (80% olive oil and 20% SO), or MOSF (30% MCTs, 25% olive oil, 30% SO, and 15% FO). Phytosterols in the LEs and in plasma (on postnatal day 7 and day 14) were measured by gas chromatography-mass spectrometry. RESULTS: Patients in the S group had significantly higher total phytosterol intakes than did the other study groups. On PN days 7 and 14, plasma phytosterol concentrations were highest in the S group and lowest in the MOSF group. Despite similar ß-sitosterol intakes between the MS and MSF groups, plasma concentrations were significantly lower in the MSF than in the MS group. Only 3 patients (2.1%) developed cholestasis: 1 in the MS, 1 in the MSF, and 1 in the MOSF group. No cases of cholestasis were observed in the S and OS groups. CONCLUSIONS: In uncomplicated preterm infants receiving routine PN, we found a correlation between phytosterol intake and plasma phytosterol concentrations; however, cholestasis was rare and no difference in liver function at 6 wk was observed.

Parenteral nutrition of preterm infants with a lipid emulsion containing 10% fish oil: effect on plasma lipids and long-chain polyunsaturated fatty acids.

OBJECTIVE: To compare plasma lipids in preterm infants given a new lipid emulsion containing 10% fish oil, 50% medium-chain triacylglycerols, and 40% soybean oil, compared with a standard preparation containing 50:50 medium-chain triacylglycerols: soybean oil. STUDY DESIGN: Preterm infants weighing <1250 g at birth (n=47) were randomly assigned to receive parenteral nutrition with a fish oil lipid (n=23) or soybean oil (n=24). Plasma lipid classes and plasma and red blood cell fatty acids were determined by gas chromatography in cord blood and on postnatal days 7 and 14. RESULTS: On day 7, the infants receiving fish oil lipid had significantly lower plasma phospholipids, cholesterol esters, and free cholesterol but similar triglyceride concentrations. They also had significantly higher phospholipid docosahexaenoic acid (2.77 ± 0.08 versus 2.46 ± 0.01 mol%, P<.01) and eicosapentaenoic acid (1.58 ± 0.01 versus 0.25 ± 0.01 mol%, P<.01) as well as lower arachidonic acid (10.64 ± 0.29 versus 11.93 ± 0.29 mol%, P<.01) compared with those receiving soybean oil. Similar differences were found in red blood cells. CONCLUSIONS: The fish oil lipid emulsion was well tolerated, and infants receiving fish oil had lower plasma lipids and improved fatty acids status. The effect of these changes on inflammation, growth, and neurodevelopment should be explored.