NUTRITION IN LOW-BIRTH-WEIGHT INFANTS: II. Repeated Intravenous Injections of Fat Emulsion

Abstract. Gustafson, A., Kjellmer, I., Olegård, R. and Victorin, L. (Department of Paediatrics, Children's Hospital, and of Medicine I, Sahlgren's Hospital, Goteborg, Sweden). Nutrition in low-birth-weight infants. II. Repeated intravenous injections of fat emulsion. Acta Paediat Scand, 63: 177, 1974.–The elimination of an exogenous fat emulsion from the blood stream after repeated intravenous injections was investigated in two groups of low-birth-weight infants: 11 appropriate-for-date (AFD) pre-term babies and 8 light-for-date (LFD) pre- and full-term infants. During a period with six injections hourly of 0.15 g fat/kg 'b.w. the total lipids of plasma increased only moderately in the AFD group, from 264 to 351 mg/100 ml, while in the LFD group a progressive rise of total lipids occurred from 244 to 466 mg/100 ml. The plasma turbidity increased correspondingly more in the LFD than in the AFD group. In 5 LFD babies, where a progressive accumulation of total lipids occurred with each injection of fat emulsion, heparin was given intravenously after eight fat injections. The plasma was rapidly cleared of fat although fat injections were continued. It is concluded that AFD infants are able to hydrolyse fat emulsions given at an hourly rate of 0.15 g/kg b.w., while this amount of fat to LFD babies will cause an accumulation of plasma lipds unless heparin is supplied simultaneously.     

Neonatal Parenteral Nutrition with a Fat Emulsion Containing Medium Chain Triglycerides

ABSTRACT. Fifty-one newborn infants requiring parenteral nutrition were randomly assigned to receive a 50% medium chain triglyceride/50% long chain triglyceride lipid emulsion or the conventional 100% long chain triglyceride emulsion. Fat was administered daily for 20 hours, to a maximum of 3 g/kg/day. Plasma triglycerides, cholesterol, free fatty acids, ketones, glucose and capillary blood gases were monitored daily up to the sixth day of fat infusion. There were no significant differences in mean plasma triglycerides and free fatty acids between the two groups. No cases of hyperketonaemia were detected in the infants studied. Hyperglycaemic episodes were detected with similar frequency in both groups. The group who received the emulsion containing medium chain triglycerides had significantly lower mean plasma cholesterol values during the study. After 6 days of intravenous fat administration mean plasma cholesterol was more than 100% higher in the group which received the conventional emulsion. Differences in cholesterol content between the emulsions and a cholesterol lowering effect of medium chain triglycerides are possible explanations for these findings.     

Neonatal parenteral nutrition with a fat emulsion containing medium chain triglycerides

Fifty-one newborn infants requiring parenteral nutrition were randomly assigned to receive a 50% medium chain triglyceride/50% long chain triglyceride lipid emulsion or the conventional 100% long chain triglyceride emulsion. Fat was administered daily for 20 hours, to a maximum of 3 g/kg/day. Plasma triglycerides, cholesterol, free fatty acids, ketones, glucose and capillary blood gases were monitored daily up to the sixth day of fat infusion. There were no significant differences in mean plasma triglycerides and free fatty acids between the two groups. No cases of hyperketonaemia were detected in the infants studied. Hyperglycaemic episodes were detected with similar frequency in both groups. The group who received the emulsion containing medium chain triglycerides had significantly lower mean plasma cholesterol values during the study. After 6 days of intravenous fat administration mean plasma cholesterol was more than 100% higher in the group which received the conventional emulsion. Differences in cholesterol content between the emulsions and a cholesterol lowering effect of medium chain triglycerides are possible explanations for these findings.     

Effect of parenteral fat emulsion on the pulmonary and reticuloendothelial systems in the newborn infant.

Analysis of phospholipids (PL), cholesterol esters, triglycerides (TG), and free fatty acids (FFA) was performed on plasma and RBCs in two sick low-birth-weight infants who received total parenteral nutrition including Intralipid for the first 9 and 12 weeks of life, respectively. There was an increase in the total concentration of the plasma IG and FFA in the infants receiving Intralipid as compared with controls. These elevated lipid levels were not detected by visual inspection of the plasma. When compared with control infants, higher levels of linoleic acid were found in the plasma and RBCs of infants receiving Intralipid while plasma PL contained less arachidonate. Histological examination of the lung in both infants who received Intralipid revealed numerous globules of sudanophilic material in alveolar macrophages and capillaries. There is a possibility that prolonged administration of Intralipid may be associated with altered pulmonary and reticuloendothelial system function.     

Tolerance of intravenously administered lipid in newborns

The tolerance for intravenously administered Intralipid in 262 premature and sick newborns was studied. The serum concentrations of triglycerides and of free fatty acids were determined during total parenteral nutrition including Intralipid in a maximum daily dose of 2 g/kg. A serum concentration of 1.5 mmol/l or higher was found in 270 out of 985 triglyceride determinations (27.4%). In the 262 infants serum triglyceride concentrations were found elevated once or more in 117 cases (44.7%). Serum free fatty acids concentrations were normal. A highly significant inverse correlation (p less than 0.001) between birth weight and triglyceride level was found. Elevated serum triglyceride concentrations were observed especially in preterm small-for-gestational-age infants.     

Tolerance of Intravenously Administered Lipid in Newborns

ABSTRACT. The tolerance for intravenously administered Intralipid in 262 premature and sick newborns was studied. The serum concentrations of triglycerides and of free fatty acids were determined during total parenteral nutrition including Intralipid in a maximum daily dose of 2 g/kg. A serum concentration of 1.5 mmol/l or higher was found in 270 out of 985 triglyceride determinations (27.4%). In the 262 infants serum triglyceride concentrations were found elevated once or more in 117 cases (44.7 %). Serum free fatty acids concentrations were normal. A highly significant inverse correlation ( p <0.001) between birth weight and triglyceride level was found. Elevated serum triglyceride concentrations were observed especially in preterm small-for-gestational-age infants.     

Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation

To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.     

Total parenteral nutrition with intralipid in premature infants receiving TPN with heparin: effect on plasma lipolytic enzymes, lipids, and glucose

Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

A prospective study of intrapulmonary fat accumulation in the newborn lung following intralipid infusion

In order to assess the safety and stability of a parenteral fat emulsion (Intralipid) in total parenteral nutrition (TPN), 29 infants were infused Vamin glucose and Dextrose electrolyte solution as well as one of two isocaloric regimens; either 25% Dextrose (Group I) or 10% Intralipid (Group II). Regular biochemical monitoring was performed in all cases and no infants became lipaemic nor developed abnormally high levels of total free fatty acid. Eight infants died and only those who had received fat emulsion had lipid staining material distending the pulmonary vessels. One infant having low infusion rates of Intralipid had massive fat accumulation in the lungs, but biochemistry during life had been normal. We speculate that in ill infants the emulsion becomes less stable and agglomeration of fat particles occurs which are then fully filtered out by the lungs before metabolism of the exogenous fat can occur.     

Plasma metabolites after a lipid load in infants with congenital heart disease

Growth retardation is common in infants with congenital heart defects. The aim of this study was to investigate whether growth retardation or type of heart defect in infants with congenital heart defects is related to disturbances in lipid metabolism. Sixteen infants with ventricular septal defects and six infants with transposition of the great arteries were given an intravenous load of lipid emulsion (Intralipid^® 20 mg/ml) corresponding to 0.5 g fat/kg body weight for 5 min after fasting for 8 h. Blood samples were drawn immediately before the infusion and 3, 20, 60, 120 and 240 min after the infusion was completed. Plasma concentrations of triglycerides (TG), free fatty acids (FFA), ketones, lactate, pyruvate, alanine, glycerol and glucose were determined. The fatty acid patterns in the TG and FFA fractions were measured using gas chromatography. Severe growth retardation in infants with defects of these kinds was correlated to higher fasting and maximum levels of linoleic acid in plasma FFA. The maximum levels of linoleic acid in the TG fraction were positively correlated to weight SD score, and maximum glycerol levels were higher in the most growth-retarded infants, indicating faster intravascular lipolysis. Linoleic acid in the TG fraction was still elevated at 120 and 240 min after the lipid load. Some differences between the cyanotic and VSD groups could be noted. These indicate decreased metabolic capacity to utilize released FFA in the cyanotic group. Infants with cyanotic heart defects also had higher lactate and alanine levels compared to infants with VSD. Our results support the hypothesis that lipid metabolism is disturbed in infants with congenital heart defects.     

Gastric lipolysis and fat absorption in preterm infants: effect of medium-chain triglyceride or long-chain triglyceride-containing formulas

The extent of gastric lipolysis, fat absorption, and infant weight gain was studied in 12 preterm infants (gestational age 28.75 +/- 0.50 weeks, postnatal age 6.08 +/- 0.81 weeks) fed medium-chain triglyceride or long-chain triglyceride formula for 1 week in a crossover design. The former formula contained 42% of 8:0 and 10:0 and 19% of 12:0, 14:0, and 16:0; the latter formula contained only 7% of 8:0 and 10:0 and 46% of 12:0, 14:0, and 16:0. Gastric aspirates were obtained on the second and third day of formula feeding for quantitation of lipase activity and of the extent of gastric lipolysis. Fat balance studies were conducted during the last three days of each feeding regimen. The study showed that (1) there was marked hydrolysis of formula fat in the stomach during feeding of either medium-chain triglyceride formula or long-chain triglyceride formula (20% and 16%, respectively); (2) lipase activity in the gastric aspirates was less during feeding of medium-chain triglyceride formula than before the meal, which suggested stimulation of lipase secretion by long-chain fatty acid released from long-chain triglyceride formula fat or more rapid binding of lipase to ingested lipid in the medium-chain triglyceride formula; (3) fatty acid distribution in glycerides and free fatty acids showed preferential release of medium-chain (8:0, 10:0) and long-chain unsaturated (18:1, 18:2) fatty acids in the stomach. The low content of 8:0 and 10:0 in gastric triglyceride and free fatty acids suggested that medium-chain fatty acids were absorbed directly in the stomach.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early postoperative lipid administration after neonatal surgery

The ability of neonates to eliminate and utilize lipid emulsions after surgery was investigated in 12 patients. All were subjected to major surgery within 29 h of birth. All neonates were given 10% glucose iv intraoperatively. Six patients continued with 10% glucose iv for 24 h postoperatively and 6 patients received a combination of 5% glucose and soy bean emulsion (Intralipid 20%). Both regimes provided equal amounts of fluid and energy. Blood glucose, lactate, triglycerides, free fatty acids, fractions of fatty acids in triglycerides, 3-hydroxybutyrate and arterial blood gases were measured at predetermined intervals throughout this period. Administration of a lipid emulsion early after neonatal surgery was well tolerated and utilized, with some latency. Concentrations of triglycerides, free fatty acids and 3-hydroxybutyrate were higher in the lipid group, but no accumulation of these substances was found. Palmitinic and linoleic acid were also higher in the lipid group.     

A Prospective Study of Intrapulmonary Fat Accumulation in the Newborn Lung Following Intralipid Infusion

In order to assess the safety and stability of a parenteral fat emulsion (Intralipid⁸) in total parenteral nutrition (TPN), 29 infants were infused Vamin glucose and Dextrose electrolyte solution as well as one of two isocaloric regimens; either 25 % Dextrose (Group I) or 10 % Intralipid (Group II). Regular biochemical monitoring was performed in all cases and no infants became lipaemic nor developed abnormally high levels of total free fatty acid. Eight infants died and only those who had received fat emulsion had lipid staining material distending the pulmonary vessels. One infant having low infusion rates of Intralipid had massive fat accumulation in the lungs, but biochemistry during life had been normal. We speculate that in ill infants the emulsion becomes less stable and agglomeration of fat particles occurs which are then fully filtered out by the lungs before metabolism of the exogenous fat can occur.     

Effects of intravenously administered safflower oil emulsion on respiratory gas exchange of low-birth-weight infants

Safflower oil emulsion (Liposyn 10%) was infused intravenously to supplement energy intake in five low-birth-weight infants. Respiratory gas exchange was measured before and after the addition of fat emulsion in doses of 1-2 g of fat/kg/day to an intravenous feeding regimen of dextrose and amino acids. The oxygen consumption and carbon dioxide production rates were greater during fat infusion in all infants, but the mean respiratory quotient was not different. The increase in energy intake provided by the fat emulsion exceeded the increase in energy expenditure, allowing more energy to be stored for growth.     

Intralipid increases lung polyunsaturated fatty acids and protects newborn rats from oxygen toxicity.

Intralipid, derived from soybean oil and containing a high percentage of n-6 family polyunsaturated fatty acids (PUFA) and also linolenic acid, an n-3 family PUFA, is commonly the first fat source provided to very low birth weight premature infants. Following up on our previous reports that newborn rats born to dams fed high-PUFA diets demonstrate superior tolerance to hyperoxia, we examined whether the high-PUFA fat source Intralipid might also protect against oxygen toxicity. Adult female rats were fed either regular Rat Chow or fat-free diet containing 20%-Intralipid as the fat source for 3 wk before and then throughout pregnancy and lactation. One- and 5-d-old offspring of Intralipid diet-fed dams demonstrated significant increases in lung lipid n-6 family PUFA plus elevated linolenic acid compared with regular diet-fed offspring. These characteristic fatty acid patterns, apparent in total lung lipids, were even more pronounced in the triglyceride fraction compared with the phospholipid fraction. Associated with these fatty acid changes were significantly improved hyperoxic survival rates (89 out of 95 = 94% survival after 7 d of greater than 95% O2 exposure) in Intralipid offspring (versus 89 out of 106 = 84%, p less than 0.05 in regular diet offspring) and evidence of superior clinical/pathologic status. No differences in pulmonary antioxidant enzyme or surfactant system development, response of antioxidant enzymes to hyperoxic exposure, or lung prostaglandin E2, 6-keto PGF1-alpha or leukotrienes C4-F4 were present. These findings continue to support the hypothesis that increasing lung PUFA content may provide increased O2 free radical scavenging capacity, thus protecting against hyperoxic lung damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary vascular lipid deposition after administration of intravenous fat to infants

The incidence of pulmonary vascular lipid deposits in infants who did or did not receive intravenous lipid emulsion was determined through a review of the pulmonary histopathology and clinical course of 39 neonates who died during a two-year period. The relationship between pulmonary vascular lipid deposits and the duration and amount of administered intravenous fat emulsion was assessed. In addition, the effect of monitored serum triglyceride levels on the development of pulmonary vascular lipid deposits was evaluated. The incidence of pulmonary vascular lipid deposits was greater in the group that received intravenous fat emulsion (P less than .02). Both the amount (grams per kilogram per day) and duration (days) of intravenous fat emulsion infusion were correlated positively with severity (P less than .05) in infants who had pulmonary vascular lipid deposits. No relationship was seen between peak serum triglyceride levels, the frequency of elevated triglycerides, and pulmonary vascular lipid deposits. Although administered fat emulsion was a risk factor for the development of pulmonary vascular deposits, two of 13 infants who had not received intravenous fat emulsion had such deposits.     

Effect of carnitine on lipid metabolism in the newborn. I. Carnitine supplementation during total parenteral nutrition in the first 48 hours of life

The effect of carnitine administration on neonatal lipid metabolism was studied during endovenous loading with Intralipid (1 g/kg body weight over a 4-hour period). During a 6-hour period the plasma level of triglycerides, glycerol, free fatty acids (FFA), beta-hydroxybutyrate (beta-OHB), and acetoacetate were monitored in a group of newborns infused with carnitine and compared with a control group infused only with Intralipid. Carnitine administration caused an increased plasma concentration of ketone bodies, probably consequent to an increased rate of FFA mitochondrial beta-oxidation. An increased plasma level of glycerol and FFA was also observed, whereas the triglyceride plasma levels were not different between the two groups. Carnitine administration in the neonatal period seems to act by increasing ketogenesis and lipolysis.     

EFFECTS OF INJECTED LIPID EMULSION ON OXYGEN CONSUMPTION, RQ, TRIGLYCERIDE, FREE-FATTY-ACID AND β-HYDROXYBUTYRATE LEVELS IN SMALL-FOR-GESTATIONAL-AGE (SGA) INFANTS

ABSTRACT. Ten SGA infants were studied from 4 hours after birth (day 1) and again at 28 hours (day 2) before and for 4 hours after single injections of 0.5 g of Intralipid® fat/kg b. w. (IL-group). Eight other SGA infants were given 9–10 ml/kg of breast milk (BM-group). After lipid injection the elimination of triglycerides (TG) from plasma was markedly delayed. On day 2 lipolysis had improved, but was still slower than in previously studied AGA infants. The initial FFA plasma level was higher on day 1 than on day 2. Oxidation of released fatty acids was confirmed by a significant increase of V_o, and a decrease of RQ on day 1 and 2. In all infants the β-hydroxybutyrate level in plasma increased and was still elevated 4 hours after injection of fat. A negative correlation was found between β-hydroxybutyrate levels and RQ. In the BM-group changes in TG and β-hydroxybutyrate levels were small and insignificant. FFA had decreased 60 min after breast milk on day 1. In conclusion: TG elimination from plasma was impaired on day 1 and had slightly improved on day 2. The fatty acids released by lipolysis were oxidized as seen by increasing V_o, falling RQ and increasing β-hydroxybutyrate plasma levels both on day 1 and day 2.     

Lecithin:cholesterol acyltransferase (LCAT) activity during lipid infusion in premature infants

Plasma cholesterol and lecithin concentrations are regulated by the serum enzyme lecithin: cholesterol acyltransferase (LCAT). LCAT activity is low in cord blood of premature infants, suggesting that in these infants the hypercholesterolemia associated with Intralipid infusion might be due to low LCAT activity. The serum LCAT activity has not been quantitated in preterm infants receiving intravenous fat emulsions. We have therefore quantitated LCAT activity in eleven premature infants maintained on total parenteral nutrition (TPN). Ten infants were studied during the first 2 weeks after birth; they received daily infusions of Intralipid at a rate of 0.5-2.0 g/kg/day over 15 h. One infant received 3.8 g/kg/day during the second week. In addition to LCAT, serum apoprotein A1 (the cofactor of LCAT), cholesterol, triglycerides, and free fatty acids were quantitated. Blood specimens were taken before the start of the infusion and 15-45 min before its completion. The LCAT activity and apoprotein A1 concentrations remained, respectively, 21-24% and 30-35% of adult levels. However, serum cholesterol levels remained in the normal range during the fat infusion. It remains to be established whether low LCAT activity and apoprotein A1 levels are due to the administration of Intralipid (which lowers LCAT activity in rats), to the lack of enteral feedings, or to prematurity per se. Our data suggest that administration of Intralipid at a rate not exceeding 1-2 g/kg/day does not impair the clearing of Intralipid-lecithin and the metabolism of cholesterol.     

早产儿早期静脉营养耐受性的探讨

目的 探讨早产儿生后1～2d对静脉营养的耐受性。方法 将不能完全耐受肠道营养的早产儿34例(胎龄29～36周，体重900～1800g)，随机分为两组，实验组于生后48h内添加氨基酸及脂肪乳；对照组采用传统的静脉营养方法，即生后第3天应用氨基酸，第5天应用脂肪乳，同时均根据病情尽早经口微量喂养。两组患儿均于生后第1天及第7天采血，监测血清游离脂肪酸、总胆红素、直接胆红素、白蛋白、甘油三脂、总胆固醇，每天监测体重、微量血糖及经皮胆红素值。比较两组患儿恢复出生体重的时间、血清游离脂肪酸、胆红素及血脂的变化。结果 1)实验组患儿恢复出生体重的时间较对照组短；2)两组患儿生后相同日龄测得血清游脂肪酸、总胆红素、直接胆红素、甘油三脂、总胆固醇及血清游离脂肪酸与白蛋白的摩尔比均无显著差异。结论 早产儿生后1～2d可耐受全或部分肠道外营养。