Tolerancia y seguridad de las formulas enterales hipercaloricas en la primera infancia / Tolerance and segurity of enteral hypercaloric formules in infants

Se evaluó la seguridad y la tolerancia de fórmulas pediátricas entérales con altas concentraciones de energía, comparándolas con una fórmula estándar. En este estudio abierto, aleatorio, multicéntrico, de fase III, se evaluaron niños de 1 a 6 años de edad que requerían alimentación por sonda para proporcionar al menos el 75 por ciento de sus requerimientos diarios de energía, durante 21 días. Los sujetos (n = 98) recibieron una fórmula de control, Pediasure (C: 1,0 kcal/ mL) o una fórmula experimental similar en su composición nutricional, pero con mayor densidad calórica (1,5 kcal/mL) con fibra (Ef) o sin fibra (E). Los sujetos regresaron a consultas semanales. En todos los grupos mejoraron los parámetros gastrointestinales (p<0,05). La ingestión de energía fue similar entre los grupos, pero se obtuvo con volúmenes más bajos (p< 0,0001) en EyEF, en comparación con C. El aumento de peso fue mayor (p>0,01) en E vs. C. El informe de efectos adversos fue similar entre los grupos. Las fórmulas hipercalóricas son una opción en los niños con restricción de líquidos o con requerimientos aumentados de energía o de fibra, sin comprometer la seguridad o la tolerancia

Nutritional effects of surgical and medical treatment for short bowel syndrome.

BACKGROUND: The choice of treatment options in short bowel syndrome (SBS) is hampered by a lack of comparative studies. This study uses a previously validated juvenile pig model of SBS to compare nontreated controls (C), surgical treatment with either proximal colon interposition (CI) or bowel lengthening (BL), with medical treatment with codeine and cimetidine (M). METHODS: Treatment was initiated 6 weeks after resection of 75% of the small bowel, and animals were followed until sacrifice at week 16. Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment. RESULTS: BL and M treatments resulted in improved rates of weight gain; this improvement was associated with improved absorption of dietary fat. The treatments did not affect carbohydrate or protein absorption in vivo. In vitro fatty acid absorption was not increased in any group. Active uptake of glucose was increased in the colon interposition group, but phlorizin binding (reflecting sodium glucose cotransporter activity) did not differ between groups. Gross serosal and microscopic mucosal surface areas increased in all groups; however, there were no significant differences between the treatment groups. CONCLUSIONS: These results demonstrate that bowel lengthening and medical treatment improved the rate of weight gain in this model of SBS. This appeared to be due to improvement in the absorption of dietary fat, which was not caused by alterations in in vitro uptake or mucosal surface area, suggesting these treatments have their affects by altering motility or intraluminal digestion. These findings suggest that these treatments are worthy of further study in treating patients (primary pediatric) with SBS.

Polyunsaturated fatty acids and T-cell function: implications for the neonate.

Infant survival depends on the ability to respond effectively and appropriately to environmental challenges. Infants are born with a degree of immunological immaturity that renders them susceptible to infection and abnormal dietary responses (allergies). T-lymphocyte function is poorly developed at birth. The reduced ability of infants to respond to mitogens may be the result of the low number of CD45RO+ (memory/antigen-primed) T cells in the infant or the limited ability to produce cytokines [particularly interferon-y, interleukin (IL)-4, and IL-10. There have been many important changes in optimizing breast milk substitutes for infants; however, few have been directed at replacing factors in breast milk that convey immune benefits. Recent research has been directed at the neurological, retinal, and membrane benefits of adding 20:4n-6 (arachidonic acid; AA) and 22:6n-3 (docosahexaenoic acid; DHA) to infant formula. In adults and animals, feeding DHA affects T-cell function. However, the effect of these lipids on the development and function of the infant's immune system is not known. We recently reported the effect of adding DHA + AA to a standard infant formula on several functional indices of immune development. Compared with standard formula, feeding a formula containing DHA + AA increased the proportion of antigen mature (CD45RO+) CD4+ cells, improved IL-10 production, and reduced IL-2 production to levels not different from those of human milk-fed infants. This review will briefly describe T-cell development and the potential immune effect of feeding long-chain polyunsaturated fatty acids to the neonate.

Intravenous lipid composition affects hypoxic pulmonary vasoconstriction in the newborn piglet.

To examine the effects of altering the fatty acid (FA) composition of intravenous (IV) lipid emulsions on pulmonary vascular resistance (PVR) and thromboxane production, we studied three groups of newborn piglets after three days of either sow's milk (milk), or total parenteral nutrition (TPN) with either iv soy bean oil (SBO, 52% n-6 and 8% n-3 FA) or fish oil (FO, 5% n-6 and 51% n-3 FA) emulsions. At baseline, and during hypoxia at 20 min and 2 h, cardiac output (Q) was measured, PVR calculated and plasma levels of a prostacyclin metabolite (6-keto-PgF1alpha) and thromboxane B2 (TxB2) were measured. Fatty acid composition of the lung phospholipids was analyzed. There was an exaggerated increase in PVR and decrease in Q during prolonged hypoxia in the TPN-SBO group as compared with the other two groups. There was no difference in PVR and Q between the milk and TPN-FO groups. FA of lung phospholipids reflected the high dietary level of long chain n-3 FA in the TPN-FO group. However, no differences in plasma levels of 6-keto-PgF1alpha or TxB2 were found. Intravenous emulsions made from SBO reduced cardiac output and increased pulmonary vascular resistance in the hypoxic newborn piglet, whereas iv FO emulsions did not. When subjects with pulmonary hypertension are receiving TPN iv SBO may be detrimental; iv FO may be beneficial, giving similar responses as in a milk-fed subject.

Differential expression of matrix metalloproteinases and the tissue inhibitor in human milk.

There are differences in the temporal expression of MMP-2 and TIMP-4 in human milk from Day 1 to 30 postpartum in healthy mothers of term pregnancies: (i) MMP-2 activity peaked at Day 1 (colostrum) then exponentially decreased afterwards; and (ii) The expression of TIMP-4 was maximal at Day 7 and persisted thereafter. From our preliminary findings, the differential expression of MMP and the tissue inhibitor in human milk may be related to the protective action of human milk.

Lower proportion of CD45R0+ cells and deficient interleukin-10 production by formula-fed infants, compared with human-fed, is corrected with supplementation of long-chain polyunsaturated fatty acids.

BACKGROUND: The immune consequences of adding 20:4n-6 and 22:6n-3 fatty acids to preterm infant formula are not known. METHODS: The effect of feeding preterm infants (14-42 days of age) human milk (Human Milk group), infant formula (Formula group), or formula with added long-chain polyunsaturated fatty acids 20:4n-6 and 22:6n-3 (Formula + LCP group) on isolated peripheral blood lymphocytes (by flow cytometry) and lipid composition (by gas-liquid chromatography) was determined. Lymphocytes were stimulated in vitro with phytohemagglutinin to measure soluble interleukin (sIL)-2R and IL-10 production (by enzyme-linked immunosorbent assay). RESULTS: With age, the percentage of CD3+ CD4+ T cells and the percentage of CD20+ cells increased in the Human Milk and Formula + LCP groups (P < 0.05), but not in the unsupplemented Formula group. Compared with the Formula group, CD4+ cells from the Formula + LCP and Human Milk groups expressed more CD45R0 (antigen mature) and less CD45RA (antigen naive) at 42 days of age (P < 0.05). At 42 days, IL-10 production was lower (P < 0.05) in cells of the Formula group than in cells of the Human Milk group. Production of IL-10 by the cells of the Formula + LCP group was not different from that produced by the Human Milk group cells. An age-related decrease (P < 0.05) in sIL-2R production by Formula + LCP lymphocytes was observed, but sIL-2R production at 42 days in the Formula + LCP group did not differ significantly from that in the Human Milk group. Compared with Formula alone, adding LCP to formula resulted in a lower C18:2n-6 and higher C20:4n-6 content in lymphocyte phospholipids (P < 0.05). CONCLUSIONS: Adding LCP to a preterm infant formula resulted in lymphocyte populations, phospholipid composition, cytokine production, and antigen maturity that are more consistent with that in human milk-fed infants. This may affect the ability of the infant to respond to immune challenges.

Ontogeny of intestinal nutrient transport.

Children born prematurely lack the ability to digest and to absorb nutrients at rates compatible with their nutritional needs. As a result, total parenteral nutrition may need to be given. While this nutritional support may be lifesaving, the baby who receives this therapy is exposed to the risks of possible sepsis, catheter dysfunction, and liver disease. The rodent model of postnatal development provides a useful framework to investigate some of the cellular features of human intestinal development. The up-regulation of intestinal gene expression and precocious development of intestinal nutrient absorption can be achieved by providing growth factor(s) or by modifying the composition of the maternal diet during pregnancy and nursing or the weaning diet of the infant. Accelerating the digestive and absorptive functions of the intestine would thereby allow for the maintenance of infant nutrition through oral food intake, and might possibly eliminate the need for, and risks of, total parenteral nutrition. Accordingly, this review was undertaken to focus on the adaptive processes available to the intestine, to identify what might be the signals for and mechanisms of the modified nutrient absorption, and to speculate on approaches that need to be studied as means to possibly accelerate the adaptive processes in ways which would be beneficial to the newborn young.

Assessment of feeding different amounts of arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of lipoprotein lipids.

This study evaluated preterm infants of less than 2.3 kg birth weight fed commercial formula (Preemie SMA) devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32-1.1% AA and 0.24-0.75% DHA in the fat component of the formula. An analogous group of infants fed on their mothers' breast milk and a breast milk fortifier was also studied. Individual lipoprotein fractions were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. The fatty acid content of individual lipid components, isolated from each lipoprotein fraction was quantitatively determined in order to identify change in marker pools of essential fatty acid. The high density lipoproteins (HDL) and low density lipoproteins (LDL) phospholipid and cholesterol ester fractions contain most of the AA and DHA found in the lipoprotein fractions (total of 0.49% and 0.35%, respectively). Infants fed a formula without AA and DHA showed a reduction in AA level in the phospholipid fraction of all lipoproteins and in the HDL and LDL cholesterol ester fraction. A reduced level of DHA was also observed primarily in the lipoprotein phospholipid fraction in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the level of AA found in the HDL and LDL phospholipid fraction. From comparison of the fatty acid levels present in the lipoproteins it appears that a formula level of 0.49% AA and 0.35% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid content to that of infants fed breast milk for the major lipoprotein fractions examined.

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age.

BACKGROUND: The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS: In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS: Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS: The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Tonometry to estimate intestinal perfusion in newborn piglets.

AIM: To determine the correlation between gastric intramucosal pH and superior mesenteric artery (SMA) flow in newborn piglets. METHODS: Fourteen newborn piglets were randomly assigned to either a control or to an epinephrine group which received 0,1,2,4,0 microg/kg/min of epinephrine for 60 minutes, each dose. Gastric tonometry was performed, SMA flow was measured, and intramucosal pH and the ratio of tonometer pCO(2) over arterial pCO(2) (rCO(2)) were calculated. RESULTS: Intramucosal pH decreased over time in both groups, but tended to be lower in the epinephrine group. With increasing dose of epinephrine, SMA flow decreased; this in turn increased rCO(2) (p = 0.04) with a tendency to decrease intramucosal pH (p = 0.06). CONCLUSIONS: Gastric tonometry may be useful in human neonates to evaluate gut ischaemia.

Changing parenteral nutrition administration sets every 24 h versus every 48 h in newborn infants.

OBJECTIVE: To determine whether changing total parenteral nutrition fluid administration sets (TAS) every 48 h rather than every 24 h results in a greater infusate contamination rate. PATIENTS AND METHODS: Prospectively, 166 infants were assigned at random to have TAS changed either every 24 h or every 48 h. Samples of the infusate were cultured to determine contamination rates of the infusate in the sets and were tested from 149 of these infants. TAS was replaced every 24 h in the control group, and 445 amino acid plus dextrose solutions (AADS) and 449 lipid emulsions samples were taken for bacterial culture. Fungal cultures were also performed on 449 samples. The study group had TAS replaced every 48 h, and 454 samples of AADS were cultured for bacteria. The numbers of lipid emulsion samples sent for bacterial culture and fungal culture were 449 and 440, respectively. Information on type of intravenous access device, administration of antibiotics and blood cultures was also collected. RESULTS: There was no difference in bacterial contamination rates for AADS or lipid emulsion from TAS changed every 24 or 48 h (c2, P>0.05). Lipid emulsion sampled from the 24 h group showed a statistically significant higher rate of fungal contamination than specimens from the 48 h group (P<0.01). CONCLUSIONS: Changing TAS every 48 h versus 24 h does not increase the contamination rate of infusate in newborns.

Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets.

Total parenteral nutrition (TPN) causes intrahepatic cholestasis and membrane phospholipid changes. Fatty acid (FA) composition of bile and hepatocyte phospholipid is influenced by dietary FA composition. We hypothesized that altering FA composition of i.v. lipid emulsions modifies 1) severity of TPN-induced cholestasis; 2) hepatocyte membrane composition and function; 3) bile flow and composition. Newborn piglets received either sow's milk, TPN with i.v. soybean oil or TPN with i.v. fish oil (FO). After 3 wk, basal and stimulated bile flow were measured after bolus injections of 20, 50, and 100 micromol/kg of taurocholate (TCA). Bile was analyzed for bile acids, cholesterol, phospholipids, and phospholipid-FA. Sinusoidal and canalicular membrane PL-FA, fluidity, and Na+/K+-ATPase were measured. Although the soybean oil-fed animals developed cholestasis, the FO and milk group had similar liver and serum bilirubin. Basal and stimulated bile flow rates were impaired in the soybean oil but not in the FO group. Hepatocyte membrane FA composition reflected dietary FA. Changes in sinusoidal and canalicular membrane fluidity and sinusoidal Na+/K+-ATPase activity did not explain the effect of FO on TPN-induced cholestasis. Intravenous FO reduces TPN-induced cholestasis by unknown mechanisms.

Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids.

The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA), have not been clearly defined. The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula (Preemie SMA) devoid of AA and DHA and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1% AA and 0.24 to 0.76% DHA. An analogous group of infants fed their mothers' breast milk and a breast milk fortifier (when indicated) was also studied. Erythrocyte membrane phospholipids were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine, and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids. From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32-1.1% AA and 0.24-0.76% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined.

Lipids in total parenteral nutrition solutions differentially modify lipids in piglet intestinal brush border and microsomal membranes.

BACKGROUND: Fats in the diet modify the lipid composition and function of the intestinal brush border membrane (BBM) as well as the enterocyte microsomal membrane (EMM). METHODS: This study was undertaken in pigs to establish the effect of 3 weeks of total parenteral nutrition (TPN) on the fatty acids in the major phospholipids, (phosphatidylcholine [PC] and phosphatidylethenolamine [PE] in the jejunal and ileal BBM and EMM. RESULTS: In a comparison of 21-day-old milk-fed piglets and newborn animals, there were differences in the major fatty acids (palmitic, 16:0; stearic, 18:0; oleic, 18:1 omega 9, and linoleic acid, 18:2 omega 6) in PC and PE in BBM and EMM. Age-matched (3-week-old) animals fed a lipid-free glucose-containing TPN solution had different membrane fatty acids than did milk-fed piglets, or animals given a soybean oil-containing TPN solution for 21 days. Substituting fish oil or fish oil plus soybean oil altered BBM and EMM fatty acids, compared with the soybean oil-based TPN solutions. These changes varied between the class of phospholipids (PC vs PE), between intestinal site (jejunum vs ileum), and between the type of membrane (BBM vs EMM). CONCLUSIONS: The jejunum and ileum have distinctive control mechanisms for varying their membrane lipids in response to TPN. There is some postmicrosomal modification of lipids between the EMM and BBM. It remains to be established whether the lipid content of the membranes of other organs, and therefore their function, is modified by the lipid composition of parenterally infused lipids.

Systemic, pulmonary and mesenteric perfusion and oxygenation effects of dopamine and epinephrine.

The response of the systemic, pulmonary, hepatic and portal circulations to infusion of dopamine and epinephrine was studied in newborn piglets 1 to 3 d of age. Anesthetized animals were instrumented to measure cardiac index (CI), hepatic arterial flow, and portal venous blood flow. Catheters were inserted for measurement of systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and for sampling of arterial, portal venous, and mixed venous oxygen saturations and plasma lactate levels. Systemic, pulmonary and mesenteric vascular resistance indices (SVRI, PVRI, MVRI), and systemic and mesenteric oxygen extraction were calculated. Dopamine and epinephrine were infused in doses of 2, 10, 32 microg/kg/min and 0.2, 1.0, 3.2 microg/kg/min respectively, given in random order. Significant increases in SAP, PAP, and CI were demonstrated with 32 microg/kg/min of dopamine and the two higher doses (1.0 and 3.2 microg/kg/min) of epinephrine. There were no significant changes in SVRI and PVRI with dopamine infusions. Epinephrine at 3.2 microg/kg/min significantly elevated SVRI and PVRI. The SAP/PAP ratio was decreased with 32 microg/kg/min of dopamine whereas epinephrine did not affect the ratio. Dopamine had no significant effect on hepatic arterial flow, portal venous flow, or mesenteric vascular resistance. Epinephrine infusion at 3.2 microg/kg/min decreased portal venous blood flow, total hepatic blood flow, and hepatic oxygen delivery with an increase in calculated mesenteric vascular resistance. Systemic and mesenteric oxygen extraction were not affected by dopamine or epinephrine infusions. Plasma lactate levels were significantly elevated with epinephrine infusion 3.2 microg/kg/min. The differential responses of dopamine and epinephrine on pulmonary and mesenteric circulations may be significant in the pathophysiology and management of persistent fetal circulation and necrotizing enterocolitis.

Intravenous ursodeoxycholic acid reduces cholestasis in parenterally fed newborn piglets.

BACKGROUND & AIMS: Cholestasis complicates total parenteral nutrition (TPN) in preterm infants. Ursodeoxycholic acid (UDCA) is used for several cholestatic problems. The hypothesis of this study was that intravenous UDCA prevents TPN-induced cholestasis by (1) maintaining normal basal and stimulated bile flow, (2) altering bile composition, and (3) changing hepatocyte membrane composition and Na+,K(+)-adenosine triphosphatase (ATPase) activity. METHODS: Three groups of piglets were studied: group 1 received sow's milk, groups 2 and 3 received TPN, and group 3 also received 100 mumol.kg-1.day-1 UDCA intravenously. After 3 weeks, basal and stimulated bile flow were measured. Cholesterol, bile acids, phospholipids, and phospholipid fatty acids were analyzed in bile, and fluidity, phospholipid fatty acid composition, and Na+,K(+)-ATPase were analyzed in hepatocyte membranes. RESULTS: Bile acid secretion and basal and stimulated bile flow were similar in control and UDCA-treated animals but reduced to < 50% in the TPN group. Bile acid-dependent and -independent bile flow were lower in the TPN group. UDCA did not normalize abnormalities in TPN-induced bile composition. Sinusoidal but not canalicular membrane fluidity was different in TPN than in control and UDCA-treated animals. UDCA also increased Na+,K(+)-ATPase activity. Bile and membrane phospholipid fatty acids reflected dietary fatty acids. CONCLUSIONS: Intravenous UDCA improves bile flow and reduces bilirubin levels in the serum and liver in piglets with TPN-induced cholestasis.

Total parenteral nutrition impairs bile flow and alters bile composition in newborn piglet.

Cholestatic liver disease complicates total parenteral nutrition (TPN) in premature neonates. We investigated TPN-induced liver disease in the newborn piglet, hypothesizing that: (1) TPN impairs bile flow by reducing the bile acid-dependent (BADF) and the bile acid-independent component of bile flow (BAIF); and (2) TPN changes bile composition. For three weeks, eight piglets received TPN and nine piglets were fed milk. Basal bile flow was measured and bile composition analyzed for bile acids, cholesterol (C), phospholipids (PL), and PL fatty acids. Bile flow was also measured after stimulation with 20, 50, and 100 mu/kg taurocholic acid (TCA). Liver histology and bilirubin content were examined. Basal bile flow was reduced from 11.6 +/- 1.2 microliters/g liver/10 min in orally fed animals to 1.6 +/- 0.4 microliters/g liver/10 min in the TPN group. The stimulated bile flow in the TPN group did not respond to TCA and was lower than in the orally fed animals at each TCA dose. Both BADF and BAIF were significantly lower in the TPN group. Bile acid secretion was less than 50% of control values and total C and PL secretions were less than 5% of control. Liver and serum bilirubin were elevated in the TPN group. The newborn piglet is a valid model to study TPN-induced cholestasis, characterized by decreased bile acid secretion, impaired BADF and BAIF, and reduced bile flow stimulation after intravenous TCA.

Pulmonary vascular resistance during lipid infusion in neonates.

Using two-dimensional echocardiography, pulmonary vascular resistance was estimated from right ventricular pre-ejection period to ejection time (RVPEP/ET) in 11 preterm infants with respiratory distress, to test the effect of different doses of continuous lipid infusion. Echocardiography was performed at baseline with no lipid infusing 2 and 24 hours after 1.5 and 3 g/kg/day of intravenous lipid, 24 hours after discontinuing intravenous lipid emulsion, and 2 hours after restarting intravenous lipid. After 24 hours of intravenous lipid at 1.5 g/kg/day the RVPEP/ET rose to mean (SD) 0.287 (0.03) from a baseline value of 0.225 (0.02) and to 0.326 (0.05) after 24 hours of intravenous lipid at 3 g/kg/day. Pulmonary arterial pressure returned to baseline 24 hours after the intravenous lipid had been discontinued. Continuous 24 hour infusion of lipid caused significant dose and time-dependent increases in pulmonary vascular resistance. Intravenous lipid may aggravate pulmonary hypertension.

Metabolic consequences of increasing energy intake by adding lipid to parenteral nutrition in full-term infants.

The effect on energy metabolism and fuel utilization of increasing energy intake by adding intravenous lipid to a glucose and amino acid regimen was examined. Twenty fullterm, appropriate-for-gestational-age, intravenously fed neonates were entered into one of two groups: total energy intake was 261 kJ.kg-1 x d-1 (62 kcal.kg-1 x d-1) in group 1 and 355 kJ.kg-1 x d-1 (85 kcal.kg-1 x d-1) in group 2. Both groups received 2.8 g protein.kg-1 x d-1 and 14 g glucose.kg-1 x d-1. Group 2 received an additional 2 g lipid.kg-1 x d-1. Metabolic rate, respiratory gas exchange, and nonprotein substrate oxidation were similar in both groups. The addition of energy as lipid enhanced nitrogen retention (230 vs 306 mg.kg-1 x d-1; P < 0.02) and utilization (52.8% vs 66.5%; P < 0.03). Our data suggest that nitrogen utilization is improved in parenterally fed neonates by adding fat and increasing energy intake without change in metabolic rate, carbon dioxide production, oxygen consumption, and nonprotein substrate utilization. Energy expenditure does not necessarily increase with increasing energy intake independently of diet composition.

Controversy in fatty acid balance.

It is uncertain whether preterm infants can synthesize C20 and C22 (omega-6) and (omega-3) fatty acids required for structural lipids. Dietary intake of C18:2 omega-6 and C18:3 omega-3 in formulae lacking long-chain polyunsaturated fatty acids can result in reduced levels of C20 and C22 homologues in membrane phospholipids as compared with breast-fed infants. Supplementation of fish oil has been shown to alleviate this problem in part only, as synthesis and incorporation of arachidonic acid into membrane phospholipids is reduced. Presently, infant formulae do not contain C20 and C22 fatty acids. Feeding an experimental infant formula with a balance between C20 and C22 (omega-6) and (omega-3) fatty acids within the range of human milk results in plasma phospholipid levels of C20 and C22 long-chain polyunsaturated (omega-6) and (omega-3) fatty acids similar to those in breast-fed infants. On the basis of clinical studies and evolutionary data, an increase of the linolenic and a decrease of the linoleic acid content in infant formula are suggested. Balanced incorporation of both (omega-6) and (omega-3) long-chain polyunsaturated fatty acids seems advisable in view of the lack of knowledge concerning the neonate's ability to chain elongate and desaturate essential fatty acids. Recommendations for the essential fatty acid content of preterm infant formula are suggested.