Essential Fatty Acid Requirements for Term and Preterm Infants

Transcription

1 Lpds n Modern Nutrton, edted by M. Horsberger and U. Bracco. Nestld Nutrton, Vevey/Raven Press, New York 987. Essental Fatty Acd Requrements for Term and Preterm Infants Zv Fredman Department of Pedatrcs, Baylor College of Medcne, Houston, Texas The essental fatty acds (EFAs) are a group of naturally occurrng unsaturated fatty acds wth a chan length of 8, 20, or 22 carbon atoms and contanng between two and sx methylene-nterrupted double bonds n cs-confguraton. These fatty acds are essental to the det of humans and all hgher anmals, as they cannot be syntheszed de novo from other lpds or from carbohydrates and amno acds. There are two fundamental EFAs, lnolec and a-lnolenc acd, from whch all others are derved metabolcally (-3). The essentalty of the polyunsaturated fatty acds (PUFAs) s related to ther capablty to ncorporate nto lpds and to act as a precursor n the formaton of prostaglandns. PLACENTAL TRANSFER AND CORD BLOOD POLYUNSATURATED FATTY ACIDS Normal growth of nfants s dependent upon an adequate supply of EFAs (4). The human fetus, lke the adult, s unable to synthesze the EFAs, whch must therefore be derved from the maternal crculaton and pass through the placenta. We confrmed the observatons that maternal plasma lpds are elevated durng pregnancy and that these levels are sgnfcantly hgher than n the neonate (5). However, we showed no change n cord plasma phospholpds, cholesterol esters, trglycerdes, and free fatty acd concentraton throughout gestaton. No dfferences n the fatty acd composton of the phospholpds, cholesterol esters, trglycerdes, and free fatty acds were found n cord venous and arteral plasma obtaned from 32 Caucasan nfants at brth. The fatty acd composton of cord plasma phospholpds at dfferent gestatonal ages s shown n Fg.. Gestatonal age vared from 24 to 44 weeks; all were normally grown nfants. The concentraton of lnolec acd n cord plasma phospholpds was less than 40% that of the maternal value. The lowest levels of ths fatty acd were noted before 34 weeks gestaton. However, venous and arteral cord plasma contaned hgher concentratons of the more unsaturated fatty acd arachdonate than dd maternal plasma (5,6). The concentraton of docosahexaenoc acd, whch s a homologue of the a- lnolenc acd seres, was noted to be hgher n cord blood plasma at term as com- 79

2 80 FATTY ACID REQUIREMENT FOR INFANTS MOTHERS-l ** p<0.05 * p< # :2u :4o :6u :3^9 FIG.. Percent fatty acd composton of plasma phospholpds n mothers and ther nfants of 24-33, 34-37, 38-42, and weeks of gestatonal age. Note that the relatve percent of lnolec acd s lower n cord plasma phospholpds than n maternal plasma; however, the levels of arachdonate, docosahexaenoc acd, and A-5,8,-ecosatrenoc acd are hgher n cord plasma than maternal plasma. The relatve percent of the latter acds ncreased wth advanced gestatonal age. pared wth maternal levels (5,6). The combned percentages of fatty acd concentratons of the lnolec and lnolenc acd seres n cord plasma phospholpd showed a steady rse n values from 25.5 at 24 to 33 weeks to 33.7 at 34 to 37 weeks and 36.0 at term as compared wth maternal levels of The ncreased combned total of the lnolec acd seres n plasma phospholpd correlated well wth the tssue levels of these fatty acds (5). Bruce et al. (7) reported a contnuous rse n the relatve concentraton of fatty acds of the lnolec seres n skeletal muscle phosphoglycerdes, from 0% at the begnnng of the second trmester of gestaton to almost 50% at the age of year. Factors that may be responsble for these fndngs are (a) the ncreased concentraton of the polyenoc fatty acds dervatves of lnolec acd may result from ncreased actvty of the fetomaternal unt by preferental transfer of these fatty acds n later gestaton, or (b) enzymatc actvty n the placenta or the fetus may be responsble for the desaturaton and elongaton of these essental fatty acds (8). Fatty acd composton of adpose tssue trglycerdes n the newborn nfant also dffers from that of the mother (9) n the same manner as that of plasma lpds. These data are consstent wth the presence of a placental transfer mechansm for certan fatty acds, ncludng the EFAs. Because of the low concentraton of lnolec acd n fetal adpose tssue, ts contrbuton to fetal plasma free fatty acd composton durng lpolyss s small.

3 FATTY ACID REQUIREMENT FOR INFANTS 8 The concentraton of the fatty acd A5,8,l -ecosatrenoc acd was found to be hgher n cord plasma of all nfants than n maternal plasma, and the level appears to ncrease wth advanced gestaton (Fg. ). Although ths abnormal fatty acd s elevated n EFA defcency, such a dagnoss s not certan at the tme of brth snce the polyenoc acds of the lnolec acd seres may be hgher n the newborn nfant than n the mother, yet the possblty s not elmnated that the nfant may have a relatve lack of EFAs. Furthermore, ncreased A-5,8,-ecosatrenoc acd level may reflect a generalzed ncrease n desaturaton and/or elongaton of fatty acd chans n the developng fetus. TISSUE POLYUNSATURATED FATTY ACID COMPOSITION Body stores of EFAs are low n low brth weght nfants (0). The concentraton of lnolec acd n fetal tssue s less than that seen n adults, and the proporton of lnolec acd n muscle phospholpds s found to ncrease wth advancng gestatonal age (7). We have analyzed varous tssue samples from 25 human fetuses and newborns for the relatve concentraton of the fatty acds n phospholpds, cholesterol esters, trglycerdes, and free fatty acds. Ther gestatonal ages ranged from 6 to 44 weeks. Representatve tssue from kdney medulla and cortex s shown n Fg. 2. No dfferences are observed between the levels of the ndvdual EFAs, lnoleate and arachdonate, n the dfferent tssues beyond 6 weeks of gestaton. However, the level of arachdonate n the varous tssue phospholpds s markedly elevated as compared wth the level of lnolec acd. These studes demonstrate that fetal tssues are rch n the EFA arachdonate, the prostaglandn precursor. Lnoleate and arachdonate cord plasma values are a reflecton of ther tssue levels (9). Both show a reduced lnoleate level compared wth the maternal level; however, the level of hgher homolog, arachdonate, s hgher than the maternal value. The low plasma concentraton of lnoleate reflects the reduced tssue level of ths fatty acd. Ths stuaton ncreases the maternal-fetal gradent for lnolec acd, whch may facltate ts transfer across the placenta. The relatvely hgh concentraton of the hgher PUFA arachdonate n fetal tssue could result from ncreased actvty of the fetoplacental unt by preferental transfer of these fatty acds or by enzymatc actvty n the placenta or the fetus that s responsble for desaturaton and elongaton of these EFAs. Tssue enrchment n arachdonc acd may play an mportant role by mantanng the normal functon of bologcal membranes and servng as a substrate for prostaglandn bosynthess. These functons may nfluence fetal physology durng ntrauterne development. Followng brth, the det affects the fatty acd composton of adpose tssue. In the perod of rapd weght gan, durng early nfancy, changes n adpose tssue composton can occur n a relatvely short tme (,2). Wddowson et al. (3) demonstrated a profound dfference n the fatty acd composton of adpose tssue between Brtsh and Dutch nfants between brth and year. The dfferences were nfluenced drectly by the nature of the fat n the det.

4 82 FATTY ACID REQUIREMENT FOR INFANTS ' u 25 _ 20 O 00 * 8. I s g 0 8 I o ARACHIDONATE 0 o a o B 8 D a _ LINOLEATE l GESTATIONAL AGE (WEEKS) FIG. 2. Percent fatty acd composton of renal phospholpds n neonates at varous gestatonal ages. No changes are seen between the levels of lnoleate and arachdonate n the renal tssue beyond 6 weeks of gestaton. Closed crcles, arachdonc acd medulla; open crcles, arachdonc acd cortex; closed squares, lnolec acd medulla; open squares, lnolec acd cortex. ESSENTIAL FATTY ACID DEFICIENCY SYNDROME Assocated wth Oral Dets Work wth expermental anmals showed that the very young are more susceptble to develop EFA defcency due to lack of fat n the det than are adults (4). Smlarly, body stores of EFAs are low n low brth weght nfants, whch results n the defcency state becomng evdent more rapdly and the admnstraton of the defcent nutrent nducng a more rapd response than n an adult. Most of the earler studes that have been performed on humans ncluded nfants. These studes, whch started as early as 99 by Von Groer (5), show the effects of dets low n fat on growth or weght loss, susceptblty to nfecton (5,6), and skn erupton (6). The observaton that skn lesons n rats fed low-fat det were cured by the addton of fats rch n PUFAs stmulated clncal studes n nfants and chldren wth chronc eczema (7). Moreover, these results were encouragng enough to warrant further studes n order to evaluate the role of unsaturated fatty acds n human nutrton. Combes et al. (8) dd not observe skn changes unformly n premature nfants

5 FATTY ACID REQUIREMENT FOR INFANTS 83 who were fed mlk mxtures low n lnolec acd for perods of 8 to 37 days. However, hstologc features of the skn showed evdences of lnolec acd defcency and serum d-, tr-, and tetra-anoc acd levels were sgnfcantly dfferent from nfants fed 4% of the calores as lnoleate. Hansen et al. (4) fed 42% healthy nfants one of fve propretary mlk mxtures adequate n proten, mnerals, and vtamns but varyng n lnolec acd content from less than 0.% to 7.3% of the calores. Two of the mlk mxtures were found to contan nadequate amounts of lnolec acd for the nfant's requrement. One was low n fat (.0% of calores), and one contaned fat low n lnolec acd. A hgh proporton of babes who were fed the latter two mlk mxtures before 6 weeks of age and who remaned on the dets for 3 months developed dry, thck desquamated skn and retarded growth. The clncal manfestatons dsappeared after the admnstraton of dets that provded % or more of calores as lnolec acd. Further studes (9) demonstrated that nfants do not usually show overt sgns of fat defcency untl they have been on cow's mlk formula for about 2 months. The clncal syndrome of lnolec acd defcency appears as neffcent somatc growth wth poor weght gan n spte of adequate calorc ntake and skn lesons. These manfestatons showed a dramatc response to a det contanng lnolec acd. In nfants fed dets low n lnolec acd, ncreased calorc consumpton was reported by Adam (20). In spte of the dfferences of 20% to 40% n calorc ntake between nfants fed dets low n lnolec acds and nfants fed lnolec acd supplemented dets, weght curves were smlar for the majorty of nfants. Hansen et al. (4) found no sgnfcant dfference n calorc effcency for nfants between mlk mxtures contanng 2.8% or 7.3% of calores as lnolec acd. Assocated wth Parenteral Nutrton The provson of optmal nutrton for low brth weght nfants and for nfants wth congental anomales of the gastrontestnal tract and wth nflammatory bowel dsease remans a sgnfcant problem. Recently, total parenteral nutrton (TPN) has been establshed as a form of therapy for these condtons (2,22). Studes on nfants who were mantaned on long-term fat-free parenteral nutrton demonstrated the development of clncal sgns together wth bochemcal evdence of EFA defcency (23,24). The admnstraton of dets contanng lnolec acd converted these clncal and bochemcal manfestatons to normal. We studed (2) fve sck newborns who were mantaned on fat-free ntravenous almentaton and developed very rapd bochemcal changes n the plasma that were compatble wth the dagnoss of EFA defcency durng the frst week of lfe and were reversble wth oral feedngs contanng EFAs. The youngest and smallest nfants exhbted these changes as early as the second and thrd days of lfe. The body of a premature nfant of,000 g contans approxmately 0.5% glycogen, % fat, and 8.5% proten (0). In such an nfant, the total calorc reserve s

6 84 FATTY ACID REQUIREMENT FOR INFANTS 450 kcal/kg and the nonproten calore reserve s only 0 kcal/kg. The mnmal metabolc requrement of an nfant ths sze s about 30 to 40 kcal/kg/24 hr on the frst day of lfe and rses to 45 to 50 kcal/kg/24 hr thereafter. Wth ncrements for actvty, stress of hypo- or hypertherma, asphyxa, nfecton etc, the total calorc expendture s probably n the order of 50 to 75 kcal/kg/24 hr. Because of the lmted nonproten calorc reserve, these nfants must moblze fatty acds early for calorc needs when faced wth defcent detary ntake. Thus, the borderlne stores of EFAs characterstc of the premature and the hgh calorc expendture n these nfants may contrbute to the early onset of EFA defcency, whch we observed among prematures on fat-free parenteral feedngs. Furthermore, durng parenteral hyperalmentaton the outflow of lnolec acd from adpose tssue s blocked, at least n part, by the hgh nsuln levels accompanyng glucose admnstraton. Durng prolonged fat-free ntravenous hyperalmentaton, there s a correlaton between low EFA levels n plasma and n tssues (24). Smlar correlaton has been demonstrated by us (unpublshed data) n cases wth rapd onset of EFA defcency. Effect on Red Blood Cells Fatty acd composton of red blood cells changes n relaton to detary lnoleate as t does n plasma, but the changes become evdent more slowly (25). No changes n red blood cell osmotc fraglty n neonates wth rapd onset of EFA defcency were demonstrated n our study. Effect on Platelets The mportance of arachdonc acd botransformaton n platelets has been elucdated (26). In addton, hemorrhagc problems of unknown etology are common n sck low brth weght nfants (27). Many premature nfants are beng treated wth TPN, and EFA defcency s a frequent occurrence. Hence, we examned the rapd onset of EFA defcency n premature nfants and ts possble effect on platelet functon and found that the defcent nfants had mpared platelet aggregaton when compared wth controls (28). In addton, the platelets from EFA-defcent nfants demonstrated clearly evdence of dsaggregaton. On recovery from thendefcent state, the low brth weght nfants had platelet functons smlar to those of apparently healthy premature nfants. The relatonshp between the platelet dysfuncton and EFA defcency s speculated on the possble connecton between arachdonc acd depleton (.e., EFA defcency) and decreased thromboxane, a key medator of human platelet aggregaton. Decreased arachdonc acd content n platelet phospholpds was documented n our laboratory n a newborn nfant who rapdly developed EFA defcency n the neonatal perod (29).

7 Effect on Prostaglandns FATTY ACID REQUIREMENT FOR INFANTS 85 We measured the excreton of the major urnary metabolte of prostaglandns E, and E 2, 7a-hydroxy-5, -dketotetranor-prostane-l, 6-doc acd (PGE-M) n three nfants durng EFA defcency, upon recovery from the defcency state and n nne thrvng control neonates (30). A sgnfcant dfference between the PGE- M excreton n the group of nfants wth EFA defcency before and after treatment was found (p < 0.05) (Fg. 3). Sgnfcant dfferences n PGE-M excreton were also found between the control group and the EFA-defcent nfants. The bochemcal evdences of EFA defcency and the decreased levels of PGE-M excreton are rapdly corrected when patents resume a det contanng EFA. Effect on Pulmonary Surfactant We studed a low brth weght nfant who developed bochemcal evdence of EFA defcency n the plasma after sufferng from chronc bronchopulmonary dys- 40 Pre Post CONTROLS EFA RECOVERY treatment treatment DEFICIENT INTRALIPID FIG. 3. Comparson of the urnary excreton of PGE-M expressed as nanograms/mg urnary creatnne (CR) between three groups of nfants: (a) Infants pre- and posttreatment wth Intralpd; (b) thrvng neonates (controls); and (c) nfants wth EFA defcency and upon recovery. Note that PGE-M excreton followng the admnstraton of Intralpd s smlar to the levels obtaned from nfants wth essental fatty acd defcency. (From ret. 30.)

8 86 FATTY ACID REQUIREMENT FOR INFANTS plasa and recurrent epsodes of necrotzng enterocolts (3). A lower than normal level of palmtc acd and an ncreased level of palmtolec and olec acds were seen n pulmonary surfactant phospholpd components. Upon treatment and recovery from EFA defcency, the fatty acd pattern both n plasma and surfactant phospholpds returned to normal along wth clncal mprovements n the respratory llness. The mparment of surfactant phospholpds may dmnsh lung functon and so contrbute to the pathophysology of hyalne membrane dsease, chronc bronchopulmonary dysplasa, cystc fbross (32), and other respratory dseases assocated wth nadequate nutrton nvtng an EFA defcency. Effect on the Central Nervous System The avalablty of long-chan PUFAs seems to be related to the degree of bran and central nervous system development. Lnolec and a-lnolenc acds represent a small proporton of the fatty acyl components of the phosphoglycerdes of fetal bran (8). In contrast, arachdonc and docosahexaenoc acds, more unsaturated EFAs, are readly ncorporated nto the structural lpds of the developng bran (8,33). In humans, the bran undergoes an accelerated growth phase durng the last trmester of pregnancy and the frst 8 months of postnatal lfe. Durng ths vulnerable perod, EFAs are requred for structural expanson of the bran. Snce bran phospholpds contan hgh levels of PUFAs of both the lnolec and a-lnolenc acd seres, t has been shown that changes n ther rato n the det modfy the relatve proporton of PUFAs derved from these essental precursors, n tssues ncludng bran and bran subcellular structures (34). Whte et al. (35) studed the bran lpds of three premature nfants who were mantaned on fat-free parenteral nutrton and succumbed. They demonstrated fatty acd alteratons ndcatve of essental fatty acd defcency n the two major component phospholpds of bran, ethanolamne and cholne phosphoglycerdes, n the cerebrum and less so n the cerebellum. There was also a tendency toward reducton of bran phospholpd concentratons n these nfants. Crawford et al. (33) demonstrated n the human a stepwse progresson n the degree of polyunsaturaton and chan length from maternal det to maternal lver, placenta, fetal lver, and fetal bran. Thus, t s attractve to postulate that prolonged ntra- and extrauterne malnutrton may produce a low brth weght nfant and that ths ndvdual may suffer sgnfcant, perhaps rreparable, developmental damage to the central nervous system. REQUIREMENTS FOR POLYUNSATURATED FATTY ACIDS Estmates of quanttatve requrements of lnolec acd were based upon the rate of growth or the development of dermatts, phenomena to whch many factors contrbute, some of whch are unrecognzed and uncontrolled. The earlest estmate of the nfant's requrements for lnolec acd as approx-

9 FATTY ACID REQUIREMENT FOR INFANTS 87 mately % of the calores was based on clncal observatons, calorc ntake and serum levels of the d-, tr-, and tetraenoc acds (20). When the means of assessng lnoleate requrement from a curve relatng trene-tetraene rato to ntake of lnoleate was developed (), t became apparent that the requrements of nfants could be deduced from ths bochemcal parameter as well. Extensve data relatng PUFAs of human serum to ntake of lnoleate are presented n the classcal study of Hansen et al. (4). From that study t appears that % of calores s a mnmum requrement and that 4% of calores s an optmal ntake. The plot of trenetetraene rato of serum fatty acds versus lnoleate ntake n nfants reveals that the low rato ndcatve of normal EFA metabolsm was reached by about % of calores as lnolec acd (36). The effect of dose responsve detary ntake of lnolec acd upon the total denes, trenes, and tetraenes of serum revealed that % to 2% of calores as lnoleate satsfes the requrements for all the bochemcal conversons of PUFA, as well as permttng normal growth and preventng dermatts (37). The potency of arachdonc acd as EFA has been shown to be greater than that of lnolec or a-lnolenc acds, but all are effectve n the treatment of EFA defcency and promote normal growth. Although the a-lnolenc (w3) seres has been consdered to be essental, t cannot fulfll all the functons of the 6 seres and so has been questoned as possessng true essentalty (38). Although tssues, the central nervous system n partcular, contan relatvely hgh proporton of the metabolc products of 7-lnolenc acds, we must awat demonstraton of ther partcular functon. SUPPLEMENTATION OF POLYUNSATURATED FATTY ACIDS Tradtonally, lnolec acd s consdered the detary essental fatty acd for t s the commonest fatty acd that wll provde suffcently all the requrements known for PUFAs n human and anmals and can functon alone n the det to meet the EFA requrements. Det Human Breast Mlk The fatty acd composton of human mlk has been studed n detal. The patterns of fatty acds from the two breasts were found to be smlar after the same nursng, but fastng and tme of day both nfluenced total fat and fatty acd composton of the mlk (39). Fatty acd composton of breast mlk changes wth the nature of the detary fat (40). Wth the trend n the fatty acd content of the Unted States det toward a hgher proporton of unsaturated fatty acds ncludng lnoleate, there s an ncrease n breast mlk content that can vary from.0% to 43.0% fat, but an average content range from 8% to 0%. Snce fat provdes about 50%

10 88 FATTY ACID REQUIREMENT FOR INFANTS of the calores n human mlk, t contans more than an adequate amount of the EFA lnoleate. Infant Formulas The Amercan Academy of Pedatrcs has recommended (4) that nfant formulas should contan a mnmum of 3.3 g of fat/00 kcal (30% of calores) and 300 mg of lnolec acd/00 kcal (approxmately.7% of total calores) to provde a fat to carbohydrate rato wthn a range that s customary n nfant dets. The academy was concerned that excess lnolec acd would produce peroxdaton and ncrease the vtamn E requrements but dd not set an upper lmt on the lnoleate content of the det, notng that n some human mlks the lnolec acd content s 8% to 0% of the fat. Several of the most wdely used formulas are based on cow's mlk proten wth lactose. All contan vegetable ols of one type or another. All the formulas contan consderably more lnolec acd than human mlk lpds (42). The long-term effects of these detary regmens are unknown. Parenteral Fat Emulson In order to acheve complete parenteral nutrton n nfants, t s necessary to admnster adequate amounts of calores and nutrents n a restrcted volume. In the newborn nfant, t s dffcult to provde an optmal calorc ntake n the form of amno acds and carbohydrates, because excessve flud volumes are needed when sotonc solutons are used and the glucose load of hypertonc solutons s frequently not tolerated. Therefore, fat emulsons, whch have a hgh densty and low osmolalty, have been used ncreasngly to provde addtonal calores and essental fatty acds (43,44). These emulsons, lke most vegetable ols, are rch n the essental fatty acd lnoleate. Studes (30,44) documented the effcacy of the admnstraton of fat emulsons n allevatng clncal and bochemcal manfestatons of EFA defcency and that ts admnstraton would result n an ncrease of the lnolec acd level n the plasma and tssue lpds. Inuncton of Ol Inuncton of sunflower seed ol to forearms of patents wth EFA defcency lowered the rate of water loss, cured scaly lesons and corrected abnormal skn lpds (45), and restored ther abnormal plasma fatty acds, ndcatng that penetraton of the lnolec acd through the skn had occurred (46). We studed two sck newborn nfants who receved fat-free parenteral nutrton and developed bochemcal and clncal evdence of EFA defcency (25). Followng the nuncton of sunflower seed ol these manfestatons dsappeared. However, t seems mpossble from our studes to predct the exact amount of lnolec acd absorbed followng nuncton.

11 FATTY ACID REQUIREMENT FOR INFANTS 89 Even the cutaneous applcaton of relatvely large quanttes used n our patents faled to replensh tssues defcent n EFA. We demonstrated the ablty to correct platelet dysfuncton and to ncrease prostaglandn E bosynthess and turnover by the nuncton of sunflower seed ol n newborn nfants wth EFA defcency (47). EXCESSIVE INTAKE OF POLYUNSATURATED FATTY ACIDS Snce Burr and Burr demonstrated the mportance of certan fats necessary for normal growth (48), research on EFAs has been manly concerned wth the symptoms of EFA defcency and the admnstraton of the mnmal EFA requrement to prevent or treat the defcency state. However, lttle s known about the toxcty or adverse effects of hgh levels of these substances n the det. Toxc Effect of Polyunsaturated Fatty Acds The release by the Unted States Food and Drug Admnstraton of artfcal fat emulsons has made avalable for parenteral feedng a preparaton of hgh calorc densty that s rch n essental fatty acds, especally lnolec. However, several hazardous effects have been reported n the newborn nfant: a reduced clearance rate n small-for-date nfants, as well as among premature nfants born before 32 weeks of gestaton and durng an acute llness (49), dsplacement of blrubn from albumn bndng stes and an ncreased rsk of kerncterus n jaundced newborns (50), the deposton of lpd materal n macrophages that may alter mmunty (44,5), mmunosuppressve effect (52), altered pulmonary gas exchange (53), and the potental rsk for substtuton of phytosterols for cholesterol n the developng central nervous system, whch could lead to changes n myeln confguraton and functon (49). Effect on Tssue Fatty Acd Composton and Prostaglandn Bosynthess We have measured tssue lpd composton and the excreton of the major urnary metabolte of prostaglandns E] and E 2, PGE-M, n three nfants who receved total parenteral nutrton ncludng Intralpd for several weeks and compared these values wth control nfants (30). Lnolec acd s ncorporated nto the major lpd classes of the plasma, red blood cells, and tssues n nfants recevng Intralpd. Concomtantly wth the ncrease n the relatve concentraton of lnoleate, a decrease n the hgher PUFA homolog, arachdonate, s apparent (Fg. 4). Ths may ndcate a competton between these EFAs for esterfcaton and storage n tssue lpds, a balanced content of the ntake of the lnolec and lnolenc acds, a rapd turnover of the long chan PUFAs, or a combnaton of these factors. However, the sum of the two EFAs, lnoleate and arachdonate, s smlar n red blood cell and tssue phospholpds of control nfants and n nfants who receved Intralpd. A sgnfcant dfference between the PGE-M excreton n the group of nfants

12 90 FATTY ACID REQUIREMENT FOR INFANTS CONTROL INTRALIPID 2 3 Cl8:2u6 D c20:4w6 2 o *mean + SEM LU UJ Q r f f Lung 2 T I I! Lver Skeletal Muscle 2 v->: : : / ' : 2 Renal Medulla'Cortex 2 Bran W Adpose Tssue? I! Ss I-:-;:; RBC Plasma FIG. 4. Fatty acd composton of phospholpds of nfants recevng Intralpd (A/ = 3) and n controls (A/=3). Note that concomtantly wth the ncrease n the relatve concentraton of lnoleate, a decrease n arachdonate s apparent. However, the sum of the two essental fatty acds, lnoleate and arachdonate, s smlar n tssues and red blood cells of control nfants and n nfants recevng Intralpd. (From ref. 30.) before and after the admnstraton of Intralpd was found n ths study (Fg. 3). Dfferences n the urnary excreton were seen between the control group and the nfants recevng Intralpd. PGE-M excreton followng the admnstraton of Intralpd was smlar to that obtaned from nfants wth EFA defcency. The decrease n PGE-M excreton n patents recevng hgh amounts of lnolec acd s most lkely related to a decrease n the precursor EFA, arachdonate, although an nhbtng effect of lnolec acd on prostaglandn synthess s possble (54). Effect on Platelet Functon Chronc admnstraton of a det rch n lnoleate reduced platelet aggregaton n humans (55). Prolonged admnstraton of Intralpd to sck newborn nfants resulted n changes of the fatty acd composton of ther platelets' phospholpds and those platelets showed reduced aggregaton n response to dfferent agents known to nduce platelet aggregaton (Z. Fredman, unpublshed data). REFERENCES Holman RT. Bologcal actvtes of and requrements for polyunsaturated acds. In: Holman RT, ed. Progress n the chemstry of fats and other lpds, volume 9. Oxford: Pergamon Press, 97: Holman RT. Essental fatty acd defcency. In: Holman RT, ed. Progress n the chemstry of fats and other lpds, volume 9. Oxford: Pergamon Press, 97:

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