A Randomized Trial of Micropreemies Receiving Higher Amounts of Intravenous Fat Emulsion During the First Week of Life

Transcription

1 Clinicl Reserch Reports A Rndomized Tril of Micropreemies Receiving Higher Amounts of Intrvenous Ft Emulsion During the First Week of Life Dougls Drenckpohl, MS, RD, CNSC, LDN, Mtthew Niehus, PhrmD, Ctherine Schneider, RN, Connie McConnell, RN, Huping Wng, PhD, nd Kmlesh Mcwn, MD Abstrct: Objective. The gol of this study ws to determine if micropreemies could tolerte higher infusion rtes of intrvenous ft emulsions (IVFEs) during the first week of life by mintining their serum triglyceride levels t <200 mg/ dl. Methods. This ws rndomized controlled tril of 19 infnts who were clssified s pproprite for gesttionl ge nd hd birth weights between 500 nd 750 g. The primry clinicl outcome ws serum triglyceride levels; secondry outcomes lso were monitored. Results. A totl of 19 micropreemies completed the study (experimentl group: n = 10; control group: n = 9). Of the infnts in the experimentl group, 100% hd developed hypertriglyceridemi (>201 g/dl) during the first week of life compred with only 44.4% of the infnts in the control group. The experimentl group experienced lower weight loss of 8.6% ± 3.10% s compred with 16.22% ± 8.04% in the control group during the first week of life. Initilly, the experimentl group ws given significntly higher infusion rtes of IVFEs, but t the end of the week, the control group ws receiving significntly higher infusion rtes of IVFEs. Clorie intke ws significntly better initilly for the experimentl group, but becuse of the incidences of hypertriglyceridemi nd reduction of IVFEs, the control group hd significntly better clorie intke t the end of the study period. Conclusions. Micropreemies do not tolerte initil higher infusion rtes of IVFEs during the first week of life becuse of their potentil risk for developing hypertriglyceridemi. Keywords: micropreemies; hypertriglyceridemi; intrvenous ft emulsions; clories Reserch hs shown tht premture infnts lipoprotein lipse ctivity my be relted to their gesttionl ge nd birth weight. Introduction During the first weeks of life, micropreemies (<800 g t birth) re dependent on totl prenterl nutrition (TPN) to meet their energy nd protein requirements. Reserch hs shown tht premture infnts benefit from erly dministrtion of prenterl mino cids (AAs) between 2.5 to 3 g/kg/d within the first dys of life (DOL). 1-4 Initil higher infusion rtes of AA in totl prenterl nutrition (TPN) within the first DOL hs shown to reduce ctbolism, 1 improve nitrogen blnce, 3,5 stimulte lbumin synthesis, 6 decrese growth filure, 2,4 nd improve neurodevelopmentl outcomes. 4 Although there re number of studies documenting the clinicl benefits of erly prenterl AA dministrtion for extremely lowbirth-weight (ELBW) infnts, reserch studying the effects of erly initition of intrvenous ft emulsions (IVFEs) is limited. Pst theoreticl concerns for erly dministrtion of IVFE re potentil risk for intolernce 7 ; displcement of bilirubin by ftty cids, plcing the infnt t risk for kernicterus 8 ; nd incresed risk of pulmonry dysfunction DOI: / From the Neontl Intensive Cre Unit (DD, CS, CMC) n the Deprtment of Phrmcy (MN), Children s Hospitl of Illinois, Peori, IL; nd the Deprtment of Internl Medicine (HW) nd the Division of Neontology, Deprtment of Peditrics (KM), University of Illinois College of Medicine t Peori, Peori, IL. Address correspondence to Dougls Drenckpohl, MS, RD, CNSC, LDN, Neontl Intensive Cre Unit, Children s Hospitl of Illinois t OSF Sint Frncis Medicl Center, 530 NE Glen Ok Avenue, Peori, IL 61637; e-mil: Dougls.c.drenckpohl@osfhelthcre.org. For reprints nd permissions queries, plese visit SAGE s Web site t Copyright 2012 The Author(s)

2 vol. 4 no. 1 ICAN: Infnt, Child, & Adolescent Nutrition Wilson et l 10 showed tht premture infnts were ble to tolerte the initition of 0.5 g/kg/d of IVFE on the second dy of TPN without ny dverse events. Recent studies hve shown tht premture infnts my benefit from initil higher infusion rtes of IVFEs during the first week of life. 11,12 In 2008, we completed rndomized controlled tril in pproprite-forgesttionl-ge (AGA), very-low-birthweight infnts with birth weights between 750 to 1500 g, where they benefited from higher infusion rtes of IVFEs during the first week of life. 12 Results from our previous study showed tht the experimentl group received better energy intke during the first week of life, hd lower incidence of NEC nd ROP, were strted on insulin less often, nd mintined their weight-forge growth trend t or bove the 10th percentile t dischrge. We replicted this study by enrolling AGA micropreemies with birth weights between 500 nd 749 g. The primry hypothesis ws tht micropreemies could tolerte higher infusion rtes of IVFEs during the first DOL (dys 1-7), s evidenced by mintining serum triglyceride levels of 200 mg/ dl. Secondry outcomes monitored were energy intke, time to regin birth weight, serum glucose levels, initition of insulin, nthropometric mesurements, nd clinicl outcomes such s NEC, ROP, chronic lung disese (CLD), intrventriculr hemorrhge (IVH), ptent ductus rterious (PDA), PDA ligtion, length of sty, nd deth. Methods This ws rndomized, nonblinded, controlled tril tht took plce from April 2008 through Mrch 2010, t the 32-bed level III neontl intensive cre unit (NICU) t Children s Hospitl of Illinois, in Peori, Illinois. This study ws pproved by the Community Institutionl Review Bord (Peori, IL) for humn subject reserch. Written, informed consent ws obtined from prent of ech infnt fter dmission to the NICU before TPN ws initited. The primry investigtor nd co-investigtor were responsible for recruiting ll ptients into the tril. A totl of 70 seled envelopes were creted to fcilitte the rndomiztion of this tril: 35 seled envelopes rndomized the infnts to be in the control group, nd 35 rndomized the infnts into the experimentl group. The seled envelopes were shuffled nd then given study number of 1 through 70. After informed consent ws obtined from prent or gurdin, seled envelope ws opened to revel which study group the infnt ws rndomized into. The control group begn tretment with 0.5 g/kg/d of 20% IVFE on the first dy of life, nd the experimentl group begn tretment with 2 g/kg/d of IVFE on the first dy of life. The IVFE dosge ws then incresed by 0.5 g/kg/d dily, until ll infnts in ech group chieved 3 g/kg/d. The AAs in the TPN solution were strted t 3 g/kg/d nd incresed s tolerted to gol of 4 g/kg/d. The glucose infusion rte (GIR) in the initil TPN solution ws between 3 nd 4 mg/ kg/min nd incresed s tolerted until reching finl GIR between 8 nd 9 mg/kg/min. Also, 1 unit/ml of heprin ws dded to ech bg of TPN. On the first dy of life, fluids were ordered t 100 ml/kg/d for ll infnts. Serum triglycerides levels, long with other biochemicl vlues, were mesured before the initition of TPN nd then dily for the first 7 dys of TPN, through either n umbilicl line or by heelstick. The serum triglyceride levels nd other biochemicl mesurements were nlyzed by the hospitl s lbortory deprtment. If hypertriglyceridemi occurred ( 201 mg/dl), the IVFE ws decresed ccording to n pproved lgorithm (Tble 1). Infnts were weighed dily using the scle in the Girffe Omnibed isolettes (Lurel, MD) during the first week of life. The other nthropometric mesurements, such s length nd hed circumference, were completed on dmission nd t dischrge by nursing personnel. Clssifiction of newborns ccording to intruterine growth nd gesttionl ge, s described by Lubchenco nd collegues, 13,14 ws used to define AGA sttus when infnts were dmitted to the NICU. The Fenton growth chrt for preterm infnts ws used to record weight, length, nd hed circumference t dischrge. 15 Study Popultion Infnts enrolled into this study hd gesttionl ges between 23 nd 25 weeks, birth weights between 500 nd 749 g, nd were clssified s AGA s determined by n pproprite growth chrt. Singletons, twins, or triplets who met the weight nd gesttionl ge requirements were eligible to prticipte. The exclusionry criteri were s follows: infnts who were smll for gesttionl ge t birth, hd serious congenitl nomlies, nd/or were dignosed with erly sepsis. In ll, 35 infnts were deemed eligible for this study (Figure 1), nd 13 were excluded. One fmily refused, nd 12 infnts were strted on TPN before informed consent ws obtined. A totl of 22 infnts were rndomized into the study 10 in the control group nd 12 into the experimentl group. In the experimentl group, 3 infnts were excluded from nlysis for the following resons: 1 infnt ws smll for gesttionl ge t birth, 1 infnt hd congenitl nomly, nd 1 infnt hd medicl mngement discontinued within 48 hours of birth. Totl Prenterl Nutrition All TPN solutions were prepred by the Prenterl nd Enterl Nutrition Deprtment t OSF Sint Frncis Medicl Center where the Children s Hospitl of Illinois is locted. Totl nutrient dmixture (TNA) solutions were used to deliver prenterl nutrients to ech infnt over 24 hours. The TNA solutions were compounded from 70% dextrose (Bxter, Deerfield, IL), TrophAmine (Brun, Irvine, CA), nd 20% intrlipid emulsion (Bxter). The Automix Plus compounder (Bxter) ws used to blend the mcronutrients 59

3 Tble 1. Algorithm for Adjusting Intrvenous Ft Emulsions When Hypertriglyceridemi Occurs Serum Triglyceride Levels, mg/dl together into the TNA solution, wheres the electrolytes, vitmins, minerls, cysteine (75 mg/kg/d), crnitine (25 mg/ kg/d), nd heprin (1 unit/ml) were Decrese Intrlipids in TPN by Keep t current IVFE order g/kg/d g/kg/d 300 Reduce to 0.5 g/kg/d to prevent essentil ftty cid deficiency Abbrevitions: TPN, totl prenterl nutrition; IVFE, intrvenous ft emulsion. Figure 1. Digrm of the Enrollment. Intended to Tret n=35 Excluded (1 refused, 12 TPN strted before consent ws obtined) Control Group n=10 Excluded# n=0 Anlyzed n=10 22 ptients Rndomized Group n=12 Excluded* n=3 Anlyzed n=9 *1 ws smll for gesttionl ge t birth *1 hd congenitl nomly *1 prents withdrew support within 48 hours dded mnully. The TNA solution ws dministered through n umbilicl rtery ctheter, n umbilicl venous ctheter, or peripherlly inserted centrl ctheter. Dt Collection nd Outcome Vribles Dt collection ws completed by reserch nurse employed in the NICU. The reserch nurse collected the following informtion: demogrphic dt, birth weight, gesttionl ge t birth, serum triglyceride levels, other nutritionl lbortory vlues during the first 7 dys of TPN, mount of IVFE (g/kg/d) in the TPN solution, fluid intke, insulin strted, nd DOL to regin birth weight. The Dtbse Coordintor Nurse obtined clinicl outcomes from the Vermont/ Oxford Network dtbse such s NEC, CLD, IVH (with grde), ROP (with stge), nd mortlity. NEC ws defined s the presence of pneumtosis intestinlis, verified by X ry or during surgery. CLD ws defined s being dependent on oxygen t 36 weeks post menstrul ge. IVH ws defined by n ultrsound performed before dy 28 of life nd grded from 0 to 4. When retinl exmintion ws performed, it ws grded from 0 to 4. A registered dietitin clculted the totl number of clories per kilogrm per dy. Sttisticl Anlyses The purpose of the primry sttisticl nlysis ws to determine the effect tht higher infusion rtes of 20% IVFE hd on serum triglyceride levels. Smple size estimtion ws bsed on the primry end point: the serum triglyceride level of >201 mg/dl. With 2-side significnce level of.05, 35 infnts from ech group would llow us to test t lest 35% difference between control nd experimentl groups in the serum triglycerides of >201 mg/ dl with t lest 80% power, ssuming serum triglycerides of >201 mg/dl, with 25% for the control group. This smple size clcultion ws bsed on the tble described by Browner et l. 16 Person c 2 ws used to compre the 2 group differences for most ctegoricl vribles. When there ws n empty cell, Fisher s test ws used. For continuous vribles, if the normlity ssumption ws met, 2 smple t tests were performed; otherwise, the Mnn-Whitney U test ws used. Mens nd stndrd 60

4 vol. 4 no. 1 ICAN: Infnt, Child, & Adolescent Nutrition devitions were reported for continuous vribles. Frequency nd percentges were reported for ctegoricl vribles. The 2-tiled P vlues were clculted for ll tests, nd P <.05 ws considered sttisticlly significnt. All sttisticl nlyses were performed using SPSS 17.0 (Chicgo, IL). Results Demogrphics Infnts in both study groups hd similr gesttionl ges t birth (Tble 2). The infnts in the control group weighed more t birth thn infnts in the experimentl group: ± versus ± g, which ws significnt (P =.041). There were no significnt differences between the study groups for gender, birth by cesren section, or ntentl steroids. Tble 2. Chrcteristics of Infnts in the Study Groups Chrcteristics of Infnts Control Group, n = 9 Group, n = 10 Gesttionl ge (weeks), men ± SD ± ± Birth weight, men ± SD, g ± ± Gender, n (%) Mle 3 (33.3) 5 (50).463 Rce, n (%) Cucisin 7 (77.8) 6 (60) Africn Americn 0 (0) 4 (40) Totl Prenterl Nutrition There were sttisticlly significnt differences in IVFE intke between the experimentl group nd the control group on dys 2, 6, nd 7. Although there were differences in IVFE during the other study dys 1, 3, 4, nd 5 they were not sttisticlly significnt. On study dy 2, infnts in the experimentl group received greter mounts of IVFE thn infnts in the control group (Tble 3): 2.2 ± 0.63 versus 1.0 ± 0 g/ kg/d, which ws significnt (P <.002). By study dys 6 nd 7, even the infnts in the control group hd received significntly more IVFEs. On dy 6, the control group received 2.38 ± 0.79 g/ kg/d of IVFEs, wheres the experimentl group only received 1.05 ± 0.64 g/ kg/d of IVFEs (P =.003). On dy 7, the control group received 2.5 ± 0.60 g/ kg/d of IVFEs, wheres the experimentl group received 1.56 ± 0.68 g/kg/d of IVFEs (P =.015). Energy There were sttisticlly significnt differences in cloric intke between the experimentl group nd the control group on study dys 1, 2, 6, nd 7 (Tble 4). On study dy 1, the experimentl group received ± 4.44 cl/kg/d compred with ± 4.80 cl/kg/d for the control Hispnic 2 (22.2) 0 (0) Cesren section, n (%) 5 (55.6) 6 (60).845 Antintl steriods, n (%) 9 (100) 7 (70).211 Abbrevition: SD, stndrd devition. Sttisticlly significnt P <.05. Tble 3. Comprison of IVFE (g/kg/d) in Totl Prenterl Nutrition Study Dys Control Group, n = 9 Group, n = ± ± 0 N/A ± ± ± ± ± ± ± ± ± ± ± ± Abbrevition: IVFE, intrvenous ft emulsion. Sttisticlly significnt P <

5 group (P =.001). On study dy 2, infnts in the experimentl group received ± 6.05 cl/kg/d, compred with ± 4.57 cl/kg/d in the control group (P =.014). On study dy 6, infnts in the control group received ± 8.93 cl/kg/d compred with infnts in the experimentl group, who only received ± cl/kg/d (P =.005). On study dy 7, infnts in the control group hd higher cloric intke thn infnts in the experimentl group: ± versus ± cl/kg/d, which ws significnt (P =.044). Serum Triglycerides Both study groups hd similr serum triglyceride levels prior to TPN being initited (Tble 5). On study dy 1, infnts in the experimentl group verged serum triglyceride levels of ± versus ± mg/ dl when compred with the control group (P =.015). On study dy 2, infnts in the experimentl group hd verge serum triglyceride levels ± versus ± mg/dl for the control group (P =.044). On study dy 4, the verge serum triglyceride levels for the experimentl group were ± versus ± mg/dl for the control group (P =.034). In ll, 100% of the infnts in the experimentl group experienced serum triglyceride levels bove >200 mg/dl, wheres only 44% of the infnts in the control group experienced serum triglycerides of >200 mg/dl, which ws significnt (P =.011). GIRs nd Initition of Insulin On study dys 4 nd 6, the infnts in the control group hd significntly higher GIRs (Tble 6). On study dy 4, the infnts in the control group hd significntly higher GIR verges thn infnts in the experimentl group: 5.27 ± 1.14 versus 3.87 ± mg/kg/min (P =.030). On study dy 6, for infnts in the control group, verges were 6.00 ± 1.45 versus 4.42 ± 1.51 mg/kg/min (P =.039). Growth nd Anthropometrics During the first week of life, infnts in the experimentl group hd significntly less weight loss thn infnts in the Tble 4. Comprison of Dily Totl Clorie Intke (cl/kg/d) Study Dys Control Group, n = 9 Group, n = ± ± 4.44 < ± ± ± ± ± ± ± ± ± ± ± ± Sttisticlly significnt P <.05. Tble 5. Comprison of Serum Triglycerides (mg/dl) Study Dys Control Group, n = 9 Group, n = 10 Initil ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± Episodes of Hypertriglyceridemi 201 mg/dl, n (%) 4 (44.4) 10 (100) mg/dl, n (%) 2 (22.2) 6 (60).096 Sttisticlly significnt P <

6 vol. 4 no. 1 ICAN: Infnt, Child, & Adolescent Nutrition Tble 6. Comprison of Glucose Infusion Rtes nd Initition of Insulin Study Dys Control Group, n = 9 control group (Tble 7). Infnts in the experimentl group hd n 8.6% ± 3.10% initil weight loss compred with 16.22% ± 8.04% initil weight loss in the control group (P =.013). Clinicl Outcomes There were no sttisticlly significnt differences in clinicl outcomes between the 2 study groups (Tble 8). Discussion The primry outcome for this study ws to determine if micropreemies ( g) could tolerte higher infusion rtes of 20% IVFEs during the first week of life while mintining their serum triglyceride levels 200 mg/dl. The principl investigtor discontinued this study erly becuse 100% of infnts in the experimentl group developed Group, n = ± ± ± ± ± ± ± ± ± ± ± ± ± ± Insulin Strted Yes 6 (66.7) 9 (90).213 No 3 (33.3) 1 (10) Sttisticlly significnt P <.05. hypertriglyceridemi ( 201 mg/dl) s defined by our study protocol. Unfortuntely, we were not ble to reject the null hypothesis becuse 100% of the infnts in the experimentl group developed hypertriglyceridemi ( 201 mg/dl) compred with 44.4% of the infnts in the control group. Other rndomized controlled trils hve shown contrdictory conclusions regrding premture infnt s bility to tolerte higher infusion rtes of IVFEs during the first week of life while t the sme time mintining norml serum triglyceride levels. A study by Pppoe et l 17 found tht premture infnts whose birth weights were <1001 g developed hypertriglyceridemi more frequently when IVFE infusion ws initited t 2 g/ kg/d on DOL 1 compred with those infnts in the control group who were strted t 1 g/kg/d (P =.02). The highest incidence for hypertriglyceridemi for ll infnts in both study groups occurred when the IVFEs were being infused t levels between 2.5 g/kg/d nd 3.5 g/kg/d. Pppoe et l 17 hypothesized tht the reson for the incresed incidence for hypertriglyceridemi in the study ws tht premture infnts hve immture lipoprotein lipse synthesis cpbilities. Reserch hs shown tht premture infnts lipoprotein lipse ctivity my be relted to their gesttionl ge nd birth weight Both De Leeuw et l 18 nd Rovmo et l 19 found tht the premture infnt s declining birth weight correlted with vrince in lipoprotein lipse levels. There ws significnt difference in birth weight for infnts in our study (P =.041). Even though infnts in both study groups were clssified s AGA t birth, infnts in the experimentl group weighed n verge of 49 g less thn infnts in the control group. Becuse serum lipoprotein lipse levels my fluctute with declining birth weight, this difference my hve contributed to infnts in the experimentl group being more susceptible to hypertriglyceridemi. Unfortuntely, micropreemies did not consistently tolerte dditionl clories provided by IVFE during the first week of life. Infnts in the experimentl group hd significntly higher cloric intke on study dy 1 nd 2, but by study dy 6 nd 7, infnts in the control group hd significntly higher cloric intke. This chnge in cloric intke cn be relted to the decresed infusion rtes of IVFEs becuse the infnts developed hypertriglyceridemi. The incresed clorie intke in the experimentl group on study dys 1 nd 2 hd positive effect on reducing the percentge of initil weight loss experienced by the experimentl group: 8.6% ± 3.10% versus 16.22% ± 8.04% in the control group (P =.013). Both the experimentl group nd the control group hd similr incidences of growth filure. The results of this study suggest tht micropreemies who re <750 g t birth my not experience n increse in energy expenditure during the first DOL. Studies hve shown tht premture infnts <30 weeks of gesttionl ge t birth do hve incrementl increses in 63

7 Tble 7. Comprison of Growth nd Anthropometrics Chrcteristics Control Group energy expenditure during the first weeks of life. ELBW infnts with birth weights <1000 g cn hve up to 150% incrementl increse in energy expenditure during the first 5 weeks of life During the first week of life, micropreemies my hve lower energy expenditure. Buer et l 21 found tht in micropreemies with gesttionl ges between 26 nd 28 weeks, energy expenditure verged 33 cl/kg/d, which ws similr to the vlues of 27 to 35 cl/kg/d in other published dt. 23 Buer et l 21 found tht energy expenditure ws ffected by energy intke; therefore, suggesting tht energy expenditure does not increse s result of postntl ge but with energy intke Group Include ll bbies n = 9 n = 10 Percentge of weight loss Regin birth weight (dys) Weight bove 10th percentile on dmission Exclude the bbies who died At dischrge weight (n = 15) Weight bove 10th percentile on dischrge Weight bove 3rd percentile on dischrge Sttisticlly significnt P < ± ± ± ± (100) 10 (100) N/A n = 8 n = ± ± (12.5) 1 (14.3) (62.5) 3 (42.9).447 or weight gin. This dt suggests tht if too mny clories re given during the first week of life to micropreemies, incresed energy expenditure from overfeeding my occur. Buer et l 23 found tht micropreemies my only require n energy intke of 60 to 65 cl/ kg/d by DOL 7. Our study showed tht infnts in the control group tended to tolerte higher GIR thn infnts in the experimentl group, with significnt differences on study dys 4 nd 6 (P =.03 nd 039, respectively). These differences suggest tht micropreemies my be ble to better use clories from glucose for energy thn ft. Mrtin et l 24 proposed tht ELBW infnts could tolerte GIR up to 10 mg/kg/min by DOL 7. Severl studies hve suggested tht ELBW infnts cn use glycerol present in IVFEs in the gluconeogenesis pthwy for energy. 25,26 A premture infnt s bility to effectively regulte ft clories for both fuel nd dipose ccretion my be dependent on gesttionl ge t the time of birth. Chcko nd Sunehg 27 showed tht in very premture infnts, gluconeogenesis is sustined even when GIRs exceed norml infnt glucose turnover rtes. A premture infnt s bility to regulte gluconeogenesis bsed on the infusion of exogenous glucose intke does not effectively mture until the infnt is t 30 weeks gesttionl ge. 28 A study by Cooke 29 found tht certin brnds of IVFEs, such s Intrlipids, ctully stimulte the gluconeogenetic pthwys, resulting in incresed glucose production rtes nd higher serum glucose levels. The limittion of this study ws the smll smple size nd the fct tht it ws not blinded. The demogrphics for rce vried between the 2 groups. The control group hd no Africn Americns, wheres in the experimentl group, there ws no Hispnic representtion. Also, there is no concrete definition for hypertriglyceridemi. Some centers consider lipid intolernce s hving serum triglyceride levels of >150 mg/ dl, wheres other centers consider TPN-relted hypertriglyceridemi intolernce s hving levels >250 mg/ dl. 30 Adults who re receiving TPN, serum triglycerides of <400 mg/dl re considered to be cceptble. 31 Finlly, serum crnitine nd lipoprotein lipse levels were not monitored to determine if it hd n effect on lipid tolernce. In conclusion, micropreemies who weigh <750 g do not tolerte initil higher infusion rtes of IVFEs during the first week of life. Micropreemies do not hve the mturity to effectively regulte, metbolize, use, or store dditionl ftty cids from IVFEs. Clinicins should continue the prctice of strting prenterl IVFE t 0.5 to 1 g/kg/d on the first DOL nd increse IVFEs s tolerted. 64

8 vol. 4 no. 1 ICAN: Infnt, Child, & Adolescent Nutrition Tble 8. Clinicl Outcomes for Infnts Receiving Different Infusion Rtes of Intrvenous Ft Emulsions Outcomes Control Group Group Include ll bbies n = 10 n = 9 PDA present 8 (88.9) 10 (100).474 PDA ligtion 4 (40) 4 (44.4).845 IVH (ll grdes) 5 (55.6) 6 (60).845 IVH (grde 3 or 4) 2 (20) 4 (44.4).405 NEC 1 (10) 1 (11).937 Died 1 (10) 3 (33.3).313 Exclude the bbies who died n = 8 n = 7 ROP 8 (100) 7 (100) N/A CLD 4 (50) 7 (70).077 Postmenstrul ge t dischrge (weeks) 38.5 ± ± LOS (dys) ± ± Abbrevitions: PDA, ptent ductus rterious; IVH, intrventriculr hemorrhge; NEC, necrotizing enterocolitis; ROP, retinopthy of premturity; CLD, chronic lung disese; LOS, length of sty. Sttisticlly significnt P <.05. Author Note The uthors declred no potentil conflicts of interest with respect to the reserch, uthorship, nd/or publiction of this rticle. References 1. Thureen P, Melr D, Fennessey P, Willim H. Effect of low versus high intrvenous mino cid intke on very low birth weight infnts in the erly neontl period. Peditr Res. 2003;53: Poindexter BB, Lnger JC, Dusick AM, Ehrenkrnz RA. Erly provision of prenterl mino cids in extremely low birth weight infnts: reltion to growth nd neurodevelopmentl outcomes. J Peditr. 2006;148: te Brke FW, vn den Akker C, Wttimen D, Huijmns J, vn Goudoever JB. Amino cid dministrtion to premture infnts directly fter birth. J Peditr. 2005;147: Vlentine CJ, Fernndez S, Rogers LK, et l. Erly mino-cid dministrtion improves preterm weight. J Perintol. 2009;29: vn Goudoever J, Wttimen L, Huijmn J, Crnielli V, Suer P. Immedite commencement of mino cid supplementtion in preterm infnts: effect on serum mino cid concentrtions nd protein kinetics on first dy of life. J Peditr. 1995;127: vn den Akker C, te Brke F, Schierbeek H, Rietveld T, Bunt JE, vn Goudoever JB. Albumin synthesis in premture neontes is stimulted by prenterlly dministered mino cids during first dys of life. Am J Clin Nutr. 2007;86: Humont D, Deckelbum RJ, Richelle M, et l. Plsm lipid nd lipoprotein concentrtions in low birth weight infnts given twenty or ten percent lipid emulsions. J Peditr. 1989;115: vn Goudoever JB, Colen T, Wttimen JD, Huijmns JM, Crnielli VP, Suer PJ. Immedite commencement of mino cid supplementtion in preterm infnts: effect on serum mino cid concentrtions nd protein kinetics on the first dy of life. J Peditr. 1995;127: te Brke F, vn den Akker C, Wttimen D, Huijmns J, vn Goudoever J. Amino dministrtion to premture infnts directly fter birth. J Peditr. 2005;147: Wilson DC, Cirns P, Hllidy HL, Reid M, McClure G, Dodge JA. Rndomized controlled tril of ggressive nutritionl regimen in sick very low birthweight infnts. Arch Dis Child Fetl Neontl Ed. 1997;77:F4-F Ibrhim HM, Jeroudi MA, Bier RJ, Dhnireddy R, Krouskop R. Aggressive erly totl prenterl nutrition in low-birthweight infnts. J Perintol. 2004;24: Drenckpohl D, McConnell C, Gffney S, Niehus M, Mcwn K. Rndomized tril of very low birth weight infnts receiving higher rtes of infusion of intrvenous ft emulsions during the first week of life. Peditrics. 2008;122: Bttgli FC, Lubchenco LO. A prcticl clssifiction of newborn infnts by weight nd gesttionl ge. J Peditr. 1967;71: Lubchenco LO, Hnsmn C, Boyd E. Intruterine growth in length nd hed circumference s estimted from live births t gesttionl ges from 24 to 42 weeks. Peditrics. 1966;37: Fenton TR. A new growth chrt for preterm Bbson nd Bend s chrt updted with recent dt nd new formt. BMC Peditr. 2003;3: Browner W, Newmn T, Cummings S, Hulley S. Estimting smple size nd power: the nitty gritty. In: Hulley S, Cummings S, Browner W, Grdy D, Herst N, Newmn T, eds. Designing Clinicl Reserch: An Epidemiologic Approch. Bltimore, MD: Lippincott Willims & Wilkins; 2006: Pppoe TA, Wu SY, Pyti S. A rndomized controlled tril compring n ggressive nd conventionl prenterl 65

9 nutrition regimen in very low birth weight infnts. J Neontl Perintl Med. 2009;2: de Leeuw R, Kok K, De Vries J, Begnovic N. Tolernce of intrvenously dministered lipid in newborns. Act Peditr Scnd. 1985;74: Rovmo LM, Nikkil EA, Rivio KO. Lipoprotein lipse, heptic lipse, nd crnitine in premture infnts. Arch Dis Child. 1988;63: Plchevsk-Kocevsk S, Kokjik L. Associtive tolernce of intrvenously dministered lipid nd gesttionl ge in premture infnts receiving totl prenterl nutrition. Mcedonin J Med Sci. 2009;2: Buer J, Mier K, Hellstern G, Linderkmp O. Longitudinl evlution of energy expenditure in premture infnts with birth weight less thn 1000g. Br J Nutr. 2003;89: Buer K, Lurenz M, Ketteler J, Versmold H. Longitudinl study of energy expenditure in preterm neontes <30 weeks gesttion during the first three postntl weeks. J Peditr. 2003;142: Buer J, Werner C, Gerss J. Metbolic rte nlysis of helthy preterm nd full-term infnts during first weeks of life. Am J Clin Nutr. 2009;90: Mrtin CR, Brown YF, Ehrenkrnz RA, et l. Nutrition prctices nd growth velocity in the first month of life in extremely premture infnts. Peditrics. 2009;124: Sunehg A. Prenterl glycerl enhnces gluconeogenesis in very premture infnts. Peditr Res. 2003;53: Sunehg A. The role of prenterl lipids in supporting gluconeogenesis in very premture infnts. Peditr Res. 2003;54: Chcko SK, Sunehg AL. Gluconeogenesis continues in premture infnts receiving prenterl nutrition. Arch Dis Child Fetl Neontl Ed. 2010;95:F413-F vn Kempen AA, vn der Crbben SN, Ackermns MT, Endert E, Kok JH, Suerwein HP. Stimultion of gluconeogensis by intrvenous lipids in premture infnts: response depends on ftty cid profile. Am J Physiol Endrocrinol Metb. 2006;290:E723-E Cooke RW. Fctors ssocited with chronic lung disese in premture infnts. Arch Dis Child. 1991;66: Admkin D, Gelke K, Andrew B. Ft emulsions nd hypertriglyceridemi. JPEN J Prenter Enterl Nutr. 1984;8: Kumpf VJ, Gervsio J. Complictions of prenterl nutrition. In: Gottschlich MM, ed. The ASPEN Nutrition Support Core Curriculum: A Cse-Bsed Approch the Adult Ptient. 2nd ed. Silver Spring, MD: ASPEN; 2007: