Use of docosahexaenoic acid and arachidonic acid enhancing the growth of preterm infants

Abstract

A method for enhancing the growth of preterm infants involving the administration of certain long chain polyunsaturated fatty acids. It is preferred that the infants are administered an infant formula containing a combination of docosahexaenoic acid and arachidonic acid.

Description

BACKGROUND OF THE INVENTION

[0002] (1) Field of the Invention

[0003] The present invention concerns enhancing the growth of preterm infants involving administration of infant formula containing a combination of docosahexaenoic and arachidonic acid.

[0004] (2) Description of the Related Art

[0005] The long chain polyunsaturated fatty acids (LC PUFA) have been shown to be important in infant development. Particularly, arachidonic acid (ARA) and docosahexaenoic acid (DHA) are LC PUFA that are of special interest in infant nutrition because they are found in high concentrations in the brain (Sastry P S, Lipids of nervous tissue: composition and metabolism. Progress Lipid Res 1985;24:69-176) and the retina (Fliesler S J and Anderson R E. Chemistry and metabolism of lipids in the vertebrate retina. Progress Lipid Res 1983;22:79-131). ARA (20:4n-6) and DHA (22:6n-3) are derived from the parent essential fatty acids linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3) through alternate desaturation and elongation and accumulate rapidly in fetal neural tissue during the last months of gestation and the first months of postnatal life (Makrides M, Neuman M A, Byard R W, Simmer K, Gibson R A. Fatty composition of the brain, retina and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr 1994;60:189-94).

[0006] Unlike term infants, preterm infants do not fully benefit from the maternal and placental LC PUFA supply during the last trimester of pregnancy. Even though preterm infants are capable of synthesizing both DHA and ARA from their 18 carbon precursors (Carnielli V P, Wattimena D J L, Luijendijk I H T, Boerlage A, Degenhart H J, Sauer P J J. The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids. Pediat Res 1996;40:169-174), it remains unclear whether the rate of synthesis is adequate to meet the optimal needs for central nervous system accretion in the absence of a dietary supply of these fatty acids. Preterm infants are dependent on their own dietary supply of linoleic and α-linolenic acids through either human milk, which also contains small but significant amounts of ARA and DHA or through commercially available artificial formulas, none of which in the United States contain ARA end DHA.

[0007] It has been demonstrated in recent studies (Hoffman D R and Uauy R. Essentiality of dietary ω-3 fatty acids for premature infants: Plasma and red blood cell fatty acid composition. Lipids 1992;27:886-95) that the fatty acid composition of red blood cell membrane lipids in infants receiving formulas supplemented with DHA (0.35% of total fatty acids) was similar to human milk-fed infants. In the same study, Birch (Birch D G, Birch E E, Hoffman D R Uauy R D. Retinal development in very-low-birth-weight infants fed diets differing in Omega-3 fatty acids. Investigation Ophthalmology Visual Science 1992;33:2365-76) found that retinal function improved with the provision of a dietary supply of DHA in very low birth weight infants.

[0008] The first year growth of preterm infants fed standard formula compared to marine oil LC PUFA supplemented formula was studied by Carlson et al. (Carlson S E, Cooke, R J, Werkman S H, Tolley E A. First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula Lipids 1992:27:901-907). The experimental formulas provided 0.2% of total fatty acids as DHA and also provided 0.3% as EPA (20:5n-3). This EPA concentration is higher than found in human milk while the DHA level is similar to human milk. Beginning at 40 weeks from conception, marine oil supplemented infants compared to controls had significantly lower weight, length, and head circumference. From this study, Carlson (Carlson S E, Werkman S H, Peeles J M, Cooke R J, Tolley E A. Arachidonic acid status correlates with first year growth in preterm infants. Proc Natl Acad Sci USA 1993;90:1073-77) hypothesized that dietary ARA could improve first year growth of preterm infants, in the context of restoring growth to the level of control formula containing no LC PUFA.

[0009] In another study (Montalto, F B, et al., Pediatric Research, Vol 39, page 316A, abstract no. 1878) it was shown that male infants fed marine oil supplemented formula (containing DHA but essentially no ARA) had, by 4 to 6 months, lower head circumference, length, weight and fat free mass than standard formula fed infants. A third study also showed decreased weight at 9 and 12 months corrected age in preterm infants fed marine oil supplemented formula (with LC PUFA) to 2 months corrected age compared with control formula containing no LC PUFA (Carlson S E, et al., Am. J. Clin. Nutr., 63 pp 687-97, 1996).

[0010] The prior art has demonstrated that infants with altered tissue LC PUFA levels, resulting from a lack of LC PUFA in their diets, may be at risk for neurological problems, may also have reduced scores on cognitive tests, and may have lower retinal development than human milk-fed infants. Worldwide regulatory organizations such as the WHO/FAO Expert Committee on Fats and Oils in Human Nutrition have recommended that LC PUFA be included in preterm infant formula. These recommendations have been made despite the negative effects observed of DHA supplements on growth. There has been no demonstration in the literature that ARA and DHA, particularly when added to infant formula, enhances the growth of infants above that demonstrated by control formulas not containing ARA and DHA.

SUMMARY OF THE INVENTION

[0011] It has unexpectedly been discovered that preterm infants receiving infant formula supplemented with both DHA and ARA demonstrate enhanced growth. The present invention is directed to enhancing the growth of preterm infants comprising administering to said infants a growth enhancing amount of DHA and ARA.

DETAILED DESCRIPTION OF THE INVENTION

[0012] As reported in a review of preterm infant growth by Carlson, S E, (The Jrnl of Pediatrics, vol 125, pp 533-8,1994) “After adjusting for postconceptional age, preterm infants show a decline (rather than a catch-up) in the normalized weight from approximately 2 to 4 months past expected term.”

[0013] Several prior art studies have documented the value of administering DHA to infants. However, when DHA, either as the primary LC PUFA or combined with EPA, is administered to preterm infants, said infants suffer from decreased growth. It has been suggested that ARA may be beneficial to growth; however, heretofore the growth effects of administering both DHA and ARA to preterm infants have been unknown. It has been surprisingly discovered that administering the combination of ARA and DHA results in enhanced growth of infants relative to infants fed DHA alone. It has also been discovered that preterm infants administered an infant formula containing ARA and DHA exhibit enhanced growth relative to preterm infants fed control formula without DHA and ARA, such as those formulas currently used in modem nurseries. It has further been discovered that practice of the method of the invention results in growth of preterm infants catching up in an unexpected short time to a reference group of normal term breast fed infants.

[0014] The time to achieve growth similar or equivalent to normal term breast fed infants by practice of the method of the invention is less than 9 months corrected age; preferably less than 6 months corrected age, more preferably less than 4 months corrected age, even more preferably less than 2 months corrected age, and most preferably no greater than term corrected age.

[0015] The method of the invention requires a combination of DHA and ARA. The weight ratio weight of ARA:DHA can be about 1:2 to about 5:1, preferably about 1:1 to about 3:1, and more preferably about 2:1.

[0016] In the method of the invention the combination of DHA and ARA is preferably administered as part of an infant formula. The infant formula for use in the present invention is preferably nutritionally complete and typically contains suitable types and amounts of lipid, carbohydrate, protein, vitamins and minerals. The amount of lipid or fat typically can vary from about 3 to about 7 g/100 kcal. The amount of protein typically can vary from about 1 to about 5 g/100 kcal. The amount of carbohydrate typically can vary from about 8 to about 12 g/100 kcal. Protein sources can be any used in the art, e.g., nonfat milk, whey protein, casein, soy protein, hydrolyzed protein, amino acids, and the like. Carbohydrate sources can be any used in the art, e.g., lactose, glucose, corn syrup solids, maltodextrins, sucrose, starch, rice syrup solids, and the like. Lipid sources can be any used in the art, e.g., vegetable oils such as palm oil, soybean oil, palmolein, coconut oil, medium chain triglyceride oil, high oleic sunflower oil, high oleic safflower oil, and the like. Conveniently, commercially available infant formula can be used. For example, Enfamil®, Enfamil® Premature Formula, Enfamil® with Iron, Lactofree®, Nutramigen®, Pregestimil®, ProSobee® (available from Mead Johnson & Company, Evansville, Ind., U.S.A.), Similac®, Isomil®, Alimentum®, Neocare®, and Similac® Special Care (available from Ross Laboratories, Columbus, Ohio, U.S.A.), may be supplemented with suitable levels of ARA and DHA at the proper ratios and used in practice of the method of the invention.

[0017] The form of administration of the DHA and ARA in the method of the invention is not critical, as long as a growth enhancing amount is administered. Most conveniently, the DHA and ARA are supplemented into infant formula which is then fed to the infants. Alternatively, the DHA and ARA can be administered as a supplement not integral to the formula feeding, for example, as oil drops, sachets, in combination with other nutrient supplements such as vitamins, and the like.

[0018] The growth enhancing amount of DHA is typically about 2.5 mg/kg of body weight/day to about 60 mg/kg of body weight/day, preferably about 6 mg/kg of body weight/day to about 40 mg/kg of body weight/day, more preferably about 12 mg/kg body weight/day to about 30 mg/kg body weight/day, and even more preferably about 18 mg/kg of body weight/day to about 24 mg/kg of body weight/day.

[0019] The growth enhancing amount of ARA is typically about 5 mg/kg of body weight/day to about 120 mg/kg of body weight/day, preferably about 12 mg/kg of body weight/day to about 80 mg/kg of body weight/day, more preferably about 24 mg/kg body weight/day to about 60 mg/kg body weight/day, and even more preferably about 36 mg/kg of body weight/day to about 48 mg/kg body weight/day.

[0020] The amount of DHA in infant formulas for use in the present invention typically varies from about 2 mg/100 kilocalories (kcal) to about 50 mg/100 kcal, preferably about 5 mg/100 kcal to about 33 mg/100 kcal, more preferably about 10 mg/100 kcal to about 25 mg/100 kcal, and even more preferably about 15 mg/100 kcal to about 20 mg/100 kcal.

[0021] The amount of ARA in infant formula for use in the present invention typically varies from about 4 mg/100 kcal to about 100 mg/100 kcal, preferably about 10 mg/100 kcal to about 67 mg/100 kcal, more preferably about 20 mg/100 kcal to about 50 mg/100 kcal, and even more preferably about 30 mg/100 kcal to about 40 mg/100 kcal.

[0022] The infant formula supplemented with oils containing DHA and ARA for use in the present invention can be made using standard techniques known in the art. For example, replacing an equivalent amount of an oil normally present, e. g., high oleic sunflower oil.

[0023] The source of the ARA and DHA can be any source known in the art such as fish oil, single cell oil, egg yolk lipid, brain lipid, and the like. The DHA and ARA can be in natural form, provided that the remainder of the LC PUFA source does not result in any substantial deleterious effect on the infant. Alternatively, the DHA and ARA can be used in refined form. It is preferred that the LC PUFA used in the invention contain little or no EPA. For example, it is preferred that the infant formulas used herein contain less than about 20 mg/100 kcal EPA; preferably less than about 10 mg/100 kcal EPA; more preferably less than about 5 mg/100 kcal EPA; and most preferably substantially no EPA.

[0024] Preferred sources of DHA and ARA are single cell oils as taught in U.S. Pat. Nos. 5,374,657, 5,550,156, and 5,397,591, the disclosures of which are incorporated herein by reference in their entirety.

[0025] The following examples are to illustrate the invention but should not be interpreted as a limitation thereon.

EXAMPLES

I

CLINICAL STUDY DESIGN

[0026] 1. Introduction

[0027] This study is a double-blind, randomized, controlled parallel design, prospective trial of premature infant formulas containing microalgae and fungi-derived oils which contain a part of their constituents arachidonic acid and docosahexaenoic acid. Formula feeding subjects will be randomized into one of 3 feeding groups:

[0028] premature formula plus DHA (about 0.13% of energy) and ARA (about 0.26% of energy)

[0029] premature formula plus DHA (about 0.13% of energy)

[0030] premature formula WITHOUT DHA and ARA

[0031] The products have the same nutrient composition (see Appendix A) and differ only in the level of DHA and ARA. The products will be blinded. The present order of formula has no relationship to randomization.

[0032] Normal, term, breast fed infants will be enrolled to provide a normal visual acuity reference.

[0033] Fifty evaluable subjects will be completed in each group. Premature infants will remain on study formulas after reaching 90 kcal/kg/d for a minimum of 28 days or until hospital discharge whichever is longer. After 28 days or discharge, whichever is longer, all premature infants will receive Enfamil or Enfalac with Iron. If medically indicated, ProSobee, Lactofree, Alactamil, Nutramigen, or Pregestimil may be used in place of Enfamil or Enfalac with Iron. Term infants will receive at least 85% of their nutrition from breast milk. Primary measures of effectiveness will include visual acuity and red blood cell membrane fatty acid profiles (i.e. DHA and ARA levels). The measure of safety will be growth and adverse experience reports.

[0034] 2. Subjects

[0035] 2.1 Source and Characterization of Study Group

[0036] Acceptable preterm subjects will be relatively healthy premature infants taking preterm formula. Anticipated hospitalization should be sufficient to allow for 28 days of enteral intake ≧90 kcal/kg/d and ≧85% study formula intake. All races and both sexes will be eligible for the study.

[0037] 2.2. Inclusion Criteria

[0038] Preterm infants:

[0039] Birth weight ≧900 g

[0040] Formula feeding at time of study enrollment

[0041] Anticipate enteral intake of ≧90 kcal/kg/day for ≧28 days before discharge home

[0042] Informed consent obtained

[0043] Term Infants:

[0044] 38 to 42 weeks gestation

[0045] Committed to breast feeding

[0046] Informed Consent obtained

[0047] 2.3 Exclusion Criteria

[0048] Preterm infants:

[0049] ≧1500 g at birth

[0050] Preterm and Term Infants:

[0051] History of underlying disease or congenital malformation which in the opinion of the investigator is likely to interfere with the evaluation of the subject

[0052] More than 24 days between birth and full oral feeds (≧90 kcal/kg/d)

[0053] Small (<10th percentile) for gestational age at birth (SGA)

[0054] Necrotizing enterocolitis as diagnosed by the physician

[0055] Other gastrointestinal disease

[0056] Impaired visual or ocular status at birth

[0057] 2.4 Concomitant Medications, Hospitalizations, Illnesses

[0058] No medication which may affect FPL response may be used within 3 days of measurement.

[0059] No evidence of viral of bacterial infection during FPL testing.

[0060] No medications known to affect lipid metabolism (e.g., heparin at therapeutic levels)

[0061] 3. Study Product Information

[0062] 3.1 Formulations

[0063] Nutrient composition is included as Appendix A.

[0064] 4. Study Procedures

[0065] 4.2.1 Enrollment

[0066] Enrollment will take place over a 6 month period. Ideally, sufficient subjects will be enrolled so that 10 subjects in each group complete the study at each site for the multi-center trial. A total of 50 infants per formula group will complete this trial.

[0067] 4.2.2 Schedule of Events (See Flow Chart, Section 8.4)

[0068] 4.2.2.1 Recruitment

[0069] Mothers of eligible, healthy, preterm formula fed infants and term, breastfed infants will be contacted, the study explained to them, and if they are agreeable, written informed consent obtained.

[0070] Term infants may be enrolled anytime from birth until or during the 48 week visit.

[0071] 4.2.2.2 Randomization

[0072] Recruited formula fed subjects will be randomized into study groups. Randomization can occur anytime after enteral feeds reach 50 kcal/kg/day until commencement of full enteral feeds (i.e., ≧90 kcal/kg/day).

[0073] 4.2.2.3 Feeding

[0074] All premature infants will receive their assigned study formula after informed consent has been granted and enteral feeds are at least 50 kcal/kg/day. The infant will remain on study formula 28 days after reaching 90 kcal/kg/d or until hospital discharge, whichever is longer. Oral feeding amount, strength and rate will advance as appropriate for the clinical management of the infant.

[0075] All parents will be instructed not to feed solid foods during the study. The parents will be instructed that the study formula or breast milk is to serve as the sole source of food from enrollment to study end.

[0076] 4.2.2.4 Baseline Data Collection

[0077] The following data will be collected by the Investigator at the time of enrollment and randomization on the case report forms:

[0078] Informed consent of parent obtained.

[0079] Post conceptual age.

[0080] That the subject is a premature infant, with Birth weight ≧900 gm and ≧1500 gm or a normal term infant between 38 and 42 weeks gestational age.

[0081] That the preterm subject is receiving infant formula or term infant is committed to breast feeding.

[0082] Anticipated preterm infant enteral intake of ≧90 kcal/kg/day for ≧28 days prior to discharge home.

[0083] That the subject has no history of underlying disease, inborn error of metabolism, or congenital malformation which in the opinion of the Investigator is likely to interfere with the evaluation of the study formulas.

[0084] That the subject is not small (<10th percentile) for gestational age at birth.

[0085] That the subject does not have necrotizing enterocolitis as diagnosed by a physician.

[0086] That the subject does not have a gastrointestinal disease.

[0087] No more than 24 days between birth and full enteral feeds (i.e., >90 kcal/kg/day).

[0088] That the subject did not have impaired visual or ocular status at birth.

[0089] Birth date, sex, race.

[0090] Birth weight, length and head circumference

[0091] 4.2.2.5 Investigator Periodic Data Collection

[0092] “During hospitalization, preterm subjects will have their weight recorded daily while they are receiving study formula. Length and head circumference will be recorded weekly, along with an additional weight measurement. For a given subject, the same scale should be used for the weekly weight measurement.”“Weight, length, and head circumference will also be recorded at the 40, 48, and 57 week post conceptual age visit (preterm) and 56 and 119 days of age visit (term).”

[0093] 4.2.2.6 Blood Draw

[0094] When preterm infant enrolls in the study and again at termination of study formula (i.e., hospital discharge or 28 days after reaching 90 kcal/kg/d of study product), the Investigator will ascertain that the infant is essentially solely formula fed. If this criteria is met, 1.2 ml/blood will be drawn for blood lipids. The sample will be processed as described in Appendix B.

[0095] An attempt will also be made to draw a similar blood sample at the 48 weeks PCA visit when visual acuity is measured in both term and preterm infants.

[0096] 4.2.2.7 Visual Acuity by Forced Choice Preferential Looking (FPL) at 48 and 57 Weeks±4 Days Post-Conceptual Age

[0097] When the infant is 48 and 57 weeks±4 days post-conceptual age, trained persons at each study site will follow the Teller Acuity Card Procedure for the measurement of visual acuity of all study subjects. It is essential that only persons who are trained in the FPL procedure for determining visual acuity do the testing. If necessary, training of responsible persons and documentation of completion of successful training will be done at Children's Hospital Medical Center Ophthalmology Department in Seattle, Wash., according to the procedure attached as Appendix C.

[0098] If the infant cannot complete the procedure at 48 or 57 weeks±4 days postconceptual age (i.e., too fussy, too sleepy, too inattentive) the test should be repeated within 7 days.

[0099] 4.2.2.8 Interim Evaluation

[0100] At preterm infant hospital discharge or 28 days after reaching 90 kcal/kg/d of study formula feeding, whichever is longer, the Investigator will fill out an “Interim Evaluation” form. After reviewing the subject's records and discussion with the parents and staff, the Investigator will indicate:

[0101] Whether or not the subject completed at least 28 days of study formula intake ≧90 kcal/kg/d and both blood samples obtained

[0102] If the study was not completed, and reason

[0103] Whether or not the subject received steroids (glucorticoids)

[0104] Investigator's evaluation of the study formula

[0105] The first and last dates study material was taken will be recorded.

[0106] 4.2.2.9 Final Evaluation

[0107] At the final study visit (57 weeks postconceptual age) or earlier if the subject drops out, the Investigator will fill out a “Final Evaluation” Case Report Form. After reviewing the subject's records and discussion with the parents, the Investigator will indicate whether the subject:

[0108] (1) Completed feeding regiment and all study parameters (i.e., anthropometrics and visual acuity measured).

[0109] (2) Did not complete feeding regimen.

[0110] (3) Not completed and reason.

[0111] 4.3 Clinical Observations

[0112] 4.3.1 Physical Examinations

[0113] Subjects will have weight, length and head circumferences recorded at birth, weekly while hospitalized, then at 40, 48, and 57 weeks±4 days postconceptual age.

[0114] Body weight will be measured using an electronic balance or a double beam balance accurate to 10 g or ½ oz with non-detachable weights. During hospitalization, if more than one such balance is employed in the practice, either one balance should be designated the study balance and all study weights will be carried out on that balance for a particular subject, or the balances will be checked and certified to register the same weight throughout the range of weights expected. Outpatient weights will be obtained on a calibrated office scale.

[0115] Documentation indicating balance calibration of the outpatient balance carried out within 12 months of study initiation will be supplied to the Sponsor.

[0116] Length will be measured with the infant in recumbent position with the help of two examiners and a suitable measuring apparatus. One person holds the subject's head in contact with a fixed vertical headboard and a second person holds the subject's feet, toes pointing directly upward and, also applying gentle traction. The baby is measured from the headboard to the soles of the feet with a non-stretching tape measure.

[0117] Head circumference will be measured, employing a flexible, non-stretchable cloth or vinyl tape.

[0118] 4.3.2 Visual Acuity by Forced Choice Preferential Looking (FPL)

[0119] Visual acuity will be determined at 48 and 57 weeks±4 days postconceptual age according to procedures outlined in Appendix C.

[0120] 4.3.3 Laboratory Tests

[0121] Blood will be drawn from preterm infants by heel prick or venipuncture when study formula is begun and terminated. An attempt will be made to draw blood at 48 weeks±4 days PCA from both term and preterm infants. Procedures for handling the blood are described in Appendix B.

4.4 FLOWCHART
	PRETERM	TERM
		Enteral	Termination	Visit 1	Visit 2	Visit 3	Visit 1	Visit 2	Visit 3
		Intake >50	of Study	40 wks ± 4d	48 wks ± 4d	57 wks ± 4d	40 wks ± 4d	48 wks ± 4d	57 wks ± 4d
EVENT	Birth	kcal/kg/d	Formula †	PCA	PCA	PCA	PCA	PCA	PCA
Randomization		✓
Study Formula		✓
Enfamil w/iron			✓	✓	✓	✓
Human Milk							✓	✓	✓
	Physical	Physical
Weight	✓	✓*	✓	✓	✓	✓	✓	✓	✓
Length	✓	✓*	✓	✓	✓	✓	✓	✓	✓
Head	✓	✓*	✓	✓	✓	✓	✓	✓	✓
Circumference
Blood Draw		✓	✓		✓			✓
Visual Acuity					✓	✓		✓	✓
Test
Illness				✓	✓	✓		✓	✓
Interim			✓
Assessment
Final	(when the subject discontinues or completes)	(when the subiect discontinues or completes)
Assessment
Medical problems related to or affecting formula consumption will be recorded when they occur.
*recorded daily and weekly during hospitalization
†At hospital discharge or 28 days of study formula intake (after reaching 90 kcal/kg/d), whichever is later

[0122] 5. Criteria for Response

[0123] Criteria for response will depend upon the following:

[0124] Visual Acuity better than the control formula.

[0125] Visual Acuity comparable to breastfed term infant.

[0126] Red Blood Cell phosphatidyl ethanolamine DHA and ARA weight % greater than formula control group.

[0127] Growth as measured by weight achieved at 48 and 57 weeks postconceptual age comparable to formula control group.

[0128] 6. Statistics

[0129] 6.1 Randomization

[0130] If the subject meets the inclusion and exclusion criteria, randomization to one of three formula groups will take place. The randomization schedule will be provided by Mead Johnson Research Center. A separate randomization schedule will be provided for males and females.

[0131] 6.2 Sample Size

[0132] The primary parameter of interest is visual acuity as measured by the Forced Choice Preferential Looking (FPL). The minimal clinically relevant difference was determined to be 0.5 octave. A consultant in the field of visual acuity estimated the standard deviation to be 0.5 octave. This value was increased to 0.7 octave in case more variability was experienced in this study. Thirty-two subjects per group are needed to attain 80% power when testing at an alpha level of 0.05.

[0133] A sample size estimate of 50 per group was determined to achieve α+0.05, β+0.20, for weight of infants receiving study oil being greater than 400 gm below control at 48 weeks postconceptual age or 500 g below control at 57 weeks postconceptual age with a standard deviation of 800 g. It was therefore determined that 50 subjects per group will be used in the study.

[0134] 6.3 Analytical Plan

[0135] Visual acuity data will be recorded in cycles per cm. These values will be converted to cycles per degree using the following formula: 1$\text{cycles/degree}=\frac{38\times \text{cycles/cm}}{55}$

[0136] A log transformation will be applied to the data prior to analysis. Analysis of variance techniques will be used to assess feeding regimen group differences in visual acuity. If the overall F test for feeding regimen is significant at an alpha level of 0.05, pairwise comparisons will be made at an alpha level of 0.05. If no significant differences are detected, then a post-study power analysis will be performed to demonstrate that the study had adequate power to detect the minimal clinically relevant difference.

[0137] Analysis of variance will be used to assess feeding regimen differences in phosphatidyl choline DHA and ARA levels and in phosphatidyl ethanolamine DHA and ARA levels at each time point. If the overall F test is significant at an alpha level of 0.05, then pairwise comparisons will be made at an alpha level of 0.05.

[0138] Analysis of variance will be used to assess feeding regiment differences in weight at 48 and 57 weeks postconceptual age. The statistical model will include terms for feeding regimen, study center, sex and all two-way interactions. Non-significant interactions will be removed from the final statistical model. Two one-sided tests will be performed comparing each experimental formula (EC) with the control formula (CF). The hypothesis to be tested is as follows:

H 0 =Weight (CF)≧Weight (EF).

[0139] The alternative hypothesis is as follows:

H 1 =Weight (CF)≧Weight (EF).

[0140] If H0 is rejected and the mean weight of the control formula exceeds that of the experimental formula by more than 400 mg at 48 weeks postconceptual age or by 500 g at 57 weeks postconceptual age then the conclusion is that the experimental formula does not exceed that of the experimental formula by more than 400 g at 48 weeks postconceptual age or by 500 mg at 57 weeks postconceptual age then the conclusion is that the experimental formula does provide adequate growth. If H0 is not rejected then a post-study power analysis will be performed to demonstrate that the study had adequate power to detect the above mentioned clinically relevant differences. If adequate power is achieved then the conclusion is that the experimental formula does provide adequate growth.

[0141] Fisher's exact test will be used to compare the proportion of subjects in each group with illness/symptoms of concern during the study. The analysis will be performed for each type of illness/symptom reported, with classification of investigator terms into similar terminology made as necessary.

APPENDIX A

Nutrient Composition of Formulas

[0142] All study formulas are 24 kcal/fl oz and are identical in composition to marketed Enfamil Premature Formula except for the study oils employed. These oils are described in the protocol.

	STUDY FORMULAS
NUTRIENT	AMOUNT/100 kcal	ENFAMIL WITH Fe
Protein g	3	2.2
Fat, g	5.1	5.6
Carbohydrate, g	11.1	10.3
Vitamin A IU	1250	310
Vitamin D IU	270	63
Vitamin E IU	6.3	.2
Vitamin K mcg	8	8
Thiamine, mcg	200	78
Riboflavin, mcg	300	150
Vitamin B6, mcg	150	63
Vitamin B12, mcg	0.25	0.23
Niacin, mcg	4000	1250
Folic Acid, mcg	35	15.6
Pantothenate, mcg	1200	470
Biotin, mcg	4	2.3
Vitamin C, mg	20	8.1
Choline, mg	12	15.6
Inositol, mg	17	4.7
Calcium, mg	165	78
Phosphorus, mg	83	53
Magnesium, mg	6.3	7.8
Iron, mg	1.8	0.5
Zinc, mg	1.5	0.78
Manganese, mcg	6.3	15.6
Copper, mcg	125	94
Iodine, mcg	25	6
Sodium mg (mEq)	39 (1.7)	27 (1.17)
Potassium mg(Meq)	103 (2.6)	108 (2.8)
Chloride mg (Meq)	85 (2.4)	63 (1.77)

II

FINAL STUDY REPORT

[0143] Study Design:

[0144] This double-blind, parallel-group study (project 3338) was carried out in 16 neonatal centers (study numbers 9698-9709, 9712, 9723, 9743, and 9746) in North America. Three premature infant feedings were compared. Each had the same composition except for the incorporation of fungal and/or micro algal oils up to about 3% of the fat blend to provide the experimental levels of docosahexaenoic acid (DHA) and arachidonic acid (ARA). The control formula (C, Enfamil® Premature Formula) contained no DHA or ARA, the DHA formula (D) contained about 0.15% of energy as DHA (0.34% of fat), and the DHA+ARA formula (DA) contained about 0.14% of energy as DHA (0.33% of fat) and 0.27% of energy as ARA (0.60% of fat). The formulas were fed to 284 randomized infants weighing 846 to 1560 grams at birth for at least 28 days. Upon completion of study formula intake, they were given routine infant formula and followed through 4 months gestationally corrected age. A group of 90 exclusively human milk fed term infants were enrolled and followed to 4 months of age as a reference group (H).

[0145] Study Objective and Statistical Analysis:

[0146] The primary objective of this study was to establish the safety of feeding D or DA to preterm infants during their initial hospitalization as measured 1) by growth, acceptance and tolerance while consuming the formula for at least 1 month and 2) by close monitoring and observation for a 4 to 5 month follow-up period (4-5 times the treatment period) while consuming unsupplemented routine term infant formula. The primary growth parameter selected was weight with evaluation of the proposition that weight on test formula was greater than or equal to weight on control formula. The one sided statistical test for an adverse effect on growth maximized the power to detect a difference should one be present. A two-sided test was used for all other parameters. A p-value of less than 0.05 was used to establish significance.

[0147] Secondary objectives of the study were 1) to evaluate the impact of fatty acid levels in erythrocyte phospholipids at the end of study feeding and 2) to determine if any effect on mean visual acuity greater than half an octave could be demonstrated at 2 and 4 months corrected age.

[0148] Results:

[0149] Six infants were just outside the weight parameters and five infants just older than the less than 24 days chronological age parameter for enrollment in the study. In each case, judgement by the clinical or medical monitor was made to include them in the study prior to enrollment based on their homogeneity with other study infants in all other particulars, e.g., state of health, type of medical complications, and weight for gestational age. All these infants were included in the analysis of the study results.

[0150] The formula groups were comparable at enrollment (See table 1). Post-conceptual age, weight, length, and head circumference at enrollment did not differ among the groups.

[0151] All groups experienced comparable final study status (See table 2). Drop outs did not differ among the formula fed groups during hospitalization. There also were no differences in drop outs among the four groups at study completion.

[0152] Both formulas D and DA provide adequate growth when compared to formula C (See table 3, FIG. 1, and Appendix 1). Weight gain during hospitalization was no less on D or DA than on C, 33.3, 34.7, and 30.7 g/day, respectively. Furthermore, no less weight was achieved on D or DA than on C at 40, 48, and 57 weeks post-conceptual age (See table 4, FIG. 2, and Appendix 1); statistical power was greater than 0.89 to detect a clinically relevant decrease.

[0153] Post-hoc analysis reveals that infants on DA grew faster than infants receiving C and D (See table 5 and FIG. 1). This enhanced growth provided faster “premature infant catch-up” compared to C and D. Weight achieved by the DA group (3198 g) was higher than C (3075 g) and D (3051 g) at 40 weeks post-conceptual age but had not fully caught up to the term birth weight (3438 g) of group H (See table 4 and FIG. 2). This catch up trend continued through 48 to 57 weeks by which time the mean weight of group DA did not differ from group H while groups C and D remained significantly lower.

[0154] Length was not different among the formula groups either during hospitalization or the follow-up period, although the ordered sequence of mean lengths was the same as for the weights (See table 7 and FIG. 3). This is likely at least partially due to length being a less sensitive parameter of growth than weight. For the same reason, the mean lengths of group H infants were higher than that of all the premature infant groups at 40, 48 and 57 weeks post-conceptual age indicating slower catch up in this parameter.

[0155] Head circumference is the least sensitive parameter of growth and was not different among any of the four groups at any time measured except at 40 weeks postconceptual age (See table 8 and FIG. 4). At this time, as expected, the birth head circumference of group H was smaller than the formula fed premature infants possibly due to molding of labor and to insufficient time for adjustment to the extrauterine environment.

[0156] Visual acuity has reportedly been enhanced in studies where DHA supplemented formulas were fed to premature infants both in the hospital and continuing after discharge. In this study, visual acuity was measured about 3 months and then about 5 months after stopping study formula to determine whether a residual beneficial effect of at least half an octave might be observed. Although no difference in visual acuity was found among the formula groups at these times (See table 8 and FIG. 5), the acuity card method used, the length of study formula feeding, and/or the length of time not on study formula at the time of measurement may have precluded its detection. However, at 57 weeks post-conceptual age, the breast fed term infant group did have statistically higher visual acuity scores than the test formula groups. But even these differences were at most only 0.33 octave and were clinically insignificant (See FIG. 6). It is important to note that the breast fed infants continued to receive DHA and ARA during the 3-5 month follow-up period while the formula fed groups did not. Thus, this minor difference in performance was not unexpected based on previous study findings and on developmental differences between term and preterm infants even at the same gestational age.

[0157] Individual fatty acid levels were determined in the phosphatidylcholine and phosphatidylethanolamine fractions of red blood cells before formula feeding, at the conclusion of test formula feeding, and at 48 weeks post-conceptual age (See tables 9 and 10). The premature infant groups were comparable at the beginning of test formula feeding. At the conclusion of test formula feeding, individual fatty acid levels varied among the groups. DHA and ARA were statistically significantly higher in the respectively supplemented groups. Other fatty acid levels reflected the impact of the supplementation. No clinically significant alterations in fatty acid levels or metabolism were identified. After discontinuing study formula and consuming a diet without DHA or ARA for about 3 months, no differences in fatty acid levels among formula fed groups were detectable, except for phosphatidylethanolamine levels of 18:2 (range 8.9-9.3%) and DHA (range 3.2-4.1%) which differences were not identified as being clinically significant. However, the breast fed group shows statistically significant differences in 13 fatty acid levels compared to the formula fed infants. These differences are undoubtedly due to the differences in fatty acid composition of human milk and the term formulas including the lack of DHA and ARA in the latter.

[0158] Preterm infant complications were similar in all groups (See table 11). Over 80% of all infants were opthamologically examined and over 90% had ultrasound evaluation of their heads. Specifically, the incidence and severity of retinopathy of prematurity (ROP or retrolental fibroplasia/RLF) and the incidence of intraventricular hemorrhage or its complications did not differ among formula groups. No feeding group related complications were identified.

[0159] Serious adverse experiences did not differ (p=0.93) among the formula groups and were in the range of those expected in a premature infant population while on study formula: 6% in group C, 5% in group D, and 6% in group DA (See table 12). After the experimental formula phase, serious adverse experiences still did not differ among the preterm groups (See table 13): 13% in group C, 15% in group D, and 15% in group DA. However, the term infant breast fed group had significantly fewer serious adverse experiences (1%, p=0.002) as expected. Two infants reportedly suffered sudden infant death syndrome (SIDS), one in group C and one in group D; there was no significant difference in this complication among all four groups.

[0160] Conclusions:

[0161] We conclude that feeding 0.13% of calories as DHA from micro algal oil and feeding 0.13% of calories as DHA from micro algal oil plus 0.26% of calories as ARA from fungal oil in the matrix of premature infant formula to premature infants during the period of their initial hospitalization prior to 40 weeks post conceptual age is safe. These micro algal and fungal oil supplements do not result in any adverse effect on growth, clinical complications, or untoward events. Furthermore, this study reveals that growth benefits accrue to premature infants fed Enfamil Premature Formula supplemented with DHA and ARA from these sources compared to unsupplemented formula or formula supplemented with only DHA. No measurable benefit on visual acuity was identified when infants were tested at about 3 and 5 months after the supplemented formula was discontinued (2 and 4 months corrected age). However, providing human milk levels of intake of long chain polyunsaturated acids are warranted because they are critical to brain development and foster enhanced catch-up growth during this early development period.

TABLE 1
Birth Statistics of Premature Subjects
	n	Mean (std)	Range	p-value
Post-Conceptual
Age (Weeks)
Control	62	29.5 (1.7)	25-33	0.076
DHA	66	30.0 (1.4)	26-32
DHA + ARA	66	29.7 (1.7)	26-34
Birth Weight (g)
Control	62	1233.1 (176.6)	846-1560	0.25
DHA	66	1272.8 (168.1)	900-1545
DHA + ARA	66	1278.9 (177.6)	910-1535
Birth Length (cm)
Control	60	38.4 (2.3)	34-43.75	0.62
DHA	66	38.6 (2.2)	33-43.5
DHA + ARA	66	38.7 (2.3)	33-44
Birth Head
Circumference (cm)
Control	61	26.9 (1.5)	23.5-30.5	0.53
DHA	64	27.3 (2.1)	22-37
DHA + ARA	65	27.2 (1.6)	23.5-30

[0162]

TABLE 2
Summary of Final Study Status
	Regimen
	Control	DHA	DHA + ARA	HM	p-value
Immediate dropout, study formula			2		2
never consumed
Study Formula Phase*
Completed	52	(84%)	59	(89%)	62	(94%)		0.20
Discontinued	10	(16%)	7	(11%)	4	(6%)
Reason discontinued
>96 cumulative hours NPO	3		1
<28 days of intake >= 90 kcal/kg/day	3		3
Complications unrelated to study	1
formula
NEC or other GI disease			1		1
Formula intolerance					1
Parents request	2		2		1
Not off oxygen prior to discharge					1
Protocol violation	1
Term Formula Phase**
Completed	45	(87%)	47	(80%)	53	(85%)	77	(86%)	0.74
Discontinued	7	(13%)	12	(20%)	9	(15%)	13	(14%)
*The CRFs for 9709-003 (DHA) and 9743-304 (DHA) were marked discontinued because the subjects met the study formula intake criteria for only 27 days. These subjects are counted completed here because subjects at other sites with similar intakes were marked completed.
**Based on subjects who completed the Study Formula phase. During the Term Formula phase, subjects were fed marketed formula. Switching to a different marketed formula did not result in termination from the Term Formula phase.

[0163]

TABLE 3
Weight Growth Rate During Study Formula Phase
		Least Square	Standard		Comparison	Study	Gender	Gender-by-Regimen
Regimen	n	Mean	Error	Comparison	p-value*	p-value	p-value	p-value
Control	60	30.7	1.1	Control vs DHA	0.967	0.00	0.17	0.87
DHA	65	33.3	1.1	Control vs	0.998
				DHA + ARA
DHA +	66	34.7	1.1
ARA
*One-sided test of the null hypothesis: Test Mean >= Control MeaN

[0164]

TABLE 4
Weight at 40, 48, and 57 Weeks Post-Conceptual Age
Weeks
Post-Conceptual			Least Square	Standard		Comparison	Study	Gender	Gender-by-Regimen
Age	Regimen	n	Mean	Error	Comparison	p-value*	p-value	p-value	p-value
40	Control	52	3075.3	67.9	Control vs DHA	0.388	0.59	0.45	1.00
	DMA	54	3051.4	66.8	ControL vs DHA + ARA	0.931
	DHA + ARA	59	3198.2	62.9	HM vs DHA	0.000
	HM	90	3437.7	60.6	HM vs DHA + ARA	0.001
					HM vs Control	0.000
48	Control	53	4711.0	94.6	Control vs DHA	0.360	0.58	0.13	0.29
	DMA	51	4663.8	97.3	Control vs DHA + ARA	0.995
	DHA + ARA	57	5039.1	93.0	HM vs DHA	0.000
	HM	81	5181.5	85.9	HM vs DHA + ARA	0.114
					HM vs Control	0.000
57	Control	47	6045.4	139.5	Control vs DHA	0.371	0.58	0.29	0.33
	DHA	49	5987.2	137.6	Control vs DHA + ARA	0.940
	DHA + ARA	55	6312.9	127.9	HM vs DHA	0.005
	HM	76	6405.0	126.7	HM vs DHA + ARA	0.278
					HM vs Control	0.014
*One-sided test of the null hypothesis: Test Mean >= Control Mean

[0165]

TABLE 5
Post-hoc Analysis of Weight
		Two-sided
Time	Comparison	p-value
Weight Gain During Study	C vs. DHA	0.067
Formula Phase	C vs. DHA + ARA	0.004
	DHA vs. DHA + ARA	0.30
Weight at 40 Weeks pca	C vs. DHA	0.78
	C vs. DHA + ARA	0.14
	DHA vs. DHA + ARA	0.074
	HM vs. DHA	<0.001
	HM vs. DHA + ARA	0.002
	HM vs. C	<0.001
Weight at 48 Weeks pca	C vs. DHA	0.72
	C vs. DHA + ARA	0.011
	DHA vs. DHA + ARA	0.004
	HM vs. DHA	<0.001
	HM vs. DHA + ARA	0.23
	HM vs. C	<0.001
Weight at 57 Weeks pca	C vs. DHA	0.74
	C vs. DHA + ARA	0.12
	DHA vs. DHA + ARA	0.057
	HM vs. DNA	0.010
	HM vs. DHA + ARA	0.56
	HM vs. C	0.028

[0166]

TABLE 6
Length at 40, 48, and 57 Weeks Post-Conceptual Age
Weeks										Gender-by-
Post-Conceptual			Least Square	Standard	Regimen	Pairwise	Pairwise	Study	Gender	Regimen
Age	Regimen	n	Mean	Error	p-value	Comparison	p-value	p-value	p-value	p-value
40	Control	52	48.4	0.4	0.000	Control vs DHA	0.242	0.03	0.88	0.63
	DHA	54	47.8	0.4		Control vs DHA + ARA	0.233
	DHA + ARA	58	49.0	0.4		HM vs DHA	0.000
	HM	89	50.6	0.4		HM vs DSA + ARA	0.000
						Control vs HM	0.000
						DHA vs DHA + ARA	0.017
48	Control	53	54.7	0.3	0.000	Control vs DHA	0.824	0.00	0.14	0.52
	DHA	52	54.6	0.3		Control vs DSA + ARA	0.079
	DHA + ARA	57	55.5	0.3		HM vs DHA	0.000
	HM	81	57.4	0.3		HM vs DHA + ARA	0.000
						Control vs HM	0.000
						DHA vs DHA + ARA	0.050
57	Control	47	60.7	0.4	0.000	Control vs DHA	0.615	0.00	0.02	0.84
	DHA	49	60.5	0.4		Control vs DHA + ARA	0.236
	DHA + ARA	54	61.3	0.3		HM vs DHA	0.000
	HM	76	62.4	0.3		HM vs DHA + ARA	0.006
						Control vs HM	0.000
						DHA vs GHA + ARA	0.087

[0167]

TABLE 7
Head Circumference at 40, 48, and 57 Weeks Post-Conceptual Age
Weeks										Gender-by-
Post-Conceptual			Least Square	Standard	Regimen	Pairwise	Pairwise	Study	Gender	Regimen
Age	Regimen	n	Mean	Error	p-value	Comparison	p-value	p-value	p-value	p-value
40	Control	51	35.4	0.2	0.000	Control vs DHA	0.931	0.91	0.00	0.38
	DHA	53	35.4	0.2		Control vs DHA + ARA	0.900
	DHA + ARA	58	35.5	0.2		HM vs DHA	0.000
	HM	85	34.5	0.2		HM vs DHA + ARA	0.000
						Control vs HM	0.000
						DHA vs DHA + ARA	0.829
48	Control	52	39.1	0.2	0.983			0.81	0.00	1.00
	DHA	51	39.0	0.2
	DHA + ARA	56	39.0	0.2
	HM	81	39.0	0.1
57	Control	47	41.9	0.2	0.689			0.64	0.00	0.85
	DHA	49	41.6	0.2
	DHA + ARA	53	41.7	0.2
	HM	76	41.7	0.2

[0168]

TABLE 8
Visual Acuity at 48 and 57 Weeks Post-Conceptual Age
Weeks			Geometric	Least Square	Standard
Post-Conceptual			mean	Mean	Error	Regimen	Pairwise	Pairwise	Study
Age	Regimen	n	(cycles/deg)	(log base2 cycles/deg)	(octaves)	p-value	Comparison	p-value	p-value
48	ControL	51	1.72	0.78	0.10	0.950			0.000
	DHA	50	1.80	0.85	0.10
	DHA + ARA	57	1.72	0.78	0.09
	HM	81	1.75	0.81	0.09
57	Control	46	3.47	1.79	0.08	0.004	Control vs DHA	0.697	0.000
	DHA	47	3.37	1.75	0.08		Control vs DHA + ARA	0.071
	DHA + ARA	55	3.06	1.61	0.07		HM vs DHA	0.042
	HM	77	3.85	1.94	0.07		HM vs DHA + ARA	0.000
							Control vs HM	0.113
							DMA vs DHA + ARA	0.158

[0169]

TABLE 9
Red Blood Cell Phosphatidylcholine Fatty Acids
	Fatty			Arithmetic	Standard		Regimen	Pairwise	Pairwise
Time	Acid	Regimen	n	Mean	Error	Median	p-value	Comparison	p-value
Study Form Initiation	12:0	Control	52	0.081	0.019	0.036	0.762
		DHA	58	0.066	0.013	0.030
		DHA + ARA	61	0.057	0.009	0.031
Study Form Initiation	14:0	Control	52	0.623	0.036	0.599	0.559
		DHA	58	0.663	0.031	0.686
		DHA + ARA	61	0.661	0.031	0.656
Study Form Initiation	14:1	Control	52	0.045	0.009	0.021	0.165
		DHA	58	0.026	0.005	0.016
		DHA + ARA	61	0.035	0.006	0.018
Study Form Initiation	16:0	Control	52	36.706	0.540	36.594	0.884
		DHA	58	36.363	0.462	35.578
		DHA + ARA	61	36.877	0.445	35.987
Study Form Initiation	16:1	Control	52	0.940	0.049	0.845	0.441
		DHA	58	0.981	0.050	0.976
		DHA + ARA	61	1.094	0.064	0.931
Study Form Initiation	18:0	Control	52	11.660	0.243	11.468	0.243
		DHA	58	11.402	0.238	11.201
		DHA + ARA	61	11.016	0.192	11.174
Study Form Initiation	18:1	Control	52	17.053	0.298	17.308	0.679
		DHA	58	17.219	0.391	16.935
		DHA + ARA	61	17.256	0.271	16.988
Study Form Initiation	18:2	Control	52	18.614	0.525	18.952	0.830
		DHA	58	18.631	0.505	19.603
		DHA + ARA	61	18.573	0.466	18.824
Study Form Initiation	18:3n6	Control	52	0.120	0.008	0.116	0.034	Control vs DHA	0.196
		DHA	58	0.136	0.008	0.130		Control vs DHA + ARA	0.010
		DHA + ARA	61	0.150	0.009	0.134		DHA vs DHA + ARA	0.176
Study Form Initiation	20:0	Control	52	0.399	0.050	0.224	0.647
		DHA	58	0.337	0.035	0.236
		DHA + ARA	61	0.310	0.037	0.188
Study Form Initiation	18:3n3	Control	52	0.315	0.033	0.246	0.234
		DHA	58	0.257	0.014	0.246
		DHA + ARA	61	0.233	0.010	0.216
Study Form Initiation	20:1	Control	52	0.287	0.020	0.262	0.723
		DHA	58	0.287	0.015	0.281
		DHA + ARA	61	0.268	0.011	0.269
Study Form Initiation	18:4	Control	52	0.017	0.003	0.000	0.290
		DHA	58	0.025	0.004	0.017
		DHA + ARA	61	0.017	0.003	0.008
Study Form Initiation	20:2n6	Control	52	0.632	0.025	0.632	0.673
		DHA	58	0.628	0.025	0.640
		DHA + ARA	61	0.602	0.021	0.614
Study Form Initiation	20:3n6	Control	52	2.144	0.098	2.096	0.507
		DHA	58	2.208	0.080	2.296
		DHA + ARA	61	2.218	0.074	2.135
Study Form Initiation	20:4n6	Control	52	7.657	0.262	8.124	0.819
		DHA	58	8.164	0.347	7.876
		DHA + ARA	61	8.090	0.310	8.207
Study Form Initiation	22:1	Control	52	0.106	0.010	0.105	0.155
		DHA	58	0.127	0.010	0.130
		DHA + ARA	61	0.126	0.010	0.139
Study Form Initiation	20:5n3	Control	52	0.351	0.057	0.298	0.911
		DHA	58	0.322	0.015	0.302
		DHA + ARA	61	0.321	0.015	0.329
Study Form Initiation	22:4n6	Control	52	0.578	0.144	0.423	0.331
		DHA	58	0.493	0.030	0.481
		DHA + ARA	61	0.443	0.021	0.425
Study Form Initiation	24:1	Control	52	0.205	0.054	0.075	0.665
		DHA	58	0.115	0.019	0.084
		DHA + ARA	61	0.180	0.056	0.096
Study Form Initiation	22:5n6	Control	52	0.266	0.020	0.232	0.923
		DHA	58	0.259	0.017	0.239
		DHA + ARA	61	0.265	0.018	0.256
Study Form Initiation	22:4n3	Control	52	0.000	0.000	0.000	0.199
		DHA	58	0.001	0.001	0.000
		DHA + ARA	61	0.002	0.001	0.000
Study Form Initiation	22:5n3	Control	52	0.213	0.019	0.203	0.885
		DHA	58	0.215	0.013	0.195
		DHA + ARA	61	0.203	0.010	0.193
Study Form Initiation	22:6n3	Control	52	0.984	0.051	1.000	0.858
		DHA	58	1.075	0.053	1.034
		DHA + ARA	61	1.006	0.050	0.970
Study Form Termination	12:0	Control	53	0.100	0.026	0.035	0.843
		DHA	56	0.111	0.042	0.031
		DHA + ARA	59	0.064	0.012	0.032
Study Form Termination	14:0	Control	53	0.808	0.039	0.806	0.834
		DHA	56	0.781	0.035	0.783
		DHA + ARA	59	0.755	0.036	0.758
Study Form Termination	14:1	Control	53	0.047	0.008	0.033	0.155
		DHA	56	0.036	0.009	0.015
		DHA + ARA	59	0.036	0.007	0.018
Study Form Termination	16:0	Control	53	35.837	0.512	34.798	0.767
		DHA	56	35.560	0.595	34.841
		DHA + ARA	59	35.069	0.584	33.890
Study Form Termination	16:1	Control	53	0.566	0.026	0.526	0.013	Control vs DHA	0.118
		DHA	56	0.594	0.042	0.475		Control vs DHA + ARA	0.003
		DHA + ARA	59	0.526	0.029	0.472		DHA vs DHA + ARA	0.152
Study Form Termination	18:0	Control	53	13.972	0.261	14.197	0.886
		DHA	56	14.065	0.237	13.867
		DHA + ARA	59	14.341	0.253	14.108
Study Form Termination	18:1	Control	53	14.456	0.277	14.291	0.686
		DHA	56	14.116	0.272	13.998
		DHA + ARA	59	14.344	0.380	14.218
Study Form Termination	18:2	Control	53	21.673	0.340	21.506	0.001	Control vs DHA	0.600
		DHA	56	22.045	0.457	22.517		Control vs DHA + ARA	0.005
		DHA + ARA	59	19.899	0.337	20.662		DHA vs DHA + ARA	0.001
Study Form Termination	18:3n6	Control	53	0.080	0.006	0.074	0.527
		DHA	56	0.088	0.009	0.076
		DHA + ARA	59	0.087	0.013	0.066
Study Form Termination	20:0	Control	53	0.504	0.050	0.392	0.424
		DHA	56	0.472	0.053	0.281
		DHA + ARA	59	0.430	0.049	0.251
Study Form Termination	18:3n3	Control	53	0.321	0.020	0.283	0.031	Control vs DHA	0.503
		DHA	56	0.335	0.030	0.285		Control vs DHA + ARA	0.068
		DHA + ARA	59	0.273	0.009	0.256		DHA vs DHA + ARA	0.011
Study Form Termination	20:1	Control	53	0.318	0.014	0.302	0.149
		DHA	56	0.300	0.013	0.283
		DHA + ARA	59	0.307	0.013	0.283
Study Form Termination	18:4	Control	53	0.022	0.004	0.015	0.672
		DHA	56	0.022	0.003	0.018
		DHA + ARA	59	0.014	0.002	0.008
Study Form Termination	20:2n6	Control	53	0.893	0.026	0.910	0.051
		DHA	56	0.880	0.023	0.873
		DHA + ARA	59	0.824	0.022	0.821
Study Form Termination	20:3n6	Control	53	2.032	0.073	2.091	0.208
		DHA	56	2.017	0.070	2.043
		DHA + ARA	59	1.908	0.064	1.904
Study Form Termination	20:4n6	Control	53	6.046	0.240	6.029	0.000	Control vs DHA	0.097
		DHA	56	5.774	0.220	5.892		Control vs DHA + ARA	0.000
		DHA + ARA	59	8.465	0.255	8.891		DHA vs DHA + ARA	0.000
Study Form Termination	22:1	Control	53	0.117	0.010	0.125	0.946
		DHA	56	0.110	0.009	0.114
		DHA + ARA	59	0.115	0.011	0.104
Study Form Termination	20:5n3	Control	53	0.214	0.022	0.189	0.000	Control vs DHA	0.004
		DHA	56	0.246	0.012	0.233		Control vs DHA + ARA	0.108
		DHA + ARA	59	0.186	0.014	0.169		DHA vs DHA + ARA	0.000
Study Form Termination	22:4n6	Control	53	0.484	0.048	0.390	0.093
		DHA	56	0.489	0.061	0.426
		DHA + ARA	59	0.496	0.027	0.487
Study Form Termination	24:1	Control	53	0.127	0.039	0.062	0.303
		DHA	56	0.143	0.036	0.086
		DHA + ARA	59	0.177	0.040	0.089
Study Form Termination	22:5n6	Control	53	0.181	0.013	0.163	0.006	Control vs DHA	0.005
		DHA	56	0.145	0.011	0.133		Control vs DHA + ARA	0.895
		DHA + ARA	59	0.172	0.009	0.165		DHA vs DHA + ARA	0.006
Study Form Termination	22:4n3	Control	53	0.001	0.001	0.000	0.359
		DHA	56	0.001	0.001	0.000
		DHA + ARA	59	0.003	0.002	0.000
Study Form Termination	22:5n3	Control	53	0.306	0.019	0.289	0.221
		DHA	56	0.293	0.026	0.260
		DHA + ARA	59	0.265	0.013	0.255
Study Form Termination	22:6n3	Control	53	0.895	0.072	0.812	0.000	Control vs DHA	0.000
		DHA	56	1.380	0.063	1.352		Control vs DHA + ARA	0.000
		DHA + ARA	59	1.244	0.049	1.259		DHA vs DHA + ARA	0.141
48 Weeks PCA	12:0	Control	37	0.032	0.005	0.026	0.729
		DHA	32	0.028	0.006	0.016
		DHA + ARA	38	0.026	0.004	0.021
		HM	56	0.059	0.016	0.020
48 Weeks PCA	14:0	Control	37	0.402	0.039	0.331	0.943
		DHA	32	0.353	0.032	0.324
		DHA + ARA	38	0.353	0.024	0.328
		HM	56	0.381	0.026	0.335
48 Weeks PCA	14:1	Control	37	0.025	0.006	0.013	0.448
		DHA	32	0.026	0.007	0.011
		DHA + ARA	38	0.026	0.006	0.015
		HM	56	0.024	0.003	0.020
48 Weeks PCA	16:0	Control	37	34.627	0.577	34.319	0.000	Control vs DHA	0.527
		DHA	32	35.272	0.689	34.473		Control vs DHA + ARA	0.593
		DHA + ARA	38	34.802	0.506	34.165		HM vs DHA	0.000
		HM	56	33.037	0.506	32.228		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.906
48 Weeks PCA	16:1	Control	37	0.435	0.043	0.338	0.000	Control vs DHA	0.524
		DHA	32	0.380	0.023	0.352		Control vs DHA + ARA	0.467
		DHA + ARA	38	0.395	0.024	0.368		HM vs DHA	0.000
		HM	56	0.507	0.020	0.473		HM vs DHA + ARA	0.006
								Control vs HM	0.000
								DHA vs DHA + ARA	0.183
48 Weeks PCA	18:0	Control	37	13.016	0.313	12.759	0.000	Control vs DHA	0.760
		DHA	32	12.944	0.249	12.786		Control vs DHA + ARA	0.589
		DHA + ARA	38	12.804	0.235	12.793		HM vs DHA	0.000
		HM	56	14.583	0.287	14.729		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.661
48 Weeks PCA	18:1	Control	37	17.894	0.453	18.636	0.256
		DHA	32	17.766	0.429	18.492
		DHA + ARA	38	17.850	0.289	18.227
		HM	56	18.662	0.305	18.727
48 Weeks PCA	18:2	Control	37	23.469	0.518	23.552	0.000	Control vs DHA	0.840
		DHA	32	23.538	0.516	23.717		Control vs DHA + ARA	0.527
		DHA + ARA	38	23.738	0.422	23.839		HM vs DHA	0.000
		HM	56	18.650	0.344	18.482		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.685
48 Weeks PCA	18:3n6	Control	37	0.071	0.008	0.061	0.002	Control vs DHA	0.950
		DHA	32	0.069	0.005	0.067		Control vs DHA + ARA	0.774
		DHA + ARA	38	0.069	0.006	0.062		HM vs DHA	0.004
		HM	56	0.042	0.004	0.039		HM vs DHA + ARA	0.001
								Control vs HM	0.003
								DHA vs DHA + ARA	0.831
48 Weeks PCA	20:0	Control	37	0.348	0.075	0.197	0.785
		DHA	32	0.339	0.061	0.206
		DHA + ARA	38	0.304	0.061	0.172
		HM	56	0.409	0.044	0.215
48 Weeks PCA	18:3n3	Control	37	0.222	0.019	0.182	0.001	Control vs DHA	0.812
		DHA	32	0.211	0.015	0.182		Control vs DHA + ARA	0.918
		DHA + ARA	38	0.203	0.010	0.190		HM vs DHA	0.001
		HM	56	0.182	0.022	0.120		HM vs DHA + ARA	0.002
								Control vs HM	0.001
								DHA vs DHA + ARA	0.737
48 Weeks PCA	20:1	Control	37	0.418	0.019	0.420	0.000	Control vs DHA	0.579
		DHA	32	0.406	0.025	0.435		Control vs DHA + ARA	0.588
		DHA + ARA	38	0.382	0.016	0.375		HM vs DHA	0.001
		HM	56	0.311	0.014	0.309		HM vs DHA + ARA	0.001
								Control vs HM	0.000
								DHA vs DHA + ARA	0.974
48 Weeks PCA	18:4	Control	37	0.018	0.005	0.000	0.010	Control vs DHA	0.822
		DHA	32	0.016	0.004	0.000		Control vs DHA + ARA	0.161
		DHA + ARA	38	0.007	0.002	0.000		HM vs DHA	0.039
		HM	56	0.024	0.004	0.015		HM vs DHA + ARA	0.001
								Control vs HM	0.054
								DHA vs DHA + ARA	0.262
48 Weeks PCA	20:2n6	Control	37	0.543	0.023	0.537	0.629
		DHA	32	0.557	0.032	0.543
		DHA + ARA	38	0.636	0.053	0.550
		HM	56	0.560	0.014	0.531
48 Weeks PCA	20:3n6	Control	37	1.709	0.086	1.741	0.000	Control vs DHA	0.610
		DHA	32	1.702	0.073	1.684		Control vs DHA + ARA	0.735
		DHA + ARA	38	1.844	0.090	1.717		HM vs DHA	0.000
		HM	56	2.265	0.086	2.166		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.405
48 Weeks PCA	20:4n6	Control	37	4.738	0.255	4.736	0.000	Control vs DHA	0.508
		DHA	32	4.475	0.196	4.499		Control vs DHA + ARA	0.505
		DHA + ARA	38	4.550	0.185	4.746		HM vs DHA	0.000
		HM	56	7.408	0.250	7.666		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.672
48 Weeks PCA	22:1	Control	37	0.166	0.036	0.131	0.664
		DHA	32	0.116	0.014	0.118
		DHA + ARA	38	0.131	0.024	0.105
		HM	56	0.160	0.030	0.104
48 Weeks PCA	20:5n3	Control	37	0.102	0.015	0.077	0.000	Control vs DHA	0.633
		DHA	32	0.084	0.006	0.083		Control vs DHA + ARA	0.086
		DHA + ARA	38	0.099	0.009	0.078		HM vs DHA	0.000
		HM	56	0.138	0.009	0.123		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.239
48 Weeks PCA	22:4n6	Control	37	0.426	0.059	0.373	0.244
		DHA	32	0.382	0.029	0.417
		DHA + ARA	38	0.440	0.054	0.384
		HM	56	0.406	0.022	0.377
48 Weeks PCA	24:1	Control	37	0.247	0.070	0.112	0.000	Control vs DHA	0.337
		DHA	32	0.210	0.062	0.116		Control vs DHA + ARA	0.247
		DHA + ARA	38	0.179	0.055	0.108		HM vs DHA	0.000
		HM	56	0.115	0.020	0.079		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.578
48 Weeks PCA	22:5n6	Control	37	0.210	0.016	0.212	0.000	Control vs DHA	0.505
		DHA	32	0.189	0.012	0.186		Control vs DHA + ARA	0.647
		DHA + ARA	38	0.231	0.022	0.198		HM vs DHA	0.000
		HM	56	0.264	0.016	0.265		HM vs DHA + ARA	0.001
								Control vs HM	0.000
								DHA vs DHA + ARA	0.270
48 Weeks PCA	22:4n3	Control	37	0.000	0.000	0.000	1.000
		DHA	32	0.000	0.000	0.000
		DHA + ARA	38	0.000	0.000	0.000
		HM	56	0.000	0.000	0.000
48 Weeks PCA	22:5n3	Control	37	0.286	0.029	0.260	0.000	Control vs DHA	0.598
		DHA	32	0.253	0.017	0.251		Control vs DHA + ARA	0.759
		DHA + ARA	38	0.268	0.026	0.256		HM vs DHA	0.000
		HM	56	0.339	0.018	0.314		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.817
48 Weeks PCA	22:6n3	Control	37	0.595	0.047	0.569	0.000	Control vs DHA	0.111
		DHA	32	0.685	0.048	0.676		Control vs DHA + ARA	0.052
		DHA + ARA	38	0.662	0.043	0.663		HM vs DHA	0.000
		HM	56	1.475	0.081	1.333		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.776

[0170]

TABLE 10
Red Blood Cell Phosphatidylethanolamine Fatty Acids
	Fatty			Arithmetic	Standard		Regimen	Pairwise	Pairwise
Time	Acid	Regimen	n	Mean	Error	Median	p-value	Comparison	p-value
Study Form Initiation	12:0	Control	52	0.069	0.015	0.022	0.546			5
		DHA	57	0.075	0.013	0.033
		DHA + ARA	61	0.063	0.010	0.039
Study Form Initiation	14:0	Control	52	0.307	0.038	0.220	0.792
		DHA	57	0.278	0.025	0.206
		DHA + ARA	61	0.277	0.021	0.246
Study Form Initiation	14:1	Control	52	0.080	0.015	0.032	0.181
		DHA	57	0.061	0.012	0.028
		DHA + ARA	61	0.062	0.009	0.050
Study Form Initiation	16:0	Control	52	20.021	0.736	17.945	0.967
		DHA	57	19.847	0.622	19.295
		DHA + ARA	61	19.796	0.451	19.035
Study Form Initiation	16:1	Control	52	0.731	0.035	0.698	0.337
		DHA	57	0.769	0.034	0.746
		DHA + ARA	61	0.836	0.035	0.837
Study Form Initiation	18:0	Control	52	8.857	0.329	8.469	0.142
		DHA	57	8.434	0.227	8.308
		DHA + ARA	61	8.201	0.215	7.904
Study Form Initiation	18:1	Control	52	16.450	0.301	16.698	0.412
		DHA	57	16.208	0.326	16.308
		DHA + ARA	61	16.415	0.375	16.001
Study Form Initiation	18:2	Control	52	6.615	0.253	6.682	0.773
		DHA	57	6.336	0.280	6.346
		DHA + ARA	61	6.175	0.294	5.682
Study Form Initiation	18:3n6	Control	52	0.165	0.018	0.145	0.040	Control vs DHA	0.373
		DHA	57	0.190	0.019	0.152		Control vs DHA + ARA	0.013
		DHA + ARA	61	0.192	0.016	0.169		DHA vs DHA + ARA	0.101
Study Form Initiation	20:0	Control	52	0.372	0.043	0.291	0.151
		DHA	57	0.314	0.030	0.244
		DHA + ARA	61	0.259	0.024	0.186
Study Form Initiation	18:3n3	Control	52	0.305	0.023	0.261	0.641
		DHA	57	0.269	0.018	0.249
		DHA + ARA	61	0.257	0.016	0.225
Study Form Initiation	20:1	Control	52	0.573	0.036	0.517	0.395
		DHA	57	0.615	0.034	0.555
		DHA + ARA	61	0.571	0.027	0.544
Study Form Initiation	18:4	Control	52	0.025	0.005	0.000	0.371
		DHA	57	0.031	0.004	0.025
		DHA + ARA	61	0.030	0.007	0.021
Study Form Initiation	20:2n6	Control	52	0.479	0.023	0.460	0.706
		DHA	57	0.463	0.024	0.437
		DHA + ARA	61	0.443	0.028	0.427
Study Form Initiation	20:3n6	Control	52	1.843	0.072	1.829	0.099
		DHA	57	1.965	0.077	1.820
		DHA + ARA	61	1.973	0.064	1.911
Study Form Initiation	20:4n6	Control	52	25.817	0.618	26.820	0.353
		DHA	57	26.475	0.611	27.376
		DHA + ARA	61	26.747	0.645	27.708
Study Form Initiation	22:1	Control	52	0.150	0.017	0.138	0.572
		DHA	57	0.167	0.015	0.151
		DHA + ARA	61	0.168	0.017	0.141
Study Form Initiation	20:5n3	Control	52	0.378	0.024	0.357	0.997
		DHA	57	0.384	0.024	0.370
		DHA + ARA	61	0.366	0.022	0.335
Study Form Initiation	22:4n6	Control	52	7.290	0.182	7.402	0.875
		DHA	57	7.431	0.186	7.638
		DHA + ARA	61	7.456	0.167	7.270
Study Form Initiation	24:1	Control	52	0.100	0.028	0.041	0.068
		DHA	57	0.059	0.009	0.031
		DHA + ARA	61	0.072	0.010	0.047
Study Form Initiation	22:5n6	Control	52	1.757	0.083	1.782	0.555
		DHA	57	1.809	0.070	1.857
		DHA + ARA	61	1.851	0.075	1.775
Study Form Initiation	22:4n3	Control	52	0.001	0.001	0.000	0.257
		DHA	57	0.001	0.001	0.000
		DHA + ARA	61	0.005	0.002	0.000
Study Form Initiation	22:5n3	Control	52	1.496	0.109	1.308	0.195
		DHA	57	1.375	0.109	0.988
		DHA + ARA	61	1.380	0.097	1.041
Study Form Initiation	22:6n3	Control	52	6.119	0.200	6.381	0.375
		DHA	57	6.444	0.185	6.468
		DHA + ARA	61	6.407	0.220	6.579
Study Form Termination	12:0	Control	53	0.093	0.015	0.033	0.630
		DHA	55	0.093	0.019	0.036
		DHA + ARA	58	0.067	0.012	0.035
Study Form Termination	14:0	Control	53	0.360	0.031	0.279	0.782
		DHA	55	0.380	0.039	0.265
		DHA + ARA	58	0.348	0.030	0.256
Study Form Termination	14:1	Control	53	0.086	0.020	0.041	0.592
		DHA	55	0.066	0.013	0.000
		DHA + ARA	58	0.066	0.011	0.043
Study Form Termination	16:0	Control	53	19.326	0.673	17.617	0.560
		DHA	55	19.062	0.614	17.556
		DHA + ARA	58	18.357	0.467	17.568
Study Form Termination	16:1	Control	53	0.511	0.034	0.476	0.604
		DHA	55	0.579	0.045	0.509
		DHA + ARA	58	0.618	0.049	0.555
Study Form Termination	18:0	Control	53	9.614	0.266	9.406	0.024	Control vs DHA	0.130
		DHA	55	9.173	0.208	8.818		Control vs DHA + ARA	0.006
		DHA + ARA	58	8.961	0.242	8.697		DHA vs DHA + ARA	0.219
Study Form Termination	18:1	Control	53	14.763	0.437	14.695	0.333
		DHA	55	15.177	0.299	14.927
		DHA + ARA	58	14.814	0.330	14.499
Study Form Termination	18:2	Control	53	9.405	0.192	9.359	0.000	Control vs DHA	0.908
		DHA	55	9.180	0.207	9.188		Control vs DHA + ARA	0.000
		DHA + ARA	58	7.756	0.141	7.586		DHA vs DHA + ARA	0.000
Study Form Termination	18:3n6	Control	53	0.169	0.012	0.163	0.160
		DHA	55	0.187	0.017	0.157
		DHA + ARA	58	0.198	0.018	0.161
Study Form Termination	20:0	Control	53	0.404	0.044	0.278	0.146
		DHA	55	0.336	0.037	0.208
		DHA + ARA	58	0.288	0.029	0.208
Study Form Termination	18:3n3	Control	53	0.382	0.017	0.364	0.134
		DHA	55	0.368	0.016	0.354
		DHA + ARA	58	0.329	0.015	0.305
Study Form Termination	20:1	Control	53	0.553	0.029	0.526	0.164
		DHA	55	0.579	0.028	0.537
		DHA + ARA	58	0.507	0.025	0.483
Study Form Termination	18:4	Control	53	0.042	0.010	0.018	0.108
		DHA	55	0.026	0.005	0.019
		DHA + ARA	58	0.022	0.004	0.000
Study Form Termination	20:2n6	Control	53	0.754	0.029	0.765	0.065
		DHA	55	0.774	0.030	0.750
		DHA + ARA	58	0.654	0.026	0.663
Study Form Termination	20:3n6	Control	53	2.253	0.111	2.073	0.203
		DHA	55	2.295	0.094	2.206
		DHA + ARA	58	2.066	0.073	1.992
Study Form Termination	20:4n6	Control	53	24.279	0.527	25.132	0.000	Control vs DHA	0.119
		DHA	55	23.464	0.520	24.038		Control vs DHA + ARA	0.000
		DHA + ARA	58	26.760	0.437	27.372		DHA vs DHA + ARA	0.000
Study Form Termination	22:1	Control	53	0.149	0.019	0.122	0.229
		DHA	55	0.176	0.016	0.169
		DHA + ARA	58	0.146	0.012	0.130
Study Form Termination	20:5n3	Control	53	0.519	0.020	0.493	0.000	Control vs DHA	0.286
		DHA	55	0.563	0.025	0.575		Control vs DHA + ARA	0.000
		DHA + ARA	58	0.411	0.015	0.415		DHA vs DHA + ARA	0.000
Study Form Termination	22:4n6	Control	53	7.309	0.208	7.656	0.007	Control vs DHA	0.025
		DHA	55	7.135	0.154	6.885		Control vs DHA + ARA	0.461
		DHA + ARA	58	7.592	0.155	7.635		DHA vs DHA + ARA	0.002
Study Form Termination	24:1	Control	53	0.092	0.023	0.038	0.294
		DHA	55	0.056	0.009	0.042
		DHA + ARA	58	0.062	0.008	0.041
Study Form Termination	22:5n6	Control	53	1.444	0.064	1.423	0.010	Control vs DHA	0.003
		DHA	55	1.231	0.034	1.213		Control vs DHA + ARA	0.255
		DHA + ARA	58	1.347	0.040	1.330		DHA vs DHA + ARA	0.050
Study Form Termination	22:4n3	Control	53	0.000	0.000	0.000	0.137
		DHA	55	0.004	0.002	0.000
		DHA + ARA	58	0.004	0.002	0.000
Study Form Termination	22:5n3	Control	53	2.694	0.110	2.839	0.003	Control vs DHA	0.004
		DHA	55	2.334	0.091	2.400		Control vs DHA + ARA	0.002
		DHA + ARA	58	2.237	0.069	2.269		DHA vs DHA + ARA	0.943
Study Form Termination	22:6n3	Control	53	4.798	0.151	4.815	0.000	Control vs DHA	0.000
		DHA	55	6.762	0.183	7.043		Control vs DHA + ARA	0.000
		DHA + ARA	58	6.389	0.150	6.498		DHA vs DHA + ARA	0.027
48 Weeks PCA	12:0	Control	37	0.053	0.019	0.024	0.587
		DHA	32	0.054	0.016	0.019
		DHA + ARA	38	0.047	0.014	0.018
		HM	56	0.045	0.011	0.023
48 Weeks PCA	14:0	Control	37	0.243	0.030	0.169	0.598
		DHA	32	0.251	0.041	0.162
		DHA + ARA	38	0.235	0.025	0.188
		HM	56	0.230	0.016	0.210
48 Weeks PCA	14:1	Control	37	0.080	0.017	0.037	0.092
		DHA	32	0.055	0.017	0.000
		DHA + ARA	38	0.078	0.019	0.044
		HM	56	0.053	0.011	0.021
48 Weeks PCA	16:0	Control	37	17.319	0.595	16.314	0.177
		DHA	32	17.101	0.729	15.692
		DHA + ARA	38	17.225	0.538	16.997
		HM	56	18.138	0.395	17.607
48 Weeks PCA	16:1	Control	37	0.440	0.050	0.349	0.000	Control vs DHA	0.601
		DHA	32	0.390	0.035	0.336		Control vs DHA + ARA	0.524
		DHA + ARA	38	0.390	0.022	0.376		HM vs DHA	0.000
		HM	56	0.596	0.027	0.562		HM vs DHA + ARA	0.000
								Control vs HM	0.001
								DHA vs DHA + ARA	0.928
48 Weeks PCA	18:0	Control	37	7.935	0.327	7.174	0.000	Control vs DHA	0.347
		DHA	32	7.962	0.293	7.552		Control vs DHA + ARA	0.483
		DHA + ARA	38	7.443	0.270	7.173		HM vs DHA	0.020
		HM	56	8.754	0.230	8.409		HM vs DHA + ARA	0.000
								Control vs HM	0.001
								DHA vs DHA + ARA	0.108
48 Weeks PCA	18:1	Control	37	19.438	0.368	19.410	0.038	Control vs DHA	0.401
		DHA	32	19.066	0.421	19.534		Control vs DHA + ARA	0.234
		DHA + ARA	38	19.302	0.332	19.433		HM vs DHA	0.067
		HM	56	18.469	0.278	18.141		HM vs DHA + ARA	0.118
								Control vs HM	0.005
								DHA vs DHA + ARA	0.758
48 Weeks PCA	18:2	Control	37	9.328	0.261	9.267	0.000	Control vs DHA	0.024
		DHA	32	8.867	0.210	8.696		Control vs DHA + ARA	0.187
		DHA + ARA	38	9.257	0.216	8.840		HM vs DHA	0.000
		HM	56	6.291	0.193	6.027		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.318
48 Weeks PCA	18:3n6	Control	37	0.198	0.020	0.182	0.050	Control vs DHA	0.879
		DHA	32	0.219	0.031	0.171		Control vs DHA + ARA	0.590
		DHA + ARA	38	0.158	0.021	0.158		HM vs DHA	0.029
		HM	56	0.129	0.012	0.112		HM vs DHA + ARA	0.061
								Control vs HM	0.014
								DHA vs DHA + ARA	0.714
48 Weeks PCA	20:0	Control	37	0.263	0.058	0.146	0.728
		DHA	32	0.262	0.042	0.145
		DHA + ARA	38	0.212	0.037	0.125
		HM	56	0.295	0.031	0.240
48 Weeks PCA	18:3n3	Control	37	0.291	0.025	0.225	0.001	Control vs DHA	0.559
		DHA	32	0.270	0.017	0.262		Control vs DHA + ARA	0.848
		DHA + ARA	38	0.265	0.015	0.245		HM vs DHA	0.008
		HM	56	0.226	0.020	0.169		HM vs DHA + ARA	0.002
								Control vs HM	0.001
								DHA vs DHA + ARA	0.689
48 Weeks PCA	20:1	Control	37	0.715	0.031	0.648	0.000	Control vs DHA	0.339
		DHA	32	0.772	0.032	0.782		Control vs DHA + ARA	0.512
		DHA + ARA	38	0.936	0.188	0.738		HM vs DHA	0.000
		HM	56	0.533	0.024	0.492		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.115
48 Weeks PCA	18:4	Control	37	0.017	0.005	0.003	0.057
		DHA	32	0.017	0.005	0.000
		DHA + ARA	38	0.023	0.006	0.000
		HM	56	0.027	0.004	0.019
48 Weeks PCA	20:2n6	Control	37	0.672	0.035	0.698	0.000	Control vs DHA	0.543
		DHA	32	0.668	0.026	0.684		Control vs DHA + ARA	0.532
		DHA + ARA	38	0.715	0.032	0.689		HM vs DHA	0.000
		HM	56	0.444	0.016	0.412		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.995
48 Weeks PCA	20:3n6	Control	37	2.138	0.099	1.999	0.012	Control vs DHA	0.896
		DHA	32	2.165	0.100	2.045		Control vs DHA + ARA	0.935
		DHA + ARA	38	2.172	0.114	2.132		HM vs DHA	0.015
		HM	56	1.715	0.053	1.637		HM vs DHA + ARA	0.006
								Control vs HM	0.007
								DHA vs DHA + ARA	0.835
48 Weeks PCA	20:4n6	Control	37	24.508	0.536	24.774	0.950
		DHA	32	24.428	0.491	25.206
		DHA + ARA	38	24.788	0.429	25.122
		HM	56	24.625	0.384	25.189
48 Weeks PCA	22:1	Control	37	0.168	0.016	0.172	0.121
		DHA	32	0.189	0.022	0.188
		DHA + ARA	38	0.154	0.022	0.133
		HM	56	0.148	0.013	0.134
48 Weeks PCA	20:5n3	Control	37	0.382	0.026	0.368	0.497
		DHA	32	0.369	0.015	0.377
		DHA + ARA	38	0.347	0.011	0.347
		HM	56	0.384	0.016	0.360
48 Weeks PCA	22:4n6	Control	37	8.580	0.267	8.761	0.001	Control vs DHA	0.612
		DHA	32	8.791	0.250	9.132		Control vs DHA + ARA	0.416
		DHA + ARA	38	8.576	0.188	8.472		HM vs DHA	0.000
		HM	56	7.727	0.203	7.618		HM vs DHA + ARA	0.013
								Control vs HM	0.001
								DHA vs DHA + ARA	0.199
48 Weeks PCA	24:1	Control	37	0.067	0.016	0.035	0.943
		DHA	32	0.049	0.009	0.034
		DHA + ARA	38	0.046	0.008	0.036
		HM	56	0.062	0.016	0.027
48 Weeks PCA	22:5n6	Control	37	1.401	0.066	1.411	0.000	Control vs DHA	0.977
		DHA	32	1.353	0.057	1.414		Control vs DHA + ARA	0.997
		DHA + ARA	38	1.364	0.054	1.359		HM vs DHA	0.000
		HM	56	1.883	0.056	1.889		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.975
48 Weeks PCA	22:4n3	Control	37	0.000	0.000	0.000	1.000
		DHA	32	0.000	0.000	0.000
		DHA + ARA	38	0.000	0.000	0.000
		HM	56	0.001	0.001	0.000
48 Weeks PCA	22:5n3	Control	37	2.567	0.092	2.681	0.000	Control vs DHA	0.884
		DHA	32	2.561	0.086	2.630		Control vs DHA + ARA	0.148
		DHA + ARA	38	2.436	0.066	2.443		HM vs DHA	0.000
		HM	56	1.942	0.065	1.978		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.213
48 Weeks PCA	22:6n3	Control	37	3.196	0.159	3.013	0.000	Control vs DHA	0.000
		DHA	32	4.143	0.177	4.079		Control vs DHA + ARA	0.000
		DHA + ARA	38	3.801	0.134	3.721		HM vs DHA	0.000
		HM	56	7.283	0.201	7.341		HM vs DHA + ARA	0.000
								Control vs HM	0.000
								DHA vs DHA + ARA	0.281

[0171]

TABLE 11
Preterm Infant Complications
	Regimen
			DHA +
	Control	DHA	ARA	p-value*
Retinopathy of
Prematurity Test Results
Absent	34 (76%)	44 (76%)	41 (79%)	0.91
I	8 (18%)	11 (19%)	6 (12%)
II	2 (4%)	2 (3%)	4 (8%)
III	1 (2%)	1 (2%)
Present, but not			1 (2%)
graded
Ultrasound Examination
for Intraventricular
Hemorrhage
None	47 (81%)	52 (84%)	49 (80%)	0.78
Stage 1	6 (10%)	9 (15%)	7 (11%)
Stage 2	3 (5%)		2 (3%)
Stage 3	1 (2%)		1 (2%)
Stage 4	1 (2%)		2 (3%)
Questionable		1 (2%)
Posthemorrhagic
Hydrocephalus
developed?
No	61 (98%)	65 (98%)	64 (97%)	1.00
Yes	1 (2%)	1 (2%)	2 (3%)
*The statistical test was based on a dichotomous response: present or absent.

[0172]

TABLE 12
Serious Adverse Events Reported During Study Formula Phase
	Regimen
			DHA +
Event	Control	DHA	ARA	p-value
Any Event	4 (6%)	3 (5%)	4 (6%)	0.93
Other Respiratory Conditions	2 (3%)	0	0	0.10
of Fetus and Newborn
Other Infection Specific to	1 (2%)	0	0	0.32
the Perinatal Period
Intraventricular Hemorrhage	0	0	1 (2%)	1.00
Other Specified Perinatal	0	1 (2%)	0	1.00
Disorders of Digestive System
Convulsions in Newborn	1 (2%)	0	0	0.32
Feeding Problems in Newborn	0	1 (2%)	1 (2%)	1.00
Hernia	0	0	1 (2%)	1.00
Other	0	1 (2%)	1 (2%)	1.00

[0173]

TABLE 13
Serious Adverse Events Reported During the Term Formula Phase
	Regimen
Event	Control	DHA	DHA + ARA	HM	p-value
Any Event	7 (13%)	9 (15%)	9 (15%)	1 (1%)	0.002
					C vs D	0.79
					C vs D + A	0.79
					D vs D + A	1.00
					C vs HM	0.006
					D vs HM	0.001
					D + A vs HM	0.001
Infectious Colitis,	0	0	1 (2%)	0	0.67
Enteritis, and
Gastroenteritis
Croup	0	0	1 (2%)	0	0.67
Bronchopneumonia,	2 (4%)	3 (5%)	6 (10%)	0	0.013
Organism Unspecified					C vs D	1.00
					C vs D + A	0.27
					D vs D + A	0.49
					C vs HM	0.15
					D vs HM	0.064
					D + A vs HM	0.004
Asthma, Unspecified	1 (2%)	0	0	0	0.21
Esophageal Reflux	0	1 (2%)	2 (3%)	0	0.23
Dyspepsia and Other	0	0	0	1 (1%)	1.0
Stomach Function
Disorder
Other Respiratory	1 (2%)	1 (2%)	3 (5%)	0	0.11
Conditions of Fetus
and Newborn
Convulsions	1 (2%)	0	0	0	0.21
Sudden Infant Death	1 (2%)	1 (2%)	0	0	0.34
Syndrome
Hernia	2 (4%)	2 (3%)	0	0	0.11
Other	0	3 (5%)	2 (3%)	0	0.063

[0174]

APPENDIX 1
Listing of Weights Included in the Statistical Analyses
Gender	Regimen	Subject	Variable	Wgt1	Wgt2	Wgt3	Wgt4	Wgt5	Wgt6	Wgt7	Wgt8	Wgt9
Male	Control	9698-0301	Weight (g)	1120	1240	1360	1590	1870
			Age (weeks pca)	30.3	31.3	32.1	33.1	34.1
Male	Control	9698-0304	Weight (g)	1450	1630	1940	2180
			Age (weeks pca)	32.6	33.4	34.7	35.4
Male	Control	9699-0302	Weight (g)	958.0	1108	1251	1378	1659
			Age (weeks pca)	30.7	31.7	32.7	33.7	34.7
Male	Control	9699-0306	Weight (g)	1185	1261	1437	1647	1933
			Age (weeks pca)	31.0	32.0	33.0	34.0	35.0
Male	Control	9699-0308	Weight (g)	1600	1840	2752
			Age (weeks pca)	34.4	35.4	38.3
Male	Control	9700-0301	Weight (g)	1810	1855	2075	2330	2595	3120
			Age (weeks pca)	32.1	32.6	33.4	34.4	35.4	37.4
Male	Control	9701-0303	Weight (g)	1181	1298	1494	1785	2012
			Age (weeks pca)	32.4	33.4	34.4	35.4	36.3
Male	Control	9701-0304	Weight (g)	1412	1566	1851	2117	2318
			Age (weeks pca)	31.9	32.9	33.7	34.7	35.9
Male	Control	9702-0302	Weight (g)	1480	1775	2045	2240	2340	2570
			Age (weeks pca)	31.0	32.1	33.0	34.0	34.6	35.6
Male	Control	9703-0302	Weight (g)	1785	2040	2375	2685	2955
			Age (weeks pca)	33.3	34.6	35.6	36.4	37.4
Male	Control	9703-0304	Weight (g)	1475	1705	1920	2190	2425
			Age (weeks pca)	31.7	33.0	34.0	34.9	35.7
Male	Control	9703-0308	Weight (g)	1140	1230	1445	1665	1945
			Age (weeks pca)	31.7	32.6	33.7	34.7	35.7
Male	Control	9704-0303	Weight (g)	975.0	1205	1270	1450	1665	1760	2045
			Age (weeks pca)	32.3	33.4	34.4	35.4	36.3	37.3	38.3
Male	Control	9704-0305	Weight (g)	1315	1475	1640	1860
			Age (weeks pca)	30.9	32.0	33.0	34.1
Male	Control	9705-0302	Weight (9)	1280	1389	1588	1786	2240
			Age (weeks pca)	33.0	34.0	35.0	36.0	37.4
Male	Control	9705-0304	Weight (g)	1270	1280	1570	1810
			Age (weeks pca)	31.3	32.3	33.3	34.6
Male	Control	9706-0302	Weight (g)	1645	1865	2130	2435
			Age (weeks pca)	35.7	36.6	37.7	38.7
Male	Control	9706-0303	Weight (g)	1875	1984	2135	2185	2465
			Age (weeks pca)	33.7	34.7	35.6	36.4	37.3
Male	Control	9706-0308	Weight (9)	1655	1734	2005	2495
			Age (weeks pca)	32.9	33.1	34.0	35.4
Male	Control	9707-0302	Weight (g)	1544	1820	2215	2450	2460
			Age (weeks pca)	31.6	32.9	34.4	35.4	35.7
Male	Control	9707-0303	Weight (g)	1415	1600	1850	2195	2310
			Age (weeks pca)	33.1	34.1	35.1	36.6	37.1
Male	Control	9707-0309	Weight (g)	1046	1442	1644	1910
			Age (weeks pca)	30.9	32.7	33.7	34.9
Male	Control	9708-0303	Weight (g)	1730	1960	2205	2520
			Age (weeks pca)	32.7	33.7	34.7	35.7
Male	Control	9709-0302	Weight (g)	1090	1440	1660	1910	2040
			Age (weeks pca)	29.9	31.7	32.7	33.7	34.3
Male	Control	9712-0301*	Weight (g)	1245	1221	1245	1291	1294	1330	1369	1402	1433
			Age (weeks pca)	31.6	31.7	31.9	32.0	32.1	32.3	32.4	32.6	32.7
Male	Control	9712-0302	Weight (g)	1292	1345	1456	1670	1835	1985
			Age (weeks pca)	33.1	34.1	35.1	36.1	37.1	38.1
Male	Control	9743-0301	Weight (g)	1520	1570	1670	1720
			Age (weeks pca)	34.1	35.0	36.0	37.1
Male	Control	9746-0301	Weight (g)	2065	2465	2760	3085	3085
			Age (weeks pca)	37.6	38.9	39.7	40.6	40.6
Male	DHA	9698-0302	Weight (g)	1640	1860	3170
			Age (weeks pca)	35.1	36.1	39.9
Male	DHA	9698-0306	Weight (g)	1620	1830	2090	2575
			Age (weeks pca)	35.1	36.3	37.3	40.0
Male	DHA	9699-0301	Weight (g)	1018	1207	1360	1617
			Age (weeks pca)	31.3	32.3	33.3	34.3
Male	DHA	9699-0303	Weight (g)	1258	1435	1631	1882	2724
			Age (weeks pca)	32.4	33.4	34.4	35.4	36.4
Male	DHA	9699-0307	Weight (g)	1182	1358	1484	1666
			Age (weeks pca)	34.7	35.7	36.7	37.7
Male	DHA	9700-0303	Weight (g)	1830	1980	2450	3045
			Age (weeks pca)	33.9	34.4	35.9	37.7
Male	DHA	9701-0301	Weight (g)	1098	1234	1365	1689	1902	2019	2104	2276	2288
			Age (weeks pca)	29.6	30.6	31.6	33.4	34.6	35.6	36.4	37.4	38.6
Male	DHA	9701-0305	Weight (g)	1621	1829	1880	2253	2582
			Age (weeks pca)	31.7	33.1	33.7	34.7	35.7
Male	DHA	9703-0303	Weight (g)	1775	2030	2285	2595	2780
			Age (weeks pca)	33.3	34.1	35.1	36.0	37.1
Male	DHA	9703-0306	Weight (g)	1725	1870	2180
			Age (weeks pca)	33.4	34.0	35.0
Male	DHA	9703-0307	Weight (g)	1525	1725	2020	2390
			Age (weeks pca)	32.7	33.7	34.9	36.0
Male	DHA	9704-0304	Weight (g)	1380	1570	1730	1960	2140
			Age (weeks pca)	32.1	33.1	34.1	35.0	35.9
Male	DHA	9704-0306	Weight (g)	1320	1370	1550	1760	2020	2170
			Age (weeks pca)	30.7	31.7	32.7	33.7	34.7	35.9
Male	DHA	9705-0303	Weight (g)	1380	1446	1616	1843	2330
			Age (weeks pca)	33.0	34.0	35.0	36.0	37.4
Male	DHA	9705-0305	Weight (g)	1490	1770	1980	2240
			Age (weeks pca)	31.1	32.1	33.1	34.0
Male	DHA	9706-0304	Weight (g)	1490	1655	1915	2260
			Age (weeks pca)	33.0	33.7	34.7	36.0
Male	DHA	9706-0306	Weight (g)	1604	1908	2160
			Age (weeks pca)	34.4	35.4	36.3
Male	DHA	9707-0001	Weight (g)	1305	1429
			Age (weeks pca)	31.0	32.0
Male	DHA	9707-0304	Weight (g)	1555	1740	1990	2400	2570
			Age (weeks pca)	32.0	33.0	34.0	35.4	36.0
Male	DHA	9707-0306	Weight (g)	1728	2040	2260	3050	3050
			Age (weeks pca)	36.1	37.3	38.1	40.6	40.6
Male	DHA	9707.0307*	Weight (g)	1649	1675	1699	1732	1778	1811	1858	1882	1938
			Age (weeks pca)	32.4	32.6	32.7	32.9	33.0	33.1	33.3	33.4	33.6
Male	DHA	9707-1308	Weight (g)	1780	2045	3004	3004
			Age (weeks pca)	34.4	35.7	39.3	39.3
Male	DHA	9707-2308	Weight (g)	1651	1923	2850	2850
			Age (weeks pca)	34.4	35.7	39.3	39.3
Male	DHA	9708-0302	Weight (g)	1485	1740	2500
			Age (weeks pca)	33.3	34.3	37.0
Male	DHA	9709-0301	Weight (g)	1490	1740	2000	2400	2800
			Age (weeks pca)	32.4	33.4	34.4	35.4	36.7
Male	DHA	9709-0304	Weight (g)	1470	1520
			Age (weeks pca)	34.4	35.4
Male	DHA	9712-0304	Weight (g)	1545	1800	1985	2160	2550
			Age (weeks pca)	33.0	34.0	35.0	36.0	37.6
Male	DHA	9712-0306	Weight (g)	1240	1435	1695	1945
			Age (weeks pca)	31.5	32.5	33.5	34.5
Male	DHA	9743-0303	Weight (g)	1700	1810	2100	2300
			Age (weeks pca)	32.9	33.9	34.9	35.7
Male	DHA	9743-0304	Weight (g)	1530	1880	2160	2375	2440
			Age (weeks pca)	32.3	34.0	35.0	36.0	36.4
Male	DHA + ARA	9698-0305	Weight (g)	1120	1340	1550
			Age (weeks pca)	30.7	32.6	33.6
Male	DHA + ARA	9698-0308	Weight (g)	1410	1690	1870	2120
			Age (weeks pca)	31.1	32.4	33.3	34.3
Male	DHA + ARA	9699-0304	Weight (g)	1499	1689	1950	2355
			Age (weeks pca)	36.1	37.1	38.1	40.3
Male	DHA + ARA	9699-0305	Weight (g)	1056	1134	1290	1490
			Age (weeks pca)	32.0	33.0	34.0	35.7
Male	DHA + ARA	9700-0302	Weight (g)	1635	1880	2235	2570	2735
			Age (weeks pca)	33.9	34.7	35.9	36.9	37.9
Male	DHA + ARA	9701-0302	Weight (g)	1442	1686	2045	2835
			Age (weeks pca)	33.6	34.6	35.6	37.7
Male	DHA + ARA	9701-0306	Weight (g)	1587	2037	2245	2460	2756	3072	3228
			Age (weeks pca)	32.3	33.4	34.4	35.3	36.3	37.3	37.7
Male	DHA + ARA	9701-0307	Weight (g)	1397	1710	1919	2932
			Age (weeks pca)	33.3	34.3	35.1	38.4
Male	DHA + ARA	9702-0301	Weight (g)	1670	1865	2160	2660
			Age (weeks pca)	32.0	33.0	34.0	36.0
Male	DHA + ARA	9702-0303	Weight (g)	1650	1905	2660
			Age (weeks pca)	32.9	33.9	36.4
Male	DHA + ARA	9703-0301	Weight (g)	1255	1460	1745	2055	2415
			Age (weeks pca)	29.4	30.4	31.3	32.3	33.4
Male	DHA + ARA	9703-0305	Weight (g)	1440	1635	1830	2115	2390	2590
			Age (weeks pca)	32.0	33.0	34.0	35.0	36.1	36.9
Male	DHA + ARA	9704-0301	Weight (g)	1110	1270	1490	1740	2050
			Age (weeks pca)	30.6	31.6	32.4	33.4	34.4
Male	DHA + ARA	9704-0302	Weight (g)	1080	1230	1370	1520	1680	1840
			Age (weeks pca)	32.0	33.0	34.0	34.9	36.0	36.9
Male	DHA + ARA	9705-0301	Weight (g)	1300	1440	1620	1870
			Age (weeks pca)	32.7	33.7	34.7	35.7
Male	DHA + ARA	9705-0306	Weight (g)	1320	1490	1700	2020	2300
			Age (weeks pca)	31.4	32.4	33.4	34.4	35.9
Male	DHA + ARA	9705-0307	Weight (g)	1480	1650	1810	2240
			Age (weeks pca)	34.4	35.4	36.1	37.4
Male	DHA + ARA	9706-0305	Weight (g)	1330	1455	1660	1930
			Age (weeks pca)	33.9	34.4	35.4	36.6
Male	DHA + ARA	9706-0307	Weight (g)	1355	1585	1825	2270
			Age (weeks pca)	31.9	33.0	33.9	35.1
Male	DHA + ARA	9706-0309	Weight (g)	1620	1910	2150
			Age (weeks pca)	34.1	35.3	36.0
Male	DHA + ARA	9707-0301	Weight (g)	1553	1980	2280	2720
			Age (weeks pca)	32.6	34.3	35.3	36.6
Male	DHA + ARA	9707-0305	Weight (g)	1755	1990	2245	2505	2770
			Age (weeks pca)	33.9	34.7	35.7	36.7	37.7
Male	DHA + ARA	9707-0310	Weight (g)	1620	1828	2140	3195
			Age (weeks pca)	32.7	33.7	34.7	37.9
Male	DHA + ARA	9708-0301	Weight (g)	1640	1880	2200	2420
			Age (weeks pca)	32.7	33.7	34.7	35.7
Male	DHA + ARA	9708-0304	Weight (g)	1680	2180
			Age (weeks pca)	34.6	35.9
Male	DHA + ARA	9709-0303	Weight (g)	1470	1810
			Age (weeks pca)	32.6	33.6
Male	DHA + ARA	9709-0305	Weight (g)	1410	1655	1900	2160
			Age (weeks pca)	34.4	35.4	36.4	37.4
Male	DHA + ARA	9712-0303	Weight (g)	1180	1210	1450	1590
			Age (weeks pca)	31.4	32.3	33.4	34.4
Male	DHA + ARA	9712-0305	Weight (g)	1325	1505	1785	2010	2300
			Age (weeks pca)	31.5	32.5	33.5	34.5	35.6
Male	DHA + ARA	9723-0301	Weight (g)	1630	1728	1961	2214
			Age (weeks pca)	33.9	34.9	35.9	36.9
Male	HM	9698-0601
Male	HM	9698-0602
Male	HM	9698-0603
Male	HM	9698-0604
Male	HM	9698-0605
Male	HM	9699-0501
Male	HM	9699-0502
Male	HM	9701-0601
Male	HM	9701-0602
Male	HM	9701-0603
Male	HM	9701-0604
Male	HM	9701-0605
Male	HM	9701-0606
Male	HM	9702-0601
Male	HM	9702-0602
Male	HM	9703-0502
Male	HM	9703-0503
Male	HM	9703-0504
Male	HM	9704-0502
Male	HM	9704-0503
Male	HM	9705-0601
Male	HM	9705-0602
Male	HM	9706-0601
Male	HM	9706-0602
Male	HM	9706-0603
Male	HM	9706-0604
Male	HM	9706-0605
Male	HM	9706-0606
Male	HM	9707-0601
Male	HM	9707-0602
Male	HM	9707-0603
Male	HM	9707-0604
Male	HM	9707-0605
Male	HM	9707-0606
Male	HM	9707-0607
Male	HM	9707-0608
Male	HM	9707-0609
Male	HM	9708-0601
Male	HM	9708-0602
Male	HM	9708-0603
Male	HM	9708-0604
Male	HM	9708-0605
Male	HM	9708-0606
Male	HM	9708-0607
Male	HM	9709-0505
Female	Control	9698-0003*	Weight (g)	1020	1050	1070	1080	1080	1060	1080	1070
			Age (weeks pca)	31.1	31.3	31.4	31.6	31.7	31.9	32.0	32.1
Female	Control	9699-0001	Weight (g)	1464	1672	1862	2000	2145
			Age (weeks pca)	32.7	33.7	34.7	35.7	36.7
Female	Control	9699-0003	Weight (g)	1473	1629	1860	2497
			Age (weeks pca)	34.0	35.0	36.0	38.0
Female	Control	9701-0003	Weight (g)	1480	1633	1903	1975	2292
			Age (weeks pca)	34.6	35.6	36.6	37.3	38.6
Female	Control	9701-0005	Weight (g)	1174	1366	1555	1745	1976
			Age (weeks pca)	30.7	31.7	32.7	33.7	34.7
Female	Control	9701-0008	Weight (g)	1391	1569	1898	2198	2406
			Age (weeks pca)	34.3	35.3	36.4	37.3	37.9
Female	Control	9701-0011	Weight (g)	1050	1254	1492	1756	2044
			Age (weeks pca)	30.6	31.4	32.4	33.4	34.4
Female	Control	9702-0002	Weight (g)	1222	1371	1570	1750	1995	2390
			Age (weeks pca)	31.7	32.7	34.1	35.1	36.0	37.1
Female	Control	9702-0004	Weight (g)	1454	1555	1840	2530
			Age (weeks pca)	31.0	31.9	33.1	36.0
Female	Control	9702-0010	Weight (g)	1775	2065	2410	2645
			Age (weeks pca)	34.0	35.0	36.0	37.0
Female	Control	9703-0002	Weight (g)	1170	1250	1390	1570	1825	2130
			Age (weeks pca)	29.1	30.4	31.3	32.4	33.4	34.3
Female	Control	9703-0005	Weight (g)	1420	1590	1765	1900	2220
			Age (weeks pca)	31.4	32.3	33.3	33.9	35.3
Female	Control	9703-0008	Weight (g)	1495	1715	2095	2445	2685
			Age (weeks pca)	33.0	34.0	35.0	36.0	36.6
Female	Control	9705-0004	Weight (g)	1120	1290	1490	1660
			Age (weeks pca)	31.3	32.3	33.3	34.0
Female	Control	9706-0003	Weight (g)	1515	1673	1965	2330
			Age (weeks pca)	35.1	36.3	37.1	38.3
Female	Control	9706-0005	Weight (g)	1485	1610	1805	2150
			Age (weeks pca)	33.0	33.7	34.7	36.0
Female	Control	9706-0009	Weight (g)	1525	1620	1960
			Age (weeks pca)	32.3	32.9	34.3
Female	Control	9706-0010	Weight (g)	1905	2185
			Age (weeks pca)	34.3	35.0
Female	Control	9706-0013	Weight (g)	1185	1270	1585	1810
			Age (weeks pca)	31.6	32.4	33.6	34.6
Female	Control	9706-0016	Weight (g)	1510	1765	1935
			Age (weeks pca)	32.0	33.1	33.9
Female	Control	9707-0003	Weight (g)	1465	1505	1655	2010	2325	2765
			Age (weeks pca)	32.0	32.6	33.6	35.3	36.4	38.3
Female	Control	9707-0006	Weight (g)	1866	3430	3430
			Age (weeks pca)	34.6	40.0	40.0
Female	Control	9707-1006	Weight (g)	1815	3330	3330
			Age (weeks pca)	34.6	40.0	40.0
Female	Control	9708-0001	Weight (g)	1410	1600	1850	2050
			Age (weeks pca)	33.4	34.4	35.4	36.9
Female	Control	9708-0003	Weight (g)	940.0	970.0
			Age (weeks pca)	30.0	31.0
Female	Control	9708-0008	Weight (g)	1380	1605	1860	2180
			Age (weeks pca)	32.9	33.7	34.9	36.3
Female	Control	9709-0002	Weight (g)	1980	2225	2400
			Age (weeks pca)	32.7	33.7	34.7
Female	Control	9709-0005	Weight (g)	1175	1425	1665	1945	2200
			Age (weeks pca)	31.9	33.3	34.6	35.6	36.3
Female	Control	9712-0005	Weight (g)	972.0	1145	1290	1490	1695
			Age (weeks pca)	29.1	30.1	31.1	32.1	33.1
Female	Control	9712-0006	Weight (g)	1203	1358	1585	1790
			Age (weeks pca)	31.9	32.9	33.9	34.9
Female	Control	9743-0003	Weight (g)	1300	1520	1740	1890
			Age (weeks pca)	31.6	33.4	34.1	35.1
Female	Control	9746-0001	Weight (g)	1420	1740	2075	2320	2625
			Age (weeks pca)	32.6	33.6	34.6	35.6	36.6
Female	DHA	9698-0004	Weight (g)	1410	1650	1890	2140
			Age (weeks pca)	30.1	31.1	32.1	33.1
Female	DHA	9698-0006	Weight (g)	1110	1240	1420	1720
			Age (weeks pca)	30.7	31.7	32.7	33.7
Female	DHA	9698-0009	Weight (g)	1205	1310	1520	1630	2020
			Age (weeks pca)	30.3	31.4	32.4	33.1	34.9
Female	DHA	9698-0307	Weight (g)	1790	2110	2450
			Age (weeks pca)	34.4	35.7	37.6
Female	DHA	9699-0002	Weight (g)	1313	1477	1669	1929	2380
			Age (weeks pca)	32.9	33.9	34.9	35.9	36.9
Female	DHA	9700-0001	Weight (g)	1580	1820	2050	2295	2500
			Age (weeks pca)	32.4	33.4	34.3	35.3	36.3
Female	DHA	9701-0001	Weight (g)	1300	1356	1586	1924	2125
			Age (weeks pca)	33.0	34.0	35.0	36.0	36.6
Female	DHA	9701-0004	Weight (g)	1108	1261	1441	1671	1897
			Age (weeks pca)	30.7	31.7	32.7	33.7	34.7
Female	DHA	9701-0012	Weight (g)	1674	1928	2151	2311	2685	2685
			Age (weeks pca)	34.9	35.9	36.9	37.6	39.6	39.6
Female	DHA	9701-0014	Weight (g)	1422	1631	1858	2455
			Age (weeks pca)	33.9	34.9	35.9	37.9
Female	DHA	9702-0001	Weight (g)	1780	2115	2390	3000
			Age (weeks pca)	31.6	32.9	33.9	36.4
Female	DHA	9702-0006	Weight (g)	1850	2005	2650	2650
			Age (weeks pca)	35.4	36.1	39.6	39.6
Female	DHA	9702-0007	Weight (g)	1285	1459	1780	1965	2035
			Age (weeks pca)	31.1	32.1	33.6	34.4	34.9
Female	DHA	9702-0008	Weight (g)	1605	1930	3540	3540
			Age (weeks pca)	34.1	35.1	39.6	39.6
Female	DHA	9703-0003	Weight (g)	1255	1355	1535	1845	2150
			Age (weeks pca)	34.4	35.1	36.1	37.1	38.1
Female	DHA	9703-0004	Weight (g)	1170	1340	1550	1795	2225
			Age (weeks pca)	32.6	33.3	34.3	35.3	37.0
Female	DHA	9703-0009	Weight (g)	1570	1830	2095	2395	2655
			Age (weeks pca)	33.3	34.3	35.1	36.3	37.9
Female	DHA	9704-0004	Weight (g)	1440	1670	1740
			Age (weeks pca)	33.6	34.6	35.0
Female	DHA	9704-0005	Weight (g)	1050	1310	1490	1700	1890
			Age (weeks pca)	29.7	30.9	31.7	32.7	33.7
Female	DHA	9705-0001	Weight (g)	1220	1370	1590	1880	2098
			Age (weeks pca)	32.7	33.6	34.7	35.7	36.7
Female	DHA	9706-0006	Weight (g)	1270	1405	1630	1930
			Age (weeks pca)	33.0	33.7	34.7	36.0
Female	DHA	9706-0008	Weight (g)	990.0	1188	1345	1485
			Age (weeks pca)	33.4	34.6	35.7	36.4
Female	DHA	9706-0012	Weight (g)	1610	1830	2130	2280
			Age (weeks pca)	31.6	32.4	33.6	34.6
Female	DHA	9706-0014	Weight (g)	1080	1170	1395	1560	1804
			Age (weeks pca)	31.3	32.6	33.4	34.4	35.3
Female	DHA	9707-0004	Weight (g)	1635	1771	2850
			Age (weeks pca)	34.0	35.0	38.7
Female	DHA	9707-0308	Weight (g)	2005	3440	3440
			Age (weeks pca)	34.4	39.3	39.3
Female	DHA	9708-0004	Weight (g)	1460	1665	1955	2280	2485
			Age (weeks pca)	32.6	33.6	34.6	35.6	36.6
Female	DHA	9708-0006	Weight (g)	1485	1775	2110	2380
			Age (weeks pca)	33.7	34.7	35.7	37.0
Female	DHA	9709-0001	Weight (g)	1250	1490	1755	1970	2250	2520
			Age (weeks pca)	29.6	31.0	32.0	33.0	34.0	35.0
Female	DHA	9709-0003	Weight (g)	1540	1725	2015	2155
			Age (weeks pca)	34.4	35.4	36.4	37.4
Female	DHA	9712-0001	Weight (g)	987.0	1120	1270	1470	1685
			Age (weeks pca)	30.0	31.0	32.0	33.0	34.0
Female	DHA	9712-0002	Weight (g)	1060	1230	1430
			Age (weeks pca)	32.7	33.7	34.7
Female	DHA	9712-0007	Weight (g)	1082	1230	1440	1650
			Age (weeks pca)	32.7	33.7	34.7	35.7
Female	DHA	9743-0001	Weight (g)	1000	1170	1470	1800	1930
			Age (weeks pca)	32.1	33.1	34.4	35.7	36.1
Female	DHA	9743-0002	Weight (g)	1380	1570	1845	1975
			Age (weeks pca)	32.1	33.3	34.1	35.1
Female	DHA + ARA	9698-0001	Weight (g)	1550	1690	2000	2380
			Age (weeks pca)	31.6	32.6	33.6	34.9
Female	DHA + ARA	9698-0002	Weight (g)	1580	1870	2130	2260
			Age (weeks pca)	32.6	33.7	34.6	35.7
Female	DHA + ARA	9699-0004	Weight (g)	985.0	1122	1283	1536	1788
			Age (weeks pca)	31.0	32.0	33.0	34.0	35.0
Female	DHA + ARA	9699-0005	Weight (g)	1330	1542	1688	2000	2330
			Age (weeks pca)	31.9	32.9	33.9	34.9	35.9
Female	DHA + ARA	9700-0002	Weight (g)	1315	1525	1885	2035	2220	2480
			Age (weeks pca)	30.3	31.3	32.3	33.3	34.1	35.6
Female	DHA + ARA	9701-0002	Weight (g)	1398	1609	1887	2210	2420
			Age (weeks pca)	33.4	34.4	35.4	36.4	37.4
Female	DHA + ARA	9701-0006	Weight (g)	1720	1859	2113	2456	2728
			Age (weeks pca)	32.3	33.3	34.3	35.3	36.1
Female	DHA + ARA	9701-0007	Weight (g)	1469	1427	1590	1982	2227
			Age (weeks pca)	33.7	34.9	35.7	36.7	37.7
Female	DHA + ARA	9701-0010	Weight (g)	1488	1703	1978	2234	2433	2759
			Age (weeks pca)	32.3	33.4	34.4	35.3	36.1	37.7
Female	DHA + ARA	9701-0013	Weight (g)	1841	2019
			Age (weeks pca)	33.0	33.7
Female	DHA + ARA	9702-0003	Weight (g)	1293	1488	1820	2155	2400
			Age (weeks pca)	30.1	31.1	32.1	33.4	34.1
Female	DHA + ARA	9702-0005	Weight (g)	1895	2060	2300	2525	2710
			Age (weeks pca)	34.0	35.0	36.0	37.0	38.0
Female	DHA + ARA	9702-0009	Weight (g)	1725	2000	2230	2595	2655
			Age (weeks pca)	34.0	35.0	36.0	37.0	37.3
Female	DHA + ARA	9703-0001	Weight (g)	1145	1255	1450	1680	1955
			Age (weeks pca)	31.3	32.1	33.1	34.3	35.3
Female	DHA + ARA	9703-0006	Weight (g)	1865	2200	2560	2880
			Age (weeks pca)	34.0	35.0	35.9	37.0
Female	DHA + ARA	9703-0007	Weight (g)	1390	1495	1620	1880	2030	2240
			Age (weeks pca)	32.0	33.1	34.0	35.0	35.7	36.6
Female	DHA + ARA	9704-0002	Weight (g)	960.0	1090	1200	1370	1570	1780	2070
			Age (weeks pca)	29.0	30.0	30.9	31.9	32.9	33.9	34.9
Female	DHA + ARA	9704-0003	Weight (g)	1690	1840
			Age (weeks pca)	32.7	33.4
Female	DHA + ARA	9705-0003	Weight (g)	1760	2260	2500	2920
			Age (weeks pca)	34.4	35.7	36.6	37.7
Female	DHA + ARA	9705.0005*	Weight (g)	1075	1120	1185	1280	1310	1310	1265	1350	1380
			Age (weeks pca)	31.1	31.4	31.7	32.1	32.4	32.7	33.0	33.3	33.4
Female	DHA + ARA	9706-0001	Weight (g)	1290	1515	1685	2060
			Age (weeks pca)	31.7	32.9	33.7	34.9
Female	DHA + ARA	9706-0002	Weight (g)	1395	1710	1884	2275
			Age (weeks pca)	31.9	33.0	33.9	35.4
Female	DHA + ARA	9706-0004	Weight (g)	1550	1705	2050
			Age (weeks pca)	36.7	37.6	38.7
Female	DHA + ARA	9706-0007	Weight (g)	1235	1490	1820	1930
			Age (weeks pca)	33.4	34.6	35.7	36.4
Female	DHA + ARA	9706-0011	Weight (g)	1900	2105
			Age (weeks pca)	34.3	35.0
Female	DHA + ARA	9706-0015	Weight (g)	1670	1975	2210
			Age (weeks pca)	34.6	35.6	36.4
Female	DHA + ARA	9706-0017	Weight (g)	1465	1700	1895	2170
			Age (weeks pca)	32.3	33.4	34.3	35.3
Female	DHA + ARA	9707-0002	Weight (g)	1775	2240	2385	2610
			Age (weeks pca)	34.3	36.0	36.9	37.9
Female	DHA + ARA	9708-0002	Weight (g)	1535	1700	1980	2200
			Age (weeks pca)	33.0	34.0	35.0	36.0
Female	DHA + ARA	9708-0005	Weight (g)	1125	1345	1610	1980
			Age (weeks pca)	32.4	33.4	34.4	35.4
Female	DHA + ARA	9708-0007	Weight (g)	1200	1440	1680	1975
			Age (weeks pca)	31.3	32.3	33.3	34.3
Female	DHA + ARA	9709-0004	Weight (g)	1350	1560	1885	2250	2475
			Age (weeks pca)	31.9	33.3	34.6	35.6	36.3
Female	DHA + ARA	9712-0003	Weight (g)	1283	1410	1590	1850	2010
			Age (weeks pca)	32.0	33.0	34.0	35.0	36.0
Female	DHA + ARA	9712-0004	Weight (g)	1575	1780	1890	2080	2530
			Age (weeks pca)	33.0	34.0	34.6	35.6	37.6
Female	DHA + ARA	9712-0008	Weight (g)	1590	1780	1990	2475
			Age (weeks pca)	34.0	35.0	35.8	37.4
Female	DHA + ARA	9746-0002	Weight (g)	1249	1429	1597	1814	2110
			Age (weeks pca)	32.7	33.7	34.7	35.7	36.7
Female	HM	9698-0501
Female	HM	9698-0502
Female	HM	9698-0503
Female	HM	9698-0504
Female	HM	9698-0505
Female	HM	9699-0601
Female	HM	9699-0602
Female	HM	9699-0603
Female	HM	9699-0604
Female	HM	9699-0605
Female	HM	9701-0501
Female	HM	9701-0502
Female	HM	9701-0503
Female	HM	9701-0504
Female	HM	9702-0501
Female	HM	9702-0502
Female	HM	9702-0503
Female	HM	9702-0504
Female	HM	9702-0505
Female	HM	9702-0506
Female	HM	9702-0507
Female	HM	9702-0508
Female	HM	9703-0501
Female	HM	9703-0505
Female	HM	9703-0506
Female	HM	9703-0507
Female	HM	9704-0501
Female	HM	9705-0501
Female	HM	9705-0502
Female	HM	9706-0501
Female	HM	9706-0502
Female	HM	9707-0501
Female	HM	9707-0502
Female	HM	9707-0503
Female	HM	9708-0501
Female	HM	9708-0502
Female	HM	9708-0503
Female	HM	9705-0504
Female	HM	9708-0505
Female	HM	9709-0501
Female	HM	9709-0502
Female	HM	9709-0503
Female	HM	9709-0504
Female	HM	9709-0506
	Growth
	Rate
	g/day	Wgt_40	Wgt_48	Wgt_57
	27.7
	36.1	3731	5752	6816
		40.3	48.3	56.6
	23.9	3064	4993	6553
		39.9	48.0	57.9
	26.9	3575	4936	6014
		40.3	48.3	57.1
	43.3	3688	5504	6922
		40.3	48.3	57.3
	36.2	3745	5080	6610
		40.1	47.6	56.7
	31.5	3070	3895	4965
		41.6	48.6	57.6
	34.1	3070	5445	7135
		39.9	48.3	56.9
	33.8	3590	4840	6110
		40.1	48.6	58.4
	41.7	3620	5850	7470
		39.7	48.6	57.3
	34.2	3170	5240	6970
		40.1	47.7	57.1
	28.9	2520	4010	5030
		39.7	48.4	56.9
	24.4	2150	3700	4950
		39.3	48.3	57.4
	23.7
	30.9	2540	4936	5646
		39.6	47.4	56.4
	25.3	3291	5816	7490
		39.7	47.7	56.7
	37.1	2800	4660	6170
		40.1	48.7	56.7
	22.2	3050	4550	6675
		41.0	48.6	56.9
	46.9	3835	5155	6090
		40.6	48.0	56.3
	32.8	2930	3795	5185
		40.1	47.7	56.6
	32.7	2530	4235	6530
		39.7	47.7	57.1
	30.7	2965	4465
		39.9	48.0
	37.4	3680	5470	7330
		40.1	48.1	57.0
	30.8	3845	5700	6775
		39.9	48.0	56.7
	26.1
	21.0	2160	3300	3980
		40.1	47.7	57.3
	10.0	2260	4535
		41.0	50.0
	48.9	3085	4795	6695
		40.6	47.6	57.6
	47.5	3170	5206	7036
		39.9	47.9	57.1
	28.3	2575	4334	6022
		40.0	48.0	57.0
	27.9	3121	5192	6752
		39.9	48.0	57.9
	48.3	2724	4341	5674
		40.1	48.1	57.0
	22.5	1986	3206	4511
		40.0	48.0	57.0
	45.4	3585	5420	7035
		39.6	47.4	56.7
	20.4	2805	3405	4660
		40.4	47.6	57.0
	34.7	3660
		39.7
	38.2	3080	3940	5260
		39.9	48.0	56.9
	41.7
	37.6	3120	4410	5600
		40.7	47.9	56.9
	29.3	2880	3900	4300
		40.3	48.3	57.3
	25.6		3750	4800
			48.0	57.0
	30.8	2370	4170	5787
		39.6	47.4	56.4
	36.7	3291
		39.6
	36.8	3335	5265	6900
		40.0	48.1	57.3
	42.8	3310	4205	5600
		41.4	47.6	56.9
	17.7
	36.9	3280	5115	6755
		39.9	48.0	57.6
	43.2	3050	5100	7150
		40.6	48.6	57.6
	39.6
	36.7	3004	4420	6090
	39.3	47.3	57.7
	35.8	2850	4375	5930
		39.3	47.3	57.7
	39.2	3873	6256
		42.9	57.3
	44.4	3150	5080	6750
		39.4	47.4	56.4
	7.1
	30.5	3160	5200	7300
		40.3	48.1	57.1
	33.9	3040	4680	5860
		39.6	48.6	57.6
	31.1	3100	5500
		40.6	48.6
	32.2	3628	5840
		38.1	50.6
	20.9	2440	5525	6646
		37.4	47.6	56.6
	32.0	3553	6007	7937
		40.3	47.6	57.3
	29.8	2355	3404	4993
		40.3	48.0	57.1
	17.2	2610	4256	5050
		40.6	48.7	57.6
	40.7	3255	5540	7380
		39.7	47.7	56.7
	48.9	3240	5055	6600
		39.7	46.7	56.7
	41.4	3960	5200
		42.3	48.4
	42.5	3445	5930	7475
		40.6	48.6	57.4
	36.0	3780	5250
		40.6	47.6
	40.7	3500	5160	6520
		40.0	48.0	56.4
	42.3	4350	6020	6720
		40.4	47.4	56.6
	34.1	3170	4330	5630
		40.0	47.9	56.7
	35.1	3220	5460	7050
		39.9	47.7	56.7
	22.2	2570	6540	8050
		40.0	48.1	57.4
	27.0	2979	4400	5873
		40.1	48.1	58.0
	32.7	3631	5447	6809
		39.9	47.9	56.9
	36.4	3007	5589	6596
		39.9	48.4	56.7
	31.4	2695	4820	6225
		39.9	48.1	58.1
	40.0	3585	5955	6925
		40.4	49.1	57.6
	40.3	3460	5255	5775
		40.9	48.7	57.4
	41.5	3395	4950	6285
		40.1	47.9	56.9
	37.4
	44.8	3585	5170	6725
		39.7	47.9	56.3
	38.0	3730	4835	6185
		40.1	47.9	57.0
	55.6
	48.6
	35.6	2630	4570	5520
		39.7	47.7	57.1
	20.9	2520	3500	5010
		40.4	47.4	56.4
	34.1	3030	4350	5510
		39.6	48.6	57.6
	28.4	3104		5986
		40.3		58.9
		3518	5497	6582
		40.0	48.3	56.9
		3177	5220	6355
		40.0	48.1	57.0
		3858	5447	6454
		40.0	48.0	57.0
		4355	5092	6383
		40.0	48.0	57.0
		3433	4979	6426
		40.0	48.1	57.1
		3915	6639	7773
		40.0	48.3	57.4
		3802	5787	7178
		40.0	48.4	57.4
		3317	5555	7070
		40.0	47.9	56.4
		3487	5833	8070
		40.0	47.3	58.3
		3232	4940	5855
		40.0	47.4	56.4
		3600	5215	6285
		40.0	47.9	56.9
		3402	5575	7210
		40.0	47.6	57.6
		3090	4485	5445
		40.0	47.7	56.7
		3480	5780	6530
		40.0	48.6	56.6
		3165	5060	6660
		40.0	48.3	57.1
		2670	5420	7220
		40.0	48.3	57.1
		4100	6740	8330
		40.0	47.4	56.4
		3435	6000	7930
		40.0	48.1	57.1
		3285	5220	6560
		40.0	48.1	56.6
		3400	5200	6725
		40.0	48.7	56.9
		3200	5617	6752
		40.0	48.3	57.3
		3860	6227
		40.0	48.0
		3152	5105	6545
		40.0	49.0	57.0
		3557	5175	7315
		40.0	47.4	57.7
		3192	5070	6970
		40.0	47.9	56.7
		3461	4225	5525
		40.0	48.0	57.1
		3870	6220	7660
		40.0	48.1	56.4
		4315	5975	6720
		40.0	48.3	56.6
		3263	4730	5825
		40.0	48.1	57.0
		3206	4515	6220
		40.0	48.1	57.7
		4256	6930	8810
		40.0	48.0	57.0
		3419	5460	6130
		40.0	48.0	56.7
		3433
		40.0
		3603	5825
		40.0	48.4
		3569	5410	6870
		40.0	47.9	56.9
		3348	5135	6370
		40.0	48.0	57.0
		3348
		40.0
		3064	5220	6595
		40.0	47.6	56.4
		4085
		40.0
		3319	5135	6327
		40.0	48.4	57.1
		3291
		40.0
		3796
		40.0
		4020	4645	5405
		40.0	48.4	57.1
		3333	4043	5180
		40.0	47.9	56.7
		3400
		40.0
	5.6
	24.1	2610	4369	5220
		39.7	47.9	56.9
	37.3	2780	4596	5816
		40.0	48.0	57.0
	29.1	2675	4165	5200
		40.6	48.6	55.6
	28.3	3175	5140	6280
		39.7	48.4	56.4
	41.1	2980	4425	5815
		40.4	47.4	56.4
	36.6	2870	4420	5505
		39.7	48.6	57.4
	29.4	3380	4900
		40.4	47.6
	31.6	3600	5160	6900
		39.9	47.7	56.7
	42.2	3060	4820	6690
		39.9	48.3	57.6
	26.4	3210	4750
		39.6	47.4
	29.5	2610	4330	5640
		37.3	46.0	55.0
	48.3	3360	4780	6410
		40.1	47.7	56.1
	28.3	2722	4085	5646
		39.7	46.6	55.0
	37.9
	31.7	2740	4165	5305
		40.0	48.1	57.3
	31.6	3640	5495	7225
		40.3	47.6	53.4
	56.0	3655	5390	6535
		40.0	48.4	56.7
	31.1	2680	3800
		40.1	48.4
	32.6	3320	4535	5297
		40.7	48.7	56.6
	30.2	3110	4125	4995
		40.1	48.1	57.1
	41.2	3430	5385	7250
		40.0	48.9	57.3
	39.9	3330	5490	6920
		40.0	48.9	57.3
	27.2	2910	4734
		40.6	48.4
	4.3
	33.1	2582	4110	5361
		39.3	47.4	57.1
	30.0
	32.3	2975	4700	5900
		39.6	48.4	56.7
	25.6	2930	4450	5880
		40.3	47.6	57.1
	28.4	3030	4560	6230
		39.7	48.0	57.0
	24.0		4000	5160
			48.4	57.4
	42.7	3170	4145	5192
		39.7	47.6	56.6
	34.7	3787	4795	6291
		40.0	48.0	57.0
	28.7
	25.9	2891	3979	5121
		40.0	48.0	57.0
	29.7	3135	5185	6695
		39.4	47.4	56.4
	36.9	3177	5787	7093
		39.7	47.7	56.7
	34.5	3210	5110	6300
		40.1	48.1	57.1
	34.2	2910	4325	5625
		39.6	48.0	57.0
	28.4	3020	4855	6040
		39.7	48.4	56.4
	30.1	2685
		39.6
	37.2	2970	4605	5140
		39.9	47.7	56.9
	35.8	3850	5610	6600
		40.0	49.6	57.0
	27.3	2650	4450	6020
		39.6	48.4	56.4
	29.6
	51.3	3540	5920	7820
		39.6	47.6	57.1
	34.8	2430	4130	5010
		39.4	48.0	56.1
	33.9	2870	4610	6490
		39.4	48.1	57.1
	34.6	3160	4480	5570
		40.4	48.4	58.0
	30.5	3100	5830	8630
		40.0	48.0	57.0
	30.0	3360	4860	6100
		39.6	48.0	57.0
	31.9	3092	4795	5986
		40.1	48.1	57.1
	31.7	2705	4145	5320
		40.0	48.1	57.3
	23.0	2120
		39.9
	32.5	3530	4790
		40.1	48.4
	26.2	3295	5600	7675
		40.6	49.4	58.0
	38.1	3045	4595	5765
		40.0	48.0	57.0
	42.2	3440	4800	6360
		39.3	47.3	57.7
	38.1
	39.5	3010	4620	6530
		40.1	48.1	57.0
	33.8	3500
		40.1
	30.5	2580	4080	5420
		40.3	47.7	57.1
	24.9	2940	3980	5250
		40.1	48.1	57.1
	26.4
	27.3	2425	4250	5340
		39.7	47.9	56.9
	33.5		4140	5400
			48.3	57.3
	29.7		4540	5160
			48.4	57.4
	37.1	3530	5348	6582
		40.0	47.7	56.7
	31.8	3241
		40.7
	28.9	3177	5107	6979
		41.3	48.3	57.3
	35.1	4029	6752	8341
		40.0	48.0	57.0
	31.9	3340	4930	6420
		40.3	48.1	57.1
	37.8	2930	5115	6525
		39.4	48.4	56.4
	38.3	3600	5045	6270
		40.3	48.0	57.3
	29.8	2680	4935	6955
		39.9	47.9	56.9
	34.6	3500	5545
		41.1	48.4
	35.6		4545	5550
			48.7	57.4
	39.9	4190	6220	7500
		40.0	48.4	56.9
	29.9	3025	4300	5340
		40.0	47.4	56.4
	40.9	2905	4680	6410
		39.9	48.3	57.6
	28.9	3030	4250	5420
		41.0	48.1	57.3
	49.1	3600	5400	6650
		40.0	48.1	56.7
	27.4	2850	4190	5850
		40.0	47.9	56.7
	26.7	3110	5150	6800
		40.0	48.0	57.3
	30.0	4000	5400	6640
		40.0	48.0	57.0
	49.8	3376	5107	6894
		39.9	48.4	56.9
	22.1	2600	4000	5050
		40.4	48.0	57.0
	34.5	4100	6550	7655
		40.1	48.6	56.7
	34.8	2845	4645	5550
		40.3	48.9	57.3
	36.1	2645	4225	4935
		41.7	49.7	58.0
	34.3	2505
		40.3
	41.0	3430	5175	6140
		40.0	48.4	56.7
	41.6	3005	4465	5810
		40.9	48.4	57.6
	33.4
	33.2
	32.5	2724	4645	6315
		38.1	47.6	55.4
	40.4	3121	5855	7875
		39.4	47.4	57.4
	36.6
	37.0	3295	5250	6685
		39.7	48.4	56.7
	27.1	2580	4130	5640
		40.0	48.2	57.5
	29.7	3220	4920	6600
		40.3	48.1	57.1
	37.2	2960	4470	5760
		40.1	48.1	57.1
	30.1	2680	4010	5362
		39.9	46.9	56.9
		3546	4880
		40.0	48.3
		3518	5972
		40.0	47.9
		3390	4213	5319
		40.0	48.3	57.1
		3383	5234	6667
		40.0	48.7	57.9
		3646	4638	5653
		40.0	48.3	57.0
		2582	4766	5731
		40.0	49.0	57.0
		4284	4823	5986
		40.0	48.0	57.0
		3716	4482	5674
		40.0	47.7	56.7
		3660	4738	6355
		40.0	48.0	57.0
		3433	5617	7603
		40.0	48.4	57.6
		3884	5630	6450
		40.0	47.7	57.7
		3858	5420	6700
		40.0	48.6	57.6
		3430	4265	5085
		40.0	47.4	57.4
		3317	5020	6230
		40.0	48.1	57.1
		3302	5540	6630
		40.0	47.7	56.7
		2658	5310	6800
		40.0	47.4	57.1
		2895	3430	4530
		40.0	47.7	57.4
		3401	5390	6270
		40.0	48.0	57.4
		3141	4210	5320
		40.0	47.9	57.0
		3762	6040	7600
		40.0	48.9	57.7
		2718	4050	4940
		40.0. 48.9	57.4
		2927	4240	5860
		40.0	47.4	57.0
		4085	5260	6360
		40.0	48.1	57.1
		3390	5760	7670
		40.0	48.3	57.3
		3405	6170	7490
		40.0	47.9	56.9
		3085	5090	6550
		40.0	48.0	56.3
		3194	4700	5880
		40.0	48.1	57.4
		3120	4500	5702
		40.0	48.1	57.1
		4080	6327	7348
		40.0	48.3	57.3
		3396	5000	6645
		40.0	48.3	58.1
		3041	4315	5525
		40.0	47.7	57.6
		4653	5515	6770
		40.0	47.9	56.6
		3419	5500	7080
		40.0	48.0	57.1
		3773	5785	7675
		40.0	47.9	56.9
		3716
		40.0
		3688	5440	6890
		40.0	48.1	57.6
		3454	5192	5950
		40.0	48.1	57.4
		2977	5165	7040
		40.0	48.1	57.4
		3864	5660	6705
		40.0	48.4	57.4
		3831	5800	7435
		40.0	47.7	57.6
		3550
		40.0
		3715	5205	6100
		40.0	48.0	56.9
		3195
		40.0
		3190	4590
		40.0	48.3
		3505	4500	5910
		40.0	48.0	57.1
Gender	Regimen	SUBJECT	Variable	Wgt1	Wgt2	Wgt3	Wgt4	Wgt5	Wgt6	Wgt7	Wgt8	Wgt9
Male	Control	9712-0301	Weight (g)	1245	1221	1245	1291	1294	1330	1369	1402	1433
			Age (weeks pca)	31.6	31.7	31.9	32.0	32.1	32.3	32.4	32.6	32.7
Male	DHA	9707-0307	Weight (g)	1649	1675	1699	1732	1778	1811	1858	1882	1938
			Age (weeks pca)	32.4	32.6	32.7	32.9	33.0	33.1	33.3	33.4	33.6
Female	Control	9698-0003	Weight (g)	1020	1050	1070	1080	1080	1060	1080	1070
			Age (weeks pca)	31.1	31.3	31.4	31.6	31.7	31.9	32.0	32.1
Female	DHA + ARA	9705-0005	Weight (g)	1075	1120	1185	1280	1310	1310	1265	1350	1380
			Age (weeks pca)	31.1	31.4	31.7	32.1	32.4	32.7	33.0	33.3	33.4
										Growth
										Rate
	Wgt10	Wgt11	Wgt12	Wgt13	Wgt14	Wgt15	Wgt16	Wgt17	Wgt18	g/day
	1448	1465								26.1
	32.9	33.0
	1994	2030	2075							39.6
	33.7	33.9	34.0
										5.6
	1440	1450	1510	1515	1565	1585	1640	1680	1670	22.1
	33.7	33.9	34.0	34.1	34.3	34.4	34.6	34.7	34.9
	Four subjects had more the 9 weights used in growth rate calculation. A complete listing appears on the last page.

Claims

1. A method for enhancing the growth of preterm infants comprising administering to the preterm infants a preterm nutritional product or nutritional supplement having a growth-enhancing amount of DHA and ARA.

2. The method according to claim 1, wherein the nutritional product or supplement is a preterm infant formula.

3. The method according to claim 1, wherein the ratio of ARA:DHA is about 1:2 to about 5:1.

4. The method according to claim 1, wherein the ratio of ARA:DHA is about 1:1 to about 3:1.

5. The method according to claim 1, wherein the ratio of ARA:DHA is about 2:1.

6. The method according to claim 1, wherein the DHA and ARA are derived from a source comprising fish oils.

7. The method according to claim 1, wherein the DHA and ARA are derived from a source comprising single cell oils.

8. The method according to claim 1, wherein the DHA and ARA are derived from a source comprising egg or yolk lipids.

9. The method according to claim 1, wherein the DHA and ARA are derived from a source comprising brain lipids.

10. The method according to claim 2, wherein the infant formula is nutritionally complete and comprises lipid in an amount of from about 3 g/100 kcal to about 7 g/100 kcal, protein in an amount of from about 1 g/100 kcal to about 5 g/100 kcal, and carbohydrate in an amount of from about 8 g/100 kcal to about 12 g/100 kcal.

11. The method according to claim 1, wherein the nutritional supplement is selected from the group consisting of oil drops, sachets, and vitamins.

12. A preterm infant formula for enhancing the growth of preterm infants, the preterm infant formula comprising a growth-enhancing amount of DHA and ARA.

13. The preterm infant formula according to claim 12, wherein the ratio of ARA:DHA is about 1:2 to about 5:1.

14. The preterm infant formula according to claim 12, wherein the ratio of ARA:DHA is about 1:1 to about 3:1.

15. The preterm infant formula according to claim 12, wherein the ratio of ARA:DHA is about 2:1.

16. The preterm infant formula according to claim 12, wherein the infant formula is nutritionally complete and comprises lipid in an amount of from about 3 g/100 kcal to about 7 g/100 kcal, protein in an amount of from about 1 g/100 kcal to about 5 g/100 kcal, and carbohydrate in an amount of from about 8 g/100 kcal to about 12 g/100 kcal.

17. A method for enhancing the growth of a preterm infant comprising feeding said infant a nutrient-enriched formula containing DHA and ARA in quantities that, if said infant formula were the sole source of caloric intake, would deliver an average daily intake per kg body weight of about 2.5 to 60 mg DHA and about 5 to 120 mg ARA, said feeding continuing until said preterm infant reaches a corrected age of about six months.

18. A method for enhancing the neurological development of a preterm infant comprising feeding said infant a nutrient-enriched formula containing DHA and ARA in quantities that, if said infant formula were the sole source of caloric intake, would deliver an average daily intake per kg body weight of about 2.5 to 60 mg DHA and about 5 to 120 mg ARA, said feeding continuing until said preterm infant reaches a corrected age of about six months.