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Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity

Primary Purpose

Retinopathy of Prematurity

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Omegaven
Standard lipids (primarily omega-6 fatty acids)
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Retinopathy of Prematurity focused on measuring ROP, Premature infant

Eligibility Criteria

undefined - 7 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Infants born less than or equal to 30 weeks gestation or less than 1500 g at birth

Exclusion Criteria:

  • Patients with liver disease as tested by liver function tests (LFTs)
  • ≤ 500 grams birthweight

Sites / Locations

  • University of California, San Diego Jacobs Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care (Standard Nutrition)

Omegaven

Arm Description

Infants in this group will receive standard lipids (predominantly Omega-6 fatty acids).

Infants in this group will receive lipid supplementation with omega-3 fatty acids.

Outcomes

Primary Outcome Measures

Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T0
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T1
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Changes in mRNA Expression in Blood of STAT3, PPAR-gamma, and STC-1 at T2
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Changes in mRNA Expression in Blood of STAT3 and PPAR-ɣ at T3
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.

Secondary Outcome Measures

Pilot Assay of Basic Fatty Acid Concentrations in Blood at Time T2
We measured concentrations of basic fatty acids in the blood plasma samples: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA). Blood samples were processed by the University of California San Diego lipidomics core and fatty acid concentrations in pmol/ml plasma were determined using gas chromatography-mass spectrometry.
Percentage of Eyes at the Furthest Stage of ROP Achieved
Furthest severity stage of ROP achieved by patients in Arm 1 compared to Arm 2, per eye as assessed by weekly ROP screenings from approximately 31 weeks through 40 weeks adjusted age. Severity staging was determined in an eye exam per accepted clinical guidelines by a trained clinician and retinopathy of prematurity specialist. Briefly, staging is assigned based on the junction of the vascularized and avascular retina when viewed using indirect ophthalmoscopy. The higher the stage, the more severe the ROP. Per the American Association for Pediatric Ophthalmology and Strabismus, Stage 0: no clear demarcation line between vascularized and non-vascularized retina Stage 1: demarcation line that separates normal from premature retina Stage 2: ridge with height and width Stage 3: growth of fragile new abnormal blood vessels
Number of Patients Requiring Laser Treatment in Arm 1 Versus Arm 2
Number of patients with retinopathy of prematurity severe enough to require laser treatment by the adjusted age of 40 weeks, as assessed by weekly ROP screenings from approximately 31 weeks through 40 weeks adjusted age.

Full Information

First Posted
June 26, 2015
Last Updated
November 30, 2022
Sponsor
University of California, San Diego
Collaborators
The Hartwell Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02486042
Brief Title
Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity
Official Title
Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity: Proposal for a Prospective Randomized Controlled Masked Clinical Trial With Lipidomic and Transcriptomic Analyses
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
December 2019 (Actual)
Study Completion Date
December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
The Hartwell Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Retinopathy of prematurity (ROP) is a blinding disease affecting infants born prematurely. These infants do not have enough essential fatty acids to structurally support the retina, the nerve tissue in the eye which allows us to see. A recent study showed that giving omega-3 (n-3) fatty acids to these infants soon after birth made them less likely to need invasive treatments for eye disease. This research trial will give young infants born prematurely n-3 fish oil treatment and look at how this changes factors in the blood that promote disease. Detailed blood studies comparing infants with and without ROP will be performed and the infants will be followed over time to assess their eye development.
Detailed Description
Approximately 517,000 infants are born prematurely every year. As low birth weight and premature infants are surviving longer, they are at risk of developing severe retinopathy of prematurity (ROP). ROP is a disease of the eye affecting prematurely-born babies. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. ROP can be mild and may resolve spontaneously, but it may lead to blindness in serious cases. ROP is the leading cause of irreversible childhood blindness in the United States. As such, all preterm babies are at risk for ROP, and very low birth weight is an important risk factor. Researchers have found that increasing omega-3 fatty acids and decreasing omega-6 fatty acids in the diet of mice with eye disease similar to ROP had reduced areas of blood vessel loss and abnormal blood vessel growth. These findings represent new evidence suggesting the possibility that omega-3 fatty acids act as protective factors in diseases that affect retinal blood vessels. Omega-3 fatty acids make compounds that protect against the growth of abnormal blood vessels by preventing inflammation. In two European studies, this treatment decreased the risk of needing laser treatment in the eye for ROP. This study has not yet been repeated in the United States. The purpose of this study is to learn how omega-3 fatty acid supplementation in low birth weight infants changes the blood profile of infants receiving this nutritional treatment. Infants are enrolled in this study shortly after birth and receive IV and/or oral supplementation until they are full term or the retinal blood vessels have completely developed, shortly after term. Once the treatment is over, these infants will continue to be followed for growth and development of their eyes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinopathy of Prematurity
Keywords
ROP, Premature infant

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care (Standard Nutrition)
Arm Type
Active Comparator
Arm Description
Infants in this group will receive standard lipids (predominantly Omega-6 fatty acids).
Arm Title
Omegaven
Arm Type
Experimental
Arm Description
Infants in this group will receive lipid supplementation with omega-3 fatty acids.
Intervention Type
Drug
Intervention Name(s)
Omegaven
Other Intervention Name(s)
Omega-3
Intervention Description
Infants will receive nutritional supplementation with omega-3 fatty acids (omegaven).
Intervention Type
Dietary Supplement
Intervention Name(s)
Standard lipids (primarily omega-6 fatty acids)
Other Intervention Name(s)
Intralipid
Intervention Description
Infants will receive nutritional supplementation with standard intralipid, composed primarily of omega-6 fatty acids.
Primary Outcome Measure Information:
Title
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T0
Description
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Time Frame
T0 as defined in study protocol: prior to parental nutrition, within first three days of life
Title
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T1
Description
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Time Frame
T1 as defined in study protocol: 5 days after parenteral nutrition is started; grace period +/-3 days therefore total 2-8 days after parenteral nutrition started.
Title
Changes in mRNA Expression in Blood of STAT3, PPAR-gamma, and STC-1 at T2
Description
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Time Frame
T2 as defined in study protocol: 5 days after enteral nutrition full feeds have arrived; grace period +/-3 days therefore total 2-8 days after full enteral nutrition arrived.
Title
Changes in mRNA Expression in Blood of STAT3 and PPAR-ɣ at T3
Description
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Time Frame
T3 as defined in study protocol: Prior to discharge from hospital coinciding with time that ROP may be present, ≥35 weeks adjusted age.
Secondary Outcome Measure Information:
Title
Pilot Assay of Basic Fatty Acid Concentrations in Blood at Time T2
Description
We measured concentrations of basic fatty acids in the blood plasma samples: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA). Blood samples were processed by the University of California San Diego lipidomics core and fatty acid concentrations in pmol/ml plasma were determined using gas chromatography-mass spectrometry.
Time Frame
T2 as defined in study protocol: 5 days after enteral nutrition full feeds have arrived; grace period +/-3 days therefore total 2-8 days after full enteral nutrition arrived.
Title
Percentage of Eyes at the Furthest Stage of ROP Achieved
Description
Furthest severity stage of ROP achieved by patients in Arm 1 compared to Arm 2, per eye as assessed by weekly ROP screenings from approximately 31 weeks through 40 weeks adjusted age. Severity staging was determined in an eye exam per accepted clinical guidelines by a trained clinician and retinopathy of prematurity specialist. Briefly, staging is assigned based on the junction of the vascularized and avascular retina when viewed using indirect ophthalmoscopy. The higher the stage, the more severe the ROP. Per the American Association for Pediatric Ophthalmology and Strabismus, Stage 0: no clear demarcation line between vascularized and non-vascularized retina Stage 1: demarcation line that separates normal from premature retina Stage 2: ridge with height and width Stage 3: growth of fragile new abnormal blood vessels
Time Frame
approximately 31 to 40 weeks (adjusted age = gestation + post-natal age)
Title
Number of Patients Requiring Laser Treatment in Arm 1 Versus Arm 2
Description
Number of patients with retinopathy of prematurity severe enough to require laser treatment by the adjusted age of 40 weeks, as assessed by weekly ROP screenings from approximately 31 weeks through 40 weeks adjusted age.
Time Frame
approximately 31 to 40 weeks (adjusted age = gestation + post-natal age)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
7 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Infants born less than or equal to 30 weeks gestation or less than 1500 g at birth Exclusion Criteria: Patients with liver disease as tested by liver function tests (LFTs) ≤ 500 grams birthweight
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shira L. Robbins, M.D.
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego Jacobs Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23364006
Citation
Gould JF, Smithers LG, Makrides M. The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2013 Mar;97(3):531-44. doi: 10.3945/ajcn.112.045781. Epub 2013 Jan 30.
Results Reference
background
PubMed Identifier
7285840
Citation
Clandinin MT, Chappell JE, Heim T, Swyer PR, Chance GW. Fatty acid utilization in perinatal de novo synthesis of tissues. Early Hum Dev. 1981 Sep;5(4):355-66. doi: 10.1016/0378-3782(81)90016-5.
Results Reference
background
PubMed Identifier
23935289
Citation
Arsic A, Vucic V, Prekajski N, Tepsic J, Ristic-Medic D, Velickovic V, Glibetic M. Different fatty acid composition of serum phospholipids of small and appropriate for gestational age preterm infants and of milk from their mothers. Hippokratia. 2012 Jul;16(3):230-5.
Results Reference
background
PubMed Identifier
23963690
Citation
Pawlik D, Lauterbach R, Walczak M, Hurkala J, Sherman MP. Fish-oil fat emulsion supplementation reduces the risk of retinopathy in very low birth weight infants: a prospective, randomized study. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):711-6. doi: 10.1177/0148607113499373. Epub 2013 Aug 20.
Results Reference
background
PubMed Identifier
17589522
Citation
Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, Hong S, Pravda EA, Majchrzak S, Carper D, Hellstrom A, Kang JX, Chew EY, Salem N Jr, Serhan CN, Smith LEH. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007 Jul;13(7):868-873. doi: 10.1038/nm1591. Epub 2007 Jun 24.
Results Reference
background
PubMed Identifier
20634487
Citation
Stahl A, Sapieha P, Connor KM, Sangiovanni JP, Chen J, Aderman CM, Willett KL, Krah NM, Dennison RJ, Seaward MR, Guerin KI, Hua J, Smith LE. Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy. Circ Res. 2010 Aug 20;107(4):495-500. doi: 10.1161/CIRCRESAHA.110.221317. Epub 2010 Jul 15.
Results Reference
background
PubMed Identifier
18708611
Citation
Smith LE. Through the eyes of a child: understanding retinopathy through ROP the Friedenwald lecture. Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5177-82. doi: 10.1167/iovs.08-2584. Epub 2008 Aug 15. No abstract available.
Results Reference
background
PubMed Identifier
15555528
Citation
SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005 Jan;24(1):87-138. doi: 10.1016/j.preteyeres.2004.06.002.
Results Reference
background
PubMed Identifier
21199856
Citation
Pawlik D, Lauterbach R, Turyk E. Fish-oil fat emulsion supplementation may reduce the risk of severe retinopathy in VLBW infants. Pediatrics. 2011 Feb;127(2):223-8. doi: 10.1542/peds.2010-2427. Epub 2011 Jan 3.
Results Reference
background
PubMed Identifier
23319354
Citation
Klein CJ, Havranek TG, Revenis ME, Hassanali Z, Scavo LM. Plasma fatty acids in premature infants with hyperbilirubinemia: before-and-after nutrition support with fish oil emulsion. Nutr Clin Pract. 2013 Feb;28(1):87-94. doi: 10.1177/0884533612469989.
Results Reference
background
PubMed Identifier
11236724
Citation
Heird WC. The role of polyunsaturated fatty acids in term and preterm infants and breastfeeding mothers. Pediatr Clin North Am. 2001 Feb;48(1):173-88. doi: 10.1016/s0031-3955(05)70292-3.
Results Reference
background
PubMed Identifier
11483801
Citation
O'Connor DL, Hall R, Adamkin D, Auestad N, Castillo M, Connor WE, Connor SL, Fitzgerald K, Groh-Wargo S, Hartmann EE, Jacobs J, Janowsky J, Lucas A, Margeson D, Mena P, Neuringer M, Nesin M, Singer L, Stephenson T, Szabo J, Zemon V; Ross Preterm Lipid Study. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics. 2001 Aug;108(2):359-71. doi: 10.1542/peds.108.2.359.
Results Reference
background
PubMed Identifier
16048149
Citation
Fleith M, Clandinin MT. Dietary PUFA for preterm and term infants: review of clinical studies. Crit Rev Food Sci Nutr. 2005;45(3):205-29. doi: 10.1080/10408690590956378.
Results Reference
background
PubMed Identifier
18400714
Citation
Smithers LG, Gibson RA, McPhee A, Makrides M. Effect of long-chain polyunsaturated fatty acid supplementation of preterm infants on disease risk and neurodevelopment: a systematic review of randomized controlled trials. Am J Clin Nutr. 2008 Apr;87(4):912-20. doi: 10.1093/ajcn/87.4.912.
Results Reference
background
PubMed Identifier
12093949
Citation
Fewtrell MS, Morley R, Abbott RA, Singhal A, Isaacs EB, Stephenson T, MacFadyen U, Lucas A. Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics. 2002 Jul;110(1 Pt 1):73-82. doi: 10.1542/peds.110.1.73.
Results Reference
background
PubMed Identifier
15812447
Citation
Clandinin MT, Van Aerde JE, Merkel KL, Harris CL, Springer MA, Hansen JW, Diersen-Schade DA. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. J Pediatr. 2005 Apr;146(4):461-8. doi: 10.1016/j.jpeds.2004.11.030.
Results Reference
background
PubMed Identifier
21328248
Citation
Schulzke SM, Patole SK, Simmer K. Long-chain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD000375. doi: 10.1002/14651858.CD000375.pub4.
Results Reference
background
Citation
Born Too Soon | March of Dimes. March Dimes Found. Partnersh. Matern. Newborn Child Heal. Save Child. World Heal. Organ. 2012. Available at: http://www.marchofdimes.com/mission/global-preterm.aspx.
Results Reference
background

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Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity

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