Bridging the Docosahexaenoic Acid (DHA) Gap: The Effects of Omega-3 Fatty Acid Supplementation in Premature Infants

• Sponsor: Sanford Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01908907
• Collaborator: The Gerber Foundation (Other)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

The purpose of this study is to understand if the "DHA gap" can be corrected by giving a daily dose of DHA oil to preterm babies.

DHA is an essential omega-3 fatty acid, which means our body cannot make DHA. We have to take it in through our diet. DHA is important for normal brain and eye health and it may also decrease inflammation. This is important for premature babies because they are at a greater risk for getting diseases related to inflammation, especially in their lungs, eyes and intestines. Since DHA is so important for normal growth, you will find DHA naturally in breast milk and it is now added to infant formula. But the amount in breast milk and infant formula is about half of what your infant should expect to get in the womb (about 13-29mg per day in breast milk vs. 50-75mg per day in the womb). Very premature babies are at an even greater disadvantage because they cannot always eat very much right away and that is the only way they can get essential fatty acids in their body. This means premature babies are getting less DHA than they would in the womb and then the "DHA gap" continues for a longer period of time. This gap also comes at a time when their brain is growing most rapidly and their bodies need it the most. This trial is designed to see if giving DHA, even before the baby can take food orally, will raise his/her DHA blood levels to those of normal term babies.

Condition or Disease	Intervention/Treatment	Phase
Prematurity	Dietary Supplement: DHA oil; Dietary Supplement: (MCT) Control oil	N/A

Detailed Description

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective is to develop a DHA supplementation strategy to overcome these barriers. This single-center, double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels will be analyzed at baseline, full feedings and near discharge in DHA or placebo supplemented preterm infants. Term peers will also have blood FA levels analyzed for comparison. Growth, feeding tolerance and adverse outcomes (NEC, intraventricular hemorrhage (IVH), thrombocytopenia, sepsis) will be evaluated. Study progress and safety will be monitored by an external Data Safety Monitoring Board (DSMB). Overall, the study aims to determine if daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Bridging the Docosahexaenoic Acid (DHA) Gap: The Effects of Omega-3 Fatty Acid Supplementation in Premature Infants
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: DHA oil DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one.	Dietary Supplement: DHA oil; Therapy Group:DHA oil administered at 50 mg/d (0.18ml) as an oil emulsion enterally with feedings or by gavage tube if the infant has one.
Placebo Comparator: (MCT) control oil MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one.	Dietary Supplement: (MCT) Control oil; Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one.

Outcome Measures

Primary Outcome Measures

1. Days to Reach Full Enteral Feedings and Days on Study Oil. [From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.]

   This study was designed to determine feasibility and tolerability of enteral DHA supplementation, but was not intended to determine the effects of DHA on health related outcomes. Tolerability was measured by days to reach full enteral feedings, days on study oil, GA at completion of the study and postnatal growth. The days to reach full enteral feedings was defined as enteral intake of 100kcal/kg/d. Safety and tolerability was closely monitored under the oversight of an independent DSMB.

2. Feasibility and Tolerability of Daily Enteral DHA Oil - Weight Change [30 days from birth]

   A linear mixed model was used to explore weight over time.

3. Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood [At baseline (enrollment, < 1 week of age), full feedings, discharge]

   Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).

4. Feasibility and Tolerability of Daily Enteral DHA Oil - Length Change [30 days from birth]

   A linear mixed model was used to explore length over time.

5. Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference [30 days from birth]

   A linear mixed model was used to explore head circumference over time.

Secondary Outcome Measures

1. LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood [At baseline (enrollment, <1 week of age), full feedings and discharge]

   Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).

Other Outcome Measures

1. LCPUFA Levels - Alpha-linolenic Acid (ALA) in Whole Blood [Baseline (<1 week of age), full enteral feedings and discharge]

   Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).

2. LCPUFA Levels - Linoleic Acid (LNA) [Baseline, full feedings and discharge]

   Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 24 Weeks to 33 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Preterm infants between 24 and 33 6/7 weeks gestation

• must be less than or equal to 1 week of age

Exclusion Criteria:

• infants who are considered by the medical team to be non-viable

• infants with multiple or severe congenital anomalies such as gastroschisis, congenital chylothorax or other illnesses that do not allow a feeding tube to be placed or utilized at 7 days of age.

• term infants: who are born to mothers with diabetes or are small for gestational age (SGA-less than the 10th% for adjusted gestational age

• All families consented for this study will need to be able to read and write English

• Mother must be 18 years of age or older

• Taking Omegaven

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanford Health USD	Sioux Falls	South Dakota	United States	57117

Sponsors and Collaborators

• Sanford Health
• The Gerber Foundation

Investigators

• Principal Investigator: Michelle L Baack, MD, Sanford Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanford Health
• ClinicalTrials.gov Identifier: NCT01908907
• Other Study ID Numbers: DHA Gap
• First Posted: Jul 26, 2013
• Last Update Posted: Mar 21, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sanford Health: Premature Infants; DHA(docosahexaenoic acid); DHA deficit
• Additional relevant MeSH terms: Premature Birth

Study Results

Participant Flow

Recruitment Details	Ninety infants, less than or equal to one week of age, were recruited from the Sanford Health Boekelheide Neonatal Intensive Care Unit (NICU) between October 2012 and March 2014.
Pre-assignment Detail	Preterm infants were between 24 and 33 6/7 weeks gestational age (GA) at birth. Adaptive enrollment was used to assure that infants <28 weeks GA were enrolled over the same time period as more commonly admitted preterm infants >28 weeks GA.

Arm/Group Title	DHA Oil	Medium Chain Triglyceride (MCT) Control Oil
Arm/Group Description	DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Period Title: Overall Study
STARTED	31	29
COMPLETED	29	29
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	DHA Supplemented	Placebo Supplemented	Total
Arm/Group Description	Preterm infants (31) randomized to receive 50mg/d of enteral DHA supplementation	Preterm infants (29) randomized to receive placebo study oil	Total of all reporting groups
Overall Participants	31	29	60
Age (weeks of GA) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks of GA]	30.69 (2.42)	30.35 (2.46)	30.52 (2.43)
Sex: Female, Male (Count of Participants)
Female	15 48.4%	15 51.7%	30 50%
Male	16 51.6%	14 48.3%	30 50%
Race/Ethnicity, Customized (Count of Participants)
Hispanic	0 0%	0 0%	0 0%
Non-Hispanic	28 90.3%	25 86.2%	53 88.3%
Unknown	3 9.7%	4 13.8%	7 11.7%
Region of Enrollment (Count of Participants)
United States	31 100%	29 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Days to Reach Full Enteral Feedings and Days on Study Oil.
Description	This study was designed to determine feasibility and tolerability of enteral DHA supplementation, but was not intended to determine the effects of DHA on health related outcomes. Tolerability was measured by days to reach full enteral feedings, days on study oil, GA at completion of the study and postnatal growth. The days to reach full enteral feedings was defined as enteral intake of 100kcal/kg/d. Safety and tolerability was closely monitored under the oversight of an independent DSMB.
Time Frame	From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.

Outcome Measure Data

Analysis Population Description

Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made.

Arm/Group Title	DHA Oil	(MCT) Control Oil
Arm/Group Description	DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml	MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
Measure Participants	31	29
Days to reach full enteral feedings	20.00 (8.32)	16.21 (7.41)
Days on Study oil	34.00 (19.2)	33.71 (16.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DHA Oil, (MCT) Control Oil
	Comments	All analyses used the intent-to-treat study population. A linear mixed model was used to assess differences in time to full feeds, days on study drug, and gestational age at discharge. These models included a random effect for multiples, which was maintained in the model after testing. Fixed effects included treatment and GA group for time to full feeds and days on study drug and treatment effect for gestational age at discharge.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Regression, Linear
	Comments	Outcome was transformed using a natural logarithm transformation. Models included gestational age group since the randomization was blocked.
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	13.5
	Confidence Interval	(2-Sided) 95%; 0.2 to 28.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.5
	Estimation Comments	Since analyzed on the log scale, estimates provide are % change rather than absolute change between group.

2. Primary Outcome

Title	Feasibility and Tolerability of Daily Enteral DHA Oil - Weight Change
Description	A linear mixed model was used to explore weight over time.
Time Frame	30 days from birth

Outcome Measure Data

Analysis Population Description

Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU.

Arm/Group Title	DHA Supplemented	MCT (Placebo Control Group)
Arm/Group Description	Preterm infants supplemented with 50mg/d (0.18ml) of enteral DHA from the first week of life until term GA or discharge, whichever came first.	Preterm infants receiving 0.18 ml of MCT (control oil) from the first week of life until term GA or discharge, whichever came first.
Measure Participants	31	29
Mean (Standard Error) [Grams per day]	18.4 (0.57)	18.4 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DHA Oil, (MCT) Control Oil
	Comments	Linear mixed models were used to explore growth over time (weight, length and head circumference). These models included a random effect for intercepts and slopes to account for subject specific growth over time as well as a random effect for possible correlation between twins and triplets present in the data set. Fixed effects included both a linear and quadratic time effect, GA at birth, treatment group, full feeds (yes/no), and interactions. Non-significant interactions were eliminated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	Regression, Linear
	Comments	This is a complex regression model including linear and quadratic growth and interactions as specified above.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.016
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.008
	Estimation Comments

3. Primary Outcome

Title	Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood
Description	Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Time Frame	At baseline (enrollment, < 1 week of age), full feedings, discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DHA Supplemented	MCT (Placebo Control Group)
Arm/Group Description	Preterm infants supplemented with 50mg/d (0.18ml) of enteral DHA from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.	Preterm infants receiving 0.18 ml of MCT (control oil) from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.
Measure Participants	31	29
Baseline Comparisons	2.91 (0.45)	2.88 (0.68)
Full Enteral Feedings	2.83 (0.50)	3.03 (0.54)
Discharge	2.87 (0.50)	3.55 (0.44)

4. Primary Outcome

Title	Feasibility and Tolerability of Daily Enteral DHA Oil - Length Change
Description	A linear mixed model was used to explore length over time.
Time Frame	30 days from birth

Outcome Measure Data

Analysis Population Description

Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU.

Arm/Group Title	DHA Supplemented	MCT (Placebo Control Group)
Arm/Group Description	Preterm infants supplemented with 50mg/d (0.18ml) of enteral DHA from the first week of life until term GA or discharge, whichever came first.	Preterm infants receiving 0.18 ml of MCT (control oil) from the first week of life until term GA or discharge, whichever came first.
Measure Participants	31	29
Mean (Standard Error) [Centimeters per day]	0.13 (0.006)	0.12 (0.004)

5. Primary Outcome

Title	Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference
Description	A linear mixed model was used to explore head circumference over time.
Time Frame	30 days from birth

Outcome Measure Data

Analysis Population Description

Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU.

Arm/Group Title	DHA Supplemented	MCT (Placebo Control Group)
Arm/Group Description	Preterm infants supplemented with 50mg/d (0.18ml) of enteral DHA from the first week of life until term GA or discharge, whichever came first.	Preterm infants receiving 0.18 ml of MCT (control oil) from the first week of life until term GA or discharge, whichever came first.
Measure Participants	31	29
Mean (Standard Error) [Centimeters per day]	0.10 (0.004)	0.10 (0.004)

6. Secondary Outcome

Title	LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood
Description	Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Time Frame	At baseline (enrollment, <1 week of age), full feedings and discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DHA Supplemented	MCT (Placebo Control Group)
Arm/Group Description	Preterm infants supplemented with 50mg/d (0.18ml) of enteral DHA from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.	Preterm infants receiving 0.18 ml of MCT (control oil) from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.
Measure Participants	31	29
Baseline	13.21 (2.22)	14.89 (1.89)
Full Enteral Feedings	14.35 (1.51)	14.87 (1.50)
Discharge	14.31 (1.26)	13.94 (1.67)

7. Other Pre-specified Outcome

Title	LCPUFA Levels - Alpha-linolenic Acid (ALA) in Whole Blood
Description	Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Time Frame	Baseline (<1 week of age), full enteral feedings and discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DHA Supplemented	MCT (Placebo Control Group)
Arm/Group Description	Preterm infants supplemented with 50mg/d (0.18ml) of enteral DHA from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.	Preterm infants receiving 0.18 ml of MCT (control oil) from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.
Measure Participants	31	29
Baseline	0.74 (0.50)	0.55 (0.33)
Full enteral feedings	0.21 (0.13)	0.20 (0.11)
Discharge	0.24 (0.13)	0.26 (0.13)

8. Other Pre-specified Outcome

Title	LCPUFA Levels - Linoleic Acid (LNA)
Description	Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Time Frame	Baseline, full feedings and discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DHA Supplemented	MCT (Placebo Control Group)
Arm/Group Description	Preterm infants supplemented with 50mg/d (0.18ml) of enteral DHA from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.	Preterm infants receiving 0.18 ml of MCT (control oil) from the first week of life until term GA or discharge, whichever came first. LCPUFA levels were measured at baseline, after reaching full enteral feedings and at discharge or term GA, whichever came first.
Measure Participants	31	29
Baseline	18.45 (4.51)	16.45 (3.39)
Full feedings	14.72 (2.05)	14.95 (2.04)
Discharge	15.37 (2.39)	16.64 (3.18)

Adverse Events

Time Frame	Monitored for 30 days after last dose of study medication.
Arm/Group Title	DHA Oil		(MCT) Control Oil
Arm/Group Description	DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml		MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion
All Cause Mortality
	DHA Oil		(MCT) Control Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	DHA Oil		(MCT) Control Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/31 (3.2%)		0/29 (0%)
General disorders
Death	1/31 (3.2%)	1	0/29 (0%)	0
Infections and infestations
Sepsis	1/31 (3.2%)	1	0/29 (0%)	0
Other (Not Including Serious) Adverse Events
	DHA Oil		(MCT) Control Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/31 (100%)		29/29 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	1/31 (3.2%)	1	0/29 (0%)	0
Anemia	20/31 (64.5%)	20	14/29 (48.3%)	14
Other Blood and lymphatic disorders	0/31 (0%)	0	4/29 (13.8%)	5
Cardiac disorders
Periventricular Leukomalacia	0/31 (0%)	0	1/29 (3.4%)	1
Other Cardiac Disorders	1/31 (3.2%)	1	1/29 (3.4%)	1
Congenital heart defect	0/31 (0%)	0	1/29 (3.4%)	1
Patent Ductus Arteriosus	3/31 (9.7%)	3	3/29 (10.3%)	3
Physiologic murmur	13/31 (41.9%)	15	6/29 (20.7%)	7
Endocrine disorders
Adrenal insufficiency	1/31 (3.2%)	1	0/29 (0%)	0
Other Endocrine Disorders	1/31 (3.2%)	1	0/29 (0%)	0
Hypothyroidism	0/31 (0%)	0	1/29 (3.4%)	1
Eye disorders
Retinopathy of Prematurity	7/31 (22.6%)	7	5/29 (17.2%)	5
Gastrointestinal disorders
Gastro-esophageal Reflux Disease	6/31 (19.4%)	6	4/29 (13.8%)	4
Constipation	0/31 (0%)	0	2/29 (6.9%)	2
Dysfunctional bottling/swallowing	7/31 (22.6%)	7	1/29 (3.4%)	1
Gastritis	0/31 (0%)	0	1/29 (3.4%)	1
Gastrointestinal Disorder NOS	0/31 (0%)	0	1/29 (3.4%)	1
General disorders
Other General Disorder	2/31 (6.5%)	2	2/29 (6.9%)	2
Pain	0/31 (0%)	0	1/29 (3.4%)	1
Hepatobiliary disorders
Cholecystitis	1/31 (3.2%)	1	1/29 (3.4%)	2
Infections and infestations
Sepsis (Grade 4)	3/31 (9.7%)	3	3/29 (10.3%)	3
Conjunctivitis	1/31 (3.2%)	1	2/29 (6.9%)	2
Other Infections and Infestations	0/31 (0%)	0	1/29 (3.4%)	1
Meningitis	0/31 (0%)	0	1/29 (3.4%)	1
Pneumonia	2/31 (6.5%)	2	0/29 (0%)	0
Tracheitis	0/31 (0%)	0	2/29 (6.9%)	2
Urinary Tract Infection	1/31 (3.2%)	1	1/29 (3.4%)	1
Investigations
Blood bilirubin increased	2/31 (6.5%)	2	1/29 (3.4%)	1
Metabolism and nutrition disorders
Milk Soy Protein Intolerance	4/31 (12.9%)	5	4/29 (13.8%)	4
Hypercalcemia	1/31 (3.2%)	1	0/29 (0%)	0
Other Metabolism and Nutrition Disorders	1/31 (3.2%)	1	0/29 (0%)	0
Musculoskeletal and connective tissue disorders
Other Musculoskeletal Disorders	0/31 (0%)	0	1/29 (3.4%)	3
Osteoporosis	1/31 (3.2%)	1	0/29 (0%)	0
Scoliosis	0/31 (0%)	0	1/29 (3.4%)	1
Nervous system disorders
Intraventricular Hemorrhage	0/31 (0%)	0	1/29 (3.4%)	1
Psychiatric disorders
Irritability	2/31 (6.5%)	2	0/29 (0%)	0
Renal and urinary disorders
Other Renal and Urinary Disorders	1/31 (3.2%)	1	2/29 (6.9%)	2
Urinary Tract Obstruction	0/31 (0%)	0	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary Dysplasia	2/31 (6.5%)	2	3/29 (10.3%)	3
Apnea	6/31 (19.4%)	6	9/29 (31%)	9
Hypoxia	1/31 (3.2%)	1	0/29 (0%)	0
Periodic Breathing	2/31 (6.5%)	2	5/29 (17.2%)	5
Pneumothorax	1/31 (3.2%)	1	0/29 (0%)	0
Respiratory Failure	1/31 (3.2%)	1	0/29 (0%)	0
Other Respiratory Disorder	5/31 (16.1%)	5	3/29 (10.3%)	3
Skin and subcutaneous tissue disorders
Rash	5/31 (16.1%)	5	4/29 (13.8%)	4
Other Skin Disorders	2/31 (6.5%)	2	0/29 (0%)	0
Vascular disorders
Thromboembolic Event	1/31 (3.2%)	1	0/29 (0%)	0
Other Vascular Disorders	1/31 (3.2%)	1	0/29 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.