Preemie Tots: A Pilot Study to Understand the Effects of Prematurity in Toddlerhood - Study Results

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions	Preterm Birth Child Development Child Behavior
Interventions	Drug: LCPUFA oil supplement Other: Canola Oil Placebo
Enrollment	31

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement	Canola Oil Placebo
Arm/Group Description	Eicosapentaenoic acid (EPA) + Docos...	Canola Oil Placebo: 2.5mL per day f...
Arm/Group Description	Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) + Gamma-Linolenic acid (GLA) + Oleic Acid (OA) LCPUFA oil supplement: 2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg	Canola Oil Placebo: 2.5mL per day for 90 days
Period Title: Overall Study
Started	15	16
Completed	12	15
Not Completed	3	1
Reason Not Completed
Lost to Follow-up	2	0
Discontinued Intervention	1	1

Baseline Characteristics

Arm/Group Title		Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement	Canola Oil Placebo	Total
Arm/Group Description		Eicosapentaenoic acid (EPA) + Docos...	Canola Oil Placebo: 2.5mL per day f...	Total of all reporting groups
Arm/Group Description		Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) + Gamma-Linolenic acid (GLA) + Oleic Acid (OA) LCPUFA oil supplement: 2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg	Canola Oil Placebo: 2.5mL per day for 90 days	Total of all reporting groups
Overall Number of Baseline Participants		15	16	31
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	15 participants	16 participants	31 participants
	<=18 years	15 100.0%	16 100.0%	31 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous Median (Inter-Quartile Range) Unit of measure: Months
	Number Analyzed	15 participants	16 participants	31 participants
		30 (25 to 36)	25 (23 to 25)	27 (23 to 36)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	15 participants	16 participants	31 participants
	Female	7 46.7%	3 18.8%	10 32.3%
	Male	8 53.3%	13 81.3%	21 67.7%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	15 participants	16 participants	31 participants
United States		15	16	31

Outcome Measures

1.Primary Outcome


Title	Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2
Description	The Pervasive Developmental Disorders Screening Test-II stage 2 (PDDST...
Description	The Pervasive Developmental Disorders Screening Test-II stage 2 (PDDST-II) is a 14-item measure designed to discriminate Autism Spectrum Disorders from a related non-autistic developmental disorder in children ages 12 to 48 months old. The min score is 0 and the max score is 14. Scores equal to or greater than five yield a positive screen for autism. PDDST-II scores were measured at baseline and then again at study completion (90 days post randomization). The scores were calculated as the PDDST-II value at 90 days minus the PDDST-II value at baseline.
Time Frame	Baseline to 90 days post randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement	Canola Oil Placebo
Arm/Group Description:	Eicosapentaenoic acid (EPA) + Docos...	Canola Oil Placebo: 2.5mL per day f...
Arm/Group Description:	Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) + Gamma-Linolenic acid (GLA) + Oleic Acid (OA) LCPUFA oil supplement: 2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg	Canola Oil Placebo: 2.5mL per day for 90 days
Overall Number of Participants Analyzed	15	16
Mean (Standard Deviation) Unit of Measure: score on a scale
	-1.0 (2.6)	-0.2 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement, Canola Oil Placebo
	Comments	The sample size was determined based on the goal of confirming trial feasibility and estimating effect sizes for a full-scale trial, not for a definitive test of efficacy. The enrollment goal was 40, which would have provided an indication of an expected effect size for a larger full-scale trial (e.g., 53% power to detect a 2-point decrease (approximately 0.7-SD based on a prior study) in Pervasive Developmental Disorders Screening Test-II score). Funding limitations capped enrollment at 31.
	Type of Statistical Test	Other
	Comments	Analyses compared the change in Pervasive Developmental Disorders Screening Test-II scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect. Group mean differences divided by the standard deviation were also calculated as effect sizes.

Statistical Test of Hypothesis	P-Value	0.67
	Comments	Threshold for statistical significance (<0.05)
	Method	Mixed Models Analysis
	Comments	[Not Specified]

2.Primary Outcome


Title	Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA)
Description	Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 ...
Description	Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit. Scores were measured at baseline and then again at study completion (90 days post randomization). The change in BITSEA scores were calculated as the value at 90 days - the value at baseline.
Time Frame	Baseline to 90 days post randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement	Canola Oil Placebo
Arm/Group Description:	Eicosapentaenoic acid (EPA) + Docos...	Canola Oil Placebo: 2.5mL per day f...
Arm/Group Description:	Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) + Gamma-Linolenic acid (GLA) + Oleic Acid (OA) LCPUFA oil supplement: 2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)	Canola Oil Placebo: 2.5mL per day for 90 days
Overall Number of Participants Analyzed	15	16
Mean (Standard Deviation) Unit of Measure: score on a scale
Competence	1.9 (3.2)	0.9 (3.6)
Problems	3.2 (6.1)	-3.2 (5.0)
Dysregulation	-0.9 (2.3)	-0.8 (2.2)
Externalizing	0.3 (1.3)	-0.7 (2.3)
Internalizing	-0.9 (2.3)	-0.5 (2.3)
Austism Spectrum Disorder	-1.5 (2.6)	0.8 (3.8)
Red Flag	-2.5 (3.8)	-1.0 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in Competence scores between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.

Statistical Test of Hypothesis	P-Value	0.22
	Comments	Threshold for statistical significance (<0.05).
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in Problem scores between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Analyses compared the change in the BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes

Statistical Test of Hypothesis	P-Value	0.92
	Comments	Threshold for statistical significance (<0.05).
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in Dysregulation scores between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.

Statistical Test of Hypothesis	P-Value	0.88
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in Externalizing scores between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.

Statistical Test of Hypothesis	P-Value	0.23
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in Internalizing scores between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.

Statistical Test of Hypothesis	P-Value	0.91
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in Austism Spectrum Disorder scores between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.

Statistical Test of Hypothesis	P-Value	0.03
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in Red Flag scores between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.

Statistical Test of Hypothesis	P-Value	0.07
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

3.Secondary Outcome


Title	Fatty Acid
Description	The secondary outcome measures in this trial involve an examination of...
Description	The secondary outcome measures in this trial involve an examination of change in fatty acids from the first study visit to the final study visit.
Time Frame	Baseline to 90 days post randomization

Outcome Measure Data

Analysis Population Description

Rows titles are fatty acids with different C:D ratio where, "C" stands for Carbohydrate; "D" stands for Double bond; "C:D" is the ratio of the total amount of Carbon atoms of the fatty acid in relation to the number of double (unsaturated) bonds in it.


Arm/Group Title	LCPUFA Oil Supplement	Canola Oil Placebo
Arm/Group Description:	EPA + DHA + GLA + OA oil supplement...	Canola Oil Placebo: 2.5mL per day f...
Arm/Group Description:	EPA + DHA + GLA + OA oil supplement LCPUFA oil supplement: 2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)	Canola Oil Placebo: 2.5mL per day for 90 days
Overall Number of Participants Analyzed	13	15
Mean (Standard Deviation) Unit of Measure: nmol/mL
10:0	2.15 (3.23)	-4.91 (7.37)
12:0	2.56 (2.90)	-2.43 (6.68)
14:0	-3.07 (4.62)	-8.42 (6.84)
16:0	177 (99.60)	-28.0 (116.05)
16:1n-7	7.83 (9.90)	27.0 (17.75)
18:0	138 (69.25)	-40.3 (99.18)
18:1n-9	80.5 (46.66)	-21.6 (50.19)
18:1n-7	11.0 (4.98)	-2.13 (6.23)
18:2n-6	18.7 (69.83)	-8.72 (56.53)
18:3n-6	1.69 (2.54)	-4.29 (5.36)
18:3n-3	2.44 (2.19)	-3.81 (5.50)
18:4n-3	-0.15 (1.19)	-3.44 (3.75)
20:3n-6	6.24 (9.05)	-17.1 (15.30)
20:4n-6	60.3 (57.74)	-7.72 (70.23)
20:5n-3	38.7 (8.21)	-2.73 (12.90)
22:5n-3	-3.27 (4.88)	-2.84 (4.97)
22:6n-3	109 (26.50)	-1.44 (26.69)
total omega-6	86.9 (122.71)	-37.9 (138.07)
total omega-3	146 (34.13)	-14.3 (43.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (10:0 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.31
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (12:0 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.47
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (14:0 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.38
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (16:0 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.02
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (16:1n-7 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.16
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:0 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.02
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:1n-9 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.02
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:2n-6 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.21
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:3n-6 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.34
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:3n-3 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.24
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:4n-3 nmol/mL ) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.50
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (20:3n-6 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.07
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (20:4n-6 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.10
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (20:5n-3 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.001
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (22:5n-3 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.71
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (22:6n-3 nmol/mL) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.001
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (Total Omega-6) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.10
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	LCPUFA Oil Supplement, Canola Oil Placebo
	Comments	The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (total omega-3) between groups (LCPUFA vs. Placebo).
	Type of Statistical Test	Other
	Comments	Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.

Statistical Test of Hypothesis	P-Value	0.10
	Comments	P-values <0.05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]

4.Other Pre-specified Outcome


Title	Feasibility: Future Full-scale Multi-site Study
Description	Feasibility of a future full-scale multi-site study is assessed by exa...
Description	Feasibility of a future full-scale multi-site study is assessed by examining the number of children screened, the proportion of these children who screen positive for ASD, the number of children who agree to participate in the trial, the number of children who return for the second and third study visits, baseline differences in individual fatty acids between the intervention and comparison groups, and adherence to the assigned treatment.
Time Frame	Pre-baseline to 90 days post randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	LCPUFA Oil Supplement	Canola Oil Placebo
Arm/Group Description:	EPA + DHA + GLA + OA oil supplement...	Canola Oil Placebo: 2.5mL per day f...
Arm/Group Description:	EPA + DHA + GLA + OA oil supplement LCPUFA oil supplement: 2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)	Canola Oil Placebo: 2.5mL per day for 90 days
Overall Number of Participants Analyzed	15	16
Measure Type: Count of Participants Unit of Measure: Participants
	15 100.0%	16 100.0%

Adverse Events

Time Frame	Baseline to 90 days post randomization
Adverse Event Reporting Description	Information to be collected includes event description, time of onset, Study Doctor's assessment of severity, relationship to study product,and time of resolution/stabilization of the event. All AEs occurring during study participation must be documented appropriately regardless of relationship.

Arm/Group Title	LCPUFA Oil Supplement	Canola Oil Placebo
Arm/Group Description	EPA + DHA + GLA + OA oil supplement...	Canola Oil Placebo: 2.5mL per day f...
Arm/Group Description	EPA + DHA + GLA + OA oil supplement LCPUFA oil supplement: 2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)	Canola Oil Placebo: 2.5mL per day for 90 days
All-Cause Mortality
	LCPUFA Oil Supplement	Canola Oil Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/16 (0.00%)
Serious Adverse Events Serious Adverse Events
	LCPUFA Oil Supplement	Canola Oil Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/16 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	LCPUFA Oil Supplement	Canola Oil Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	15/15 (100.00%)	16/16 (100.00%)
Ear and labyrinth disorders
Ear Nose Throat Symptoms ^†	6/15 (40.00%)	9/16 (56.25%)
Gastrointestinal disorders
Gastrointestinal Symptoms ^†	10/15 (66.67%)	11/16 (68.75%)
Infections and infestations
Cold/Fever ^† [1]	2/15 (13.33%)	5/16 (31.25%)
Psychiatric disorders
Behavioral Symptoms ^†	3/15 (20.00%)	3/16 (18.75%)
Respiratory, thoracic and mediastinal disorders
Respiratory symptoms ^†	4/15 (26.67%)	7/16 (43.75%)
Skin and subcutaneous tissue disorders
Skin and Limb Symptoms ^†	4/15 (26.67%)	1/16 (6.25%)
† Indicates events were collected by systematic assessment [1] Multi-symptom illnesses reported by caregivers which typically included more than 1 body system and/or fever

Limitations and 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.

Results Point of Contact

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Name/Title:	Dr. Sarah Keim
Organization:	Nationwide Children's Hospital
Phone:	614-722-3177
EMail:	Sarah.Keim@nationwidechildrens.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Boone KM, Klebanoff MA, Rogers LK, Rausch J, Coury DL, Keim SA. Effects of Omega-3-6-9 fatty acid supplementation on behavior and sleep in preterm toddlers with autism symptomatology: Secondary analysis of a randomized clinical trial. Early Hum Dev. 2022 Jun;169:105588. doi: 10.1016/j.earlhumdev.2022.105588. Epub 2022 May 19.

Keim SA, Gracious B, Boone KM, Klebanoff MA, Rogers LK, Rausch J, Coury DL, Sheppard KW, Husk J, Rhoda DA. omega-3 and omega-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers. J Nutr. 2018 Feb 1;148(2):227-235. doi: 10.1093/jn/nxx047.

Boone KM, Gracious B, Klebanoff MA, Rogers LK, Rausch J, Coury DL, Keim SA. Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: A randomized controlled trial. Early Hum Dev. 2017 Dec;115:64-70. doi: 10.1016/j.earlhumdev.2017.09.015. Epub 2017 Sep 20. Erratum In: Early Hum Dev. 2018 Mar 2;:

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Responsible Party:	Sarah Keim, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:	NCT01683565
Other Study ID Numbers:	752311
First Submitted:	September 4, 2012
First Posted:	September 12, 2012
Results First Submitted:	July 25, 2018
Results First Posted:	January 3, 2019
Last Update Posted:	January 3, 2019