Preterm Birth, Child Development, Child Behavior
Conditions
Brief summary
The purpose of this study is to examine whether supplementation with certain polyunsaturated fatty acids can help development and behavior of children born preterm.
Interventions
2.5mL per day for 90 days Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)
OTHERCanola Oil Placebo
2.5mL per day for 90 days
Sponsors
Cures Within Reach
Marci and Bill Ingram Fund for Autism Spectrum Disorders Research
Sarah Keim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Months to 39 Months
Healthy volunteers
No
Inclusion criteria
1. Child born at less than or equal to 29 completed weeks' gestation; 2. Child between 18 months, 0 days and 38 months, 30 days old chronological age; 3. Child admitted to NICU and/or had a Neonatology Clinic follow up visit scheduled. 4. Child showing some autistic symptoms; 5. Child between the 5th and 95th percentiles (per WHO growth chart) for weight at his/her most recent hospital visit; 6. English spoken in the home, demonstrate ability to communicate in English well-enough to understand study, informed consent, and study questionnaires; and 7. Have informed consent on file.
Exclusion criteria
1. Consume LCPUFA supplement drops, chews, powders, Pediasure, or fatty fish more than 2x per week; 2. Unable to tolerate venipuncture; 3. Any major malformation that would preclude participation; 4. Cerebral Palsy (quadriparesis only); 5. Deafness; 6. Blindness; 7. Bleeding disorder; 8. Type I diabetes; 9. Fragile X Syndrome, Rett Syndrome, Angelman Syndrome, Tuberous Sclerosis; 10. Non febrile seizure in the last month without a clear and resolved etiology; 11. Feeding problem that may inhibit full participation; 12. Known fish allergy; 13. Known canola/rapeseed allergy or sensitivity; or 14. Recorded score of \<70 on Bayley Cognitive Section within the past year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2 | Baseline to 90 days post randomization | 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. |
| Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Baseline to 90 days post randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatty Acid | Baseline to 90 days post randomization | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Feasibility: Future Full-scale Multi-site Study | Pre-baseline to 90 days post randomization | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement 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 | 15 |
| Canola Oil Placebo Canola Oil Placebo: 2.5mL per day for 90 days | 16 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued Intervention | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Canola Oil Placebo | Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 15 Participants | 31 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 25 Months | 30 Months | 27 Months |
| Region of Enrollment United States | 16 participants | 15 participants | 31 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 16 |
| other Total, other adverse events | 15 / 15 | 16 / 16 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 |
Outcome results
Primary
Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA)
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Dysregulation | -0.9 score on a scale | Standard Deviation 2.3 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Internalizing | -0.9 score on a scale | Standard Deviation 2.3 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Problems | 3.2 score on a scale | Standard Deviation 6.1 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Austism Spectrum Disorder | -1.5 score on a scale | Standard Deviation 2.6 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Externalizing | 0.3 score on a scale | Standard Deviation 1.3 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Red Flag | -2.5 score on a scale | Standard Deviation 3.8 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Competence | 1.9 score on a scale | Standard Deviation 3.2 |
| Canola Oil Placebo | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Red Flag | -1.0 score on a scale | Standard Deviation 2.8 |
| Canola Oil Placebo | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Competence | 0.9 score on a scale | Standard Deviation 3.6 |
| Canola Oil Placebo | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Problems | -3.2 score on a scale | Standard Deviation 5 |
| Canola Oil Placebo | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Dysregulation | -0.8 score on a scale | Standard Deviation 2.2 |
| Canola Oil Placebo | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Externalizing | -0.7 score on a scale | Standard Deviation 2.3 |
| Canola Oil Placebo | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Internalizing | -0.5 score on a scale | Standard Deviation 2.3 |
| Canola Oil Placebo | Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA) | Austism Spectrum Disorder | 0.8 score on a scale | Standard Deviation 3.8 |
Comparison: The reported p-value is for the comparison of the change in Competence scores between groups (LCPUFA vs. Placebo).p-value: 0.22Mixed Models Analysis
Comparison: The reported p-value is for the comparison of the change in Problem scores between groups (LCPUFA vs. Placebo).p-value: 0.92Mixed Models Analysis
Comparison: The reported p-value is for the comparison of the change in Dysregulation scores between groups (LCPUFA vs. Placebo).p-value: 0.88Mixed Models Analysis
Comparison: The reported p-value is for the comparison of the change in Externalizing scores between groups (LCPUFA vs. Placebo).p-value: 0.23Mixed Models Analysis
Comparison: The reported p-value is for the comparison of the change in Internalizing scores between groups (LCPUFA vs. Placebo).p-value: 0.91Mixed Models Analysis
Comparison: The reported p-value is for the comparison of the change in Austism Spectrum Disorder scores between groups (LCPUFA vs. Placebo).p-value: 0.03Mixed Models Analysis
Comparison: The reported p-value is for the comparison of the change in Red Flag scores between groups (LCPUFA vs. Placebo).p-value: 0.07Mixed Models Analysis
Primary
Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2 | -1.0 score on a scale | Standard Deviation 2.6 |
| Canola Oil Placebo | Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2 | -0.2 score on a scale | Standard Deviation 1.9 |
Comparison: 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.p-value: 0.67Mixed Models Analysis
Secondary
Fatty Acid
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 20:5n-3 | 38.7 nmol/mL | Standard Deviation 8.21 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 22:6n-3 | 109 nmol/mL | Standard Deviation 26.5 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 22:5n-3 | -3.27 nmol/mL | Standard Deviation 4.88 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | total omega-6 | 86.9 nmol/mL | Standard Deviation 122.71 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | total omega-3 | 146 nmol/mL | Standard Deviation 34.13 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 10:0 | 2.15 nmol/mL | Standard Deviation 3.23 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 12:0 | 2.56 nmol/mL | Standard Deviation 2.9 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 14:0 | -3.07 nmol/mL | Standard Deviation 4.62 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 16:0 | 177 nmol/mL | Standard Deviation 99.6 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 16:1n-7 | 7.83 nmol/mL | Standard Deviation 9.9 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 18:0 | 138 nmol/mL | Standard Deviation 69.25 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 18:1n-9 | 80.5 nmol/mL | Standard Deviation 46.66 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 18:1n-7 | 11.0 nmol/mL | Standard Deviation 4.98 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 18:2n-6 | 18.7 nmol/mL | Standard Deviation 69.83 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 18:3n-6 | 1.69 nmol/mL | Standard Deviation 2.54 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 18:3n-3 | 2.44 nmol/mL | Standard Deviation 2.19 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 18:4n-3 | -0.15 nmol/mL | Standard Deviation 1.19 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 20:3n-6 | 6.24 nmol/mL | Standard Deviation 9.05 |
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Fatty Acid | 20:4n-6 | 60.3 nmol/mL | Standard Deviation 57.74 |
| Canola Oil Placebo | Fatty Acid | 20:3n-6 | -17.1 nmol/mL | Standard Deviation 15.3 |
| Canola Oil Placebo | Fatty Acid | 18:0 | -40.3 nmol/mL | Standard Deviation 99.18 |
| Canola Oil Placebo | Fatty Acid | 20:5n-3 | -2.73 nmol/mL | Standard Deviation 12.9 |
| Canola Oil Placebo | Fatty Acid | 18:3n-3 | -3.81 nmol/mL | Standard Deviation 5.5 |
| Canola Oil Placebo | Fatty Acid | 22:6n-3 | -1.44 nmol/mL | Standard Deviation 26.69 |
| Canola Oil Placebo | Fatty Acid | 18:1n-9 | -21.6 nmol/mL | Standard Deviation 50.19 |
| Canola Oil Placebo | Fatty Acid | total omega-6 | -37.9 nmol/mL | Standard Deviation 138.07 |
| Canola Oil Placebo | Fatty Acid | 22:5n-3 | -2.84 nmol/mL | Standard Deviation 4.97 |
| Canola Oil Placebo | Fatty Acid | total omega-3 | -14.3 nmol/mL | Standard Deviation 43.64 |
| Canola Oil Placebo | Fatty Acid | 18:1n-7 | -2.13 nmol/mL | Standard Deviation 6.23 |
| Canola Oil Placebo | Fatty Acid | 10:0 | -4.91 nmol/mL | Standard Deviation 7.37 |
| Canola Oil Placebo | Fatty Acid | 18:4n-3 | -3.44 nmol/mL | Standard Deviation 3.75 |
| Canola Oil Placebo | Fatty Acid | 12:0 | -2.43 nmol/mL | Standard Deviation 6.68 |
| Canola Oil Placebo | Fatty Acid | 18:2n-6 | -8.72 nmol/mL | Standard Deviation 56.53 |
| Canola Oil Placebo | Fatty Acid | 14:0 | -8.42 nmol/mL | Standard Deviation 6.84 |
| Canola Oil Placebo | Fatty Acid | 20:4n-6 | -7.72 nmol/mL | Standard Deviation 70.23 |
| Canola Oil Placebo | Fatty Acid | 16:0 | -28.0 nmol/mL | Standard Deviation 116.05 |
| Canola Oil Placebo | Fatty Acid | 18:3n-6 | -4.29 nmol/mL | Standard Deviation 5.36 |
| Canola Oil Placebo | Fatty Acid | 16:1n-7 | 27.0 nmol/mL | Standard Deviation 17.75 |
Comparison: 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).p-value: 0.31t-test, 2 sided
Comparison: 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).p-value: 0.47t-test, 2 sided
Comparison: 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).p-value: 0.38t-test, 2 sided
Comparison: 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).p-value: 0.02t-test, 2 sided
Comparison: 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).p-value: 0.16t-test, 2 sided
Comparison: 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).p-value: 0.02t-test, 2 sided
Comparison: 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).p-value: 0.02t-test, 2 sided
Comparison: 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).p-value: 0.21t-test, 2 sided
Comparison: 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).p-value: 0.34t-test, 2 sided
Comparison: 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).p-value: 0.24t-test, 2 sided
Comparison: 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).p-value: 0.5t-test, 2 sided
Comparison: 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).p-value: 0.07t-test, 2 sided
Comparison: 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).p-value: 0.1t-test, 2 sided
Comparison: 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).p-value: 0.001t-test, 2 sided
Comparison: 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).p-value: 0.71t-test, 2 sided
Comparison: 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).p-value: 0.001t-test, 2 sided
Comparison: The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (Total Omega-6) between groups (LCPUFA vs. Placebo).p-value: 0.1t-test, 2 sided
Comparison: The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (total omega-3) between groups (LCPUFA vs. Placebo).p-value: 0.1t-test, 2 sided
Other Pre-specified
Feasibility: Future Full-scale Multi-site Study
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement | Feasibility: Future Full-scale Multi-site Study | 15 Participants |
| Canola Oil Placebo | Feasibility: Future Full-scale Multi-site Study | 16 Participants |