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DHA, a type of fatty acid, is important in early development, both in terms of reproductive physiology of gestation and in postnatal behavioral and cognitive function. In adults, DHA has been shown to lower triglycerides and is important to cardiovascular health and autonomic control, lowering heart rate and blood pressure and increasing heart variability. Little is known about how fatty acids impact cardiac control in infants, children or the fetus. Our hypothesis is that maternal DHA supplementation (600 mg/day) will lower fetal HR and increase fetal HRV.
We have observed that maternal DHA supplementation during pregnancy results in lower fetal heart rate (HR) and higher heart-rate variability (HRV). In another study, we found that infants on DHA supplemented formula have lower HR. Because DHA supplementation in infancy is associated with improved neurobehavioral outcomes and infants with lower HR and higher vagal control have been found to have improved developmental outcomes, the first aim is to conduct a randomized, placebo-controlled trial to determine whether maternal DHA supplementation during pregnancy results in lower HR and higher HRV in the fetal period. We will document other fetal neurobehaviors (body and breathing movements) as they are hallmarks of fetal well-being and influence HR and HRV.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Docosahexaenoic Acid (DHA) | Active Comparator | Docosahexaenoic Acid (DHA) |
|
| Placebo | Placebo Comparator | soy/corn oil placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DHA | Dietary Supplement | Docosahexaenoic Acid (DHA) from algal oil |
|
| Measure | Description | Time Frame |
|---|---|---|
| Heart Rate | Mean fetal heart rate calculated from the magnetocardiogram recorded at 24, 32 and 36 weeks gestational age. | 24, 32 and 36 weeks gestational age |
| Measure | Description | Time Frame |
|---|---|---|
| Neonatal Behavioral Assessment Scale (NBAS) Scores | The Neonatal Behavioral Assessment Scale (NBAS) measure 6 areas. For behavioral items a higher score corresponds to more desirable outcomes:
Reflexes: Sum across the 18 items, scored on a scale of 0-3. Range: 0 to 54. The supplementary items are each scored on a scale of 1-9 and do not combine to form a composite. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kathleen Gustafson, PhD | University of Kansas Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23433688 | Background | Gustafson KM, Carlson SE, Colombo J, Yeh HW, Shaddy DJ, Li S, Kerling EH. Effects of docosahexaenoic acid supplementation during pregnancy on fetal heart rate and variability: a randomized clinical trial. Prostaglandins Leukot Essent Fatty Acids. 2013 May;88(5):331-8. doi: 10.1016/j.plefa.2013.01.009. Epub 2013 Feb 20. | |
| 32662379 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | soy/corn oil placebo |
| FG001 | Docosahexaenoic Acid (DHA) | 600 mg Docosahexaenoic Acid (DHA) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Allocation |
| |||||||||||||
| Follow-Up at 24 Weeks |
| |||||||||||||
| Follow-Up at 32 Weeks |
| |||||||||||||
| Follow-Up at 36 Weeks |
| |||||||||||||
| Neonatal Behavioral Assessment Scale (NB |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | soy/corn oil placebo |
| BG001 | Docosahexaenoic Acid (DHA) | 600 mg Docosahexaenoic Acid (DHA) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Heart Rate | Mean fetal heart rate calculated from the magnetocardiogram recorded at 24, 32 and 36 weeks gestational age. | Placebo: 19 subjects @ 24 wks GA, 25 subjects @ 32 wks GA, 24 subjects @ 36 wks GA DHA: 21 subjects @ 24 wks GA, 23 subjects @ 32 wks GA, 22 subjects @ 36 wks GA | Posted | Mean | Standard Deviation | Beats per minute | 24, 32 and 36 weeks gestational age |
|
Adverse Event Data were reviewed and reported by the Data Safety and Monitoring Board (DSMB) every 6 months for the 2 year duration of the study.
Adverse events were categorized by body system affected by the study monitor (systematic assessment). Serious AEs were reported within 24 hours of their occurrence, AEs were reported every 3 months. The DSMB met every 6 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | soy/corn oil placebo |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathleen Gustafson, Ph.D. | University of Kansas Medical Center | (913) 588-0065 | kgustafson@kumc.edu |
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| ID | Term |
|---|---|
| D004281 | Docosahexaenoic Acids |
| ID | Term |
|---|---|
| D015525 | Fatty Acids, Omega-3 |
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
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| Placebo | Other | Placebo capsule |
|
|
| within 2 weeks of delivery |
| Maternal Red Blood Cell (RBC) Phospholipids at Delivery | Maternal red blood cell phospholipid collected at delivery. These results were compared to baseline red blood cell phospholipid that was collected at study enrollment. A weighed standard fatty acid mixture (Supelco 37 component fatty acid methyl ester mix,Sigma Aldrich) was employed to correct final DHA weight percent of total fatty acids (wt%TFA). | Time of delivery, 36 weeks to term |
| Cord Blood Phospholipids DHA | Newborn red blood cell phospholipids collected at birth. | Birth |
| Cardiac Conduction Time | Change from Baseline to 2 Months Post-natal |
| Christifano DN, Taylor MK, Carlson SE, Colombo J, Gustafson KM. Higher maternal weight is related to poorer fetal autonomic function. J Dev Orig Health Dis. 2021 Jun;12(3):354-356. doi: 10.1017/S2040174420000653. Epub 2020 Jul 14. |
| 31071684 | Derived | Hoyer D, Schmidt A, Gustafson KM, Lobmaier SM, Lakhno I, van Leeuwen P, Cysarz D, Preisl H, Schneider U. Heart rate variability categories of fluctuation amplitude and complexity: diagnostic markers of fetal development and its disturbances. Physiol Meas. 2019 Jul 3;40(6):064002. doi: 10.1088/1361-6579/ab205f. |
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| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Enrollment BMI | Mean | Standard Deviation | kg/m^2 |
|
| Education | Mean | Standard Deviation | Years |
|
| Gestational Age (GA) | Mean | Standard Deviation | Weeks |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Neonatal Behavioral Assessment Scale (NBAS) Scores | The Neonatal Behavioral Assessment Scale (NBAS) measure 6 areas. For behavioral items a higher score corresponds to more desirable outcomes:
Reflexes: Sum across the 18 items, scored on a scale of 0-3. Range: 0 to 54. The supplementary items are each scored on a scale of 1-9 and do not combine to form a composite. | Posted | Mean | Standard Deviation | units on a scale | within 2 weeks of delivery |
|
|
|
| Secondary | Maternal Red Blood Cell (RBC) Phospholipids at Delivery | Maternal red blood cell phospholipid collected at delivery. These results were compared to baseline red blood cell phospholipid that was collected at study enrollment. A weighed standard fatty acid mixture (Supelco 37 component fatty acid methyl ester mix,Sigma Aldrich) was employed to correct final DHA weight percent of total fatty acids (wt%TFA). | Posted | Median | Inter-Quartile Range | weight percent Total Fatty Acids | Time of delivery, 36 weeks to term |
|
|
|
| Secondary | Cord Blood Phospholipids DHA | Newborn red blood cell phospholipids collected at birth. | Posted | Median | Inter-Quartile Range | weight percent total fatty acids | Birth |
|
|
|
| Secondary | Cardiac Conduction Time | Posted | Mean | Standard Deviation | milliseconds | Change from Baseline to 2 Months Post-natal |
|
|
|
| 0 |
| 32 |
| 0 |
| 32 |
| EG001 | Docosahexaenoic Acid (DHA) | 600 mg Docosahexaenoic Acid (DHA) | 0 | 35 | 0 | 35 |
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| D008055 |
| Lipids |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D005395 | Fish Oils |
| D009821 | Oils |
| Motor |
|
| State Organization |
|
| State Regulation |
|
| Autonomic |
|
| Reflexes |
|