Pregnancy
Conditions
Keywords
DHA
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTDHA
Docosahexaenoic Acid (DHA) from algal oil
OTHERPlacebo
Placebo capsule
Sponsors
University of Kansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Pregnant females 16.0-35.99 years of age who are 12 to 20 weeks gestation at the time of enrollment (by dates or ultrasound) * Agree to consume study capsules from enrollment until delivery * BMI \<40 at baseline or weight does not exceed 300 pounds * No serious illnesses likely to confound study outcomes * Available by phone
Exclusion criteria
* Less than 16 or greater than 35.99 years of age at enrollment * BMI \>40 at baseline * Any serious illness likely to confound primary study outcomes * Expecting multiple infants * Diabetes (Type I, II or gestational) at baseline * Elevated blood pressure due to any cause (systolic BP \>= 140 mm Hg * Gestational age at baseline \< 12 weeks or \> 20 weeks * Unable to provide informed consent in English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate | 24, 32 and 36 weeks gestational age | Mean fetal heart rate calculated from the magnetocardiogram recorded at 24, 32 and 36 weeks gestational age. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neonatal Behavioral Assessment Scale (NBAS) Scores | within 2 weeks of delivery | The Neonatal Behavioral Assessment Scale (NBAS) measure 6 areas. For behavioral items a higher score corresponds to more desirable outcomes: 1. Habituation: Sum of scores across 3 items, scored on a scale of 1-9. Range: 3-27. 2. Orientation: Sum of scores across 7 items, scored on a scale of 1-9. Range: 7 - 63. 3. Motor: Sum of scores across 5 items; 3 scored on a scale of 1-9, 1 scored on a scale of 1-6, and 1 scored on a scale of 1-5. Range: 5-38. 4. Range of State: Sum of scores across 4 items; 2 scored on a scale of 1-6 and 2 scored on a scale of 1-5. Range: 4-22. 5. Regulation of State: Sum of scores across 4 items, scored on a scale of 1-9. Range: is 4-36. 6. Autonomic Stability: Sum of scores across 3 items; 1 scored on a scale of 1-9, 1 on a scale of 1-8, and 1 on a scale of 1-6. Range: 3-23. 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. |
| Maternal Red Blood Cell (RBC) Phospholipids at Delivery | Time of delivery, 36 weeks to term | 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). |
| Cord Blood Phospholipids DHA | Birth | Newborn red blood cell phospholipids collected at birth. |
| Cardiac Conduction Time | Change from Baseline to 2 Months Post-natal | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo soy/corn oil placebo | 32 |
| Docosahexaenoic Acid (DHA) 600 mg Docosahexaenoic Acid (DHA) | 35 |
| Total | 67 |
Baseline characteristics
| Characteristic | Docosahexaenoic Acid (DHA) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 25.5 years STANDARD_DEVIATION 4.3 | 25.5 years STANDARD_DEVIATION 4.51 | 25.6 years STANDARD_DEVIATION 4.8 |
| Education | 14.0 Years STANDARD_DEVIATION 3.1 | 14 Years STANDARD_DEVIATION 2.89 | 13.9 Years STANDARD_DEVIATION 2.7 |
| Enrollment BMI | 26.8 kg/m^2 STANDARD_DEVIATION 5.5 | 27.9 kg/m^2 STANDARD_DEVIATION 6.21 | 29.0 kg/m^2 STANDARD_DEVIATION 7 |
| Gestational Age (GA) | 13.6 Weeks STANDARD_DEVIATION 4.1 | 14.4 Weeks STANDARD_DEVIATION 3.88 | 15.2 Weeks STANDARD_DEVIATION 3.7 |
| Region of Enrollment United States | 35 participants | 67 participants | 32 participants |
| Sex: Female, Male Female | 35 Participants | 67 Participants | 32 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 0 / 35 |
| serious Total, serious adverse events | 0 / 32 | 0 / 35 |
Outcome results
Primary
Heart Rate
Mean fetal heart rate calculated from the magnetocardiogram recorded at 24, 32 and 36 weeks gestational age.
Time frame: 24, 32 and 36 weeks gestational age
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Heart Rate | Heart Rate 24 weeks Gestational Age | 146.0 Beats per minute | Standard Deviation 6.5 |
| Placebo | Heart Rate | Heart Rate 32 weeks Gestational Age | 142.5 Beats per minute | Standard Deviation 7.7 |
| Placebo | Heart Rate | Heart Rate 36 weeks Gestational Age | 145.0 Beats per minute | Standard Deviation 8.6 |
| Docosahexaenoic Acid (DHA) | Heart Rate | Heart Rate 36 weeks Gestational Age | 141.7 Beats per minute | Standard Deviation 9.3 |
| Docosahexaenoic Acid (DHA) | Heart Rate | Heart Rate 24 weeks Gestational Age | 145.2 Beats per minute | Standard Deviation 6.8 |
| Docosahexaenoic Acid (DHA) | Heart Rate | Heart Rate 32 weeks Gestational Age | 140.8 Beats per minute | Standard Deviation 7.6 |
Secondary
Cardiac Conduction Time
Time frame: Change from Baseline to 2 Months Post-natal
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cardiac Conduction Time | 38.98 milliseconds | Standard Deviation 3.62 |
| Docosahexaenoic Acid (DHA) | Cardiac Conduction Time | 39.49 milliseconds | Standard Deviation 2.798 |
Secondary
Cord Blood Phospholipids DHA
Newborn red blood cell phospholipids collected at birth.
Time frame: Birth
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Cord Blood Phospholipids DHA | 6.18 weight percent total fatty acids |
| Docosahexaenoic Acid (DHA) | Cord Blood Phospholipids DHA | 7.75 weight percent total fatty acids |
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).
Time frame: Time of delivery, 36 weeks to term
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Maternal Red Blood Cell (RBC) Phospholipids at Delivery | 4.99 weight percent Total Fatty Acids |
| Docosahexaenoic Acid (DHA) | Maternal Red Blood Cell (RBC) Phospholipids at Delivery | 7.09 weight percent Total Fatty Acids |
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: 1. Habituation: Sum of scores across 3 items, scored on a scale of 1-9. Range: 3-27. 2. Orientation: Sum of scores across 7 items, scored on a scale of 1-9. Range: 7 - 63. 3. Motor: Sum of scores across 5 items; 3 scored on a scale of 1-9, 1 scored on a scale of 1-6, and 1 scored on a scale of 1-5. Range: 5-38. 4. Range of State: Sum of scores across 4 items; 2 scored on a scale of 1-6 and 2 scored on a scale of 1-5. Range: 4-22. 5. Regulation of State: Sum of scores across 4 items, scored on a scale of 1-9. Range: is 4-36. 6. Autonomic Stability: Sum of scores across 3 items; 1 scored on a scale of 1-9, 1 on a scale of 1-8, and 1 on a scale of 1-6. Range: 3-23. 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.
Time frame: within 2 weeks of delivery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Neonatal Behavioral Assessment Scale (NBAS) Scores | Motor | 23.08 units on a scale | Standard Deviation 11.4 |
| Placebo | Neonatal Behavioral Assessment Scale (NBAS) Scores | State Regulation | 16.42 units on a scale | Standard Deviation 20.02 |
| Placebo | Neonatal Behavioral Assessment Scale (NBAS) Scores | Orienting | 19.75 units on a scale | Standard Deviation 15.45 |
| Placebo | Neonatal Behavioral Assessment Scale (NBAS) Scores | Autonomic | 14.83 units on a scale | Standard Deviation 16.9 |
| Placebo | Neonatal Behavioral Assessment Scale (NBAS) Scores | State Organization | 13.50 units on a scale | Standard Deviation 13.89 |
| Placebo | Neonatal Behavioral Assessment Scale (NBAS) Scores | Reflexes | 21.92 units on a scale | Standard Deviation 14.45 |
| Placebo | Neonatal Behavioral Assessment Scale (NBAS) Scores | Habituation | 9.92 units on a scale | Standard Deviation 9.28 |
| Docosahexaenoic Acid (DHA) | Neonatal Behavioral Assessment Scale (NBAS) Scores | Reflexes | 22.60 units on a scale | Standard Deviation 14.33 |
| Docosahexaenoic Acid (DHA) | Neonatal Behavioral Assessment Scale (NBAS) Scores | Habituation | 8.47 units on a scale | Standard Deviation 9.26 |
| Docosahexaenoic Acid (DHA) | Neonatal Behavioral Assessment Scale (NBAS) Scores | Orienting | 23.40 units on a scale | Standard Deviation 18.32 |
| Docosahexaenoic Acid (DHA) | Neonatal Behavioral Assessment Scale (NBAS) Scores | Motor | 26.07 units on a scale | Standard Deviation 18.13 |
| Docosahexaenoic Acid (DHA) | Neonatal Behavioral Assessment Scale (NBAS) Scores | State Organization | 15.13 units on a scale | Standard Deviation 8.02 |
| Docosahexaenoic Acid (DHA) | Neonatal Behavioral Assessment Scale (NBAS) Scores | State Regulation | 16.93 units on a scale | Standard Deviation 20.06 |
| Docosahexaenoic Acid (DHA) | Neonatal Behavioral Assessment Scale (NBAS) Scores | Autonomic | 18.13 units on a scale | Standard Deviation 14.48 |