Effects of Docosahexaenoic Acid (DHA) on Fetal Cardiac Outcomes

• ClinicalTrials.gov Identifier: NCT01007110
• Recruitment Status: Completed
• First Posted: November 3, 2009
• Results First Posted: May 14, 2014
• Last Update Posted: June 9, 2014
• Sponsor: University of Kansas
• Information provided by (Responsible Party): Kathleen Gustafson, Ph.D., University of Kansas

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pregnancy	Dietary Supplement: DHA; Other: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Official Title: The Effects of Docosahexaenoic Acid (DHA) on Fetal Cardiac Outcomes
• Study Start Date: May 2009
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: July 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Docosahexaenoic Acid (DHA); Docosahexaenoic Acid (DHA)	Dietary Supplement: DHA; Docosahexaenoic Acid (DHA) from algal oil; Other Name: Docosahexaenoic acid
Placebo Comparator: Placebo; soy/corn oil placebo	Other: Placebo; Placebo capsule; Other Name: Algal oil

Outcome Measures

Primary Outcome Measures :

1. Heart Rate [ Time Frame: 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 Outcome Measures :

1. Neonatal Behavioral Assessment Scale (NBAS) Scores [ Time Frame: 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.

2. Maternal Red Blood Cell (RBC) Phospholipids at Delivery [ Time Frame: 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).
3. Cord Blood Phospholipids DHA [ Time Frame: Birth ]
   Newborn red blood cell phospholipids collected at birth.
4. Cardiac Conduction Time [ Time Frame: Change from Baseline to 2 Months Post-natal ]

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 35 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

Sponsors and Collaborators

University of Kansas

Investigators

• Principal Investigator: Kathleen Gustafson, PhD; University of Kansas Medical Center

More Information

Publications:

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.

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

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.

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.

• Responsible Party: Kathleen Gustafson, Ph.D., Research Assistant Professor, University of Kansas
• ClinicalTrials.gov Identifier: NCT01007110
• Other Study ID Numbers: 11625
• First Posted: November 3, 2009
• Results First Posted: May 14, 2014
• Last Update Posted: June 9, 2014
• Last Verified: June 2014

Keywords provided by Kathleen Gustafson, Ph.D., University of Kansas:

DHA