Depression
Conditions
Brief summary
This study is designed to test whether an alternative medicine treatment, fish oil, will prevent depressive symptoms in pregnant and postpartum women who have been found to be at risk for depression. Epidemiologists have observed that people who live in countries where people on average eat a diet high in fish have a lower risk of depression than people who live in populations that eat less fish. Postpartum depression is also less common in these countries. The omega-3 fatty acids found in fish oil are thought to be responsible for this beneficial effect of eating fish. The two major omega-3 fatty acids found in fish are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA is an essential building block of the brain and nerve tissue. EPA may act to optimize the electrical signals between nerve cells and brain cells and may help the immune system to function well. Some researchers have treated people who are already suffering from depression with fish oil. Some of these studies have shown a benefit for the fish oil treatment and others have not. These studies have tested EPA and DHA alone and in various combinations. Currently, it is not known whether EPA or DHA is more effective in preventing and treating depression. Some of the researchers involved in this study have learned how to identify mothers who are most at risk for developing depression during and after pregnancy. This study is designed to learn whether EPA-rich and DHA-rich fish oil supplements will prevent depressive symptoms in women who are at risk to develop depression.
Interventions
DRUGEPA-rich fish oil supplement
1060 mg EPA plus 274 mg DHA
DRUGDHA-rich fish oil supplement
900 mg DHA plus 180 mg EPA
DRUGplacebo
control arm
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Women who are more than 12 weeks pregnant but less than 20 weeks pregnant * Women who are found to be at risk for depression * Women who have been treated for depression in the past * Women with depression after a previous pregnancy * Women planning to deliver at University of Michigan Hospital
Exclusion criteria
* Women who have major depression or other psychiatric disorders (current substance abuse, schizophrenia, bipolar disorder) at the time of screening * Women who are currently taking anti-depressant or other psychiatric medications * Women who routinely eat more than 2 fish meals per week * Women on anticoagulants (blood thinners) * Women currently taking omega-3 fatty acid dietary supplements (fish oil, flaxseed oil or cod liver oil) * Women with bleeding disorders such as von Willebrand's disease * Women under the age of 18 * Women with a multiple gestation (twins, for example) * Women planning to deliver at another hospital * Women planning to move away before 6 weeks after delivery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Beck Depression Inventory | 6 - 8 weeks postpartum | The Beck Depression inventory scores depression based on 21 items, with a score of 0 - 3 on each item where 0 is no depression and a score of 31 or more is clinically depressed. The 21 items were summed to obtain the total score (The maximum possible score is 63.) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gestational Age at Delivery (Weeks) | delivery date was assessed by medical record review between 1 day and 8 weeks after delivery | — |
| Estimated Blood Loss (ml) | Within 24 hours after delivery | — |
| Neonatal Birthweight | immediately after birth | Mean weight in grams: where \<2500 gm is considered small for gestational age and \>4500 gm is considered large for gestational age. |
| Maternal Outcomes | visits at 26 - 28 weeks gestational age, 34-36 weeks gestational age during pregnancy and at the post partum visit 6- 8 weeks after delivery | While the maternal outcomes assess criteria during pregnancy and relating to delivery they were assessed at visits 26 - 28 weeks gestational age, 34-36 weeks gestational age and at the post partum visit 6- 8 weeks after delivery. |
| One Minute Apgar Score | 1 minute after birth | Apgar scores are based on a scale of 0 - 10 where 0 is a dead baby and 10 is an optimally vigorous newborn. The Apgar score analyzed here is the one minute Apgar. |
| Five Minute Apgar Score | 5 minutes after birth | Apgar scores are based on a scale of 0 - 10 where 0 is a dead baby and 10 is an optimally vigorous newborn. The Apgar score analyzed here is the five minute Apgar. |
| Cord Arterial pH | Immediately after birth (collected within the first hour after delivery) | Arterial blood gas analysis of umbilical cord blood |
| NICU (Neonatal Intensive Care Unit) Admissions | 6 weeks post delivery | Admission to the NICU |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EPA-rich Fish Oil Supplement EPA-rich fish oil supplement
EPA-rich fish oil supplement: 1060 mg EPA plus 274 mg DHA | 39 |
| DHA-rich Fish Oil Supplement DHA-rich fish oil supplement
DHA-rich fish oil supplement: 900 mg DHA plus 180 mg EPA | 38 |
| Soy Oil Placebo placebo: control arm | 41 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 4 | 1 |
Baseline characteristics
| Characteristic | DHA-rich Fish Oil Supplement | EPA-rich Fish Oil Supplement | Total | Soy Oil Placebo |
|---|---|---|---|---|
| Age, Continuous | 30.6 years STANDARD_DEVIATION 4.5 | 29.9 years STANDARD_DEVIATION 5 | 30.3 years STANDARD_DEVIATION 5.18 | 30.4 years STANDARD_DEVIATION 5.9 |
| BDI (Beck Depression Inventory) score | 7.79 units on a scale STANDARD_DEVIATION 5.29 | 8.41 units on a scale STANDARD_DEVIATION 5.65 | 7.72 units on a scale STANDARD_DEVIATION 5.38 | 7.15 units on a scale STANDARD_DEVIATION 5.21 |
| EPDS Screen (Edinburgh Prenatal Depression Scale) | 7.56 units on a scale STANDARD_DEVIATION 4.49 | 7.93 units on a scale STANDARD_DEVIATION 4.63 | 7.80 units on a scale STANDARD_DEVIATION 4.51 | 7.34 units on a scale STANDARD_DEVIATION 4.4 |
| Gestational age at enrollment | 17 weeks STANDARD_DEVIATION 2.3 | 15.9 weeks STANDARD_DEVIATION 2.6 | 16.36 weeks STANDARD_DEVIATION 2.4 | 16.2 weeks STANDARD_DEVIATION 2.3 |
| Parity | 1.08 number of previous deliveries STANDARD_DEVIATION 0.94 | 0.87 number of previous deliveries STANDARD_DEVIATION 0.83 | 0.93 number of previous deliveries STANDARD_DEVIATION 1.01 | 0.85 number of previous deliveries STANDARD_DEVIATION 1.2 |
| Past history of depression(self reported) | 30 participants | 32 participants | 95 participants | 33 participants |
| Race/Ethnicity, Customized African-American | 4 Participants | 4 Participants | 10 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic-Latina | 4 Participants | 0 Participants | 7 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific ethnicity | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 29 Participants | 33 Participants | 96 Participants | 34 Participants |
| Region of Enrollment United States | 38 Participants | 39 Participants | 118 Participants | 41 Participants |
| Sex: Female, Male Female | 38 Participants | 39 Participants | 118 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 42 | 23 / 42 | 22 / 42 |
| serious Total, serious adverse events | 8 / 42 | 5 / 42 | 5 / 42 |
Outcome results
Primary
Beck Depression Inventory
The Beck Depression inventory scores depression based on 21 items, with a score of 0 - 3 on each item where 0 is no depression and a score of 31 or more is clinically depressed. The 21 items were summed to obtain the total score (The maximum possible score is 63.)
Time frame: 6 - 8 weeks postpartum
Population: Per protocol analysis is reported here.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EPA-rich Fish Oil Supplement | Beck Depression Inventory | BDI at 34-36 weeks' gestation | 7.4 units on a scale | Standard Deviation 5 |
| EPA-rich Fish Oil Supplement | Beck Depression Inventory | BDI at 24-28 weeks' gestation | 7.9 units on a scale | Standard Deviation 3.7 |
| EPA-rich Fish Oil Supplement | Beck Depression Inventory | BDI at 6-8 weeks postpartum | 6.6 units on a scale | Standard Deviation 5.2 |
| DHA-rich Fish Oil Supplement | Beck Depression Inventory | BDI at 34-36 weeks' gestation | 5.9 units on a scale | Standard Deviation 4.9 |
| DHA-rich Fish Oil Supplement | Beck Depression Inventory | BDI at 24-28 weeks' gestation | 6.5 units on a scale | Standard Deviation 4.7 |
| DHA-rich Fish Oil Supplement | Beck Depression Inventory | BDI at 6-8 weeks postpartum | 5.1 units on a scale | Standard Deviation 4.4 |
| Soy Oil Placebo | Beck Depression Inventory | BDI at 24-28 weeks' gestation | 6.3 units on a scale | Standard Deviation 4.1 |
| Soy Oil Placebo | Beck Depression Inventory | BDI at 6-8 weeks postpartum | 6.2 units on a scale | Standard Deviation 6.5 |
| Soy Oil Placebo | Beck Depression Inventory | BDI at 34-36 weeks' gestation | 7.2 units on a scale | Standard Deviation 5.2 |
Comparison: Significance for the BDI test at 26-28 weeksp-value: 0.29ANOVA
Comparison: Significance for BDI at 34-36 weeks gestationp-value: 0.51ANOVA
Comparison: BDI score at 6-8 weeks postpartump-value: 0.56ANOVA
Other Pre-specified
Cord Arterial pH
Arterial blood gas analysis of umbilical cord blood
Time frame: Immediately after birth (collected within the first hour after delivery)
Population: Umbilical cord gases (pH) were sent at the discretion of the delivering physician and so were not available for all participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPA-rich Fish Oil Supplement | Cord Arterial pH | 7.26 pH | Standard Deviation 0.09 |
| DHA-rich Fish Oil Supplement | Cord Arterial pH | 7.27 pH | Standard Deviation 0.05 |
| Soy Oil Placebo | Cord Arterial pH | 7.27 pH | Standard Deviation 0.06 |
p-value: 0.54ANOVA
Other Pre-specified
Estimated Blood Loss (ml)
Time frame: Within 24 hours after delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPA-rich Fish Oil Supplement | Estimated Blood Loss (ml) | 507 mL | Standard Deviation 481 |
| DHA-rich Fish Oil Supplement | Estimated Blood Loss (ml) | 508 mL | Standard Deviation 325 |
| Soy Oil Placebo | Estimated Blood Loss (ml) | 454 mL | Standard Deviation 296 |
p-value: 0.81ANOVA
Other Pre-specified
Five Minute Apgar Score
Apgar scores are based on a scale of 0 - 10 where 0 is a dead baby and 10 is an optimally vigorous newborn. The Apgar score analyzed here is the five minute Apgar.
Time frame: 5 minutes after birth
Population: One set of twins from EPA group; Soy oil arm has data for only 40 as one baby was born elsewhere so Apgar data is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPA-rich Fish Oil Supplement | Five Minute Apgar Score | 8.6 units on a scale | Standard Deviation 0.8 |
| DHA-rich Fish Oil Supplement | Five Minute Apgar Score | 9.1 units on a scale | Standard Deviation 0.2 |
| Soy Oil Placebo | Five Minute Apgar Score | 8.9 units on a scale | Standard Deviation 0.5 |
p-value: <0.01ANOVA
Other Pre-specified
Gestational Age at Delivery (Weeks)
Time frame: delivery date was assessed by medical record review between 1 day and 8 weeks after delivery
Population: Gestational age is measured based on the pregnancy not the neonates, therefore although there were 40 babies born to the 39 mothers randomized to the EPA-rich fish oil, it is proper to consider the participants analyzed to be the 39 participating mothers. This is clarified still further by identifying the units appropriately as pregnancies.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPA-rich Fish Oil Supplement | Gestational Age at Delivery (Weeks) | 39.1 weeks | Standard Deviation 1.5 |
| DHA-rich Fish Oil Supplement | Gestational Age at Delivery (Weeks) | 40.4 weeks | Standard Deviation 0.9 |
| Soy Oil Placebo | Gestational Age at Delivery (Weeks) | 39.1 weeks | Standard Deviation 1.5 |
p-value: <0.0001ANOVA
Other Pre-specified
Maternal Outcomes
While the maternal outcomes assess criteria during pregnancy and relating to delivery they were assessed at visits 26 - 28 weeks gestational age, 34-36 weeks gestational age and at the post partum visit 6- 8 weeks after delivery.
Time frame: visits at 26 - 28 weeks gestational age, 34-36 weeks gestational age during pregnancy and at the post partum visit 6- 8 weeks after delivery
Population: Gestational hypertension and diabetes were self-reported for all participants so her data is included for those two rows.~One woman in the soy placebo arm delivered out of the geographic area, so documentation of delivery outcome is unavailable for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EPA-rich Fish Oil Supplement | Maternal Outcomes | Operative Vaginal Delivery | 4 participants |
| EPA-rich Fish Oil Supplement | Maternal Outcomes | Induced Labor | 15 participants |
| EPA-rich Fish Oil Supplement | Maternal Outcomes | Spontaneous Vaginal Delivery | 25 participants |
| EPA-rich Fish Oil Supplement | Maternal Outcomes | Gestational Hypertension or Preeclampsia | 8 participants |
| EPA-rich Fish Oil Supplement | Maternal Outcomes | Cesarean Section | 10 participants |
| EPA-rich Fish Oil Supplement | Maternal Outcomes | Gestational Diabetes Mellitus | 7 participants |
| DHA-rich Fish Oil Supplement | Maternal Outcomes | Cesarean Section | 12 participants |
| DHA-rich Fish Oil Supplement | Maternal Outcomes | Spontaneous Vaginal Delivery | 25 participants |
| DHA-rich Fish Oil Supplement | Maternal Outcomes | Gestational Diabetes Mellitus | 1 participants |
| DHA-rich Fish Oil Supplement | Maternal Outcomes | Operative Vaginal Delivery | 1 participants |
| DHA-rich Fish Oil Supplement | Maternal Outcomes | Gestational Hypertension or Preeclampsia | 2 participants |
| DHA-rich Fish Oil Supplement | Maternal Outcomes | Induced Labor | 12 participants |
| Soy Oil Placebo | Maternal Outcomes | Induced Labor | 8 participants |
| Soy Oil Placebo | Maternal Outcomes | Gestational Hypertension or Preeclampsia | 5 participants |
| Soy Oil Placebo | Maternal Outcomes | Gestational Diabetes Mellitus | 2 participants |
| Soy Oil Placebo | Maternal Outcomes | Operative Vaginal Delivery | 1 participants |
| Soy Oil Placebo | Maternal Outcomes | Cesarean Section | 11 participants |
| Soy Oil Placebo | Maternal Outcomes | Spontaneous Vaginal Delivery | 28 participants |
Comparison: Gestational diabetes mellitusp-value: 0.06Fisher Exact
Comparison: Hypertension or preeclampsiap-value: 0.12Fisher Exact
Comparison: Induced laborp-value: 0.2Fisher Exact
Comparison: Cesarean sectionp-value: 0.08Fisher Exact
Comparison: Spontaneous vaginal deliveryp-value: 0.88Fisher Exact
Comparison: Operative vaginal deliveryp-value: 0.32Fisher Exact
Other Pre-specified
Neonatal Birthweight
Mean weight in grams: where \<2500 gm is considered small for gestational age and \>4500 gm is considered large for gestational age.
Time frame: immediately after birth
Population: Data is provided for all babies on whom delivery weights were available with a set of twins in EPA rich fish oil arm and a delivery elsewhere for whom no birth weight was available for one baby from a mother in the Soy oil placebo arm. Thus there is 1 more participant than mothers participating in the EPA-rich arm and one less in the soy oil arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPA-rich Fish Oil Supplement | Neonatal Birthweight | 3402 grams | Standard Deviation 550 |
| DHA-rich Fish Oil Supplement | Neonatal Birthweight | 3774 grams | Standard Deviation 438 |
| Soy Oil Placebo | Neonatal Birthweight | 3309 grams | Standard Deviation 555 |
p-value: <0.001ANOVA
Other Pre-specified
NICU (Neonatal Intensive Care Unit) Admissions
Admission to the NICU
Time frame: 6 weeks post delivery
Population: One set of twins in group A
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EPA-rich Fish Oil Supplement | NICU (Neonatal Intensive Care Unit) Admissions | 6 Participants |
| DHA-rich Fish Oil Supplement | NICU (Neonatal Intensive Care Unit) Admissions | 2 Participants |
| Soy Oil Placebo | NICU (Neonatal Intensive Care Unit) Admissions | 4 Participants |
p-value: 0.39ANOVA
Other Pre-specified
One Minute Apgar Score
Apgar scores are based on a scale of 0 - 10 where 0 is a dead baby and 10 is an optimally vigorous newborn. The Apgar score analyzed here is the one minute Apgar.
Time frame: 1 minute after birth
Population: One set of twins from EPA group; Soy oil arm has data for only 40 as one baby was born elsewhere so Apgar data is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPA-rich Fish Oil Supplement | One Minute Apgar Score | 7.3 units on a scale | Standard Deviation 2.2 |
| DHA-rich Fish Oil Supplement | One Minute Apgar Score | 7.9 units on a scale | Standard Deviation 1.8 |
| Soy Oil Placebo | One Minute Apgar Score | 7.9 units on a scale | Standard Deviation 1.9 |
p-value: 0.19ANOVA