Anxiety, Depression, Postpartum
Conditions
Keywords
oxytocin, bonding, child development
Brief summary
The purpose of this study is to test a new treatment for preventing childbirth-related mental illness in postpartum mothers. The treatment is aimed at enhancing maternal bonding, reducing postpartum depression (PPD) and anxiety in mothers at risk, and promoting child development. To this end, the investigators will test the clinical utility of intranasal (IN) oxytocin (OXT) administered to mothers during the first postpartum days.
Detailed description
Postpartum depression (PPD) is a debilitating disorder which imposes a threat to mother and infant health. An estimated 600,000 American women suffer from PPD annually, making it one of the most frequent complications of pregnancy. Available secondary preventive interventions are often ineffective, which calls for identifying novel means for prevention. Impaired mother-infant bonding is a hallmark of PPD. Depressed mothers may have difficulties developing maternal feelings and providing sensitive care. In turn, impaired bonding may worsen mother's depression. Conventional pharmacotherapy does not help with bonding impairment. This study will attempt to fill in the current gap in effective preventive interventions for pregnant mothers at risk. Evidence in postpartum mothers indicates that high peripartum OXT levels are associated with enhanced maternal behavior and low levels with depression. Data also indicates that in depressed mothers, OXT levels may decrease during the first days following childbirth rather than increase as is the norm. Therefore, the investigators will test the therapeutic effects of OXT in women at risk for PPD. It is hypothesized that administration of IN-OXT (total daily dose 48 IU) over the course of four days from as early as day one postpartum in comparison to placebo will 1) enhance mother-infant bonding, 2) reduce depressive and anxiety symptoms at 5 days postpartum, and 3) facilitate child development.
Interventions
DRUGOxytocin
Study participants will be randomized to a placebo or drug group.
DRUGPlacebo
Study participants will be randomized to a placebo or drug group.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Third-trimester pregnant women being followed at the Massachusetts General Hospital (MGH) Obstetrics Program * At risk of postpartum depression (PPD)
Exclusion criteria
* Failure to participate in regular prenatal check-ups * Current diagnosis Diagnostic and Statistical Manual of Mental Disorders (DSM-5) mental disorder pertaining to psychosis or substance abuse * Suicidality * Obstetric complication (e.g., preeclampsia, excessive hemorrhaging) * Use of potentially confounding or interacting medications * Complicating pediatric medical condition in the newborn
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Effect on Mother-infant Bonding | 5 days and 2 months postpartum (on average) | Day 5 postpartum: Self-report assessment of maternal bonding (Maternal Attachment Inventory, higher scores means better outcome, range 26 -104) 2 months postpartum: Quantitative observational assessment of mother-infant bonding (Coding Interactive Behavior; mean score represents mean score of the study sample. Negative bonding includes age-appropriate items on maternal intrusiveness, infant withdrawal, and dyad negative sub-scales, higher scores indicate higher levels of negative bonding behavior (deviation above the mean represent worse outcome); positive bonding includes maternal sensitivity, maternal limit setting, infant involvement, and dyad reciprocity sub-scales, higher scores indicate higher levels of bonding behavior, deviation above the mean represent better outcome); and repeat of self-report (MAI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Effect on Maternal Depression Symptoms | Baseline and 5 days postpartum | Self-reported assessment of severity of maternal depression symptoms (Edinburgh Postnatal Depression Scale, higher scores mean worse outcome, range 0 - 30). |
| Treatment Effect on Maternal Anxiety Symptoms | Baseline and 5 days postpartum | Self-reported severity of maternal anxiety symptoms (Brief Symptom Inventory, Anxiety sub-scale, higher scores means worse outcome, range 0 - 24). |
| Child Development | 2 months postpartum (on average) | Quantitative observational assessment of infant communication, cognitive, and motor development (Bayley Scales of Infant Development, screening, higher scores better outcome, ranges for each subscale are reported for infants 1-6 months old (items are scored either 0 or 1) - communication scale range 0-4, cognitive scale range 0-7, motor scale range 0-12; note: Bayley Scales can be performed for up to 42 months old infants; developmentally advanced infants may achieve scores above the reported range scale above) |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Massachusetts General Hospital Outpatient Obstetrics Clinic between January 2016 and December 2019. The first participant was enrolled on January 8, 2016, and the last participant was enrolled on December 4, 2019.
Pre-assignment details
Of 56 enrolled participants, 42 were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin Sub-group of participants receiving oxytocin nasal spray (Syntocinon)
Oxytocin: Study participants will be randomized to a placebo or drug group. | 20 |
| Placebo Sub-group of participants receiving placebo nasal spray
Placebo: Study participants will be randomized to a placebo or drug group. | 22 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Enrolled in study under IRB Other Event (depression screening score below inclusion criteria) | 1 | 0 |
| Overall Study | Noncompliance with study protocol | 0 | 1 |
| Overall Study | Study blind opened during assessment | 0 | 1 |
| Overall Study | Unreliable self-report data | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Oxytocin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 20 Participants | 42 Participants |
| Age, Continuous | 32.59 years STANDARD_DEVIATION 6.11 | 30.75 years STANDARD_DEVIATION 5.27 | 31.71 years STANDARD_DEVIATION 5.73 |
| Race/Ethnicity, Customized Asian or Asian American | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 11 Participants | 14 Participants | 25 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 22 participants | 20 participants | 42 participants |
| Screening Edinburgh Postnatal Depression Scale Score | 13.23 score on a scale STANDARD_DEVIATION 3.44 | 13.25 score on a scale STANDARD_DEVIATION 3.73 | 13.24 score on a scale STANDARD_DEVIATION 3.53 |
| Sex: Female, Male Female | 22 Participants | 20 Participants | 42 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 | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 3 / 20 | 3 / 22 |
| serious Total, serious adverse events | 0 / 20 | 0 / 22 |
Outcome results
Primary
Treatment Effect on Mother-infant Bonding
Day 5 postpartum: Self-report assessment of maternal bonding (Maternal Attachment Inventory, higher scores means better outcome, range 26 -104) 2 months postpartum: Quantitative observational assessment of mother-infant bonding (Coding Interactive Behavior; mean score represents mean score of the study sample. Negative bonding includes age-appropriate items on maternal intrusiveness, infant withdrawal, and dyad negative sub-scales, higher scores indicate higher levels of negative bonding behavior (deviation above the mean represent worse outcome); positive bonding includes maternal sensitivity, maternal limit setting, infant involvement, and dyad reciprocity sub-scales, higher scores indicate higher levels of bonding behavior, deviation above the mean represent better outcome); and repeat of self-report (MAI)
Time frame: 5 days and 2 months postpartum (on average)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Treatment Effect on Mother-infant Bonding | Maternal bonding, 5 days postpartum | 99.33 score on a scale | Standard Deviation 6.15 |
| Oxytocin | Treatment Effect on Mother-infant Bonding | Mother-infant bonding, 2 months postpartum (Observed, negative bonding, Z score) | -0.22 score on a scale | Standard Deviation 0.81 |
| Oxytocin | Treatment Effect on Mother-infant Bonding | Maternal bonding, 2 months postpartum | 101.11 score on a scale | Standard Deviation 5.58 |
| Oxytocin | Treatment Effect on Mother-infant Bonding | Mother-infant bonding, 2 months postpartum (Observed, positive bonding, Z score) | 0.19 score on a scale | Standard Deviation 0.82 |
| Placebo | Treatment Effect on Mother-infant Bonding | Mother-infant bonding, 2 months postpartum (Observed, positive bonding, Z score) | -0.17 score on a scale | Standard Deviation 0.59 |
| Placebo | Treatment Effect on Mother-infant Bonding | Maternal bonding, 5 days postpartum | 99.35 score on a scale | Standard Deviation 6.92 |
| Placebo | Treatment Effect on Mother-infant Bonding | Maternal bonding, 2 months postpartum | 97.90 score on a scale | Standard Deviation 7.28 |
| Placebo | Treatment Effect on Mother-infant Bonding | Mother-infant bonding, 2 months postpartum (Observed, negative bonding, Z score) | 0.20 score on a scale | Standard Deviation 0.5 |
p-value: 0.5Wilcoxon (Mann-Whitney)
p-value: 0.093Wilcoxon (Mann-Whitney)
p-value: 0.077Wilcoxon (Mann-Whitney)
p-value: 0.3Wilcoxon (Mann-Whitney)
Secondary
Child Development
Quantitative observational assessment of infant communication, cognitive, and motor development (Bayley Scales of Infant Development, screening, higher scores better outcome, ranges for each subscale are reported for infants 1-6 months old (items are scored either 0 or 1) - communication scale range 0-4, cognitive scale range 0-7, motor scale range 0-12; note: Bayley Scales can be performed for up to 42 months old infants; developmentally advanced infants may achieve scores above the reported range scale above)
Time frame: 2 months postpartum (on average)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Child Development | Infant communication subscale, 2 months postpartum | 3.44 score on a scale | Standard Deviation 0.78 |
| Oxytocin | Child Development | Infant cognition subscale, 2 months postpartum | 5.19 score on a scale | Standard Deviation 1.21 |
| Oxytocin | Child Development | Infant motor subscale, 2 months postpartum | 6.88 score on a scale | Standard Deviation 3.24 |
| Placebo | Child Development | Infant communication subscale, 2 months postpartum | 3.55 score on a scale | Standard Deviation 0.69 |
| Placebo | Child Development | Infant cognition subscale, 2 months postpartum | 5.61 score on a scale | Standard Deviation 1.3 |
| Placebo | Child Development | Infant motor subscale, 2 months postpartum | 7.73 score on a scale | Standard Deviation 3.11 |
p-value: 0.7Wilcoxon (Mann-Whitney)
p-value: 0.3Wilcoxon (Mann-Whitney)
p-value: 0.4Wilcoxon (Mann-Whitney)
Secondary
Treatment Effect on Maternal Anxiety Symptoms
Self-reported severity of maternal anxiety symptoms (Brief Symptom Inventory, Anxiety sub-scale, higher scores means worse outcome, range 0 - 24).
Time frame: Baseline and 5 days postpartum
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Treatment Effect on Maternal Anxiety Symptoms | Maternal anxiety, pregnancy | 5.67 score on a scale | Standard Deviation 5.55 |
| Oxytocin | Treatment Effect on Maternal Anxiety Symptoms | Maternal anxiety, 5 days postpartum | 5.44 score on a scale | Standard Deviation 6.71 |
| Placebo | Treatment Effect on Maternal Anxiety Symptoms | Maternal anxiety, pregnancy | 6.95 score on a scale | Standard Deviation 5.77 |
| Placebo | Treatment Effect on Maternal Anxiety Symptoms | Maternal anxiety, 5 days postpartum | 6.30 score on a scale | Standard Deviation 6.74 |
p-value: 0.5Wilcoxon (Mann-Whitney)
p-value: 0.8Wilcoxon (Mann-Whitney)
Secondary
Treatment Effect on Maternal Depression Symptoms
Self-reported assessment of severity of maternal depression symptoms (Edinburgh Postnatal Depression Scale, higher scores mean worse outcome, range 0 - 30).
Time frame: Baseline and 5 days postpartum
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin | Treatment Effect on Maternal Depression Symptoms | Maternal depression, pregnancy | 13.22 score on a scale | Standard Deviation 2.98 |
| Oxytocin | Treatment Effect on Maternal Depression Symptoms | Maternal depression, 5 days postpartum | 7.72 score on a scale | Standard Deviation 5.12 |
| Placebo | Treatment Effect on Maternal Depression Symptoms | Maternal depression, pregnancy | 13.35 score on a scale | Standard Deviation 3.53 |
| Placebo | Treatment Effect on Maternal Depression Symptoms | Maternal depression, 5 days postpartum | 9.45 score on a scale | Standard Deviation 5.49 |
p-value: >0.9Wilcoxon (Mann-Whitney)
p-value: 0.4Wilcoxon (Mann-Whitney)