PROVIDE: Preeclampsia Research on Vitamin D, Inflammation, & Depression

Sponsor

Cedars-Sinai Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03018132

Collaborator

Maternal Mental Health NOW (Other)

200

Enrollment

Location

Arm

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to comprehensively investigate the anti-inflammatory role of vitamin D in reproductive aged women, and its association with preeclampsia and depression. Findings will have substantial impact providing new information implicated in the development of preeclampsia (a condition that may include hypertension, tissue swelling caused by excessive fluid, and kidney stress) and postpartum depression (after birth).

Additionally, the study is designed to understand how early mental health screening and evaluation can help pregnant women reduce their risk of developing postpartum depression. Testing the acceptability and effectiveness of this mental health screening, education and referral program at Cedars-Sinai Medical Center will provide valuable patient centered qualitative and quantitative data that can be used in future services planning.

The study will enroll up to 200 pregnant women (in third trimester of pregnancy) in total.

Condition or Disease	Intervention/Treatment	Phase
Pre-Eclampsia Depression Inflammation Vitamin D Deficiency	Other: mental health screening, education and referral program	N/A

Detailed Description

Background information

The PROVIDE study tests the hypothesis that low vitamin D levels and increased inflammatory activity in pregnant women contributes to increased risk of preeclampsia and postpartum depression (PPD). Preeclampsia is a multisystem disorder of pregnancy commonly characterized by hypertension that occurs after 20 weeks of gestation in a woman with previously normal blood pressure accompanied by proteinuria. One pathway thought to lead to preeclampsia is chronic subclinical inflammation. Likewise, inflammation is elevated in women with major depressive disorder (MDD) and PPD and may therefore be a common physiological pathway connecting depression with preeclampsia. In addition, vitamin D deficiency, which is common in pregnancy and the postpartum period is associated with depressive symptomatology, prenatal inflammation and adverse birth outcomes, particularly preeclampsia. Research has shown that vitamin D acts as an anti-inflammatory agent regulating placental function to promote tolerance of the fetus. Prior work demonstrated that among women with elevated prenatal inflammation, higher prenatal vitamin D status was associated with lower PPD symptoms. This research tests the hypothesis that vitamin D deficiency places women with higher levels of inflammatory cytokines at highest risk for preeclampsia and PPD. Findings will have substantial impact providing new information about inflammatory mechanisms implicated in the development of preeclampsia and PPD, and will support future research, such as vitamin D supplementation to reduce risk for preeclampsia and depression.

The study also seeks a better understanding of several important biopsychosocial consequences of developing preeclampsia. In pregnancy, 8-13% of women are diagnosed with MDD, which can lead to postpartum depression (PPD) and adverse birth outcomes, specifically low birth weight and preeclampsia. Although maternal depression is associated with negative consequences for the mother, her infant and family, low rates of diagnosis and treatment for perinatal depression are common in medical settings. Rapid diagnosis and treatment is essential because the episodes are lengthy and psychosocial symptoms (including anxiety) increase with the duration of the disorder. Screening is important because it is the first step in the pathway to treatment. This study tests the acceptability and benefits of a mental health screening, education and referral program in women with and without preeclampsia. With assistance from a community partner, Maternal Mental Health-NOW (formerly the L.A. County Perinatal Mental Health Task Force), findings will provide valuable patient centered qualitative and quantitative data that can be used in future services planning. This is timely work. In 2015 ACOG recommended that clinicians screen patients at least once during the perinatal period for depression and anxiety symptoms. Post-traumatic stress symptoms are particularly common after experiencing an adverse pregnancy outcome, and approximately 9% develop Post-traumatic stress disorder (PTSD). Increased risk of major depression (40-50%) comorbid with PTSD can lead to decreased maternal bonding with infant and other long term adverse mental and physical health repercussions for the mother, child and family. Screening therefore must be coupled with appropriate follow-up and treatment when indicated, and systems should be in place to ensure follow-up for diagnosis and treatment. Most recently (2016), the US Preventive Services Task Force (USPSTF) made perinatal depression screening recommendations, adding that data are lacking on both the accuracy of screening and the benefits and harms of treatment in pregnant women. The authors highlight that research is needed to assess barriers to establishing adequate systems of care and how these barriers can be addressed.

Very little is known from the patient perspective regarding acceptance and benefits of mental health screening. There is even less understanding of the variation in preferences and need for these services in women who experience preeclampsia, for whom PPD rates are even higher. The perinatal period is an opportune time for screening and mental health education due to the frequency of contact with health care providers, unfortunately rates of diagnosis and treatment for perinatal depression are low in medical settings. New parents are often highly motivated to seek help in effecting change for the sake of their offspring and potential reduction in intergenerational family dysfunction. The perinatal period thus provides clinicians with a unique opportunity to consider universal psychosocial assessment as part of mainstream maternity and postnatal care. Early identification and treatment of psychosocial morbidity are especially important in relation to the functioning of the family unit and the critical parent-infant relationship with potential to positively impact on the health of the next generation. Routine depression screening and referral has been supported by RCTs in Primary Care. RCT work has not been conducted in the perinatal period or in the OB/GYN setting, however screening, education, and referral programs in obstetric settings have been well accepted by patients. Overall, mental health care might be most acceptable if provided as part of routine obstetrical care. Mental health screening and treatment might also be more beneficial in the subset of women who experience adverse pregnancy complications. Results from this mental health screening program will allow for early identification and intervention at a time when women are at highest risk for mental health complications, after an adverse complication such as preeclampsia.

Objectives and purpose

To our knowledge, no studies have comprehensively investigated the anti-inflammatory role of vitamin D in depressed reproductive aged women, and its association with adverse pregnancy outcomes. Findings will have substantial impact providing new information about inflammatory mechanisms implicated in the development of preeclampsia and PPD, and will support future intervention research, including vitamin D supplementation, focused on alleviating these effects. Additionally, testing the acceptability and effectiveness of a new mental health screening, education and referral program at Cedars-Sinai Medical Center (CSMC) will provide valuable patient centered qualitative and quantitative data that can be used in future services planning.

PROVIDE study hypotheses will be tested in a new cohort (N=200) recruited in the third trimester from CSMC Childbirth and Education classes, the Prenatal Diagnostic Center (PDC), or in the Maternal-Fetal Care Unit (MFCU, for those diagnosed with Preeclampsia); and followed through delivery and 2 time points (4 weeks and 3 months) postpartum. A targeted sampling strategy over a two-year period will result in 100 women who experience preeclampsia and 100 women who do not.

Specific Aim 1: Determine to what extent prenatal vitamin D deficiency (defined clinically as serum 25(OH)D < 20 ng/ml48) will be associated with increases in prenatal inflammatory cytokines (e.g. hs-CRP and Interleukin-6), prenatal depressive symptoms, and preeclampsia.

Hypothesis: Women who experience lower prenatal vitamin D levels will exhibit an increased likelihood of experiencing prenatal depression, preeclampsia, and postpartum depression. These effects will be greatest in those with high levels of prenatal inflammatory cytokines.

Specific Aim 2: Determine to what extent women who have preeclampsia will have increases in postpartum inflammatory cytokines, vitamin D deficiency and PPD.

Hypothesis: Compared to those who do not experience preeclampsia, women with preeclampsia will have higher postpartum levels of inflammatory cytokines, lower postpartum vitamin D levels, and increased symptoms of PPD.

Specific Aim 3: Determine to what extent a mental health program that includes screening, education and referral is acceptable to pregnant women and effective in reducing symptoms of postpartum depression, anxiety and/or stress following preeclampsia.

Hypothesis: Women in the preeclampsia + depression group will rate the mental health program as more acceptable and beneficial, and will follow up on referral suggestions more than depressed-only group.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

The PROVIDE Study; Preeclampsia Research on Vitamin D, Inflammation, & Depression

Actual Study Start Date :

Apr 1, 2017

Actual Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: Mental Health Screening Education and Referral Investigators will prospectively assign all 200 women to this screening, education and referral intervention, without concurrent comparison or control groups, to study the cause-and-effect relationship between a health-related intervention and a health outcome. The health-related intervention, in this case, is an educational program and related process-of-care changes.	Other: mental health screening, education and referral program I. Psychosocial assessments: Mental health screening for: (1) depressive symptoms with the EPDS, (2) post-traumatic stress symptoms with the IES, (3) for perceived stress with the PSS (4) for anxiety with the OASIS. Exercise, smoking & substance use, sleep and nutrition. II. If women are above cutoff values the SCID will be conducted. III. Education and referral information via Maternal Mental Health NOW: All receive a brochure entitled, Speak Up When You Are Down If above cutoffs, participants will also receive referral information; and will be scheduled for a SCID Trained study staff will review the brochure and show the woman how to use the MMHN online referral system to input their zip code and find preferred maternal mental health practitioners. IV. Follow up with a survey at 3 months postpartum: acceptability of screening, benefit of referral service, and outcome of this referral.

Arm

Intervention/Treatment

Other: Mental Health Screening Education and Referral

Investigators will prospectively assign all 200 women to this screening, education and referral intervention, without concurrent comparison or control groups, to study the cause-and-effect relationship between a health-related intervention and a health outcome. The health-related intervention, in this case, is an educational program and related process-of-care changes.

Other: mental health screening, education and referral program

I. Psychosocial assessments: Mental health screening for: (1) depressive symptoms with the EPDS, (2) post-traumatic stress symptoms with the IES, (3) for perceived stress with the PSS (4) for anxiety with the OASIS. Exercise, smoking & substance use, sleep and nutrition. II. If women are above cutoff values the SCID will be conducted. III. Education and referral information via Maternal Mental Health NOW: All receive a brochure entitled, Speak Up When You Are Down If above cutoffs, participants will also receive referral information; and will be scheduled for a SCID Trained study staff will review the brochure and show the woman how to use the MMHN online referral system to input their zip code and find preferred maternal mental health practitioners. IV. Follow up with a survey at 3 months postpartum: acceptability of screening, benefit of referral service, and outcome of this referral.

Outcome Measures

Primary Outcome Measures

Depressive symptoms [5 months]
as measured by reliable and validated screening tool (EPDS)
Depression Diagnosis [5 months]
as measured by diagnostic interview (SCID)

Secondary Outcome Measures

Anxiety symptoms [5 months]
as measured by the OASIS
Post-traumatic stress symptoms [5 months]
as measured by the IES
Perceived stress [5 months]
as measured by the PSS
Acceptability of Mental Health Program [5 months]
Results will be based on data from structured (Likert-scale) surveys completed at 4 time points, from the patient perspective
Benefits of Mental Health Program [5 months]
Results will be based on data from the follow-up structured (Likert-scale) survey
Feasibility of Mental Health Program [5 months]
The program's feasibility and MMH-Now training will be rated by clinic staff according to structured surveys completed at multiple time points, e.g. pre/post training.
Inflammation_IL6 [5 months]
as measured by serum Interleukin-6
Inflammation_CRP [5 months]
as measured by serum hs_CRP
Vitamin D deficiency [5 months]
as measured by serum 25(OH)D levels

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Female
Minimum 18 years of age
Patient at Cedars Sinai Medical Center, Los Angeles, CA
Between 20 and 40 weeks gestation (majority recruited at start of 3rd trimester between 26-32 weeks)
English or Spanish language preference

Exclusion Criteria:

Any diagnosis of psychosis, past or current (evident by either meds taken via medical intake, or in clinical assessment - SCID)
Current substance abuse (evident either via medical intake, or in clinical assessment
SCID)