Preeclampsia Research on Vitamin D, Inflammation, & Depression
Preeclampsia Research on Vitamin D, Inflammation, & Depression
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.
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.
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)