Therapeutic Writing to Reduce Stress

Study Overview
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Brief Summary
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Purpose: The investigators hypothesize that exposure to chronic environmental stress is a risk factor for adverse pregnancy outcomes related to preterm birth and preeclampsia among high-risk pregnant women. Additionally, the investigators hypothesize that women can be screened for high levels of environmental stress through the perceived stress scale, and therapeutic writing can be used as a low-resource intervention to help decrease maternal perceived stress and inflammation - measured through analysis of maternal serum and placental samples. Participants: Pregnant women at high risk for adverse pregnancy outcomes, including pre-eclampsia and preterm birth, enrolled in prenatal care at UNC will be recruited for participation Procedures: Using results from the perceived stress scale, the investigators will identify women who screen positive for high environmental stress. Women meeting inclusion criteria will be contacted for possible participation at regularly scheduled prenatal visits. Women who are enrolled will be randomized to generalized writing prompts, therapeutic writing prompts, or no writing during their pregnancy to be administered at each prenatal visit. Maternal blood sample for biochemical markers of stress and gene expression will be obtained at the initial visit; a followup blood sample will be obtained later in pregnancy, and a small portion of the placenta saved at delivery. Delivery outcomes will be obtained through medical record review.

Detailed Description
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During pregnancy, women regularly interact with healthcare professionals, an often untapped resource and opportune time to optimize mental health, positively impacting outcomes. Cumulative psychosocial stress is a risk factor for several adverse obstetric outcomes including preterm birth (PTB), preeclampsia, fetal growth restriction, and postpartum depression. The overarching hypothesis of this study is that pregnant women with high levels of stress can be identified through easily-implemented screening tools; importantly, the investigators propose that these women can be engaged in care via a cost-effective therapeutic writing intervention combined with the availability of expert pastoral and perinatal psychiatry resources. Women will be enrolled early in pregnancy and followed prospectively. Some women (if randomized to a writing group) will complete a standardized writing prompt at several time points during gestation. The investigators will follow their outcomes prospectively.

Official Title
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Writing to Reduce Stress in Expectant Moms: The RESet Study

Conditions
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Pregnancy Complications, Stress, Physiological, High Risk Pregnancy

Intervention / Treatment
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* Other: Writing exercises


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women will be prospectively recruited. Gestational age: All women presenting for prenatal care at 8.0 to 19.9 weeks' gestation through the UNC-Hospitals High Risk obstetrics clinic will be screened for high risk of an adverse pregnancy outcome (ex: preterm birth or pre-eclampsia) through review of their medical record. Singleton viable intrauterine pregnancy, with dating confirmed by ultrasound or plans for ultrasound to confirm dating prior to study enrollment No structural abnormalities or aneuploidy Ability to communicate in and provide consent in English Women with at least ONE of the following high risk criteria: a. Short cervix by endovaginal ultrasound, measuring <25mm b. Prior spontaneous preterm birth 16.0 - 33.9 weeks' gestation i. Documentation of the prior spontaneous preterm birth in the patient's medical records is desirable but is not required for eligibility. ii. The previous preterm delivery cannot be an antepartum stillbirth but an intrapartum stillbirth (due to extreme prematurity) is allowable. c. Chronic hypertension on medications d. History of pre-eclampsia requiring delivery <37 weeks' gestation, or history of severe pre-eclampsia delivering at any gestational age OR Women with at least TWO of the following moderate risk criteria: Prior preterm birth 34.0-36.9 weeks Chronic hypertension not requiring medications History of term pre-eclampsia Type II diabetes on insulin Obesity with a BMI >30 Smoking during pregnancy Black race Maternal age <18 years old or >40 years old Nulliparous Uninsured, or medicaid insurance Women who meet at least one major or 2 minor inclusion criteria along with the other criteria above will then be screened for high levels of acute and chronic stress and trauma using the Perceived Stress questionnaire to determine final eligibility for the study Exclusion Criteria: Persistent Illicit drug or alcohol abuse during current pregnancy >12 weeks. Use of tobacco and/or marijuana is not an exclusion. Methadone or suboxone use in an approved treatment program is not an exclusion. Prior preterm birth or preeclampsia was in a pregnancy complicated by fetal aneuploidy or major congenital fetal anomalies in the absence of another pregnancy meeting above inclusion criteria Major congenital anomaly such as major structural deficit of the heart, lungs, or brain or aneuploidy Mild renal abnormalities, clubfoot, isolated cleft lip/palate, etc. in the fetus are not a reason for exclusion For a detailed list of major anomalies, see Table 3 - Major Fetal Anomalies / Congenital Malformations, below. Two or more minor anomalies observed together (see Table 2 - Minor Fetal Anomalies / Congenital Malformations) count as a major anomaly Isolated 'soft markers' for aneuploidy (such as choroid plexus cysts, echogenic bowel, etc.) are not a reason for exclusion If aneuploidy screening is performed, any aneuploidy screen positive test with a risk for aneuploidy greater than 1 in 25 without negative confirmatory definitive aneuploidy testing is reason for exclusion Spanish speaking women Women participating in other intervention-based studies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Writing Prompts<br>Participants will be given writing prompts that discuss events that have been perceived as stressful in their lives and how they may or may not have cultivated resilience and coping strategies because of it. | Other: Writing exercises<br>* Participants will be given journals with writing prompts to be completed throughout their pregnancy.<br>|
| Placebo Comparator: General Writing Prompts<br>Participants will be given writing prompts that discuss neutral topics unrelated to their life stress, resilience, or coping. | Other: Writing exercises<br>* Participants will be given journals with writing prompts to be completed throughout their pregnancy.<br>|
| No Intervention: No Writing<br>Participants will not be given writing prompts during their prenatal care. They will be given blank journals that will NOT contain any instructions or writing prompts. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Participation in Writing Activity | The percentage of women who respond that they completed their assigned writing activity will be measured. | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Statistically significant improvement (reduction) in the Perceived Stress Scale Score | Psychological instrument used to measure one's perception of stress (score range 0-40) will be assessed before and after the assigned writing activity. Higher scores on the scale indicate a higher vulnerability for those with a high levels of perceived stress in their life. Prior studies have noted the average score for a female age 30-44 is approximately 14. | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Proportion of women with adverse perinatal outcomes | We will define adverse pregnancy outcomes as a composite of preterm birth <37 weeks, intrauterine growth restriction, preeclampsia, and placental abruption; outcomes will be compared between randomization groups | outcome will be ascertained at delivery | 
| Change in pro-inflammatory biomarkers in maternal blood by randomization group | All women participating in the study will have a blood draw. Levels of stress biomarkers (e.g., interleukin-6) will be compared by randomization group | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Change in pro-inflammatory biomarkers in maternal blood by outcome | All women participating in the study will have a blood draw. Levels of stress biomarkers (e.g., interleukin-6) will be compared between women who develop the adverse perinatal outcome and those who do not | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Change in stress-related gene expression in maternal blood by randomization group | All women participating in the study will have a blood draw. We will evaluate gene expression of the CTRA gene panel (conserved transcriptional response to adversity gene panel) by randomization group | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Change in stress-related gene expression in maternal blood by outcome | All women participating in the study will have a blood draw. We will evaluate gene expression of the CTRA gene panel (conserved transcriptional response to adversity gene panel) by whether or not the patient developed the adverse perinatal outcome | through study completion, an average of 7 months per participant and 2 years for entire study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Utilization of professional psychiatric care | proportion of women who initiate or continue therapy with professional psychiatric care provider | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Stress related pathways gene expression - placental tissue - by randomization group | After delivery, we will evaluate whether there are differences in the conserved transcriptional response to adversity gene panel (CTRA gene panel) by randomization groups | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Stress related pathways gene expression - placental tissue - by diagnosis of adverse perinatal outcome | After delivery, we will evaluate whether there are differences in the conserved transcriptional response to adversity gene panel (CTRA gene panel) by whether or not the patient developed the adverse perinatal outcome | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Rate of preterm birth less than 37 weeks' gestation by randomization group | we will individually evaluate the outcomes of preterm birth <37 weeks, intrauterine growth restriction, preeclampsia, and placental abruption; outcomes will be compared between randomization groups | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Rate of diagnosis of intrauterine growth restriction, using sex-specific curves, by randomization group | we will individually evaluate the outcomes of preterm birth <37 weeks, intrauterine growth restriction, preeclampsia, and placental abruption; outcomes will be compared between randomization groups | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Rate of diagnosis of preeclampsia by randomization group | we will individually evaluate the outcomes of preterm birth <37 weeks, intrauterine growth restriction, preeclampsia, and placental abruption; outcomes will be compared between randomization groups | through study completion, an average of 7 months per participant and 2 years for entire study | 
| Rate of diagnosis of placental abruption by randomization group | we will individually evaluate the outcomes of preterm birth <37 weeks, intrauterine growth restriction, preeclampsia, and placental abruption; outcomes will be compared between randomization groups | through study completion, an average of 7 months per participant and 2 years for entire study |