Therapeutic Writing to Reduce Stress (RESeT)

Writing to Reduce Stress in Expectant Moms: The RESet Study

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.

Study Overview

• Status: Terminated
• Conditions: Pregnancy Complications; Stress, Physiological; High Risk Pregnancy
• Intervention / Treatment: Other: Writing exercises

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women will be prospectively recruited.

  1. 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.
  2. Singleton viable intrauterine pregnancy, with dating confirmed by ultrasound or plans for ultrasound to confirm dating prior to study enrollment
  3. No structural abnormalities or aneuploidy
  4. Ability to communicate in and provide consent in English

  5. 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

  6. Women with at least TWO of the following moderate risk criteria:

     1. Prior preterm birth 34.0-36.9 weeks
     2. Chronic hypertension not requiring medications
     3. History of term pre-eclampsia
     4. Type II diabetes on insulin
     5. Obesity with a BMI >30
     6. Smoking during pregnancy
     7. Black race
     8. Maternal age <18 years old or >40 years old
     9. Nulliparous
     10. Uninsured, or medicaid insurance
  7. 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:

1. 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.
2. 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

3. Major congenital anomaly such as major structural deficit of the heart, lungs, or brain or aneuploidy

   1. Mild renal abnormalities, clubfoot, isolated cleft lip/palate, etc. in the fetus are not a reason for exclusion
   2. 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
   3. Isolated 'soft markers' for aneuploidy (such as choroid plexus cysts, echogenic bowel, etc.) are not a reason for exclusion
   4. 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
4. Spanish speaking women
5. Women participating in other intervention-based studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Therapeutic Writing Prompts; 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; Participants will be given journals with writing prompts to be completed throughout their pregnancy.
Placebo Comparator: General Writing Prompts; Participants will be given writing prompts that discuss "neutral" topics unrelated to their life stress, resilience, or coping.	Other: Writing exercises; Participants will be given journals with writing prompts to be completed throughout their pregnancy.
No Intervention: No Writing; 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?

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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Tracy A Manuck, MD, University of North Carolina

Publications and helpful links

General Publications

• McEwen BS. Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci. 1998 May 1;840:33-44. doi: 10.1111/j.1749-6632.1998.tb09546.x.
• Geronimus AT, Hicken M, Keene D, Bound J. "Weathering" and age patterns of allostatic load scores among blacks and whites in the United States. Am J Public Health. 2006 May;96(5):826-33. doi: 10.2105/AJPH.2004.060749. Epub 2005 Dec 27.
• Schulkin J, Gold PW, McEwen BS. Induction of corticotropin-releasing hormone gene expression by glucocorticoids: implication for understanding the states of fear and anxiety and allostatic load. Psychoneuroendocrinology. 1998 Apr;23(3):219-43. doi: 10.1016/s0306-4530(97)00099-1.
• Anding JE, Rohrle B, Grieshop M, Schucking B, Christiansen H. Couple comorbidity and correlates of postnatal depressive symptoms in mothers and fathers in the first two weeks following delivery. J Affect Disord. 2016 Jan 15;190:300-309. doi: 10.1016/j.jad.2015.10.033. Epub 2015 Oct 28.
• Edwards B, Galletly C, Semmler-Booth T, Dekker G. Does antenatal screening for psychosocial risk factors predict postnatal depression? A follow-up study of 154 women in Adelaide, South Australia. Aust N Z J Psychiatry. 2008 Jan;42(1):51-5. doi: 10.1080/00048670701739629.
• Juul SH, Hendrix C, Robinson B, Stowe ZN, Newport DJ, Brennan PA, Johnson KC. Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function. Arch Womens Ment Health. 2016 Feb;19(1):17-23. doi: 10.1007/s00737-015-0528-x. Epub 2015 May 9.
• Meltzer-Brody S, Boschloo L, Jones I, Sullivan PF, Penninx BW. The EPDS-Lifetime: assessment of lifetime prevalence and risk factors for perinatal depression in a large cohort of depressed women. Arch Womens Ment Health. 2013 Dec;16(6):465-73. doi: 10.1007/s00737-013-0372-9. Epub 2013 Aug 1.
• Oh W, Muzik M, McGinnis EW, Hamilton L, Menke RA, Rosenblum KL. Comorbid trajectories of postpartum depression and PTSD among mothers with childhood trauma history: Course, predictors, processes and child adjustment. J Affect Disord. 2016 Aug;200:133-41. doi: 10.1016/j.jad.2016.04.037. Epub 2016 Apr 20.
• McDonald SW, Kingston D, Bayrampour H, Dolan SM, Tough SC. Cumulative psychosocial stress, coping resources, and preterm birth. Arch Womens Ment Health. 2014 Dec;17(6):559-68. doi: 10.1007/s00737-014-0436-5. Epub 2014 Jun 20.
• Meshberg-Cohen S, Svikis D, McMahon TJ. Expressive writing as a therapeutic process for drug-dependent women. Subst Abus. 2014;35(1):80-8. doi: 10.1080/08897077.2013.805181.
• Blasio PD, Camisasca E, Caravita SC, Ionio C, Milani L, Valtolina GG. THE EFFECTS OF EXPRESSIVE WRITING ON POSTPARTUM DEPRESSION AND POSTTRAUMATIC STRESS SYMPTOMS. Psychol Rep. 2015 Dec;117(3):856-82. doi: 10.2466/02.13.PR0.117c29z3. Epub 2015 Nov 23.
• Smyth JM, Hockemeyer JR, Tulloch H. Expressive writing and post-traumatic stress disorder: effects on trauma symptoms, mood states, and cortisol reactivity. Br J Health Psychol. 2008 Feb;13(Pt 1):85-93. doi: 10.1348/135910707X250866.
• Carver CS, Scheier MF, Weintraub JK. Assessing coping strategies: a theoretically based approach. J Pers Soc Psychol. 1989 Feb;56(2):267-83. doi: 10.1037//0022-3514.56.2.267.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Actual): February 17, 2022
• Study Completion (Actual): February 17, 2022

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications
• Other Study ID Numbers: 18-2187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All information that is collected for this study will be stored in locked filing cabinets and/or offices and on the secure UNC server on the RedCap database. Participants will be assigned a unique study-id number for this study. Only the PI and Sponsor for the study will have access to the key linking this study id number to their personal clinical information and identifiers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No