Stress Phenotypes and Preterm Birth (PTB)

Stress Phenotypes and Preterm Birth: Immune and Energetic Cellular Dysregulation and the Preventive Effect of Social Support

Pregnancy ends in preterm birth (PTB) for approximately 1 in 10 women, though more often for Non-Hispanic Black women, 14.12% PTB rate, compared to 9.09% for Non-Hispanic White women. Psychosocial stress and childhood trauma each are associated with risk for PTB and PTB has an intergenerational impact: mothers born preterm are more likely to give birth preterm, especially amongst Black women. In this project, we will study mitochondria, which contain their own genome, the mitochondria DNA, and are inherited from the mother, as they represent a potential intersection point between psychosocial experiences and their biological embedding in underlying disease outcomes such as PTB

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Stress; Preterm Birth; Mental Health Issue
• Intervention / Treatment: Other: Cognitive Challenge

Detailed Description

At odds with common assumptions - and hope, pregnancy ends in preterm birth (PTB) for approximately 1 in 10 women. Yearly PTB affects 15 million infants worldwide and 386,580 in the United States. PTB is the leading cause of global, and U.S., neonatal mortality and morbidity and is associated with future risk for poor physical (higher blood pressure, chronic kidney disease, wheeze/asthma) and mental (ADHD, IQ decrements) health. Maternal health is not spared: women who deliver preterm are at an increased risk for depression, hypertension, cardiovascular and renal disease later in life. In the U.S., the racial and ethnic disparities in PTB rates are dramatic and independent of socio-economic status (SES): overall, 14.12% for Non-Hispanic Black compared to 9.09% for Non-Hispanic White women.

Psychosocial stress and childhood trauma each are associated with risk for PTB. PTB has an intergenerational impact: mothers born preterm are more likely to give birth preterm, especially amongst Black women. Biomarkers to predict PTB have proven unsuccessful, and do not account for this emerging recognition of intergenerational transmission of PTB risk specifically via maternal heritage. Mitochondria, which contain their own genome, the mitochondria DNA, are inherited from the mother and represent a potential intersection point between psychosocial experiences and their biological embedding, including via immune dysregulation, in underlying disease outcomes. We aim to apply a mitochondria psychobiology approach to delineate by which mechanisms life stress - including discrimination and childhood trauma - results in disproportionate risk of PTB in minority women, and evaluate mitochondria as potential biomarkers of this birth outcome.

In a sample of post-attrition n=175 pregnant women we will test the following three aims: Aim 1: To determine whether a data driven approach to multiple, 1st trimester psychosocial (self- report stress discrimination, social support), lifecourse (hair cortisol, childhood trauma), and biological variables (acute laboratory physiological stress reactivity) generate unique stress profiles that partially explain the racial/ethnic differences in gestational age at birth. Aim 2: To identify molecular indices of mitochondrial and immune functioning in the mother (3x blood draw), placenta, and fetal cord blood that mediate the association between 1st trimester maternal stress phenotypes and risk for earlier gestational age at birth. Aim 3: To evaluate if reduction in stress levels and/or improvement in social support over the course of pregnancy is associated with molecular indices of mitochondrial and immune functioning and (exploratory) reduced risk of earlier birth relative to national and hospital norms.

This new conceptual framing of this adverse health outcome (1) incorporates evidence of the psychosocial factors contributing to risk, (2) aims to account for the racial/ethnic disparities, and (3) harnesses cutting-edge mitochondria knowledge and tools to better characterize PTB's pathophysiology and identify novel targets for its intervention and prevention.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine Monk, PhD; Phone Number: 646-774-8941; Email: cem31@cumc.columbia.edu
• Study Contact Backup: Name: Elizabeth Werner, PhD; Phone Number: 646-774-8835; Email: ew150@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Catherine Monk, PhD; Phone Number: 917-543-6031; Email: cem31@columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Pregnant women 18 years of age or older (based on self-report)
• Not currently smoking, drinking alcohol, or taking drugs (based on self-report)
• Planning to deliver at CUIMC/NYP (based on self-report)
• In the first or second trimester of pregnancy (prior to 28 weeks gestation) (based on self-report of estimated date of delivery)

Exclusion Criteria

• Multi-fetal pregnancy (based on self-report)

• Taking medications regularly that affect the cardiovascular and inflammatory systems, including NSAIDS and other anti-inflammatories, α blockers, β blockers, corticosteroids, chronic-use asthma medications (e.g. beta2- adrenoceptor agonists) (based on self-report)

  • This does NOT include baby aspirin or low-dose aspirin, as baby aspirin / low-dose aspirin is not normally considered to be an NSAID.
• Inflammatory conditions including rheumatoid arthritis, lupus, and multiple sclerosis (based on self-report)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cognitive Challenge; A cognitive challenge (Stroop Color-Word Test) administered at 36-38 weeks gestation to assess fetal heart rate reactivity in response to maternal acute stress.	Other: Cognitive Challenge; A cognitive challenge (Stroop Color-Word Test) administered at 36-38 weeks gestation to assess fetal heart rate reactivity in response to maternal acute stress.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Higher percentage of Black and Hispanic women in high stress group	The high stress group is calculated using various measures including multiple psychosocial, life course, biological variables, and acute stress reactivity to a cognitive challenge (Stroop test).	At 12 - 38 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relatively earlier gestational age at birth in high stress group	The high stress phenotype is calculated using various measures including, multiple psychosocial, life course, biological variables, and acute stress reactivity to a cognitive challenge (Stroop test).	At birth, approximately 32 - 42 weeks gestation

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute on Minority Health and Health Disparities (NIMHD)
• Investigators: Principal Investigator: Catherine Monk, PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Pathological Conditions, Signs and Symptoms; Premature Birth; Inflammation
• Other Study ID Numbers: AAAU9052; 8144 (Other Identifier: New York State Psychiatric Institute Institutional Review Board); R01MD016278 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No