Stress Phenotypes and Preterm Birth

Inflammation Clinical Trial

— PTB  

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05229666
• Other study ID #: 8144
• Secondary ID: R01MD016278
• Status: Suspended
• Phase: N/A
• Start date: December 9, 2021
• Est. completion date: November 2026

Study information

• Verified date: August 2023
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 pretern, 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

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 pretern, 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, 24-hour ambulatory mood, 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 180
• Est. completion date: November 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy, singleton pregnancy, between the ages of 18-45

Exclusion Criteria:

• Currently smoking cigarettes, drinking alcohol, taking dugs, taking medications regularly (other than prenatal vitamins), multiple fetal pregnancy, inflammatory conditions including rheumatoid arthritis, lupus, and multiple sclerosis, and not planning to deliver at CUMC

Related Conditions & MeSH terms

• Inflammation
• Mental Health Issue
• Premature Birth
• Preterm Birth
• Stress

Intervention

Other:
• Cognitive Challenge
Cognitive challenge delivered via computer.

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Institute on Minority Health and Health Disparities (NIMHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Between 36-38 weeks gestation
Secondary	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