Promoting Healthy Brain Development: Wellness for 2 Study

Prenatal Stress Clinical Trial

Official title:

Promoting Healthy Brain Development Via Prenatal Stress Reduction: An Innovative Precision Medicine Approach

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05052281
• Other study ID #: IRB 2019-2515
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 15, 2019
• Est. completion date: July 31, 2024

Study information

• Verified date: April 2024
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The "Promoting Healthy Brain Project" (PHBP) is part of the Lurie Children's Hospital Strategic Research Initiative on Perinatal Origins of Childhood Disease: Research & Prevention at the Maternal-Fetal Interface. The overall purpose of the PHBP is to test whether reducing maternal stress during pregnancy is associated with improved neurodevelopment in the first year of life. This will be tested via a randomized controlled trial (n = 100) of a technology and mindfulness enhanced prenatal stress-reduction intervention (Mothers and Babies; MB).

Description:

The "Promoting Healthy Brain Project" (PHBP) aims to improve infant neurodevelopmental trajectories by intervening on the fetal environment. The PHBP will experimentally test whether reducing prenatal maternal stress is associated with improved neurodevelopment in the first year of life. A randomized controlled trial (RCT) of a technology and mindfulness-enhanced prenatal maternal stress-reduction intervention (The Mothers and Babies Course; MB), compared to usual prenatal care. Prospective evaluation of infant neurodevelopmental outcomes will take place through infant age 24 months. Participants assigned to the intervention group will be offered the 12-session MB intervention, a well-studied intervention that will include new mindfulness practice enhancements designed to promote practice of awareness and attention to the present moment. MB visits will be delivered 1-on-1 by a trained facilitator in an open and nonjudgmental way, and will be offered in-person, over the phone, and/or by video chat. Throughout the intervention, all participants (intervention group and control group) will also wear a wireless, "smart" health sensing device (BioStamp Sensor - nPoint Device) that will measure heart rate and motion. Mothers' heart rate variability and self-reported stress and emotion will be monitored using the BioStamp Sensor and brief smartphone surveys. For mothers in the intervention group, patterns of prolonged stress will trigger a "just-in-time adapted intervention" (JITAI) that will be delivered to mothers' smartphones. The booster intervention will include activities that will enhance skills learned in the MB course. All participants will complete self-report measures of prenatal maternal stress, emotion, depression, and skills related to the intervention (e.g., mindfulness). Infant neurodevelopmental health will be measured via brain and behavioral indicators of self-regulation, including performance-based indicators of executive function and corollary prefrontal cortex maturation and dimensional phenotypes of disruptive behavior, particularly irritability.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: July 31, 2024
• Est. primary completion date: July 28, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• = 18 years old;

• enrolled under 22 weeks gestation;

• receiving prenatal care from a Northwestern University prenatal care clinic & planning to deliver at Northwestern Hospitals;

• English-speaking

• Participants must own a smartphone and be must be willing to receive text messages and respond to short online surveys using their smartphone.

• Eligible participants must also agree to wear a wireless adhesive sensor, the BioStamp, daily, throughout the 12-week MB course.

• Eligible participants will also have WiFi internet access for the duration of their participation in the study, in order to complete online questionnaires and upload sensor data.

• Eligible participants must also agree to have their child participate in the neurodevelopmental assessments from birth-12 months.

Exclusion Criteria:

• Women will be ineligible to participate in this study if they have known pregnancy or chronic medical complications that may place their infant at risk for neurological disorders (e.g., HIV; acute cytomegalovirus infection (CMV); toxoplasmosis; zika virus; Phenylketonuria (PKU); chromosomal anomalies; metabolic disorder; substance use disorders) or significant mental health disorders (e.g., schizophrenia, bipolar disorder, psychosis) which could interfere with study adherence.

• Participants unable to wear the BioStamp Sensor due to known skin sensitivity (e.g., allergy to adhesives or silicone), current skin irritation, or broken skin at the placement site will not be eligible to participate.

• Participants with a pacemaker or other sensitive medical device will be excluded.

• Women will not be eligible to participate if unable to provide informed consent, complete MB sessions, or complete study assessments in English.

• Women who are currently participating in an MB course at the time of recruitment will not be eligible to participate.

Related Conditions & MeSH terms

• Prenatal Stress

Intervention

Behavioral:
• Mothers and Babies (MB) Course
The Mothers and Babies course (MB) is a 12-session manualized stress-reduction intervention that will be delivered to participants, prenatally, with an integrated technology suite designed for timely detection and response to maternal stress.
• Just in Time Intervention (JITI) Content
Participants will also receive additional MB intervention content in the form of "just-in-time" text messages, which will be sent to participants' smartphones every other day for up to 12 weeks. During the current trial, participants will receive text message prompts with links to additional stress reduction content based on a combination of their objective (sensor) and subjective (EMA) stress responses from the previous day.

Device:
• Biostamp nPoint Device
During the intervention period, participants will be asked to wear the BioStamp nPoint sensor, daily, while engaging in their usual activities (e.g., sleep, showering, exercise). The BioStamp Sensor is a thin, wearable patch, equipped with wireless high-range 6-axis gyroscope + accelerometer, and sEMG and ECG sensors, that adheres to the skin using a disposable medical-grade adhesive sticker (with adhesive similar to Band-Aid).

Locations

Country	Name	City	State
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Northwestern University (Feinberg School of Medicine)	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Ann & Robert H Lurie Children's Hospital of Chicago

Country where clinical trial is conducted

United States, 

References & Publications (8)

de Bruijn AT, van Bakel HJ, van Baar AL. Sex differences in the relation between prenatal maternal emotional complaints and child outcome. Early Hum Dev. 2009 May;85(5):319-24. doi: 10.1016/j.earlhumdev.2008.12.009. Epub 2009 Jan 21. — View Citation

Grizenko N, Fortier ME, Zadorozny C, Thakur G, Schmitz N, Duval R, Joober R. Maternal Stress during Pregnancy, ADHD Symptomatology in Children and Genotype: Gene-Environment Interaction. J Can Acad Child Adolesc Psychiatry. 2012 Feb;21(1):9-15. — View Citation

Kinsella MT, Monk C. Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. Clin Obstet Gynecol. 2009 Sep;52(3):425-40. doi: 10.1097/GRF.0b013e3181b52df1. — View Citation

Mendelson T, Leis JA, Perry DF, Stuart EA, Tandon SD. Impact of a preventive intervention for perinatal depression on mood regulation, social support, and coping. Arch Womens Ment Health. 2013 Jun;16(3):211-8. doi: 10.1007/s00737-013-0332-4. Epub 2013 Mar 2. — View Citation

O'Connor TG, Heron J, Golding J, Glover V; ALSPAC Study Team. Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis. J Child Psychol Psychiatry. 2003 Oct;44(7):1025-36. doi: 10.1111/1469-7610.00187. — View Citation

Talge NM, Neal C, Glover V; Early Stress, Translational Research and Prevention Science Network: Fetal and Neonatal Experience on Child and Adolescent Mental Health. Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry. 2007 Mar-Apr;48(3-4):245-61. doi: 10.1111/j.1469-7610.2006.01714.x. — View Citation

Tandon SD, Leis JA, Mendelson T, Perry DF, Kemp K. Six-month outcomes from a randomized controlled trial to prevent perinatal depression in low-income home visiting clients. Matern Child Health J. 2014 May;18(4):873-81. doi: 10.1007/s10995-013-1313-y. — View Citation

Tandon SD, Perry DF, Mendelson T, Kemp K, Leis JA. Preventing perinatal depression in low-income home visiting clients: a randomized controlled trial. J Consult Clin Psychol. 2011 Oct;79(5):707-12. doi: 10.1037/a0024895. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Family Life Impairment Scale (FLIS)	The FLIS is a parent report survey that assesses the degree to which a child's behavior impacts the family's ability to participate in typical activities.	12 months, 24 months
Other	PROMIS Anxiety	Mothers complete the PROMIS Anxiety scale, which includes items that assess fear, anxious misery, hyperarousal, and somatic symptoms related to anxiety.	Prenatal, 1 month, 3 months, 7 months, 12 months, 24 months
Other	Family Relationship Index (FRI)	The FRI is a 12-item survey designed to assess family cohesion, communication and conflict-resolution.	prenatal, 3 months, 7 months, 12 months, 24 months
Primary	Disruptive Behavior Diagnostic Observation Schedule (DB DOS)	The DB DOS is a standardized observation of infant arousal, soothability, reactivity, and temper loss. During early infancy, the	12 months, 24 months
Primary	Perceived Stress Scale (PSS)	The PSS is a self-report measure of the degree to which an individual perceives their life situations to be stressful. The instrument includes 10 items that assess how unpredictable, uncontrollable, and overloaded respondents find their lives, and assess current levels of experienced stress.	Prenatal, 1 month, 3 months, 7 months, 12 months, 24 months
Primary	MAP-DB	Parent report measure of infant irritability.	1 month, 7 months, 12 months, 24 months
Primary	PROMIS Depression	Mothers complete a 28-item scale that assesses depressive symptoms experienced in the past 7 days.	Prenatal, 1 month, 3 months, 7 months, 12 months, 24 months
Primary	State Trait Anxiety Inventory (STAI)	The STAI is a 40 item self report questionnaire that assesses both state anxiety and trait anxiety.	Prenatal, 1 month, 3 months, 7 months, 12 months, 24 months
Secondary	Five Facet Mindfulness Questionnaire (FFMQ)	The FFMQ is a 39-item self report survey that taps into five areas of mindfulness, including observation, description, aware actions, non-judgmental inner experience, and non-reactivity.	Prenatal, 1 month, 3 months, 7 months, 12 months, 24 months
Secondary	NICU Neonatal Behavioral Scale (NNNS)	The NNNS is an assessment of neurobehavioral organization, neurological reflexes, motor development - active and passive tone, and signs of stress and withdrawal in neonates, developed for use with at-risk or drug-exposed infants but has been normed with typically developing infants.	1 month
Secondary	Test of Infant Motor Performance (TIMP)	The TIMP is a norm-referenced measure designed to evaluate motor control and organization of posture and movement for functional activities in infants 32 weeks gestational age to four months post-term age and measures both spontaneous behaviors and elicited items.	1 month
Secondary	General Movements Assessment (GMA)	General movements are a developmentally regulated pattern of spontaneous motor activity. By 10-15 weeks of age, the predominant general movements seen are called Fidgety Movements - a pattern of continuous, small amplitude movements of the neck, trunk and limbs during wakefulness that disappear with agitation. These patterns are identifiable and are classified as normal if present (intermittent or continual), and abnormal if exaggerated (with respect to speed and amplitude), sporadic (interspersed with long pauses) or absent. Babies are observed for up to 30 minutes in a supine position to assess for spontaneous movements.	1 month
Secondary	Alberta Infant Motor Scale (AIMS)	The Alberta Infant Motor Scale (AIMS) is a 10-20 minute norm referenced, standardized, gross motor assessment. Infants are observed in four positions: prone, sitting, supine, and standing. For each subscale, items are scored as "observed" or "not observed". A total raw score and percentile are calculated.	1 month
Secondary	Maternal Heart Rate Variability	variability/physiological stress as indicated by a machine learned model applied to electrocardiogram (ECG) signals.	Pregnancy (duration 14 weeks)
Secondary	Prefrontal cortex thickness	Cortical thickness and surface area of pre-frontal cortex regions, which have been linked to child irritability and Infant dysregulation, is measured through natural sleep MRI.	1 month, 12 months, 24 months
Secondary	Inflammatory and neuroimmune biomarkers	Placenta and cord blood will be collected at birth. Tests to be performed on these samples include measurement of inflammatory markers related to stress, such as a multiplex immunoassay panel of the following cytokines and chemokines: (IL-6, IL-8, IL-10, C-reactive protein, TNF-alpha, TGF-beta, IL-1beta, procalcitonin, cortisol).	At birth
Secondary	EEG power	The baby will complete a baseline or resting EEG for 2-5 minutes and then hear an auditory oddball paradigm with speech syllables while resting for ~10 min. EEG (electroencephalogram) power will be measured as a marker infant neurodevelopment.	1 month, 12 months, 24 months
Secondary	ERP mean amplitude	The baby will complete a baseline or resting EEG for 2-5 minutes and then hear an auditory oddball paradigm with speech syllables while resting for ~10 min. ERP (event related potential) mean amplitude will be measured as a marker of infant neurodevelopment.	1 month, 12 months, 24 months
Secondary	Birthweight	Infant birthweight will be obtained from EHR data collected at the hospital at birth	Birth
Secondary	Maternal Infant Responsiveness Instrument (MIRI)	The MIRI is a 22 item questionnaire designed to assess a mother's feelings about her infant, her recognition of her responsiveness to the infant, and her infants responses.	1 month, 7 months, 12 months
Secondary	Infant Behavior Questionnaire-Revised (IBQ-R) short form	The IBQ-R is a parent-report survey designed to measure multiple dimensions of temperament in infants up to age 12 months.	1 month, 7 months, 12 months
Secondary	Bayley Scales of Infant Development	The Bayley Scales of Infant and Toddler Development Fourth Edition (Bayley-4) is a five-domain assessment tool used to determine developmental delays in children. The developmental domains are cognitive, language, motor, social-emotional, and adaptive behavior, and include direct assessment of the child and parent report.	7 months, 12 months, 24 months
Secondary	Preschool Age Psychiatric Assessment (PAPA)	Parent structured interview for diagnosing psychiatric disorders in children ages 2-5.	24 months
Secondary	Brief Infant Toddler Social Emotional Assessment (BITSEA)	Parent report measure of behavior problems and social competencies in children ages 1-3 that identifies delays or deficits in areas of social-emotional development.	12 months, 24 months
Secondary	Early Childhood Irritability Related Impairment Interview (E-CRI)	The E-CRI is a semi-structured interview designed to measure early childhood impairment resulting from young children's tantrums and irritability across various contexts.	24 months
Secondary	Perceived Stress Scale (PSS)	Self-report measure of the degree to which an individual perceives their life situations to be stressful. The instrument includes 10 items that assess how unpredictable, uncontrollable, and overloaded respondents find their lives, and assess current levels of experienced stress.	1 month, 3 months, 7 months, 12 months, 24 months
Secondary	Behavioral Activation Depression Scale (BADS) - short form	Self-report 9-item measure of behaviors that indicate depression and can be targeted for change by cognitive behavioral therapy and behavior activation. Mothers complete this measure regarding behaviors experienced over the past week.	prenatal, 3 months, 7 months, 12 months, 24 months
Secondary	Negative Mood Regulation Scale (NMRS)	This self-report, 30-item scale measures expectancies and beliefs that the mothers have regarding their abilities to alleviate their negative mood, anger, anxiety and depression.	prenatal, 3 months, 7 months, 12 months, 24 months
Secondary	Parenting Stress Index (PSI) - Role Restriction Subscale	The PSI Role Restriction subscale includes 7 mother-report items regarding her feelings of limited freedom and restriction of her identity to the parenting role.	3 months, 7 months, 12 months, 24 months
Secondary	Parental Cognitions and Conduct Toward the Infant Scale (PACOTIS)	The PACOTIS is a mother report measure of their actions, thoughts, and feelings during interactions with their baby.	1 month, 3 months, 7 months, and 12 months
Secondary	MacArthur-Bates Communicative Development Inventories (MCDI)	The MCDI is a parent-report questionnaire about their child's communication and language development. The Words & Gestures form is used at 12 months and the Words & Sentences form is used at 24 months.	12 months, 24 months
Secondary	Medical Outcomes Study (MOS) Social Support Survey	The MOS Social Support Survey is a 19-item self-report measure of the mother's availability of social support in a variety of domains including emotional support, tangible support, affectionate support, and positive social interaction.	Prenatal, 3 months, 7 months, 12 months, 24 months