Promoting Healthy Brain Development: Wellness for 2 Study

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Prenatal Stress

Intervention / Treatment
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* Behavioral: Mothers and Babies (MB) Course
* Behavioral: Just in Time Intervention (JITI) Content
* Device: Biostamp nPoint Device


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>The first MB course session and technology training will take place in-person, prior to 23 weeks gestation. 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. Sessions are delivered 1-on-1 with a trained facilitator and are based on principles of cognitive-behavioral therapy (CBT) and attachment theory. The MB course is divided into 3 sections: 1) Pleasant Activities; 2) Thoughts; 3) Contact with Others. Throughout each module, mindfulness skills training will be integrated as a strategy to help center participants. All participants will receive a Participant Manual for Families, containing worksheets that correspond to the 12 sessions. | Behavioral: Mothers and Babies (MB) Course<br>* 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.<br>Behavioral: Just in Time Intervention (JITI) Content<br>* 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.<br>Device: Biostamp nPoint Device<br>* 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).<br>|
| Active Comparator: Stress monitoring (control) group<br>This group will not receive any additional intervention but will engage in stress monitoring via biosensors and EMA text messages through the 14 week period | Device: Biostamp nPoint Device<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 7 months | 
| 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 | 
| MAP-DB | Parent report measure of infant irritability. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Maternal Heart Rate Variability | variability/physiological stress as indicated by a machine learned model applied to electrocardiogram (ECG) signals. | Pregnancy (duration 14 weeks) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Birthweight | Infant birthweight will be obtained from EHR data collected at the hospital at birth | Birth | 
| 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 | 
| 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 | 
| 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 | 
| Preschool Age Psychiatric Assessment (PAPA) | Parent structured interview for diagnosing psychiatric disorders in children ages 2-5. | 24 months | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| MAP-DB | Parent report measure of infant irritability, temper loss, and attention | 3 months, 7 months, 12 months, 24 months | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Pre-natal, Post-Natal, Neurodevelopment