Promoting Healthy Brain Development: Wellness for 2 Study

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

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).

Study Overview

• Status: Completed
• Conditions: Prenatal Stress
• Intervention / Treatment: Behavioral: Mothers and Babies (MB) Course; Behavioral: Just in Time Intervention (JITI) Content; Device: Biostamp nPoint Device

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern University (Feinberg School of Medicine)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; 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; 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.; Behavioral: 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).
Active Comparator: Stress monitoring (control) group; 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; 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).

What is the study measuring?

Primary 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
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
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
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
MAP-DB	Parent report measure of infant irritability.	1 month, 7 months, 12 months, 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Ann & Robert H Lurie Children's Hospital of Chicago
• Investigators: Principal Investigator: Lauren Wakschlag, PhD, Northwestern University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): July 28, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: August 30, 2019
• First Submitted That Met QC Criteria: September 11, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Pregnancy; Neurodevelopment; Pre-natal; Post-Natal
• Other Study ID Numbers: IRB 2019-2515

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared with other investigators. Investigators from outside the study will be asked to sign an agreement of confidentiality in order to receive the data requested. Data will be stored for at least 7 years. We plan to archive the de-identified data in a data repository for future use by other researchers, after the study is completed. Additionally, data from this study will be used in the Mental Health Earlier Synthetic Cohort (MHESC) Study in order to generate a pragmatic clinical risk calculator to predict preschool psychopathology. MHESC pools three extramural cohorts at Northwestern University and Washington University in St. Louis, one of which is the Wellness for 2 Study to form a clinically enriched "synthetic" cohort. Therefore, data will be shared with authorized individuals at Washington University.
• IPD Sharing Time Frame: Data will be stored for at least 7 years.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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