Maternal Adversity, Vulnerability and Neurodevelopment

Study Overview
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Brief Summary
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Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project is a prospective community-based, pregnancy and birth cohort of Canadian mother-child dyads. The main objective of MAVAN project is to examine the pre- and postnatal influences, and their interaction, in determining individual differences in children development. The MAVAN project is designed to examine the consequences of fetal adversity as a function of the quality of the postnatal environment, focusing on mother-infant interactions.

Detailed Description
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In 2003 the Canadian Institutes of Health Research (CIHR) funded an ambitious and internationally unique study on the development of individual differences in vulnerability for mental illness. Increasing evidence indicates that many forms of mental illness as well as diabetes and cardiovascular disease are best considered as developmental disorders where vulnerability emerges as a function of genetic and epigenetic events. Frank pathology then develops as a function of the continuous interaction between underlying vulnerability and prevailing environmental triggers. The critical question is that of understanding the mechanisms by which specific forms of gene x environment interactions in perinatal life define the level of vulnerability/resistance to illness. Maternal adversity during fetal life including maternal stress (as well as depression), low social support, poor maternal nutrition, and tobacco/alcohol consumption predict both preterm labour and intrauterine growth restriction. These birth outcomes, in turn, represent major epidemiological risk factors for heart disease, diabetes, and depression in adulthood, and neurodevelopmental impairments in children. Postnatal maternal adversity compromises maternal care/behaviour and infant development, and predicts increased risk for obesity, heart disease, attentional deficit disorders (ADD), drug abuse, and depression. Despite the enormous potential for the interaction of prenatal and postnatal influences, research has largely been restricted to the effects of events occurring during only one developmental period which, among other things, ignores the potential importance of 'protective' factors operating at later stages in life. Moreover, the underlying mechanisms by which perinatal adversity might directly affect neurocognitive development have been very poorly studied. The investigators proposed an innovative research program that focuses on child development using a longitudinal, within-subject design examining neural and cognitive/emotional outcomes as a function of genomic and epigenomic factors. These studies focus on 500 mother-infant dyads drawn from two human studies (Montreal & Hamilton). Assessment of maternal wellbeing and infant development (cognition, socio-emotional development, temperament, and brain structure) trajectories are undertaken from mid-pregnancy until 10 years of age. Genomic and epigenomic approaches were used to assess genetic vulnerability in these populations using a GWAS approach. This represents the first longitudinal study linking neurocognitive/behavioural function with structural neurodevelopment through neuroimaging and genetic vulnerability in humans, in the presence or absence of maternal adversity. The ability to identify postnatal events that serve to reverse a condition of vulnerability has enormous implications for the development of prevention /intervention programs reducing the future rates of a broad spectrum of chronic illnesses.

Official Title
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Maternal Adversity, Vulnerability and Neurodevelopment

Conditions
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Mental Health Issue (E.G., Depression, Psychosis, Personality Disorder, Substance Abuse), Infant Development, Infant Behavior

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women recruited when they attending antenatal care clinics at the time of routine ultrasound or through advertisements at hospitals (usually at 13 to 20 weeks' gestation). Women were included in the study if they were 18 years of age or older, and fluent in either English or French. Only babies born at 37 weeks or later and above 2000 g were included in the MAVAN cohort. Exclusion Criteria: Exclusion criteria included serious obstetric complications during the pregnancy or delivery of the child, extremely low birth weight, prematurity (less than 37 weeks of gestation), or any congenital diseases.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 6 Years

Sexes Eligible for Study
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All

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prenatal and 3 to 72 months<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child's Cognitive Development Measured Using the Bayley Scales of Infant Development II. | Assessment of child development was done using the cognitive, motor and mental scales of the Bayley Scales of Infant Development II. | At 6, 12, 18 and 36 months | 
| Child Temperament Evaluated Using the Infant Behaviour Questionnaire. | Child temperament was evaluated using the Infant Behaviour questionnaire (IBQ). The items represent 14 scales but factor analysis reveals three primary factors: a) impulsivity, b) negative affectivity and c) effortful control. | 3 and 6 months | 
| Changes in Child Temperament Evaluated Using the Early Childhood Behaviour Questionnaire. | Assessment of child's temperament was done with the Early Childhood Behaviour questionnaire, the toddler version of the IBQ. It is comprised of 201 items grouped in 18 subscales and is based on a 7-point Likert scale ranging from never to always. The questionnaire yields 18 sub-scores: activity level/energy, attentional focusing, attentional shifting, cuddliness, fear, frustration, high-intensity pleasure, impulsivity, inhibitory control, low-intensity pleasure, motor activation, perceptual sensitivity, positive anticipation, sadness, shyness, sociability, and soothability. | 18 and 36 months | 
| Changes in Socio-emotional Development Measured Using the Infant Toddler Socio-emotional Assessment Questionnaire. | Socio-emotional development was measured using the Infant Toddler Socio-emotional Assessment questionnaire (ITSEA). It consists of 140 items to evaluate four independent behavioral domains: 1) externalizing, (e.g., high-activity, aggression, defiance, and negative emotional reactivity); 2) internalizing, (e.g., mood regulation problems, social withdrawal and extreme inhibition/shyness); 3) dysregulation (e.g., sleep and eating problems, mood regulation); and 4) maladaptation (e.g., repetitive and stereotypic behaviors). Items are rated on a 3-point scale. | 18 and 24 months | 
| Changes in Child's Behaviour Problems Measured With the Child Behaviour Checklist. | Child's behaviour was evaluated using the Child Behaviour Checklist (CBCL). The CBCL is a well-validated screen for childhood psychopathology. This parent-rated questionnaire contains 100 items divided in 2 broad scales : Internalizing problems includes : Withdrawn, Somatic Complaints, and Anxious/Depressed subscales. Externalizing problems : including Rule-Breaking Behavior and Aggressive subscales. Total problems score : is the sum of the scores of all the problem items. | 48 and 60 months | 
| Changes in Child's School Readiness Measured With the School Readiness Test Battery. | School and academic readiness were assessed using the School readiness test battery, including the Lollipop test, Number knowledge and Peabody Picture Vocabulary test. The NKT measures the development of number concepts. This test measures the mastery of a series of concepts required for learning math and comprises 5 levels. The Lollipop includes 52 questions, divided in 4 knowledge subtests: (1) colours and forms, (2) spatial relationships, (3) numbers and (4) letters. It is a good predictor of reading and math achievement up to 4th grade. The PPVT is a receptive vocabulary test that measures the extent of vocabulary a child can understand. A child is asked to identify a spoken word on an array of four pictures, only one of which is correct. | 48 and 60 months | 
| Evaluation or Child's Cognitive Development Using the Developmental Neuropsychological Assessment. | Child's cognitive development was assessed using the sensory-motor and visuo-spatial processing subscales of the Developmental Neuropsychological Assessment (NEPSY). | 48 months | 
| Evaluation of Child's Cognitive Development Using the Weschler Preschool and Primary Scale of Intelligence. | Child's cognitive development was assessed using the vocabulary and the bloc design subscales of the Weschler Preschool Primary Scale of Intelligence (WPPSI). | 48 months | 
| Changes in Child's Hyperactivity Problems Measured With the Conner's. | The Conner's was designed to be completed by parents and teachers to assist in evaluating children for attention-deficit/hyperactivity disorder (ADHD). The parents' short version contains 27 items and the teachers' short version has 28. The teacher version is similar but lacks the psychosomatic scale contained on the parent version. The Conner's is validated and the standard for informant-administered ADHD assessment both in clinical and research settings. Oppositional, cognitive problems/inattention, hyperactivity subscales. | 60 and 72 months | 
| Child's Fears Assessed With the Koala Fear Questionnaire. | The Koala Fear Questionnaire (KFQ) is a standardized self-report scale for assessing fears and fearfulness in children aged between 4 and 12 years. This scale consists of 31 potentially fear-provoking stimuli and situations that are all illustrated with pictures. Children rate the intensity of their fear of these stimuli by using a visual scale depicting Koala bears expressing various degrees of fear ( no fear, some fear, a lot of fear ). | 60 months | 
| Changes in Child's Emotional and Behaviour Problems Measured With the Strength and Difficulty Questionnaire. | The Strengths and Difficulties Questionnaire (SDQ) is a brief screening for child emotional and behavioural problems. It is based on 25 items on psychological attributes. emotional symptoms (5 items) conduct problems (5 items) hyperactivity/inattention (5 items) peer relationship problems (5 items) prosocial behaviour (5 items) Number 1) to 4) added together to generate a total difficulties score. | 60 and 72 months | 
| Child's Behavioural Inhibition and Behavioural Activation Were Measured Using the Behavioural Inhibition System (BIS) and the Behavioural Approach System (BAS) | The BIS/BAS was designed to assess dispositional sensitivity to the behavioral inhibition system (BIS) and the behavioral activation or behavioral approach system (BAS). Questions 20 items using 4 point scales (1 = strongly disagree to 4 = strongly agree). 2 subscales: Behavioral Inhibition System (BIS) 7 items about anticipation of punishment Behavioral Action System (BAS), which has 3 subscales of its own: Reward Responsiveness (RR) 5 items about anticipation or occurrence of reward Drive (D) 4 items about pursuit of desired goals. Fun Seeking (FS) 4 items about desire for new rewards and impulsive approach to potential rewards. | 60 months | 
| Child's Mental Health Was Evaluated Using the Dominic Questionnaire. | The Dominic questionnaire is a structured pictorial instrument assessing mental disorders in 6- to 11-year-old children. The Dominic assesses a child's perception of her/his own symptoms, which is critical to balance parents' and school professionals' perception. Ninety-nine drawings represent situations corresponding to DSM-III-R based. ADHD, Conduct Disorder, Oppositional Defiant Disorder, Major Depressive Disorder, Separation Anxiety Disorder, Generalized Anxiety Disorder and Specific Phobia. | 72 months | 
| The Child's Attributional Style Was Evaluated With the Child Attributional Style Interview. | The Child Attributional Style Interview (CASI) is a measure of attributional style in children aged five years old and older. The interactive interview consists of sixteen events, which are presented to the child as illustrations, in a storybook format. The events are equally divided on two domains: valence (positive and negative theme), and interpersonal (parents and peers) and achievement. This creates the possibility of four sub-categories for analysis (i.e. positive-achievement, negative-interpersonal etc.). After the presentation of each event, the child is asked three questions for their level of internal, stable and global attributions for each event. | 72 months | 
| Changes in Child's Feeding Behaviour Was Measured With the Child Eating Behaviour Questionnaire. | The Child Eating Behaviour Questionnaire (CEBQ) was designed to assess children's eating scale styles. It is a parent-report measure comprised of 35 items, each rated on a five-point likert scale that ranges from never to always. The instrument is ideal for use in research investigating the early precursors of eating disorders or obesity. | 48 and 72 months | 
| Child's Executive Functioning Measured With the Behavior Rating of Executive Function. | The Behavior Rating Inventory of Executive Function (BRIEF) measures executive function behaviors for children and adolescents ages 5-18. Each form of the BRIEF parent- and teacher- rating form contains 86 items in eight non-overlapping clinical scales and two validity scales. These theoretically and statistically derived scales form two indexes: a) Behavioral Regulation (three scales) and b) Metacognition (five scales), as well as a Global Executive Composite score which takes into account all of the clinical scales and represents the child's overall executive function. | 72 months | 
| Sensitivity to Punishment & Sensitivity to Reward in Children Will be Evaluated Using the Child Version of the Sensitivity to Punishment & Sensitivity to Reward Questionnaire. | The Sensitivity to Punishment & Sensitivity to Reward questionnaire (SPSRQ-C) measures parent-rated sensitivity to punishment and reward and contains 33 items, divided in a Punishment Sensitivity scale, and three Reward Sensitivity scales: Reward Responsivity, Impulsivity/Fun-Seeking, and Drive. Each item is scored on a 5-point Likert scale. | 72 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Mother's Depression Symptoms Measured With the Beck Depression Inventory. | The Beck Depression Inventory (BDI-II) is a 21-question multiple-choice self-report inventory that is one of the most widely used instruments for measuring the severity of depression. The most current version of the questionnaire is designed for individuals aged 13 and over and is composed of items relating to depression symptoms such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex (15 minutes). BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. | 60 and 72 months | 
| Changes in Mother's Depression Symptoms Measured With the Center for Epidemiological Studies, Depression Scale. | The Center for Epidemiological Studies, Depression Scale (CES-D) is a 20-item instrument that has excellent internal consistency (.90) and reasonable test-retest reliability (.54) for a scale that should be sensitive to adverse changes in the respondent's environment. Questions ake to rate how often over the past week they experienced symptoms associated with depression, such as restless sleep, poor appetite, and feeling lonely. Response options range from 0 to 3 for each item (0 = Rarely or None of the Time, 1 = Some or Little of the Time, 2 = Moderately or Much of the time, 3 = Most or Almost All the Time). Scores range from 0 to 60, with high scores indicating greater depressive symptoms. | Prenatal, 6, 12, 24, 36, 48, 60, 72 months | 
| Changes in Mother's Depression Symptoms Were Measured With the Edinburgh Postnatal Depression Scale. | Edinburgh Postnatal Depression Scale (EPDS). The Edinburgh Postnatal Depression Scale (EPDS) is a 10-item self-report scale designed to screen for postpartum depression. The scale consists of 10 short statements with four possible answers corresponding to how the mother has felt during the past week. Responses are scored 0, 1, 2 and 3 based on the seriousness of the symptom. A higher total sum score indicates more severe symptoms of depression. | 6 months | 
| Changes in Mother's Anxiety Symptoms Were Measured Using the Speilberger State-Trait Anxiety Inventory. | The Speilberger State-Trait Anxiety Inventory (STAI) is self-report scale consisting of two forms of 20 items each to measure psychic components of state and trait anxiety. The State-Anxiety scale measures intensity of current feelings at this moment: 1) not at all, 2) somewhat, 3) moderately so, and 4) very much so. The Trait-Anxiety scale measures the frequency of feelings in general: 1) almost never, 2) sometimes, 3) often, and 4) almost always. | 3, 24 and 60 months | 
| Mother's Retrospective Assessment of Parental Educational Style Using the Parental Bonding Inventory. | Parental Bonding Inventory (PBI) is a standard in retrospective assessment of parental educational style (48 items). Two scales termed 'care' and 'overprotection' or 'control', measure fundamental parental styles as perceived by the child. The measure is 'retrospective', meaning that adults (over 16 years) complete the measure for how they remember their parents during their first 16 years. The measure is to be completed for both mothers and fathers separately. There are 25 item questions, including 12 'care' items and 13 'overprotection' items. | 6 months | 
| Changes in Mother's Sensitivity Was Evaluated Using the Maternal Behaviour Q Sort (Short Version) and the Ainsworth Scales. | Mother's sensitivity was assessed using the Maternal Behaviour Q sort (short version) and the Ainsworth scales (AINS). MBQS-S and AINS assess maternal sensitivity. Trained raters scored the mother's behavior on the scale for the MBQS and four scales of the AINS scales (Acceptance, Availability, Cooperation and Sensitivity) during a 20 and 30 minutes video-taped home mother-child interaction. The scales range from -1 to 1 for the MBQS and from 1 to 9 for the AINS scales, with higher scores indicating highly sensitive mothers on both instruments. | 18 months | 
| Mother's Early Life Abuse and Neglect Were Evaluated Using the Childhood Trauma Questionnaire. | The Childhood Trauma Questionnaire (CTQ) is a 28-item self-report retrospective inventory intending to measure childhood or adolescent abuse and neglect, on a 5-point Likert scale ranging from Never True to Very Often True. The central constructs underlying the questionnaire are emotional, physical neglect and abuse, and sexual abuse. The CTQ contains five subscales : 3 subscales assessing abuse : Emotional, Physical, and Sexual abuse 2 subscales assessing neglect : Emotional and Physical neglect. | 24 months | 
| Mother's Eating Behaviours Were Evaluated Using the Dutch Eating Behavior Questionnaire. | The Dutch Eating Behavior Questionnaire is used to assess emotional, external and restrained eating. The 33 items on the DEBQ represent three separate scales: (i) Emotional Eating, with items such as 'Do you have the desire to eat when you are irritated?, contains 13 items; (ii) External Eating, with items such as 'Do you eat more than usual when you see others eating?, includes 10 items; and (iii) Restraint, with items such as 'Do you deliberately eat less in order not to become heavier? ', has 10 items. | 60 months | 
| Mother's Sensitivity to Punishment and Sensitivity to Reward Were Measured Using the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. | The Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) (Torrubia et al., 2001) is a 48 yes/no questionnaire measuring SP (sensitivity to punishment) and SR (sensitivity to reward) functioning. | 60 months | 
| Parenting Style Assessed Using the Parental Authority Questionnaire. | The Parental Authority Questionnaire (PAQ) investigates three prototypes of parental behavior: permissive, authoritative and authoritarian. Each prototype is measured on 10 items on a Likert scale from 1 (disagree strongly) to 5 (agree strongly). The questionnaire was developed to be answered by the child, however, it was adapted in order to let the mother rate her own prototype of parenting. Item scores for each scale were averaged to obtain a total prototype score, with high scores indicating that the mother rates herself to engage strongly in a given parenting prototype. | 60 months | 
| Family Functioning Assessed Using the Family Assessment Device Questionnaire. | The Family Assessment Device (FAD) questionnaire assesses family functioning on each dimension of the McMaster Model of Family Functioning (MMFF) according to individual family member's perception of their family's functioning. In addition to the six subscales of the MMFF (Problem solving, communication, roles, affective responsiveness, affective involvement, behaviour control) the FAD includes a General Functioning scale that measures the overall level of the family's functioning. Sixty statements, geared to an eighth-grade reading level, describe various aspects of family functioning. Each member of the family over the age of 12 completes the pen-and-paper questionnaire by rating how well the statement describes his or her family. There are four choices (strongly agree, agree, disagree, strongly disagree) per item for each dimension. Dimension items are purposely not listed in consecutive order. Each item matches only one dimension and may describe healthy or unhealthy functioning. | 72 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fetal growth retardation, Early adversity, Depressive Symptoms