Effective Early Interventions for Biologically Vulnerable Children: The Importance of Dosage Sharon Landesman Ramey, Ph.D. Susan H. Mayer Professor of Child and Family Studies Director, Georgetown University Center on Health and Education Early Childhood Education Rio de Janeiro December 2009

Scientific Foundations for the new “Education Science” Research on neuroplasticity (animal models) Studies of extreme deprivation (orphanages, maternal deprivation, isolation) Demonstration projects Naturalistic and longitudinal studies Randomized controlled trials (RCTs) to test the efficacy of educational and “whole child” interventions to alter the life course Traditional and innovative “treatments”

Applied Biosocial Contextual Development (ABCD): A Framework for Understanding Human Development

Randomized Controlled Trials (RCTs) we have conducted include:  The Abecedarian Project (ABC)  Project CARE  Infant Health and Development Program (8 sites)  Romanian Orphanage Studies  Intensive Pediatric CI Therapy (cerebral palsy)  National Transition Demonstration Study (31 sites)  Testing pre-K curricula and coaching models  System and statewide scale-up studies Ramey & Ramey

PRINCIPLES OF EFFECTIVE EARLY INTERVENTION 1. Timing (onset, duration, offset) 2. Intensity (per day/wk/mth/yr(s)) 3. Direct learning experiences 4. Breadth of services/supports 5. Individual differences 6. Environmental maintenance Ramey & Ramey (1998), American Psychologist

1. Principle of Timing When the intervention begins and ends significantly influences magnitude of effects Neurodevelopmental theory and research are central to understanding important features of CNS that is rapidly developing at certain ages Development at earlier stages sets conditions for later stages (Cumulative Toll Hypothesis) Clinical practices shifting to earlier treatments Principle is highly similar to that in teratology

Evidence supporting the principle of timing Derives from cross-study comparisons, meta- analyses of > 25 early childhood interventions Usually larger and more lasting effects occur when intervention begins earlier and lasts longer Affirmation in animal experiments Limitation: Inherent confounds in studies related to this principle, since most RCTs that produced the largest gains began earlier, continued longer, and probably were more fully implemented

Synaptogenesis by brain region graph illustrates plausible biological basis for Principle of Timing Adapted from Huttenlocher in Ramey & Ramey Right from Birth (1999)

2. Principle of Dosage (Intensity) Interventions which are more intensive (more hours per day, days per week, total duration) tend to produce larger changes Exact specification of “optimal doses” has not occurred, largely due to cost and pragmatic issues in intervention research Some evidence consistent with “threshold hypothesis” (mostly at lower limits) Highly similar to dose-response curve principle in teratology

Mothers’ Speech and Infant Vocabulary: Naturalistic evidence consistent with RCT support for Principle of Dosage Huttenlocher et al, Developmental Psychology, (1991)

3. Principle of Direct Learning Experiences Interventions that directly alter the child’s experiences (i.e., transactions with others and environment) have greater child benefits than indirect interventions (e.g., parenting and home visiting programs, coordination of service delivery supports, teacher training) Note: majority of early interventions have focused on indirect effects via parenting interventions, based on the hope these would lead to sustainable environmental supports

4. Principle of Breadth of Services/Supports Early interventions that are multi-component and simultaneously address a child’s needs in health, cognition, language, and social-emotional development tend to produce larger and more enduring benefits Limitations: –Research evidence has many confounds, since broader programs also tend to be more intensive and include direct learning experiences –most intervention programs tested in RCTs focused on children with multiple needs and risk conditions (due to natural co-occurrence)

Some children benefit more (or less) This principle has been affirmed primarily by: –Findings that children with greater needs for environmental supports tend to benefit more –Findings that children with more substantial CNS insult may not benefit as much from general enrichment interventions (i.e., not spectrum-specific intervention) –Analysis of individual growth curves Similar to teratology principle of differential genetic susceptibility or Gene X Environment Interaction 5. Principle of Individual Differences

6. Principle of Environmental Maintenance Benefits of early intervention are sustained longer when children continue to receive strong, appropriate environmental supports after early intervention ends Limitation: Almost impossible to separate effects of subsequent depriving or harmful environments (which could reverse benefits of early intervention) from the need for true “maintenance” Influenced by the fact that special needs children display different “issues” that result in “problems” that depend on their age and setting Opportunity to apply new learning and skills may vary, thus enhancing or constraining future development

Examples affirming these principles from some of our longitudinal RCTs Interventions for children from highly impoverished, often chaotic environments (Abecedarian Project and Project CARE; Romanian Orphanage studies) Targeted interventions for –Low birthweight, premature infants (IHDP) –Children with moderate to severe neuromotor impairments (Project ACQUIRE)

An example of a highly intensive, targeted intervention that challenges “conventional practices”

Children with Neuromotor Impairments (Cerebral Palsy) Most highly requested and provided intervention is physical and/or occupational therapy (universal) Most popular therapy is described as Neurodevelopmental Therapy (NDT) Typical dosage is 1 or 2 hourly sessions per week Evidence for 20+ years does not support its efficacy (e.g., Palmer, Shapiro, Wachtel et al, NEJM, 1988; Hur, 2005; Barry, 2001)

Intensive CI-Pediatric Therapy for Children with Cerebral Palsy Based on fundamental principles of learning theory, clinical rehab reports of adults with stroke, and animal experiments First-ever RCT to test a highly intensive form of therapy targeted for children with hemiparetic CP Results demonstrated large and sustained benefits, plus spillover effects (unanticipated) to other domains of development Taub, Ramey, DeLuca, & Echols, Pediatrics, 2002 DeLuca, Echols, & Ramey, Child Neurology, 2006

Key features of Pediatric CI Therapy (ACQUIREc Therapy) Highly intensive (6 hours per day, 21 consecutive days) Direct and active engagement of child as learner Responsive to child’s interests, initial competence Based on learning theory principles Designed to promote generalization Constraint leads child to “focus” on impaired limb, overcome “developmental disregard, eliminate competing responses, create new CNS pathways DeLuca, Echols, & Ramey (2007)

Basic ACQUIRE c Therapy Cycle: MR3 MR3 = Movement-Reinforcement- Repetition-Refinement Movement is encouraged, prompted, and stimulated; movement of the upper extremity starts the cycle Reinforcement is immediate, positive, informative, and rewarding/motivating for the child Repetition occurs immediately, many times, as well as over extended periods of time (i.e., after other MR3 therapy cycles for different skills and movements) Refinement occurs at natural times as skill progresses

The MR3 Cycle in ACQUIREc Therapy 2 Reward 3 Repeat 4 Refine 1 Move

PMAL: Quality Rating of Upper Extremity Movement

Pediatric Motor Activity Log – Frequency of Upper Extremity Use

“Spillover” Effects from Intensive Pediatric CI Therapy Increased positive social-emotional responsiveness Reduced behavioral problems Improved communication skills Decreased sensory aversion to touch Improved gross motor and mobility skills Increased self-confidence and independence DeLuca, Echols, & Ramey, 2007

Individual Differences Principle in Pediatric CI Therapy Trial

Pediatric Neuromotor Research Clinic > 160 children who received standardized full treatment protocol (with systematic documentation of treatment fidelity) Parents (and children, when appropriate) granted informed consent (assent) for participating in clinical study Standardized assessments, pre- and post- treatment

Comparison of RCT and Clinical Research Samples Pediatric Motor Activity Log – Quality of Movement gain scores: 2.0 (RCT) vs 2.4 (CRS) Pediatric Motor Activity Log – Frequency of Use gain scores: 1.9 (RCT) vs 1.9 (CRS) Emerging Behaviors Scale, # of new behaviors: 9.3 (RCT) vs (CRS) Maintenance of benefits at 6 months (and beyond) in both samples

Recent 3-site RCT designed to test dosage effects of ACQUIREc Children (ages 3 – 6) randomly assigned to receive 3 versus 6 hours per day for 21 days Therapists received common training to treatment protocol standards Therapists randomly assigned to children RESULTS presented at AACPMD meeting (Sept 2009) support benefits at both levels, but higher for children receiving 6 hours oer day KEY UNANSWERED QUESTION: Are long- term changes related to initial dosage level?

“Biologically vulnerable children” in Abecedarian Project Children born to lowest IQ (<70) mothers Children with lower APGAR Scores Children with non-optimal Ponderal Index (birthweight to length ratio) Analyses confirmed these children showed greater benefits by ages 3 and 4

ABC Project: Influences on IQ by Child Age Regression Coefficients (95% CI) Age in Months Educational Preschool Maternal IQ<70 Positive Home Environment Adapted from Martin, Ramey, & Ramey, American Journal of Public Health, 1996

Abecedarian Project: Woodcock-Johnson Age-referenced Reading Standard Scores at age 8

Campbell, Ramey, Pugello, Sparling, & Miller-Johnson (2001) Applied Developmental Science The Abecedarian (ABC) Project Longitudinal Effect Sizes for Reading by Treatment Group

Participation Index for Children in Infant Health and Development Composite score generated each year: –Number of completed weekly or bi-monthly home visits to family –Number of monthly parenting information sessions attended –Total days child attended special preschool (only from 12 to 36 months)

Participation Index predicted: Children’s Stanford-Binet scores at age 3 Significant differences in high, medium, and low participation groups – after controlling for other variables associated with levels of participation Low participation level similar to Comparison group (that only received health and social services) Ramey et al, Pediatrics, 1992

Click to edit Master text styles –Second level Third level –Fourth level »Fifth level

IHDP: Heavier LBW ( gm) Intervention Group had mean IQ scores 14 points > Controls Infant Health and Development, JAMA, 1990 Ramey, AAAS, 1996

IHDP: Lighter LBW (< 2000 gm) Intervention Group had mean IQ scores 6.6 points > Controls

Why did the biologically vulnerable LBW infants benefit less? Benefits for lower LBW group (<2000 gm) disappeared by age 5 No cognitive benefits for lower LBW children with cerebral palsy, even at age 3 In McCormick et al (Pediatrics, 2006) 18 yr follow-up hypothesized that participation levels of less than 400 (of 500 possible) days of attendance may have accounted for this weaker effect. Also, lower LBW children more likely to enter Special Education early.

Recent evidence for Dosage Principle for children from low resource environments In Louisiana, a Pre-K program was offered –Full day, Half year –Full day, Full year In Maryland, a highly similar Pre-K program was offered: –Half day

A Comparison of Children’s Academic Progress in Pre-K Programs that differ in dosage

How to think about “dosage” for future research and planned interventions? The most vigorously studied early interventions are for children from under-stimulating and sometimes neglectful life situations For low resource children, increased dosage and participation lead to greater realization of benefits (enrichment dosage) For children with major biological conditions affecting development, more specialized and higher dosage interventions may be essential to realizing benefits