Attention problems in 6-year-old boys and girls: Differentiating the impacts of being born premature vs. Small for Gestational Age James Hall Oxford Department of Education & Warwick Department of Psychology Oxford Department of Education FELL Seminar Series Wednesday 10 November 2010

Contents Introduction Background to the study Design of the Analysis Key perinatal risks to child development Differentiating the impacts of key perinatal risks Perinatal risks for attention problems: differing neurological mechanisms gender differences MRI scans Background to the study Measures Design of the Analysis Structural Equation Model Results Conclusions Email me at: James.Hall@Education.ox.ac.uk or, J.Hall@Warwick.ac.uk

Introduction Context: Objectives: While both prematurity and Small for Gestational Age births are well known risks for later attention problems, distinguishing their impacts is complicated by mixed evidence concerning mechanisms of effect and by gender differences Objectives: To reliably differentiate the impacts of prematurity from Small for Gestational Age on age 6 attention problems While considering: Potential neurological mechanisms Differences between boys and girls

Small (weight) for Gestational Age (SGA) key perinatal risks to child development At-Birth Developmental Risk: Caused by: As indicated by: Low Birth Weight Prematurity Limited Gestational Age Intrauterine Growth Restriction (IUGR) Small (weight) for Gestational Age (SGA)

differentiating the impacts of key perinatal risks Low Birth Wight (<2.5kg) IUGR Prematurity Very Low Birth Wight (<1.5kg) IUGR Prematurity Extremely Low Birth Wight (<1kg) IUGR Prematurity For ‘low’ birth weight babies, IUGR and prematurity are proportional causal risk factors... ...But as birth weight decreases, so prematurity becomes an increasingly strong predictor... ...With researchers commonly treating very low birth weight as commensurate with very preterm births

Birthweight, Gestational Age, & IUGR Common conflation of perinatal risk factors regardless of gestational age and/or birth weight: Key: Low Birth Weight (LBW) Prematurity (PT) Intrauterine Growth Restriction (IUGR; commonly measured via SGA) Small (birth weight) for Gestational Age (SGA) Birth weight Gestational Age Ex./Very Preterm: Preterm: Fullterm: Ex./Very Low: LBW, PT LBW , PT, IUGR LBW, IUGR Low: LBW, PT, IUGR Normal: PT only No-risk

perinatal risks for attention problems: differing neurological mechanisms & gender differences Differentiating prematurity from SGA is informed by research investigating underlying mechanisms and by mixed results concerning gender differences: Underlying neurological mechanisms: Gender differences: SGA/Prematurity Similarities IUGR and Prematurity: Both are associated with limited growth in infancy Including limitations to brain volume as reflected in head circumference (structure) SGA/Prematurity Differences Prematurity alone: Limited cortical folding (structure) leading to neurocognitive impairments (function) Gender Similarities Gender consistent differences in ADHD children: Same neurological structures implicated: Decreased brain volume Decreased volume of the cerebellar vermis Gender Differences Male preponderance in attention problems has prompted a bias of research aimed at boys: Indicating roles played by damaged frontal lobe and damaged basal ganglia (structures)

Mri scans Prematurity and limitations to cortical folding: Cortical Folding Patterns in Human Development and Disease. David C. Van Essen Washington University in St. Louis Structural and Diffusion MRI Course OHBM, San Francisco June, 2009

Mri scans Prematurity and limitations to brain size (volume) 3D brain model of a preterm infant born at 31 weeks 3D brain model of a fullterm infant born at 40 weeks

Delayed brain maturation in ADHD children Shaw P, Rapoport J, Evans A, et al. Attention-deficit/hyperactivity disorder is characterized by delay in cortical maturation. Proc Natl Acad Sci USA 2007; E-pub 2007 Nov. 16.

Background to the study: The Bavarian Longitudinal Study (BLS; see Wolke, Ratschinski, Ohrt, and Riegel, 1994) Prospective longitudinal study begun in Bavaria 1985-1986 Here examining the attention problems of age 6 children Participants: 1,437 children from birth to age 6 years with measures of attention problems at 6 years rated by both mothers and psychologists Main Outcome: Attention problems at 6 years as measured by: Mother: Attention Problems subscale of the CBCL Psychologists: Task Orientation subscale of the measure entitled “Testers’ Rating of Child Behavior” Developed by the BLS and used to assess child behavior during completion of cognitive tests at age 6 years

Predictor Measures Perinatal Risks: Prematurity (n=563; 39.2%) Birth prior to 37 weeks gestation and measured via : 1) Maternal records of last menstrual period 2) Serial ultrasounds during pregnancy 3) Dubowitz examination Small for Gestational Age (n=359; 25%) Child weighed less than 90% of all gestational age-equivalent Bavarian children born within initial BLS recruitment period (1985-1986)

Predictor Measures Potential Mediators: Cognition (Griffiths Scales of Babies’ Abilities for 0-2 year olds): Total developmental quotient based on: Locomotion (GROSS motor: balance, co-ordinate, control) Personal-social skills (visual recognition of mother, following moving people with eyes and holding a spoon etc) Hearing-speech (startled by sounds, searching for sounds with eyes, vocalisation other than crying etc) Hand-eye co-ordination (FINE motor: moving light with eyes etc) Performance (clasping objects placed in hand etc) Head Circumference (proxy measure for brain volume): Four ordinal categories relative to the total BLS sample: 1= < 3% (n=47; 3.3%) 2= 3-9% (n=105; 7.3%) 3= 10-90% (n=754; 52.5%) 4= > 90% (n=105; 7.3%)

Design of the analysis Girls with Age 6 attention problems rated by mothers Boys with Age 6 attention problems rated by mothers Girls with Age 6 attention problems rated by psychologists Boys with Age 6 attention problems rated by psychologists

Age 6 years: Attention Problems Design of the analysis Age 20 months: Perinatal Period: Attention Problems Head Circumference Premature? (<37 wks) Cognition (Griffiths scales of babies’ development) SGA? (<90%) + Background Confounders

Structural Equation Model Model repeated for psychologist ratings of attention problems Simply switched the measure of age 6 attention problems

Results 3-Way ANOVAs: Correlations Attention problems varied significantly according to: Gender (boys = more) Premature birth (preterms = more) SGA birth (SGA born = more) (NO significant 2- or 3-way interactions, main effects only) Correlations Gender-Specific, stronger in GIRLS: SGA birth with age 20 month head circumference (r=-0.30 compared to r=-0.21 for boys) Premature birth with age 20 month cognition (r=-0.35 compared to r=-0.28 for boys)

Results Perinatal period: Age 20 months: Age 6 years: Attention Problems Cognition Prematurity Head Circumference SGA …However, these results were most strongly apparent only when examining the attention problems of age 6 year old girls as rated by their mothers…

mother-rated age 6 attention problems: Total indirect impacts of prematurity and sga via cognition and head circumference (Stand. Betas)

Psychologist-rated age 6 attention problems: Total indirect impacts of prematurity and sga via cognition and head circumference (Stand. Betas)

Age 20 month female cognition and head circumference: Impacts of prematurity vs. sga (Stand. Betas)

Conclusions Identifying predictors of age 6 attention problems: Differences in attention problems that are commonly found for children born premature and/or SGA can be partially accounted for by interim reductions to age 20 months cognition and head circumference Differentiating preterm from SGA: Via such intermediate reductions we can differentiate the impacts of being born premature vs. SGA. Some evidence that: Prematurity → cognition (function) → attention problems SGA → head circumference (structure) → attention problems However, female prematurity may be a particularly salient risk factor despite its rarer incidence: Although significant levels of female attention problems are rare, they are also more strongly associated with prematurity and SGA than these are in boys Long-term/persistent deficits though?