1. Long-term outcomes of Prematurity Gehan Roberts Centre for Community Child Health, RCH Murdoch Childrens Research Institute Department of Paediatrics, University of Melbourne

2. Contents Introduction – Definition – Prevalence History Outcome studies – Changes over time Intervention studies Future directions

3. Definition Term: >=37 Preterm <37/40 – Late preterm: 33 to 36+6 – Very preterm: 28 to 32+6 – Extremely preterm: <28 Alternative classifications based on birthweight – LBW <2500g – VLBW <1500g – ELBW <1000g

4. Prevalence Late preterm ~7% Very preterm ~1-2% Victoria: 60-75,000 births p. year – About 5000 preterm – About 750 very preterm

5. History Victorian Infant Collaborative Study – ELBW infants (500-999g) – + <28/40 after 1991 5 cohorts – 1979-80, 1985-87, 1991-92, 1997, 2005

6. ELBW infants in Victoria 1979-80 n=351 (3.03/1000 livebirths) 175/yr 1985-87 n=560 (3.06/1000 livebirths) 187/yr 1991-92 n=429 (3.29/1000 livebirths) 215/yr 1997 n=233 (3.77/1000 livebirths) 233/yr 2005 n=257 (3.88/1000 livebirths) 257/yr

7. Traditional Outcomes Survival – Discharge – 2 years Neurological disability – Deafness – Blindness – Cerebral Palsy

8. Survival % survival Era

9. Survival % survival Era

10. Cerebral Palsy % CP Era

11. Blindness % blind Era

12. Deafness % deaf Era

13. Developmental outcomes Increasingly important – More very tiny babies surviving to school-age and adulthood Need to compare outcomes against a control group – How are they doing compared with same-age peers?

14. Cognitive Delay: age 2 % survivors Era

15. What about older children? Cognitive skills – IQ – Language – Attention, Executive function Educational outcomes Behavioural and Psychological outcomes – Autism, ADHD, mood problems

16. School readiness ‘School readiness’ – Term 1 st used a century ago – Assessment framework for understanding profiles of strengths and vulnerabilities of the preschool- age child Very preterm children are at high risk of difficulties in school – 50% have academic/ behavioural difficulties Understanding readiness to learn – potential to aid successful transition into school

17. Definition Three key attributes – Children who are ready to learn – Schools that are ready for children – Parents and communities who support the child’s development. Readiness to learn is further divided into 5 skill areas – 1) Health and physical development – 2) Emotional well-being and social competence – 3) Approaches to learning – 4) Communication skills – 5) Cognitive skills and general knowledge. – Copple, National Educational Goals Panel, 1997

18. Cumulative number of areas of difficulty 0 1 2 3 4 5

19. Meta-Analysis of Neurobehavioral Outcomes in Very Preterm Children. Pooled results from 14 studies – >4000 preterm and >3000 term children Academic outcomes – 0.6 SD lower on mathematics – 04 SD lower on reading Behavior problem – 0.4 SD higher overall, 0.6 SD higher for attention problems Executive function – 0.4 SD lower for working memory Aarnoudse-Moens, Pediatrics, 2009

20. Relationship between gestation and IQ ‘Preterm and low birth weight babies’, Dieter Wolke, Sage Handbook of Developmental Disorders

21. Relationship between gestation and IQ ‘Preterm and low birth weight babies’, Dieter Wolke, Sage Handbook of Developmental Disorders

22. ‘Preterm behavioural phenotype’: increased inattention, anxiety, social difficulties -Johnson et al, Ped Res, 2011 Prevalence of psychiatric disorders at 11 y of age in a population-based cohort 219 EPT (26 wk) children (BLUE) 152 term-born classmates (RED) -UK EPICure Study

23. Swedish national cohort of 1 180 616 children born between 1987 and 2000, followed up for ADHD medication in 2006 at the age of 6 to 19 years

24. Compared with term controls, VLBW adults (age 21 y) are… More conscientious Agreeable Less open to new experiences Less hostile or impulsive Less assertive Independent of age, gender, school achievement, parental education, maternal health Pesonen et. al, Helsinki Study of VLBW adults, J Ch Psychol. Pstychiatr. 2008 Compared with term controls, VLBW adults (age 21 y) are… More conscientious Agreeable Less open to new experiences Less hostile or impulsive Less assertive Independent of age, gender, school achievement, parental education, maternal health Pesonen et. al, Helsinki Study of VLBW adults, J Ch Psychol. Pstychiatr. 2008 Preterm personality profile

25. Meta-analysis of logistic regressions of leisure time physical activity as a function of birth weight. The points depict log(OR) and corresponding 95% confidence intervals Birth Weight in Relation to Leisure Time Physical Activity in Adolescence and Adulthood: Meta-Analysis of Results from 13 Nordic Cohorts. Andersen et al. PLoS ONE, 2009

26. Respiratory health Preterm children, compared with term controls, have… More hospital readmissions with URI/ LRIs More airway obstruction Poorer exercise tolerance ……in childhood, adolescence and early adulthood. This has not been affected by the introduction of Surfactant Smoking probably contributes to worsening of these outcomes Those who had BPD as neonates do worse than those who did not.

27. Quality of life Young adults born preterm: report no differences in the self-reported quality of life despite recognition of their disabilities ‘the disability paradox’ ELBW and control adolescents and their parents provide higher ratings of health-related quality of life for severely disabling hypothetical health states than did health professionals. Saigal, Lancet, 2008

29. Future directions Intervention – Long-term follow-up of promising NICU interventions Caffeine, DHA, antenatal Magnesium – Interventions targeted to areas of vulnerability Working memory Social-emotional development – Novel intervention delivery Web-based?

30. 25 weeks 26 weeks 30 weeks 32 weeks34 weeks40 weeks