1. WHAT IS NEXT FOR PRETERM INFANTS? l Melissa R. Johnson, Ph.D. l WakeMed l November 2008

2. DEVELOPMENTAL CHALLENGES l Medical l Social l Environmental

3. MEDICAL ISSUES l Respiratory issues »Respiratory Distress Syndrome (RDS) »Chronic Lung Disease (CDL) »Bronchopulmonary Dysplasia (BPD) »Pneumothorax

4. NEUROLOGIC ISSUES l Intraventricular hemorrhage (IVH) »Grades I-IV (some don’t use) »Outcome NOT certain l Periventricular leukomalacia (PVL) l Very worrisome but NOT certain- symmetry matters l Hypoxic-ischemic encephalopathy (HIE) l Cerebral palsy (CP) / Chronic encephalophy

5. VISUAL ISSUES l Retinopathy of prematurity (ROP) »Cause still debated »Therapies still improving »Close follow-up often critical

6. Other medical issues l Necrotizing enterocolitis (NEC) l Other infections l Other causes of prolonged illness, poor nutrition

7. PSYCHOSOCIAL CHALLENGES l Poverty and other chronic stressors l Substance abuse l Maltreatment history in family of origin l Domestic violence l Parental mental illness

8. l Attachment difficulties l Other family and community stresses –Child care –Siblings –Language –Transportation –Education

9. ENVIRONMENTAL CHALLENGES l NICU environment »Sound, light, handling, positioning, parental access l Loss of expected environment for brain development

10. DEVELOPMENTAL TRENDS IN OUTCOME l Literature keeps growing l Babies are surviving smaller, younger l Doctors have more tools to help »High frequency ventilators, better CPAP »Artificial surfactants »Better nutrition strategies

11. A look at the research l Complicated, but still helpful l Rapidly evolving l Variability- numbers, SES, percent followed, location, size at birth, age at follow-up, source of FU info, control group, etc etc etc l Below: a few of best studies from 90’s and some from 2000-2008

12. 20 MO. OUTCOME OF ELBW l 114 premies from 500-750 g l Born 1990-1992; compared to 82-88 l Survival from 600-700 grams increased from 23% to 43% l 20% MDI <70, 10% CP – Hack et al, JAMA vol. 276, 1996

13. PATTERNS OF COGNITIVE DEVELOPMENT l Looked for patterns - under 1500 g N=203 to age 6 l 37% stayed in average range l 42% declined from average to below average- mostly after age 2 l Only 8% improved – Koller et al, Pediatrics vol 99, 1997

14. ELBW OUTCOME AT 8 YEARS l 156 survivors 501-1000 compared to matched controls in Ontario, CN l Used multiattribute health status classification

15. l 14% had no functional limitation; 58% had reduced function in one or more areas; 28 % had three areas affected. Controls: 50%, 48%, 2% l Areas most likely to be affected: cognition, sensation – Saigal et al, J. Peds, vol 125, 1994

16. ELBW BEHAVIORAL OUTCOME AT 8 YEARS l 81 survivors 800 g or less; matched controls l Lower global IQ’s, fm skills l Trouble with persistence, easily discouraged, needed much adult support and approval l “Subtle organizing problems” »Grunau (quoted in Aug 1995 Peds News)

17. MATERNAL COMPLIANCE AND OUTCOME l 152 infants under 1000 g; 110 compliant, 42 noncompliant w/ EI fu l MDI scores: compliant = 75.59 noncompliant = 68.24 l PDI scores: compliant = 82.97 noncompliant = 74.54 – Bonnet et al, Pediatrics supplement, 1998

18. ELBW OUTCOME AT 18 MO. l 1151 babies 401-1000 g. l Only 1/3 under 900 g had MDI >85 l 60% 901-1000 g > 85 l Neuro exams, walking, etc better l Best predictors: IVH, BPD, family ed – Vohr et al, SPR abstract, 1998

19. OUTCOME FOR SWEDISH ELBW CHILDREN l 633 babies followed prospectively l survival over 23 wks- 59% l 362 assessed at 36 mo l 25 had CP, 16 blind l 86 % functionally nl- range from 69 % for 23-24 wks to 91 % for >27 wks – Finnstrom et al, Acta Paediatrica 1998

20. SCHOOL-AGE OUTCOME l 68 <750 g; 65 between 750-1499 g l Neonatal risk index predicted outcome better than social risk index (surprise) but proximal social risk more sig. l Of hi NRI kids, only 15 % had IQ >85 l Of lo NRI kids, 33 % had IQ > 85 l 38/26 % had behavior problems – Taylor et al, Devel. & Behav Peds, 1998

21. UNDER 801 G- AGE 5 OUTCOME l Compared survivors from ‘83-’85 vs ‘86-’89 (% survival the same- more under 600 g) l No sig. difference between cohorts l 21% had severe disabilities l Sig. factors: ICH and SES – Kilbride & Daily, J. Perinatology, 1998

22. OUTCOME FOR 12 YO VLBW CHILDREN l 138 children under 1250 g and 93 under 1500 g born from ‘80-83 (UK) l Compared to matched controls, 8 pts lower IQ- mainly due to Performance.

23. l 12% of VLBW and 7% of controls below 70. Gaps widened from age 6 to 12. l 35% of VLBW needed remediation (12% of controls) – Botting et al, Devel Med Child Neuro, 1998

24. TEEN SCHOOL OUTCOMES l 150 500-1000 g survivors, controls l Born 1977-1982 l Neurosensory impairments in 28 % of ELBW, 1% of controls l Mean IQ = 89 l Spec. Ed or retained: 58 % vs. 13 % Saigal et al, Peds, 2000

25. OUTCOME FOR ELBW TODDLERS l 1151 4001-1000 g survivors in NICH network, seen at 18-22 mo, b. 1993-1994 (78%) f/u l 25 % had abnl neuro exam l 37 % Bayley II MDI < 70 l 29 % Bayley II PDI, 70 l 9 % vision impairment l 11 % hearing impairment »Vohr et al, Pediatrics, 2000

26. MORE ELBW TODDLERS l Born 92-95, seen at 20 mo l 24 % major abnormalities l 42 % Bayley II MDI, 70 l Neurosensory abnormalities and/or low MDI = 48 % »Hack et al, Seminars in Neonat, 2000

27. SWEDISH LBW OUTCOME AT 10 l 61 of 65 10 y.o. survivors b. at under 29 wks compared to controls (b. 85-86) l Mean IQ of preterms = 90; controls = 106 l 38 % of preterms below grade level l 32 % had behavior problems; 10 % of controls

28. l 20 % had ADHD, 8 % of controls l 30 % in SE, 1.6 % of controls »Sternqvist, Ab Initio Intl, 2001-2002 www.childrenshospital.org/brazelton/abiniti o/art2.html

29. VLBW OUTCOME AT 20 l 242 survivors from 1977-1979, controls l HS grads: 74 % of preterms, 83 % of controls l Men, but not women, less likely to continue studies l 10% had neurosensory impairments; l 1 % of controls

30. l Preterms had lower rates of ETOH, drugs, pregnancy, even without impaired group. »Hack et al, NEJM, 2002

31. 15 YR F/U OF PRETERMS AFTER SURFACTANT l < 29 wks b. 1985-87 followed at 7 and 14 (126/132) l At 7, 31 % nonimpaired; 21 % severe impairment; 32 % in self-contained SE 19 % CGI < 70; 15 % CP

32. l As teens, CP same; 29 % SE; 19 % had 1 severe disability; 41 % had no impairment. l Conclusion: even with surfactant, sig minority will have ongoing compromise l D’Angio, Pediatrics, Dec. 2002

33. Chance for improvement?! l Longitudinal data on PPVT-R on 296 children under 1250 g l Scores increased from 88 at 36 months to 99 at 96 months; similar for IQ verbal and FS scores l Mat ed and 2 parents helped l NOT for children with worse IVH »Ment et al., 2003

34. Academics at ages 11 and 17 l Detroit area preterm children tested on Woodcock-Johnson l 3-5 point deficits independent of family factors and urban/suburban l At 17, preterms 50% more likely to score below the mean in both reading and math ; cog deficits noted at age 6 Breslau, Paneth & Lucia, 2004

35. ELBW infants with NL HUS l Babies born ‘95-’99 under 1000 g with NORMAL head ultrasounds l Nearly 30% had either CP or MDI ↓ 70 l Lung problems (pneumothorax, long vent) and low SES were related »Laptook et al, 2005

36. Behavioral outcomes l Large French study compared preterm to term children at age 3 l Preterms had much higher levels of behavior problems; Children in “high” total range- 20% of preterms, 9% of term. »Delobel-Ayoub et al, 2006

37. Emotional regulation and development l ER scale from Bayley II: attention, frustration tol, coop, activity, hypersensitivity l Income and ER influenced MDI l Poorer ER associated with lower MDI even controlling for income »Lowe, Woodward & Papile, 2005

38. Outcome for families l Study of impact of ELBW birth on families at school age l Impact greater in ELBW than controls l High parent/SES risk, neurodevel outcome, and functional impact of chronic conditions predicted greatest family impact »Drotar et al, 2006

39. NEC and development l Babies under 1000 g vs controls l More babies with NEC had lowered PDI l Entire preterm group had lower MDI compared to controls »Salhab et al., 2004

40. Infections and development l Multicenter study of children under 1000 g l Infections predicted more CP, lower MDI and PDI scores, and more vision impairment »Stoll et al, 2004

41. How many domains? l Under 30 week sample of 157 children seen at age 5 (Dutch) l 39% “normal” l 17% single disability l 44% multiple disabilities »Van Baar et al., 2005

42. 8 year f/u of under 1000 g l Born ‘92-’95, 219 children, controls l Need for services: 65% vs 27% l Functional limitations: 64% vs 20% l CP 14% vs 0, IQ ↓ 85 38% vs 14% l Sig impact on motor skills, academics, adaptive, health »Hack et al, 2005

43. What about bigger premies? l Study of 32-33, 34-36, and term babies l Followed K-5 l Bigger premies had a range of academic delays compared to term; more special ed, more teacher concerns »Chyi et al, 2008

44. Prematurity and later mental health l F/U to teens of non-handicapped preterms- increase in psych sx, esp anxiety and depression (Schothorst et al, 2007) l Lg group in adulthood- increased depression (Nokumura et al, 2007) l LBW predicted depression in NC teen girls, not boys (Costello et al, 2007)

45. BUT some GOOD news l Compared group of 501-1000 g with term births at ages 22-25 (Canada) l 90% follow up l Similar % grad HS (82-87%) l 33-34% in post-secondary ed l Except for disabled, similar % working or in school, living on own, married, parents »Saigal et al, 2006

46. WHAT WE DON’T KNOW AND WHY l Why disability rates have stayed high l How any individual baby will do, as specifically as families need l For certain, what interventions are most effective, when and why

47. WHY SO HARD TO ANSWER? l Research varies as to age and size group, timing of follow-up, size of N, use of controls, % followed, instruments used, definitions l Research published now based on babies born several years ago l Interaction of medical, social and environmental variables

48. l Inconsistency of early intervention l Inconsistency of special ed eligibility, definitions and services l CONCLUSION: THESE BABIES ARE SPECIAL. LET’S OFFER AS MUCH HELP AS POSSIBLE!