WHAT IS NEXT FOR PRETERM INFANTS?

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

2. DEVELOPMENTAL CHALLENGES • Medical • Social • Environmental

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

19. OUTCOME FOR SWEDISH ELBW CHILDREN • 633 babies followed prospectively • survival over 23 wks- 59% • 362 assessed at 36 mo • 25 had CP, 16 blind • 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 • 68 <750 g; 65 between 750-1499 g • Neonatal risk index predicted outcome better than social risk index (surprise) but proximal social risk more sig. • Of hi NRI kids, only 15 % had IQ >85 • Of lo NRI kids, 33 % had IQ > 85 • 38/26 % had behavior problems • Taylor et al, Devel. & Behav Peds, 1998

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

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

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

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

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

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

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

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

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

30. 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 • < 29 wks b. 1985-87 followed at 7 and 14 (126/132) • At 7, 31 % nonimpaired; 21 % severe impairment; 32 % in self-contained SE 19 % CGI < 70; 15 % CP

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

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

34. Academics at ages 11 and 17 • Detroit area preterm children tested on Woodcock-Johnson • 3-5 point deficits independent of family factors and urban/suburban • 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 • Babies born ‘95-’99 under 1000 g with NORMAL head ultrasounds • Nearly 30% had either CP or MDI ↓ 70 • Lung problems (pneumothorax, long vent) and low SES were related • Laptook et al, 2005

36. Behavioral outcomes • Large French study compared preterm to term children at age 3 • 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 • ER scale from Bayley II: attention, frustration tol, coop, activity, hypersensitivity • Income and ER influenced MDI • Poorer ER associated with lower MDI even controlling for income • Lowe, Woodward & Papile, 2005

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

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

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

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

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

43. What about bigger premies? • Study of 32-33, 34-36, and term babies • Followed K-5 • 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 • F/U to teens of non-handicapped preterms- increase in psych sx, esp anxiety and depression (Schothorst et al, 2007) • Lg group in adulthood- increased depression (Nokumura et al, 2007) • LBW predicted depression in NC teen girls, not boys (Costello et al, 2007)

45. BUT some GOOD news • Compared group of 501-1000 g with term births at ages 22-25 (Canada) • 90% follow up • Similar % grad HS (82-87%) • 33-34% in post-secondary ed • 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 • Why disability rates have stayed high • How any individual baby will do, as specifically as families need • For certain, what interventions are most effective, when and why

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

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