1. Management of Preterm, Small for Gestational Age Infants: Before Birth to Adolescence Exploring the Maze

2. Pediatrician: You are called to the high risk pregnancy unit for a consultation: Primigravida at 25 weeks Hypertensive: BP = 160/110 3+ proteinuria on dipstix Headache Peripheral oedema with 6kg weight gain in the past 4 weeks

3. Investigations: Bloods: Hb 140g/L WCC 18,000 Plats 103 x 10 9 /L MPV: 12.9 Uric Acid 467 AST 25 Albumin 29

4. Investigations Ultrasound: EFW: 450g (HC at 5th %ile, AC and FL <1%ile) AFI 76 Umb arterial doppler: S/D ratio 7.2 What else do you need to know? What are you going to say?

5. Obstetrical Determinants of Survival and Handicap Antenatal treatment with glucocorticoids: 50% reduction in RDS related mortality in later GA Willingness to perform c/section for >800g C/section for <800g associated with more handicap Obstetricians routinely underestimate neonatal prospects for survival and survival without handicap

6. Perinatal Outcomes at 23 -28 wks GA 1983-1989 n=1024 Still birth rate Synnes et al, 1994

7. Perinatal Outcomes at 23 -28 wks GA 1993-1997 n=278 Still birth rate El-Metwally et al 2000

8. LDR Deaths Synnes et al, 1994

9. LDR Deaths El-Metwally et al 2000

10. Death < 7 days Synnes et al, 1994

11. Death 7 - >28 days Synnes et al, 1994

12. Survival to discharge Synnes et al, 1994

13. Survival to discharge El-Metwally et al 2000

14. Management 25 wks gestational age by early u/s 13% still birth11% LDR death66% live to NICU 23% death < 7 days 6% death <28 days 6% death >28 days 55% survival to d/c NICU morbidity 55% PDA 23% Sepsis/Meningitis 43% Air leaks 6% NEC 18% IVH 66% BPD Synnes et al, 1994

15. Major Morbidity and Mortality vs Birth Weight NICHHD, 2001

16. 18 month outcomes for 25 wks GA 32% impaired 17% CP13% Blind2% Deaf 10% Low MDI Synnes et al, 1994

17. Other Factors to Consider Multiple gestation Gender SGA Antenatal steroids

18. Effect of SGA on Mortality: 25 wks GA Synnes et al, 1994

19. Cognition and SGA vs AGA Significantly greater cognitive and neurologic morbidity in SGA vs AGA No differences by birth weight between the groups in cognitive performance or neurologic status Cognitive impairment associated with neurologic abnormality in both groups Higher incidence of neurologic deficit in SGA infants greater cognitive impairment in the SGA infants McCarton et al, 1996

20. SGA vs AGA with Neurologic Impairment Percentage of AGA and SGA preterms with cognitive retardation as a function of neurological status Cognitive test scores as a function of neurological status at 3 years in AGA and SGA preterms. McCarton et al, 1996

21. Patient DR Resuscitated by resident with bag and mask positive pressure ventilation with 100% F i O 2 Pediatrician arrived at 1-2 minutes age Infant was pink and crying without intubation Neonatologist arrived at 10 minutes of age and full treatment was decided to be undertaken Infant intubated in DR and transported to NICU Apgars 6/7/8

22. Postpartum History Vitals: temp 34.8 HR 144 RR 52 Weight 480 g (<5%) Length 28.5 cm (<5%) HC 22 cm (5%) Bruises over scalp buttocks Hct 39%

23. NICU Course Respiratory –HMD ventilated 25 days with 105 days O2 –BPD noted on day 27 –Apnea x 54 days treated with aminophylline CNS: normal cranial u/s OPHTHO: ROP grade 2 on day 64 GU: bilateral inguinal hernia repair

24. NICU Course FEN/MET –Hyperglycemia day 9 with insulin drip –Umbilical artery catherization, TPN –Osteopenia of prematurity day 38 –Low T 4 associated prematurity HEME: –Anemia of prematurity and iatrogenic loss –Multiple blood transfusions GI: jaundice peak 7.8mg/dl onset day 2 ID: suspected sepsis x 2

25. Impact of NICU Practices on the Developing Brain Excess free radicalsO 2, iron High frequency ventilation with low lung volume? Hypocarbia/hypercariba or rapidly changing P a CO 2 levels? Caffeine? Postnatal steroids Indomethacin ok? Dopamine? Sulfite preservatives? High osmalality drugs? Anesthetics and pain meds: fentanyl vs. morphine, versed? Stimulation: visual, auditory, pain Hyperthermia Gressens et al, 2002

26. Discharge 42 ½ weeks gestational age 113 days chronological age 2440g HC 35 cm Length 43 cm Meds: vits

27. 4 months follow-up Growth –3400g (<3%) –length 51.9cm (<3%) –HC 40cm (10%) Scars: right nasal notching, heel scars Neurodevelopmental exam: –some decrease truncal tone –poor head control

28. 8 months corrected age Growth <5% –5780g –Length 61.6cm –HC 42.7cm Neurodevelopmental exam: –Slight decreased tone and strength –Poor balance –Immature uncoordinated grasp –Minimal vocalizations –Crab-crawls –Not pulling to stand Eye exam normal

29. 18 months corrected age Growth (<5%) –7590g –Length 72.5cm –45.8cm Neurodevelopmental exam: Bayley = 17month –Strongly right-handed –Babbling, using a few words –Abnormal movement: scooting on bottom using left arm –High activity, low persistence and short attention

30. 3 years Growth –10.74 kg (-2.74 SD) –88.4cm (-2.66 SD) –47.5cm (-2.65 SD) Neurodevelopment –Soft, hoarse voice referred to ENT for evaluation –Better expressive than receptive language –Difficulty following longer directions –Peabody motor scales 31 months: balance problems, right hand dominant, immature fine pincer –Stanford-Binet low average

31. 4 ½ years Growth –11.8kg (-2.98 SD) –96.2cm (-2.32 SD) –HC 47.8cm (-2.64 SD) –Bone age 4 years at 4 years 10 months PET tubes Neurodevelopment: bounced around the room –High pain tolerance –Slight incoordination –Right side preference –Cognition: 77% verbal; performance 8% –Nonverbal: 16% –Visual-motor: 9% –Visual-Motor Integration: 14%

32. 8 years Growth: –23 kg (-1.19 SD) –Height 121cm (-1.69 SD) –HC 49.7cm (-1.64 SD) Neurodevelopment: recommend learning assistance –Right-side dominant –Tight hamstrings –Brisk reflexes –Poor balance –Average cognitive, poor non cognitive –Poor recall of visual patterns/spelling –Poor arithmetic –Poor pencil use

33. 14 years Growth –48.3kg (-2.38 SD) –153.1cm (-1.39 SD) –51.5cm (-2.43 SD) Neurodevelopment –Psyched eval: complex learning problem especially with math –Poor output and distractible –Difficulty keeping on task –Verbal within normal range, better comprehension than expression –Performance 10%

34. Outcomes in Young Adulthood: Educational disadvantage associated with VLBW persists to early adulthood 20 year outcomes for 242 survivors mean 29.7 wks, 1179g vs. 233 controls with normal birth weight 51% normal IQs Fewer high school grads: 74% v 84% (p<0.04) Less postsecondary study: 30% v 53% (p<0.04) Subnormal height: 10% v 5% (p<0.04) Neurosensory impairments: 10% v 1% (p<0.001) Hack et al NEJM 2002