1. Neurodevelopmental Outcome of NICU Graduates
Beth Ellen Davis MD MPH
Developmental Behavioral Pediatrics
Clinical Professor of Pediatrics, UW

2. Disclosure Nothing to disclose
“This project is/was supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under T73MC This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government.”

3. Objectives
At the end of this presentation, participants will be able to:
Define degrees of prematurity
Calculate corrected age of preterm infant
List neonatal risk factors associated with Hearing Loss
List ages for ophthalmologic follow up for ROP
Compare and contrast near term risk /full term risks
Describe NDV risk of extremely preterm infants.
Describe the change in NDV risk when hypothermia is used for Hypoxic Ischemic Encephalopathy (HIE)
Be aware of long term disability risks associated with NICU graduates

4. We have come a LONG way!
Patrick Bouvier Kennedy Born 8/7/1963 Died 8/9/1963 Causes of death Prematurity (34.5 weeks gestation) Respiratory Distress Syndrome
5 ½ weeks premature, emergency c-section, 2.11 kg

5. Preterm birthrate down: 9.6%
C +
Great news. We hit the healthy People 2020 goal 7 years early!
This lower rate is a milestone, but still only places the US in the middle of the pack of most developed countries.
Preterm birth affects almost ½ million babies a year and is the leading cause of newborn death in the US.
1 in 9 babies are born before 37 weeks gestation.
From 2013

6. Babies are surviving the NICU NICHD NRN 2003-2007
Stoll BJ, Pediatrics 2010

7. Definitions: weight and gestation
LBW <2500g
VLBW <1500g
ELBW <1000g
Gestation (weeks):
22-26 “Micropremie”
<28 ELGAN
<32 “Very PT”
32-33 “Moderate PT”
34-36 “Late PT”
“Early Term”
39-40 “Term”
>40 “Post dates”
In 2009, most recent data 12.2% births (4,130,665 births) were PT, 9% were late preterm.
ELGAN: extremely low gestational age newborn

8. What is the “limit of viability”?
“Viable”
ELBW >=25 weeks
Unsure
ELBW weeks
“Nonviable”
ELBW <= 22 weeks
<400 grams
<23 weeks, or 400 grams ( If not IUGR )
Of week livebirths, 10% survive.
Of 10 seen at 24 months, 5 have significant developmental disabilities
Neonatal Resuscitation: 2010 AHA Guidelines.
Kattwinkel, Perlman, et al. Pediatrics 2010

9. Complications of Prematurity during NICU stay
IVH
Neonatal Seizures
Sepsis, NEC
Chronic Lung Disease (O2 after 36 weeks)
ROP
Growth and feeding problems

10. Risk of NDV morbidity (disability)
Risk = increased likelihood of disability
Not all who are AT RISK develop disability
Some who develop disability had no risk
Association between risk and NDV outcome does not imply causation
Risk factors vary in their strength of association with the disability
Multiple risk factors have at least an additive effect

11. Not all risk is biologic!
Prematurity exerts a potent but short lived influence on mental development.
Heritage (SES, maternal education) hae a more lasting effect.

12. Rates of (morbidity) major disabilities
Risk factor
Cerebral Palsy
Intellectual Disability
Full term
0.1%
0.4%
GA week
0.3%
0.7%
GA weeks 2% 1%
GA weeks
4-6%
GA weeks
6-16%
4-16%
GA <= 25 weeks
12-23%
21-54%
Full term with respiratory failure
6-13%
13-30%
Moderate HIE
6-21%
21-30%
Severe HIE
41-56%
41-67%
Hypothermia for HIE
19-28%
24-30%
CP, ID, VI, HI, SZ, SLD, Autism
The most common presentation of a developmental disability, is failure to achieve developmental milestones.
Neuromotor delays are often first delays noted.
Failure to achieve age appropriate milestones is the
Marilee Allen, 2011

13. Risk associated with Brain Injury
Ultrasound
abnormality
Cerebral Palsy
Intellectual Disability
GMH
6-8%
11-45%
IVH
12-24%
7-14%
IVH + Dilated ventricle
23-44%
27-67%
Few small cysts
17-59%
WMI/PVL
24-95%
35%
Cerebellar Hem
60%
Marilee Allen, 2011

14. Charlie 6 month old moved to WA from NM Former 34 weeker, 2200 grams
Slow to feed, stayed in NICU 3 weeks
Passed newborn hearing screen
Premature…..low birth weight……late preterm

15. Issues to consider Correcting Age Growth Charts for Premies
Nutrition – Local WA Feeding teams ( )
Late preterm neurodevelopmental outcomes
Audiology recommendations

16. Calculating Corrected Age
Chronological age (CH) = Today’s date – birth date. Charlie is 6 months 18 days.
Corrected age (CA) = CH–(# of days premature)
40 weeks = 39 7/7 weeks = Full term
39 7/7 – 34 3/7 = Infant was born 5 4/7 weeks (39 days) early.
6 months 18 days – 39 days = 5 month 9 days
All programs correct until 2 years of age, some until 3 yrs (esp if week gestation).

17. Post delivery growth of preterm infants
Until “term” or up to 2 months CA, plot growth on 2013 Fenton Preemie growth charts.
After term (due date), document CH and CA on regular growth charts .
From PEDIATRICS publication 2013

18. Immunizations RSV prophylaxis “Bronchiolitis” 1st year 2nd year
ALL infants < 29 weeks
<32 weeks + CLD
Infant with CHD
2nd year
CLD + meds
Consider for children with pulmonary, neuromuscular and immunocompromised states
synagis
Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics (2):

19. NDV risk of Late Preterm
Moderate Preterm
Late
Preterm
Early Term
Full Term
Gestational age (weeks)
32-33
34-36
37-38
39-40
Twins
14.5 %
49.8%
Triplets
35.5%
43.6%
Readmission in first 6 mo.
>9%
6-8%
Risk of CP 2%
.3%
.1%
OR of SPED at 4-19 years
(33-36 weeks)
1.53
1.0
>80% of all preterm are weekers!
At 34 weeks, the brain weight is 60% of full term brain.
Risk for dev/ behavioral and emotional morbidity
Describe risk:
Vohr, Clinical Perinatology, 2013

20. Risk Factors associated with Hearing Loss
Caregiver concern
Family history of childhood HL
NICU stay > 5 days, or various NICU interventions (assisted ventilation)
In utero infection
Exam findings c/w syndrome
Others
Every child with >= 1 risk factor should have
at least 1 diagnostic audiology
assessment by months

21. Annie 24 month old well child check with language delay.
32 1/7 week gestation, 1300 grams (VLBW)
Ventilated for 4 days
Serial cranial ultrasounds were normal
Stage 1 zone 3 ROP, resolved
Passed newborn hearing test
Moderate preterm, vlbw

22. Issues to consider Risk of HI Risk of ASD Risk of visual impairment
MCHAT-R/F
Risk of visual impairment
Refer to High Risk Infant Follow Up Clinic

23. Risk for ASD in Preterms
High rate of + MCHAT
21% if <28 weeks gestation, and still 16% when all complications of prematurity eliminated
26% if <1500g
Prevalence 1.78% <37 wk vs 1.22% >=37 wk, and increased with decr. gestational age.
Risk of ASD 3 x higher for <27 weeks ( %).
MCHAT may not be appropriate screener for HRIF clinics.
Retrospective cohort of infants born >= 24 weeks at Kaiser (N 195,021)
ASD based on KP ASD evaluation center
Kuzniewicz, JPediatr 2014;164: 20-5

24. ASD features in VLBW toddlers
Wong HS, J Pediatr 2014;164:26-33

25. Risk of Vision Impairment with Retinopathy of Prematurity
Risk for VI
1% <37 weeks
1-2% <28 weeks
9-12% weeks
American guidelines recommend ophthalmologic follow –up in children with history of ROP within 4-6 months of discharge.
Consider additional follow up at 2.5 years and upon entry to school, and adolescence.
Fierson WM, Joint Clinical Report: Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2013 Jan, 131(1)

26. FIND A NICU GRADUATE NEURODEVELOPMENTAL ASSESSMENT CLINIC
At CHDD we see: <32 weeks,
< 1500g,
And /or complications
And/or provider concerns
And/or prenatal substance exposure

27. Jeremy 750 gram, 27 week gestation RDS, required oxygen for 80 days
Grade II IVH
No ROP
Passed newborn hearing screen
At 4 months of age, parents want to know how he is doing developmentally.
Extremely low birthweight, ELGAN

28. Issues to consider NDV outcomes of ELBW
Of children born extremely preterm who received active perinatal care (2004-7) 73% had mild to no disability and NDV outcome improved with each week of gestational age!
Serenius F, ND Outcome in extremely preterm
infants at 2.5 years after active perinatal
care in Sweden, JAMA 2013;309 (17)

29. Neurodevelopmental Outcomes of 22-25 weekers
Death or disability rates at 22 wk close to 100%
Moderate to severe disability rates at wk
Rates of mod/severe disability are high but decrease at weeks
Rates of Bilateral deafness and blindness increase with decreasing gestational age
Multidisciplinary follow up, EI, and educational support are indicated for all infants weeks

30. Intraventricular Hemorrhage (IVH)

31. 5 risk factors are especially important for cerebral palsy
IVH grade 3-4, ventriculomegaly, or Cystic PVL
Postnatal sepsis, meningitis or NEC
Chronic lung disease
Severe ROP
Multiple gestation
Cerebral palsy is a disorder of movement and posture that invovles abnormalities in tone, reflexes coordination and movments, dleays in motor milesontes. Primative reflexes persist longer than typical (such as moro, and weakness emerges such as head lag).it is non progressive but can change with time, resulting from an abnormallity of the developing brain. The most common type of CP in preterm infants is spastic diplegia. Many providers use the GMFCS to classify the severity of CP.
The rate of CP in ELBW infnats at 18 months is 15%. Much more common is fine and gross motor coordination deficits. Transient dystonia (increased extensor tone and atypical movements) occurs in 21-36% of PT infants peeking at 7 months. DCD in VLBW 31-34% and 5-% of ELBW.
Michael msall’s review called Advances in Understanding CP syndromes after prematurity NeoReviews Vol 7 No 11 Nov 2006

32. “Normal” ELBW
Figure 3. Selected Neurodevelopmental and Medical Complications
at 8 to 9 Years of Age in Children with Extremely Low Birth Weight (ELBW)
but No Apparent Neurosensory Abnormalities at Initial Hospital Discharge
(termed “normal” ELBW),as Compared with Term Controls.
Data are from Hack et al. ref 17 in
Eichenwald EC, “Management and Outcomes of VLBW” NEJM :

33. Full term HIE Neuronal rescue using neonatal hypothermia
“cooling caps”
32F-34F within 5.5 hours of HIE
For hours
At age 6-7 years, more “cooled” children survived without neurologic abnormalities (45% vs 28%).
Less risk of CP
Less risk of mod/severe disability
Azzopardi D, NEJM 2014;371:

34. Risk across the lifespan….. The role of the medical home!
Parent care
School age
Adolescent and Adult

35. Issues to consider Parent screening Developmental screening
Emotional and Behavioral screening

36. Changes in your practice?
Use corrected ages
Use Preemie growth charts
Refer preemies to a High risk Infant Follow up Clinic if it is available.
Refer preemies to Early Intervention in 1st year, and subsequently, if needed.