opening pandora’s box - · pdf filesummary of the workshop sponsored by the national...

Opening Pandora’s box

Long-term outcomes of the late preterm infant

Jessie van Dyk, MD

Canadian Association of Neonatal Nurses – ONE Day of Education

Monday, October 6, 2014

9:15 a.m. – 10:15 a.m. 1

Opening Pandora’s boxLong-term outcomes of the late preterm infant

Jessie van Dyk, MD

Sunnybrook Neonatal ICU and Follow Up Clinic

October 2014

2

Overview

• Who are we talking about?

• Why should we suspect long-term problems?

• What are these problems?

• What can we do about it?



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 2

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A little bit of background

• Extremely preterm: infant born at <28 weeks GA

• Very preterm : infant born between 28 to <32 weeks GA

• Moderately preterm: infant born between 32 to <34

weeks GA

• Late preterm: infant born between 34 to <37 weeks GA

• Raju TNK, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late preterm (near-term) infants: a

summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics

2006; 118: 1207-14

• Shapiro-Mendoza CK, Lackritz EM. Epidemiology of late and moderate preterm birth. Semin Fetal Med 2012;

17:120-5

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Developmental Medicine Terminology

• Spectrum in development from typical to atypical

– Normal

– Variant

– Problem

– Disorder

• Wolraich ML, Felice ME, Drotar D, editors. The Classification of Child and Adolescent Mental Diagnoses in

Primary Care. Diagnostic and Statistical Manual for Primary Care (DSM-PC) Child and Adolescent Version. Elk

Grove Village, American Academy of Pediatrics; 1996.



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 3

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Meet Carter

• Born at 34 weeks GA

• Minimal stabilization required

• Initial difficulties establishing feeding

• Phototherapy for neonatal jaundice (rebounded)

• Discharged after 1 week in hospital

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• 9 years old

• Grade 5 this year

• Plays hockey and baseball

• ADHD & Non-verbal learning disability

• Identified at school with learning plan in place



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 4

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Why could there be problems?

• Fastest growing subset of neonates

• Approximately 74% of all preterm births

• Potential maternal and fetal prenatal and

immediate postnatal complications

• At greater risk for neonatal complications

• Increased re-hospitalization & use of

medical services in 1st year of life

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Why could there be problems?

• Brain weight at 34 weeks only 65% of term brain

• Gyral & sulcalformation incomplete

• Cortical volume increases 50% between 34-40 weeks

• 25% of cerebellardevelopment after 34 weeks GA

• Synaptogenesis & dendritic arborizationincomplete



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 5

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Neuropathophysiology

Developmental vulnerability of critical cells

Gray matter architecture distortion

White matter connectivity altered

Cerebellum underdeveloped

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Multi-factorial

Interrupted development

Injury

Co-morbidities

Social/ home



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 6

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Cognitive

development

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Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 7

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• 124 LP vs 33 term infants

• Alberta Infant Motor scale (AIMS) at 6mo & Griffiths Mental

Development Scales (GMDS) at 12 mo chronological age

• LP performed significantly lower on all subscales of GMDS� similar

scores when corrected for post conception age

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• LP infants vs term controls

• Bayley Scales of Infant Development Short Form- Research Edition

(BSF-R) at 24 months chronological age

• LP had higher odds of mental (OR 1.52) or physical (OR 1.56)

developmental delay



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 8

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24 month outcomes

Compared to term infants, increased odds of having:

• More severe mental delay (52%)

• Milder mental developmental delay (43%)

• Severe psychomotor developmental delay (43%)

• Milder psychomotor developmental delay (58%)

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• 61 LP infants vs 60 term infants

• Mental developmental index (MDI) from (BSID-II)

• Using chronological age, significantly lower scores in LP population.

Similar scores using corrected age

• Suggest using scores uncorrected for age to early identify those

who will show difficulties at school age



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 9

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0%

10%

20%

30%

40%

50%

60%

70%

Term (39-41 wks

GA)

Early term(37-38 wks

GA)

Latepreterm

(34-36 wksGA)

Moderatelypreterm

(32-33 wksGA)

Verypreterm

(<32 wksGA)

Not achieved a good level of overall achievement

Not achieved a goodlevel of overallachievement

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Motor development



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 10

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Threefold increased risk for developing cerebral palsy in LP

infants compared with term infants (RR 3.7, 95%

confidence interval 2.9-4.6)

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Children born LP >3 times as likely as term infants to be diagnosed

with cerebral palsy (hazard ratio 3.39, 95%CI 2.54-4.52)



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 11

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Behavioral issues

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• Questionnaires completed by parents and teachers

• 19% of cohort achieved ‘abnormal hyperactivity’ score (vs

population norm 10%)

• Association with poor school performance demonstrated



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 12

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Other

• Executive function deficits especially related to complex memory

tasks (Baron et al, 2012)

• Higher levels of internalizing and attention problems (Van Baar et

al, 2009; Talge et al, 2010)

• At 3, 5 & 8 yrs 20% of LP scored in clinically significant range on

CBCL vs expected 10% (Gray et al, 2004)

• Among LP’s, those admitted to NICU had higher scores on CBCL at

3yrs, especially for aggressive behavior and externalizing

problems (Boylan et al, 2014)

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• No statistical differences in cumulative incidence of ADHD or LD

between LP vs term groups.



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 13

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Medical / other sequelae

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Other outcomes

• Respiratory disease: increased risk of developing asthma (Goyal et al, 2011), recurrent wheeze at 3yrs (Escobar et al, 2010), higher

number of hospitalisations in first year of life due to respiratory

problems (Vrijlandt et al, 2013) ~ remains somewhat controversial

• Possibly higher rates of hypertension in early teenage years Gunay

et al, 2013

• Slightly higher risk to receive social security benefits early adulthood

(RR 1.15, 95% CI 1.12-1.17) Teune et al, 2011



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 14

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In summary

• There are reasons to be concerned

• Cognitive, behavioral, motor and other

• Some inconsistency in literature

• Perhaps inconsistencies due to tool

choice, splintering of skills?

• Multi-factorial pathogenesis

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Where do we go from here?



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 15

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Neonatal care

• Avoid further stressors/ complications:

Insure adequate, robust feeding

Bilirubin

Avoid early discharge

• Counsel and educate parents

• Parental resiliency

• ‘Vulnerable child’

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Social determinants and outcome

Social processes (child-environment/

parenting)

and

Social context (setting in which the child

develops)

Concept of ‘double jeopardy’



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 16

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• Elevated risk for developmental delay among LP vs term (16.7% vs

13.3%)

• No longer significant in adjusted analysis

• Strong association: parenting ability & developmental outcomes

• Consistent with previous research: lack of positive involvement,

punitive discipline because of parenting ineffectiveness,

inconsistency

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Do we really need follow-up?



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 17

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Early identification

• Assessment at 1 month (writhing phase) and 3 months (fidgety

phase)

• Ability to predict CP at 2 yrs: sensitivity 100% (at both visits),

specificity 86% (at 1 month) & 97% (at 3months)

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Early identification

• Case by case ~ understand the nature of the beast

• Individualized follow-up by paediatrician or regional centre (consider risk factors)

• Educate and inform parents & providers

• Be vigilant before & at school-age

• Provide resources where available



Jessie van Dyk, MD



9:15 a.m. – 10:15 a.m. 18

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Take-home points

• Be aware of potential problems

• Postnatal course important

• Home/ social environment

• Closer follow-up (especially with co-morbidities)

• Early identification & intervention

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Thank you

Questions?

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